bluuebunny/crossref_metadata_2025 huggingface dataset:
Gravitational constant model and correction
Authors: Chen Yu-Jie , Li Shi-Lin , Chen Yu-Zhu , Li Wen-Du , Dai Wu-Sheng
Published: November 2022

We construct a model for considering the quantum correction of the gravitational constant. In the model, the gravitational constant originates from a coupling between the gravitational field and a scalar field. If the scalar field, as it should be in the real physical world, is a quantum field, the gravitational constant will have a quantum correction. The quantum correction, generally speaking, varies with spacetime coordinates. Therefore, the gravitational constant is no longer a constant. In different spacetime, the quantum correction is different, for the coupling in different spacetime is different. As a result, the gravitational constant in different spacetime is different, though the difference is only at the quantum level. We calculate the quantum correction of the gravitational constant in the Schwarzschild spacetime, the H3 (Euclidean AdS3) spacetime, the H3/Z spacetime, the universe model, the de Sitter spacetime, and the Rindler spacetime.
Controllable semiconductor flexoelectricity by interface engineering
Authors: Wang Zhiguo , Liang Renhong , Hu Yongming , Li Chunchun , Li Fei , Ke Shanming , Shu Longlong
Published: November 2022

Flexoelectricity of semiconductors usually exhibits large flexoelectric coefficients due to their significantly enhanced surface piezoelectricity caused by surface symmetry breaking. In this Letter, we reported a general paradigm to tune the semiconductor flexoelectricity through interface engineering. We selected Nb-SrTiO3 (Nb-STO) single crystals as the targets and tuned their surface piezoelectricity through depositing TiO2-terminated and SrO-terminated ultra-thin BaTiO3 (BTO) films. The results suggested that the deposition of TiO2-terminated and SrO-terminated ultra-thin BaTiO3 films to Nb-STO can induce a downward and upward out-of-plane surface polarization, respectively, thereby significantly increasing/decreasing the apparent flexoelectric coefficients of Nb-STO single crystals. Our work proves the feasibility of interface engineering in the application of flexoelectricity and also provides a possible route to achieve the large apparent flexoelectricity of semiconductor materials.
Development of gamma-ray-induced positron age–momentum correlation measurement
Authors: Taira Yoshitaka , Yamamoto Ryohei , Sugita Kento , Okano Yasuaki , Hirade Tetsuya , Namizaki Shogo , Ogawa Toshio , Adachi Yoshitaka
Published: November 2022

In conventional positron annihilation spectroscopy using radioisotopes, source contributions are unavoidable since positrons annihilate in the material covering the radioisotopes. Part of the positrons annihilate within the radioisotopes even when radioisotopes are deposited directly on a sample. Gamma-ray-induced positron annihilation spectroscopy makes it possible to measure only the spectra of a sample without source contributions since positrons are directly generated inside the sample from the gamma rays by pair production and annihilate inside the same sample. In this study, a new positron age–momentum correlation measurement system using ultrashort pulsed gamma rays is developed. The gamma rays with an energy of 6.6 MeV are generated by the inverse Thomson scattering of laser photons by high-energy electrons and are irradiated to the sample. The laser pulse can fully control the timing of gamma-ray generation. This characteristic and the use of a digital oscilloscope with a 12-bit vertical resolution enable us to develop a simple measurement system. Time-resolved momentum distributions for stainless steel with no defects and deformed interstitial free steel show the explicit differences reflecting the type of defect; for BaF2 single crystals, the results have been interpreted by considering the formation of positronium.
Resonance effects in the radiation transfer of thin-film intracavity devices
Authors: Kivisaari Pyry , Oksanen Jani
Published: November 2022

A great deal of interest has been recently directed at exploring how the performance of photovoltaic and thermophotovoltaic systems can benefit from the use of ultra-thin layers and near-field effects. Related questions on how radiation transfer is modified if both the source and sink of the radiation are located within an optical cavity have, however, received far less attention. This question is, nevertheless, particularly relevant in the field of electroluminescence-driven thermophotonics, which could substantially benefit from the possibility to boost the energy transfer by making use of optical cavities. To gain insight into this possibility, we deploy fluctuational electrodynamics and study the fundamental resonance effects in structures where the emitter and absorber layers are separated by a vacuum nanogap and bordered by high-efficiency mirrors. We obtain the expected result that resonance effects can strongly enhance the interactions at specific wavelengths and propagation angles. Moreover, we find that even after integrating over wavelength and propagation angle, (1) the total power emitted can be tuned by adjusting the cavity thickness and the optical cavity mode structure, and (2) thinning the active layer enhances its emission in the cavity, causing a sublinear dependence between the active layer thickness and its overall emission. In plain numbers, adjusting the cavity thickness produces non-monotonous changes of over 50% in the total emission of thin layers. These observations apply also to absorption, which can become remarkably efficient even for an extremely thin absorber layer, thanks to cavity effects.
Effects of ion to electron temperatures on electrostatic solitons with applications to space plasma environments
Authors: Jao C.-S. , Hau L.-N.
Published: November 2022

Electrostatic solitary waves (ESW) and solitons are widely observed nonlinear plasma phenomena in various space environments, which may be generated by the electron streaming instability as shown in many particle simulations. The predicted electron holes associated with the ESW, however, are not observed by the recent high resolution spacecraft. This raises a possibility for the ion acoustic solitons being the potential candidate, which are described by the Sagdeev potential theory with hot electrons and cold ions being treated by the kinetic equilibrium and fluid models, respectively. The assumption of Ti/Te=0 adopted in the theoretical models for ion acoustic solitons, however, imposes a great constraint for the space applications considering that Ti/Te may vary in a wide range of 0.1–10 in the Earth's space environments. This paper examines the effect of Ti/Te on ion acoustic solitons by including a finite temperature in the fluid equations for the ions, which, however, can no longer be solved based on the standard Sagdeev potential method. It is shown based on the nonlinear theory that larger Ti/Te may result in larger propagation speeds and the critical flow velocity for the existence of steady solitons increases with increasing Ti/Te values. The nonlinear solutions for various Ti/Te values may be characterized by an effective Mach number. For Ti/Te ≫ 1 the hot ions and cold electrons shall be described by the kinetic and fluid models, respectively, which may result in negative electric potentials opposite to the standard ion acoustic solitons. Comparisons between the model calculations and observations are made.
Proton-transfer spectroscopy beyond the normal-mode scenario
Authors: Brünig Florian N. , Hillmann Paul , Kim Won Kyu , Daldrop Jan O. , Netz Roland R.
Published: November 2022

A stochastic theory is developed to predict the spectral signature of proton-transfer processes and is applied to infrared spectra computed from ab initio molecular-dynamics simulations of a single H5O2+ cation. By constraining the oxygen atoms to a fixed distance, this system serves as a tunable model for general proton-transfer processes with variable barrier height. Three spectral contributions at distinct frequencies are identified and analytically predicted: the quasi-harmonic motion around the most probable configuration, amenable to normal-mode analysis, the contribution due to transfer paths when the proton moves over the barrier, and a shoulder for low frequencies stemming from the stochastic transfer-waiting-time distribution; the latter two contributions are not captured by normal-mode analysis but exclusively reported on the proton-transfer kinetics. In accordance with reaction rate theory, the transfer-waiting-contribution frequency depends inversely exponentially on the barrier height, whereas the transfer-path-contribution frequency is rather insensitive to the barrier height.
Formation of γ-Ga2O3 by ion implantation: Polymorphic phase transformation of β-Ga2O3
Authors: García-Fernández J. , Kjeldby S. B. , Nguyen P. D. , Karlsen O. B. , Vines L. , Prytz Ø.
Published: November 2022

Ion implantation induced phase transformation and the crystal structure of a series of ion implanted β-Ga2O3 samples were studied using electron diffraction, high resolution transmission electron microscopy, and scanning transmission electron microscopy. In contrast to previous reports suggesting an ion implantation induced transformation to the orthorhombic κ-phase, we show that for 28Si+, 58Ni+, and stoichiometric 69Ga+/16O+-implantations, the monoclinic β-phase transforms to the cubic γ-phase. The γ-phase was confirmed for implantations over a range of fluences from 1014 to 1016 ions/cm2, indicating that the transformation is a general phenomenon for β-Ga2O3 due to strain accumulation and/or γ-Ga2O3 being energetically preferred over highly defective β-Ga2O3.
Studies on flow field, and instabilities in a large diameter opposed jet burner
Authors: Navaneethakrishnan P , Sesha Giri Krishna
Published: November 2022

This work reports studies on flow fields, and instabilities exhibited by opposed jets at equal momenta, for Reynolds numbers (Re) ranging from 178 to 5000 using a large diameter counterflow jet setup. Flow instability investigations were conducted over a range of aspect ratios (α) too. This study identifies the regions of bi-stability and those of oscillatory stagnation plane offsets identified by Re. Experiments on flow field were carried out using particle image velocimetry technique, and the paper presents the axial and radial velocity profiles at various locations as well as their gradients. A decreasing trend in stagnation plane displacements with the Reynolds number was observed. The experiments in comparison with the past literature suggest a possible dependence of the stagnation plane displacements on a nozzle-exit diameter. The trends in maximum stagnation plane displacements (δmax), as well as the critical Reynolds numbers (Recr) with aspect ratios (α), are analyzed and compared. The flow field studies reveal the need for two dimensional axisymmetric simulations with realistic velocity boundary conditions to predict opposed jet flow phenomena accurately. Reacting flow instability studies were also carried out for equal momenta using methane-air and ethylene–air flames at various aspect ratios. The results show an enhanced bistability for ethylene–air flames over methane–air flames.
Stable α-FAPbI3 via porous PbI2 for efficient perovskite solar cells
Authors: Xu Tie , Cai Hongkun , Ye Xiaofang , Zhu Yinbin , Ni Jian , Li Juan , Zhang Jianjun
Published: November 2022

Black-phase formamidinium lead iodide (FAPbI3), with a narrow bandgap and high thermal stability, has emerged as an in-demand material for highly efficient perovskite solar cells (PSCs). In a two-step sequential deposition, the PbI2 film plays an important role in the formation of a perovskite film with desirable qualities. This paper explores using N-methyl-2-pyrrolidone (NMP), a strong Lewis base, and N,N-dimethylformamide (DMF) as a mixed precursor solvent (DMF/NMP) of PbI2 and reports on preparing PbI2 films with a porous morphology by thermal treatment. Porous PbI2 films ensure the diffusion and sufficient reaction of the formamidinium iodide solution to form a smooth perovskite film. In addition, a dynamic spin coating method is also introduced to improve the uniformity of the perovskite film. Both methods yield a pure α-phase FAPbI3 film immediately in the unannealed state, which is necessary for the perovskite film to maintain phase stability. Finally, PSCs with a power conversion efficiency of 21.20% (0.13 cm2) are fabricated and optimized. The unencapsulated PSCs retain 90% of the initial efficiency for 1000 hours in dry air and exhibit a good thermal stability when heated to 85 °C.
The effect of intra-molecular bonds on the liquid–liquid critical point in modified-WAC models
Authors: Lascaris E.
Published: November 2022

To obtain a better understanding of liquid–liquid critical points (LLCPs) in one-component liquids, we extend the modified-WAC model by E. Lascaris, Phys. Rev. Lett. 116, 125701 (2016) which is known to have a LLCP. The original WAC model is a model for silica (SiO2) and consists of a mixture of non-bonded Si and O ions. By adding explicit intra-molecular Si–O bonds to the model, we are able to study how several parameters (Si–O bond length, O–Si–O angle, and bond stiffness) affect the existence and location of the LLCP. We find that for this model, only the Si–O bond length has a strong effect on the LLCP, while the bond angle and bond stiffness have no significant effect on the LLCP. An analysis of the relevant coordination numbers indicates that increasing the bond length decreases the ratio RSi/O of additional Si ions per additional O ion in the first coordination shell of the Si, which causes the LLCP to move to higher, more accessible temperatures. The behavior of the RSi/O parameter shows a strong correlation with the behavior of the LLCP and might be a useful tool to determine if a LLCP exists at low, hard-to-reach temperatures in other models.
Strong photon–magnon coupling at microwave and millimeter-wave frequencies in planar hybrid circuits
Authors: Ma Zhiyu , Zhang Yao , Guo Weijia , Yue Zhenxing
Published: November 2022

Photon–magnon hybrid systems have potential applications in modern information processing technologies. Although planar hybrid circuits based on split ring resonators have shown strong coherent photon–magnon coupling, none of those operates at millimeter-wave frequencies. With specially designed electric-field-coupled resonators, strong coupling between resonator modes and ferromagnetic resonance modes (either in-plane or out-of-plane) was experimentally observed in two circuits working at 4.1 and 30 GHz. Their dynamics were well described by quantum models. The miniature, integrable, and physically robust circuits pave a way for planar photon–magnon hybrid systems at even higher frequencies, demonstrating the possibility to integrate magnon-based systems with millimeter-wave devices.
Pair of particle chain self-organization in a square channel flow of Giesekus viscoelastic fluid
Authors: Hu Xiao , Chen Weijin , Lin Jianzhong , Xia Yan , Yu Zhaosheng
Published: November 2022

Pair of particle chain self-organization in a square channel flow of Giesekus viscoelastic fluid is studied by the direct forcing/fictitious domain method. The effects of particle diameter, initial particle distance, shear-thinning (n), Weissenberg number (Wi), and Reynolds number (Re) are explored to analyze the mechanism of particle chain self-organization in Giesekus viscoelastic fluid. The results show that the small particle at the equilibrium position moves faster than the larger one and then catches up with it to form a particle chain, in which the large and small particles are located at the front and the end of the chain, respectively. The particle pair with the same diameter cannot form the chain in Giesekus viscoelastic fluid. In addition, the larger the diameter ratio and the initial particle distance, the larger the absolute value of the particle velocity difference, the earlier the particle chain is formed. The particle chain will be formed early with increasing n, Re, and Wi.
Accurate determination of solid–liquid equilibria by molecular simulation: Behavior of Ne, Ar, Kr, and Xe from low to high pressures
Authors: Deiters Ulrich K. , Sadus Richard J.
Published: November 2022

We report the accurate determination of solid–liquid equilibria using a novel molecular simulation method that can be used for solid–liquid equilibria from low to high pressures. A re-evaluation is reported of the solid–liquid equilibria of the noble gases interacting via ab initio two-body potentials combined with three-body interactions and quantum corrections and the results are compared with both existing simulation data and experimental values. The new simulation method yields results that are generally in closer agreement with the experiment than exiting methods, highlighting the important role of the method in fully understanding the interatomic interactions responsible for solid–liquid equilibria. The quality of the comparison of simulation results with the experiment indicates that the solid–liquid equilibria of the noble gases can be now predicted with exceptional accuracy over a large range of pressures.
Metallization of hydrogen by intercalating ammonium ions in metal fcc lattices at lower pressure
Authors: Wan Zhongyu , Zhang Ruiqin
Published: November 2022

Metallic hydrogen is capable of showing room temperature superconductivity, but its experimental syntheses are extremely hard. Therefore, it is desirable to reduce the synthesis pressure of metallic hydrogen by adding other chemical elements. However, for most hydrides, the metallization of hydrogen by “chemical precompression” to achieve high-temperature superconductivity still requires relatively high pressure, making experimental synthesis difficult. How to achieve high-temperature superconductivity in the lower-pressure range (≤50 GPa) is a key issue for realizing practical applications of superconducting materials. Toward this end, this work proposes a strategy for inserting ammonium ions in the fcc crystal of metals. High-throughput calculations of the periodic table reveal 12 elements that can form kinetically stable and superconducting hydrides at lower pressures, where the highest superconducting transition temperatures of AlN2H8, MgN2H8, and GaN2H8 can reach up to 118, 105, and 104 K. Pressure-induced bond length changes and charge transfer reveal the physical mechanism of high-temperature superconductivity, where the H atom continuously gains electrons leading to the transition of H+ ions to atomic H, facilitating metallization of hydrogen under less extreme high pressure. Our results also reveal two strong linear scalar relationships: one is the H-atom charge vs superconducting transition temperature, and the other is the first ionization energy vs the highest superconducting transition temperature. In addition, ZnN2H8, CdN2H8, and HgN2H8 were found to be superconductors at ambient pressure, and the presence of interstitial electrons suggests that they are also electrides, whose relatively low work functions (3.03, 2.78, and 3.05 eV) imply that they can be used as catalysts for nitrogen reduction reactions as well.
A history of CSIRO’s Central Australian Laboratory 2, 1980–2018: interdisciplinary land research
Authors: Friedel Margaret H. , Morton Stephen R. , Bastin Gary N. , Davies Jocelyn , Stafford Smith D. Mark
Published: November 2022

In the first 27 years of the Central Australian Laboratory (CAL), to 1980, research focussed almost entirely on the needs of the pastoral industry. By the 1980s, ongoing campaigns for Aboriginal land rights and demands to conserve biodiversity plainly showed that there were other land uses deserving research attention. Initially CAL’s research agenda expanded to include conservation in spinifex grasslands and grazing lands but remained biophysical in nature. It subsequently became clear that people’s roles in decision-making about land use and management should be part of research. By the 2000s, scientists were able to build trusting relationships with Aboriginal people and organisations and undertake collaborative studies to improve livelihoods and wellbeing on country. Over the 38 years from 1980 to 2018, CAL’s research activities responded to diverse societal expectations but it was not enough to prevent the laboratory’s eventual closure as public investment in rangelands dwindled.
Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction?
Authors: Shilton Charlotte A. , Kahler Anne , Roach Jessica M. , Raudsepp Terje , de Mestre Amanda M.
Published: November 2022

Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5–10% of established day 15 pregnancies and a further 5–10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses in pregnancy and pregnancy loss, as well as infectious agents such as pathogens, and until recently very little was known about the both small and large genetic variants associated with reduced foetal viability in the horse. In this review, we first introduce key aspects of equine placental and foetal development. We then discuss incidence, risk factors and causes of pregnancy loss, with the latter focusing on genetic variants described to date that can impact equine foetal viability.
Neighbourhood bushfire hazard, community risk perception and preparedness in peri-urban Hobart, Australia
Authors: Lucas Chloe H. , Williamson Grant J. , Bowman David M. J. S.
Published: November 2022

Background Information campaigns about bushfire preparedness are often based on the assumption that residents of bushfire-prone neighbourhoods underestimate their risk. However, there are complex relationships between bushfire hazard, perceived risk and adaptive action. Aims We investigate how residents’ understanding of bushfire risk relates to biophysical risk in the City of Hobart, Tasmania, Australia’s most fire-prone state capital. Methods A transdisciplinary case study using a survey of 406 residents living close to the wildland–urban interface, focus groups in four bushfire-prone neighbourhoods, and geospatial fire risk assessment. Key results Neighbourhood concern about bushfire is statistically associated with biophysical measurement of local bushfire risk. This awareness does not necessarily translate into adaptive action, in part because residents underestimate the risk to their homes from fuels on their own property and overestimate the risk from bushland and neighbouring properties, leading to a common response that preparing for bushfire is futile if your neighbours do not also prepare. Neighbourhoods with high levels of positive community interaction, however, are more likely to access preparedness information, and develop fire-adaptive behaviours. Conclusions/Implications Our findings highlight the need for social adaptation pathways using local communication interventions to build the neighbourhood knowledge, networks and capacities that enable community-led bushfire preparedness.
Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation
Authors: Dierckx Tess , Vanherle Sam , Haidar Mansour , Grajchen Elien , Mingneau Fleur , Gervois Pascal , Wolfs Esther , Bylemans Dany , Voet Arnout , Nguyen Tien , Hamad Ibrahim , Kleinewietfeld Markus , Bogie Jeroen F. J. , Hendriks Jerome J. A.
Published: November 2022

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries, reduces neuroinflammation by driving macrophages toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination.
Systematic reduction of the dimensionality of natural scenes allows accurate predictions of retinal ganglion cell spike outputs
Authors: Freedland Julian , Rieke Fred
Published: November 2022

The mammalian retina engages a broad array of linear and nonlinear circuit mechanisms to convert natural scenes into retinal ganglion cell (RGC) spike outputs. Although many individual integration mechanisms are well understood, we know less about how multiple mechanisms interact to encode the complex spatial features present in natural inputs. Here, we identified key spatial features in natural scenes that shape encoding by primate parasol RGCs. Our approach identified simplifications in the spatial structure of natural scenes that minimally altered RGC spike responses. We observed that reducing natural movies into 16 linearly integrated regions described ∼80% of the structure of parasol RGC spike responses; this performance depended on the number of regions but not their precise spatial locations. We used simplified stimuli to design high-dimensional metamers that recapitulated responses to naturalistic movies. Finally, we modeled the retinal computations that convert flashed natural images into one-dimensional spike counts.
SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms
Authors: Szeto Irene Y. Y. , Chu Daniel K. H. , Chen Peikai , Chu Ka Chi , Au Tiffany Y. K. , Leung Keith K. H. , Huang Yong-Heng , Wynn Sarah L. , Mak Angel C. Y. , Chan Ying-Shing , Chan Wood Yee , Jauch Ralf , Fritzsch Bernd , Sham Mai Har , Lovell-Badge Robin , Cheah Kathryn S. E.
Published: November 2022

The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 (
SOX9
) and
SOX10
(
SOXE
) transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia

SOX9
Y440X

mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that

SOX9
Y440X

causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous
Sox9
-null mice are normal. During the ES development of

Sox9
Y440X/+

heterozygotes,
Sox10
and genes important for ionic homeostasis are down-regulated, and there is developmental persistence of progenitors, resulting in fewer mature cells.
Sox10
heterozygous null mutants also display persistence of ES/duct progenitors. By contrast, SOX10 retains its expression in the early

Sox9
Y440X/+

mutant cochlea. Later, in the postnatal stria vascularis, dominant interference by SOX9
Y440X
is implicated in impairing the normal cooperation of SOX9 and SOX10 in repressing the expression of the water channel Aquaporin 3, thereby contributing to endolymphatic hydrops. Our study shows that for a functioning endolymphatic system in the inner ear, SOX9 regulates
Sox10
, and depending on the cell type and target gene, it works either independently of or cooperatively with SOX10. SOX9
Y440X
can interfere with the activity of both SOXE factors, exerting effects that can be classified as haploinsufficient/hypomorphic or dominant negative depending on the cell/gene context. This model of disruption of transcription factor partnerships may be applicable to congenital deafness, which affects ∼0.3% of newborns, and other syndromic disorders.
A Bayesian switching linear dynamical system for estimating seizure chronotypes
Authors: Wang Emily T. , Vannucci Marina , Haneef Zulfi , Moss Robert , Rao Vikram R. , Chiang Sharon
Published: November 2022

Epilepsy is a disorder characterized by paroxysmal transitions between multistable states. Dynamical systems have been useful for modeling the paroxysmal nature of seizures. At the same time, intracranial electroencephalography (EEG) recordings have recently discovered that an electrographic measure of epileptogenicity, interictal epileptiform activity, exhibits cycling patterns ranging from ultradian to multidien rhythmicity, with seizures phase-locked to specific phases of these latent cycles. However, many mechanistic questions about seizure cycles remain unanswered. Here, we provide a principled approach to recast the modeling of seizure chronotypes within a statistical dynamical systems framework by developing a Bayesian switching linear dynamical system (SLDS) with variable selection to estimate latent seizure cycles. We propose a Markov chain Monte Carlo algorithm that employs particle Gibbs with ancestral sampling to estimate latent cycles in epilepsy and apply unsupervised learning on spectral features of latent cycles to uncover clusters in cycling tendency. We analyze the largest database of patient-reported seizures in the world to comprehensively characterize multidien cycling patterns among 1,012 people with epilepsy, spanning from infancy to older adulthood. Our work advances knowledge of cycling in epilepsy by investigating how multidien seizure cycles vary in people with epilepsy, while demonstrating an application of an SLDS to frame seizure cycling within a nonlinear dynamical systems framework. It also lays the groundwork for future studies to pursue data-driven hypothesis generation regarding the mechanistic drivers of seizure cycles.
CRISPR-based engineering of phages for in situ bacterial base editing
Authors: Nethery Matthew A. , Hidalgo-Cantabrana Claudio , Roberts Avery , Barrangou Rodolphe
Published: November 2022

Investigation of microbial gene function is essential to the elucidation of ecological roles and complex genetic interactions that take place in microbial communities. While microbiome studies have increased in prevalence, the lack of viable in situ editing strategies impedes experimental progress, rendering genetic knowledge and manipulation of microbial communities largely inaccessible. Here, we demonstrate the utility of phage-delivered CRISPR-Cas payloads to perform targeted genetic manipulation within a community context, deploying a fabricated ecosystem (EcoFAB) as an analog for the soil microbiome. First, we detail the engineering of two classical phages for community editing using recombination to replace nonessential genes through Cas9-based selection. We show efficient engineering of T7, then demonstrate the expression of antibiotic resistance and fluorescent genes from an engineered λ prophage within an
Escherichia coli
host. Next, we modify λ to express an APOBEC-1-based cytosine base editor (CBE), which we leverage to perform C-to-T point mutations guided by a modified Cas9 containing only a single active nucleolytic domain (nCas9). We strategically introduce these base substitutions to create premature stop codons in-frame, inactivating both chromosomal (
lacZ
) and plasmid-encoded genes (mCherry and ampicillin resistance) without perturbation of the surrounding genomic regions. Furthermore, using a multigenera synthetic soil community, we employ phage-assisted base editing to induce host-specific phenotypic alterations in a community context both in vitro and within the EcoFAB, observing editing efficiencies from 10 to 28% across the bacterial population. The concurrent use of a synthetic microbial community, soil matrix, and EcoFAB device provides a controlled and reproducible model to more closely approximate in situ editing of the soil microbiome.
Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression
Authors: Yang Yun-Song , Jin Xi , Li Qin , Chen Yi-Yu , Chen Fenfang , Zhang Hena , Su Ying , Xiao Yi , Di Gen-Hong , Jiang Yi-Zhou , Huang Shenglin , Shao Zhi-Ming
Published: November 2022

The transcription variation, leading to various forms of transcripts and protein diversity, remains largely unexplored in triple-negative breast cancers (TNBCs). Here, we presented a comprehensive analysis of RNA splicing in breast cancer to illustrate the biological function and clinical implications of tumor-specific transcripts (TSTs) arising from these splicing junctions. Aberrant RNA splicing or TSTs were frequently harbored in TNBC and were correlated with a poor outcome. We discovered a tumor-specific splicing variant of macrophage receptor with collagenous structure–TST (MARCO-TST), which was distinguished from myeloid cell-specific wild-type MARCO. MARCO-TST expression was associated with poor outcomes in TNBC patients and could promote tumor progression in vitro and in vivo. Mechanically, MARCO-TST interacted with PLOD2 and enhanced the stability of HIF-1α, which resulted in the metabolic dysregulation of TNBC to form a hypoxic tumor microenvironment. MARCO-TST was initiated from a de novo alternative transcription initiation site that was activated by a superenhancer. Tumors with MARCO-TST expression conferred greater sensitivity to bromodomain and extraterminal protein inhibitors. This treatment strategy was further validated in patient-derived organoids. In conclusion, our results revealed the transcription variation landscape of TNBC, highlighting MARCO-TST as a crucial oncogenic transcript and therapeutic target.
Directed evolution identifies high-affinity cystine-knot peptide agonists and antagonists of Wnt/β-catenin signaling
Authors: Hansen Simon , Zhang Yingnan , Hwang Sunhee , Nabhan Ahmad , Li Wanqing , Fuhrmann Jakob , Kschonsak Yvonne , Zhou Lijuan , Nile Aaron H. , Gao Xinxin , Piskol Robert , de Sousa e Melo Felipe , de Sauvage Frederic J. , Hannoush Rami N.
Published: November 2022

Developing peptide-based tools to fine-tune growth signaling pathways, in particular molecules with exquisite selectivity and high affinities, opens up opportunities for cellular reprogramming in tissue regeneration. Here, we present a library based on cystine-knot peptides (CKPs) that incorporate multiple loops for randomization and selection via directed evolution. Resulting binders could be assembled into multimeric structures to fine-tune cellular signaling. An example is presented for the Wnt pathway, which plays a key role in the homeostasis and regeneration of tissues such as lung, skin, and intestine. We discovered picomolar affinity CKP agonists of the human LPR6 receptor by exploring the limits of the topological manipulation of LRP6 dimerization. Structural analyses revealed that the agonists bind at the first β-propeller domain of LRP6, mimicking the natural Wnt inhibitors DKK1 and SOST. However, the CKP agonists exhibit a different mode of action as they amplify the signaling of natural Wnt ligands but do not activate the pathway by themselves. In an alveolosphere organoid model, the CKP agonists induced alveolar stem cell activity. They also stimulated growth in primary human intestinal organoids. The approach described here advances the important frontier of next-generation agonist design and could be applied to other signaling pathways to discover tunable agonist ligands.
KIF2A deficiency causes early-onset neurodegeneration
Authors: Ruiz-Reig Nuria , Chehade Georges , Hakanen Janne , Aittaleb Mohamed , Wierda Keimpe , De Wit Joris , Nguyen Laurent , Gailly Philippe , Tissir Fadel
Published: November 2022

KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabilities. While the role of this protein is well documented in neuronal migration, the relationship between its dysfunction and the pathobiology of brain disorders is unclear. Here, we report that KIF2A is dispensable for embryogenic neurogenesis but critical in postnatal stages for maturation, connectivity, and maintenance of neurons. We used a conditional approach to inactivate KIF2A in cortical progenitors, nascent postmitotic neurons, and mature neurons in mice. We show that the lack of KIF2A alters microtubule dynamics and disrupts several microtubule-dependent processes, including neuronal polarity, neuritogenesis, synaptogenesis, and axonal transport. KIF2A-deficient neurons exhibit aberrant electrophysiological characteristics, neuronal connectivity, and function, leading to their loss. The role of KIF2A is not limited to development, as fully mature neurons require KIF2A for survival. Our results emphasize an additional function of KIF2A and help explain how its mutations lead to brain disorders.
Sequestration of a dual function DNA-binding protein by
Vibrio cholerae
CRP
Authors: Gibson Jacob A. , Gebhardt Michael J. , Santos Renato E. R. S. , Dove Simon L. , Watnick Paula I.
Published: November 2022

Although the mechanism by which the cyclic AMP receptor protein (CRP) regulates global gene transcription has been intensively studied for decades, new discoveries remain to be made. Here, we report that, during rapid growth, CRP associates with both the well-conserved, dual-function DNA-binding protein peptidase A (PepA) and the cell membrane. These interactions are not present under nutrient-limited growth conditions, due to post-translational modification of three lysines on a single face of CRP. Although coincident DNA binding is rare, dissociation from CRP results in increased PepA occupancy at many chromosomal binding sites and differential regulation of hundreds of genes, including several encoding cyclic dinucleotide phosphodiesterases. We show that PepA represses biofilm formation and activates motility/chemotaxis. We propose a model in which membrane-bound CRP interferes with PepA DNA binding. Under nutrient limitation, PepA is released. Together, CRP and free PepA activate a transcriptional response that impels the bacterium to seek a more hospitable environment. This work uncovers a function for CRP in the sequestration of a regulatory protein. More broadly, it describes a paradigm of bacterial transcriptome modulation through metabolically regulated association of transcription factors with the cell membrane.
Directional takeoff, aerial righting, and adhesion landing of semiaquatic springtails
Authors: Ortega-Jimenez Victor M. , Challita Elio J. , Kim Baekgyeom , Ko Hungtang , Gwon Minseok , Koh Je-Sung , Bhamla M. Saad
Published: November 2022

Springtails (Collembola) have been traditionally portrayed as explosive jumpers with incipient directional takeoff and uncontrolled landing. However, for these collembolans that live near the water, such skills are crucial for evading a host of voracious aquatic and terrestrial predators. We discover that semiaquatic springtails,Isotomurus retardatus, can perform directional jumps, rapid aerial righting, and near-perfect landing on the water surface. They achieve these locomotive controls by adjusting their body attitude and impulse during takeoff, deforming their body in midair, and exploiting the hydrophilicity of their ventral tube, known as the collophore. Experiments and mathematical modeling indicate that directional-impulse control during takeoff is driven by the collophore’s adhesion force, the body angle, and the stroke duration produced by their jumping organ, the furcula. In midair, springtails curve their bodies to form a U-shape pose, which leverages aerodynamic forces to right themselves in less than ~20 ms, the fastest ever measured in animals. A stable equilibrium is facilitated by the water adhered to the collophore. Aerial righting was confirmed by placing springtails in a vertical wind tunnel and through physical models. Due to these aerial responses, springtails land on their ventral side ~85% of the time while anchoring via the collophore on the water surface to avoid bouncing. We validated the springtail biophysical principles in a bioinspired jumping robot that reduces in-flight rotation and lands upright ~75% of the time. Thus, contrary to common belief, these wingless hexapods can jump, skydive, and land with outstanding control that can be fundamental for survival.
WhyWolbachia-induced cytoplasmic incompatibility is so common
Authors: Turelli Michael , Katznelson Andrew , Ginsberg Paul S.
Published: November 2022

Cytoplasmic incompatibility (CI) is the most common reproductive manipulation produced byWolbachia, obligately intracellular alphaproteobacteria that infect approximately half of all insect species. Once infection frequencies within host populations approach 10%, intense CI can driveWolbachiato near fixation within 10 generations. However, natural selection amongWolbachiavariants within individual host populations does not favor enhanced CI. Indeed, variants that do not cause CI but increase host fitness or are more reliably maternally transmitted are expected to spread if infected females remain protected from CI. Nevertheless, approximately half of analyzedWolbachiainfections cause detectable CI. Why? The frequency and persistence of CI are more plausibly explained by preferential spread to new host species (clade selection) rather than by natural selection among variants within host populations. CI-causingWolbachialineages preferentially spread into new host species because 1) CI increases equilibriumWolbachiafrequencies within host populations, and 2) CI-causing variants can remain at high frequencies within populations even when conditions change so that initially beneficialWolbachiainfections become harmful. An epidemiological model describingWolbachiaacquisition and loss by host species and the loss of CI-induction withinWolbachialineages yields simple expressions for the incidence ofWolbachiainfections and the fraction of those infections causing CI. Supporting a determinative role for differential interspecific spread in maintaining CI, manyWolbachiainfections were recently acquired by their host species, many show evidence for contemporary spatial spread or retreat, and rapid evolution of CI-inducing loci, especially degradation, is common.
Aβ and tau prions feature in the neuropathogenesis of Down syndrome
Authors: Condello Carlo , Maxwell Alison M. , Castillo Erika , Aoyagi Atsushi , Graff Caroline , Ingelsson Martin , Lannfelt Lars , Bird Thomas D. , Keene C. Dirk , Seeley William W. , Perl Daniel P. , Head Elizabeth , Prusiner Stanley B.
Published: November 2022

Down syndrome (DS) is caused by the triplication of chromosome 21 and is the most common chromosomal disorder in humans. Those individuals with DS who live beyond age 40 y develop a progressive dementia that is similar to Alzheimer’s disease (AD). Both DS and AD brains exhibit numerous extracellular amyloid plaques composed of Aβ and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aβ and tau prions feature in DS. Frozen brains from people with DS, familial AD (fAD), sporadic AD (sAD), and age-matched controls were procured from brain biorepositories. We selectively precipitated Aβ and tau prions from DS brain homogenates and measured the number of prions using cellular bioassays. In brain extracts from 28 deceased donors with DS, ranging in age from 19 to 65 y, we found nearly all DS brains had readily measurable levels of Aβ and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aβ and tau prions increased with age. In contrast to DS brains, the levels of Aβ and tau prions in the brains of 37 fAD and sAD donors decreased as a function of age at death. Whether DS is an ideal model for assessing the efficacy of putative AD therapeutics remains to be determined.
Cryo-EM structures of cancer-specific helical and kinase domain mutations of PI3Kα
Authors: Liu Xiao , Zhou Qingtong , Hart Jonathan R. , Xu Yingna , Yang Su , Yang Dehua , Vogt Peter K. , Wang Ming-Wei
Published: November 2022

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that perform multiple and important cellular functions. The protein investigated here belongs to class IA of the PI3Ks; it is a dimer consisting of a catalytic subunit, p110α, and a regulatory subunit, p85α, and is referred to as PI3Kα. The catalytic subunit p110α is frequently mutated in cancer. The mutations induce a gain of function and constitute a driving force in cancer development. About 80% of these mutations lead to single–amino-acid substitutions in one of three sites of p110α: two in the helical domain of the protein (E542K and E545K) and one at the C-terminus of the kinase domain (H1047R). Here, we report the cryo-electron microscopy structures of these mutants in complex with the p110α-specific inhibitor BYL-719. The H1047R mutant rotates its sidechain to a new position and weakens the kα11 activation loop interaction, thereby reducing the inhibitory effect of p85α on p110α. E542K and E545K completely abolish the tight interaction between the helical domain of p110α and the N-terminal SH2 domain of p85α and lead to the disruption of all p85α binding and a dramatic increase in flexibility of the adaptor-binding domain (ABD) in p110α. Yet, the dimerization of PI3Kα is preserved through the ABD–p85α interaction. The local and global structural features induced by these mutations provide molecular insights into the activation of PI3Kα, deepen our understanding of the oncogenic mechanism of this important signaling molecule, and may facilitate the development of mutant-specific inhibitors.
Preparation of mullite refractories with low thermal conductivity and high strength
Authors: Ma Yuzhou , Sang Shaobai , Wan Zhuofu , Li Yawei , Zhu Tianbin
Published: November 2022

In the work, a novel mullite refractory was prepared by using coal gangue and low-grade raw bauxite as main raw materials, and the effect of the low-grade raw bauxite content and temperature on the microstructure and properties of mullite refractories was investigated. Both the green densities and cold compressive strength of mullite refractories increased with the increase of low-grade raw bauxite; also, the addition of low-grade raw bauxite had no significant effect on the thermal conductivity of such refractories treated at 1500°C. When the addition of low-grade raw bauxite was 34.5%, the compressive strength of the refractories treated at 1600°C was up to 104.3 MPa, and its thermal conductivity tested at 1000°C was only 1.02 W/(m K).
Dishevelled phase separation promotes Wnt signalosome assembly and destruction complex disassembly
Authors: Kang Kexin , Shi Qiaoni , Wang Xu , Chen Ye-Guang
Published: November 2022

The amplitude of Wnt/β-catenin signaling is precisely controlled by the assembly of the cell surface–localized Wnt receptor signalosome and the cytosolic β-catenin destruction complex. How these two distinct complexes are coordinately controlled remains largely unknown. Here, we demonstrated that the signalosome scaffold protein Dishevelled 2 (Dvl2) undergoes liquid–liquid phase separation (LLPS). Dvl2 LLPS is mediated by an intrinsically disordered region and facilitated by components of the signalosome, such as the receptor Fzd5. Assembly of the signalosome is initiated by rapid recruitment of Dvl2 to the membrane, followed by slow and dynamic recruitment of Axin1. Axin LLPS mediates assembly of the β-catenin destruction complex, and Dvl2 attenuates LLPS of Axin. Compared with the destruction complex, Axin partitions into the signalosome at a lower concentration and exhibits a higher mobility. Together, our results revealed that Dvl2 LLPS is crucial for controlling the assembly of the Wnt receptor signalosome and disruption of the phase-separated β-catenin destruction complex.