bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapie nach Progress unter Immuncheckpoint-Inhibition beim metastasierten malignen Melanom: Fallbericht und Literaturübersicht
Authors: Weilandt Juliane , Lebahn Herbert , Ludwig-Peitsch Wiebke
Published: October 2022

Hintergrund Immuncheckpoint-Inhibitoren (ICI), BRAF- und MEK-Inhibitoren haben die Prognose von Patienten mit metastasiertem malignem Melanom entscheidend verbessert. Nichtsdestotrotz spricht ein erheblicher Prozentsatz nicht oder nur vorübergehend auf diese modernen Therapien an. Insbesondere bei Patienten mit BRAF-Wildtyp-Melanom sind die Therapieoptionen nach Versagen von ICI limitiert.

Kasuistik Eine 24-jährige Patientin stellte sich im Dezember 2015 mit einem akrolentiginösen malignen Melanom am linken Fußballen im Tumorstadium IIB (pT4a, pN0, cM0, Infiltrationstiefe 7,95 mm, BRAF-V600-Wildtyp) vor, das leitliniengerecht operativ versorgt und für 18 Monate adjuvant mit Interferon-alpha behandelt wurde. Nach Diagnose von zwei Lymphknotenmetastasen links inguinal und radikaler Lymphknotendissektion erhielt die Patientin für 12 Monate eine adjuvante Therapie mit Nivolumab. Nach einem 10-monatigen tumorfreien Intervall ohne Therapie erbrachte das Staging eine paraaortale Lymphknotenmetastase. Gemäß Tumorkonferenz-Beschluss wurde bei nunmehr vorliegendem Stadium IV eine Immunkombinationstherapie mit Nivolumab und Ipilimumab begonnen, die nach 2 Gaben aufgrund einer Autoimmunkolitis und -hepatitis Grad 3 beendet und auf eine Nivolumab-Monotherapie umgestellt wurde. Bei erneutem Tumorprogress auch nach Metastasenresektion und fehlender Möglichkeit einer Studienteilnahme wurde eine palliative Chemotherapie mit Dacarbazin 850 mg/m2 alle 3 Wochen eingeleitet. Hiermit ließ sich nach 4 Zyklen eine partielle Remission und nach 10 Zyklen eine Komplettremission erzielen, die nunmehr seit 10 Monaten ohne Therapie anhält.

Diskussion Es gibt Hinweise darauf, dass die Effektivität einer Chemotherapie nach vorangegangener Immuncheckpoint-Inhibition höher ist als ohne diese Vortherapie, möglicherweise durch einen immunmodulatorischen Effekt der Chemotherapie, der synergistisch mit einer Immunaktivierung durch ICI wirkt. Bisher liegen nur wenige Studien zu dieser Therapiesequenz beim Melanom vor, bei denen es sich ausschließlich um retrospektive Analysen handelt. Diese weisen auf einen klinischen Nutzen der Therapiesequenz hin, wenngleich die Evidenz hierfür sehr gering ist. Die meisten Patienten, die nach einer Vortherapie mit ICI auf Dacarbazin oder andere Chemotherapien ansprechen, erreichen eine partielle Remission. Anhaltende Komplettremissionen wie bei unserer Patientin sind eine Rarität.
A Neutral FeCl3 Photocatalysis for C–C Bond Animation and Alkylation of Cyclic Alcohols
Authors: Zhang Zongnan , Xue Ting , Zeng Rong , Han Zhe
Published: October 2022

A modified method for iron-catalyzed C–C bond cleavage and amination and alkylation of nonactivated cyclic alcohols has been developed. Using FeCl3 as catalyst, the photoinduced ligand-to-metal charge transfer facilitates the generation of O-radicals from alcohols, the subsequent β-scission, and finally the radical trapping. Compared with the Fe(OR)3 catalysis, this mildly base-free system could enable the amination in a broader substrate scope with higher yields. Moreover, the C–C bond cleavage and alkylation of cyclic alcohols proceeds with electron-deficient olefins under these conditions.
Thermoelectric transport contribution from topological surface states vs 2D-electron gas in 10 nm Bi2Se3
Authors: Nimmagadda Lakshmi Amulya , Bai Yang , Rajagopal Manjunath C. , Suresh Babu Soorya , Eckstein James N. , Sinha Sanjiv
Published: October 2022

Topological surface states (TSSs) coexist with a rapidly formed two-dimensional electron gas (2DEG) at the surface of Bi2Se3. While this complex band structure has been widely studied for its interactions between the two states in terms of electrical conductivity and carrier density, the resulting thermopower has not been investigated as thoroughly. Here, we report measurements of the temperature dependent Seebeck coefficient (S) and electrical conductivity (σ) on an undoped 10 nm thin Bi2Se3 film over the temperature range of 100–300 K to find an overall metal-like behavior. The measured S is consistent with the theory when assuming that both the TSS and the 2DEG contribute to thermoelectric transport. Our analysis further shows that the coefficient corresponds to a Fermi level situated well above the conduction band minima of the 2DEG, resulting in comparable contributions from the TSS and the 2DEG. The thermoelectric power factor (S2σ) at 300 K increases by 10%–30% over the bulk. This work provides insights into understanding and enhancing thermoelectric phenomena in topological insulators.
Structure and magnetic properties of Fe nanoparticles in amorphous silica implanted with Fe ions and effect of subsequent energetic heavy ion irradiation
Authors: Iwase A. , Fukuda K. , Saitoh Y. , Okamoto Y. , Semboshi S. , Amekura H. , Matsui T.
Published: October 2022

Amorphous silicon dioxide (hereafter SiO2) samples were implanted with 380 keV Fe ions at room temperature. After the implantation, some samples were irradiated with 16 MeV Au ions. The magnetic property was investigated by using a SQUID magnetometer, and the morphology of Fe-implanted SiO2 samples was examined by using a transmission electron microscope and x-ray absorption spectroscopy (extended x-ray absorption fine structure and x-ray absorption near edge structure). The size of Fe nanoparticles increases with an increase in the amount of Fe implantation. A part of Fe nanoparticles consists of Fe oxides, and with an increase in the amount of Fe implantation, the valence state of Fe atoms and the structure of Fe nanoparticles gets close to those of metallic α-Fe. The room temperature magnetism was observed in Fe-implanted SiO2 samples. The magnetization–magnetic field curves for samples implanted with a small amount of Fe are reproduced by the Langevin equation, implying that Fe nanoparticles present the superparamagnetic behavior. For a large amount of Fe implantation, the magnetization–magnetic field curve shows the ferromagnetic state. Such a result of magnetic property is consistent with the results of the x-ray absorption. By the subsequent 16 MeV Au irradiation, the Fe nanoparticles were fragmentated, resulting in the decrease in magnetization. The optical absorption property of the SiO2 samples is briefly discussed.
Numerical simulation of dynamic stall flow control using a multi-dielectric barrier discharge plasma actuation strategy
Authors: Xu Zeyang , Wu Bin , Gao Chao , Wang Na
Published: October 2022

To alleviate the deterioration in wind turbine performance caused by dynamic stall, the flow control of a pitching NACA0012 airfoil is investigated through numerical simulation of an alternating current dielectric barrier discharge (AC-DBD) plasma actuator at a Reynolds number Re = 135 000. To avoid the harmonic oscillations of aerodynamic force caused by unsteady DBD actuation, this work focuses on improving the control potential for steady actuation. The control mechanisms of actuators at various positions are investigated using five groups of actuators mounted at 0%, 3%, 10%, 45%, and 80% chord lengths c above the upper surface of an airfoil. The actuator at 80%c performs more efficiently in terms of lift enhancement in the initial upstroke and the final downstroke. The actuator at 0%c suppresses the growth of the leading-edge vortex and maintains the suction of the dynamic stall vortex (DSV). After the shedding of the DSV, it suppresses the secondary separation to delay the onset of dynamic stall. At the flow reattachment stage, the actuators at 3%c and 10%c accelerate the boundary layer reattachment by momentum injection. From these results, a multi-DBD control strategy is proposed. The scheme selects the optimal actuator in operation at a certain stage of dynamic stall and takes advantage of actuators at different positions to enhance the average and maximum aerodynamic force, delay the onset of dynamic stall, accelerate flow reattachment, and avoid excessive energy consumption.
Asymptotic behavior, non-local dynamics, and data assimilation tailoring of the reduced κ−ε model to address turbulent transport of fusion plasmas
Authors: Auroux D. , Ghendrih P. , Lamerand L. , Rapetti F. , Serre E.
Published: October 2022

The high-dimensional and multiscale nature of fusion plasma flows require the development of reduced models to be implemented in numerical codes capable of capturing the main features of turbulent transport in a sufficiently short time to be useful during tokamak operation. This paper goes further in the analysis of the dynamics of the κ−ε model based on the turbulent kinetic energy κ and its dissipation rate ε [Baschetti et al., Nucl. Fusion 61, 106020 (2021)] to improve the predictability of the transverse turbulent transport in simulation codes. The present 1D results show further capabilities with respect to current models (based on constant effective perpendicular diffusion) and on the standard quasi-linear approach. The nonlinear dependence of D in κ and ε estimated from two additional transport equations allows us to introduce some non-locality in the transport model. This is illustrated by the existence of parameter ranges with turbulence spreading. The paper also addresses another issue related to the uncertainties on the inherent free parameters of such reduced model. The study proposes a new approach in the fusion community based on a variational data assimilation involving the minimization of a cost function defined as the distance between the reference data and the calculated values. The results are good and show the ability of the data assimilation to reduce uncertainties on the free parameters, which remains a critical point to ensure the total reliability of such an approach.
A laboratory frame density matrix for ultrafast quantum molecular dynamics
Authors: Gregory Margaret , Neville Simon , Schuurman Michael , Makhija Varun
Published: October 2022

In most cases, the ultrafast dynamics of resonantly excited molecules are considered and almost always computed in the molecular frame, while experiments are carried out in the laboratory frame. Here, we provide a formalism in terms of a lab frame density matrix, which connects quantum dynamics in the molecular frame to those in the laboratory frame, providing a transparent link between computation and measurement. The formalism reveals that in any such experiment, the molecular frame dynamics vary for molecules in different orientations and that certain coherences, which are potentially experimentally accessible, are rejected by the orientation-averaged reduced vibronic density matrix. Instead, molecular angular distribution moments are introduced as a more accurate representation of experimentally accessible information. Furthermore, the formalism provides a clear definition of a molecular frame quantum tomography and specifies the requirements to perform such a measurement enabling the experimental imaging of molecular frame vibronic dynamics. Successful completion of such a measurement fully characterizes the molecular frame quantum dynamics for a molecule at any orientation in the laboratory frame.
Parametric research and aerodynamic performance analysis of wind turbine airfoil with added flap
Authors: Ma Qimin , Wang Jiahao , Zhang Yang , Liu Xiaomin
Published: October 2022

A self-popped up flap is added to the airfoil (S809) suction surface to improve aerodynamic performance under large angle of attack (AOA) inspired by the slightly popped up feathers on the trailing edge of a bird’s wing. The response surface methodology (RSM) optimization of H, D, and θ is conducted. The lift–drag ratio of an airfoil is taken as the optimization response target, and the Box–Behnken design is adopted to design the experiment scheme for H, D, and θ. Multivariate quadratic polynomials are used to carry out equation regression analysis on the combined results of 17 sample schemes, and the mathematical surrogate model between the flap structure parameters and the airfoil lift–drag ratio and the optimal design parameter combination of the flap structure are obtained. The clean airfoil and the airfoil with optimal flap are compared and analyzed from the static and dynamic aerodynamic characteristics by numerical simulation. The calculation results show that the optimal flap obtained by RSM increases the pressure difference between the suction and the pressure surfaces at large AOA, suppresses flow separation on the suction surface, and delays the stall AOA. The airfoil with optimal flap leads to a smaller separation vortex and wake vortex, therefore delaying the dynamic stall effect.
Occasional coupling enhances amplitude death in delay-coupled oscillators
Authors: Ghosh Anupam , Mondal Sirshendu , Sujith R. I.
Published: October 2022

This paper aims to study amplitude death in time delay coupled oscillators using the occasional coupling scheme that implies intermittent interaction among the oscillators. An enhancement of amplitude death regions (i.e., an increment of the width of the amplitude death regions along the control parameter axis) can be possible using the occasional coupling in a pair of delay-coupled oscillators. Our study starts with coupled limit cycle oscillators (Stuart–Landau) and coupled chaotic oscillators (Rössler). We further examine coupled horizontal Rijke tubes, a prototypical model of thermoacoustic systems. Oscillatory states are highly detrimental to thermoacoustic systems such as combustors. Consequently, a state of amplitude death is always preferred. We employ the on–off coupling (i.e., a square wave function), as an occasional coupling scheme, to these coupled oscillators. On monotonically varying the coupling strength (as a control parameter), we observe an enhancement of amplitude death regions using the occasional coupling scheme compared to the continuous coupling scheme. In order to study the contribution of the occasional coupling scheme, we perform a detailed linear stability analysis and analytically explain this enhancement of the amplitude death region for coupled limit cycle oscillators. We also adopt the frequency ratio of the oscillators and the time delay between the oscillators as the control parameters. Intriguingly, we obtain a similar enhancement of the amplitude death regions using the frequency ratio and time delay as the control parameters in the presence of the occasional coupling. Finally, we use a half-wave rectified sinusoidal wave function (motivated by practical reality) to introduce the occasional coupling in time delay coupled oscillators and get similar results.
High harmonic generation by co-rotating bi-circular laser fields interaction with relativistic plasmas
Authors: Xie Duan , Yin Yan , Yu Tongpu , Zhou Hongyu , Li Dongxia
Published: October 2022

We present an investigation of high harmonic generation (HHG) from relativistic plasmas driven by two-color co-rotating circularly polarized (CP) laser fields at various frequency ratios ω2/ω1. The theoretical analysis and the particle-in-cell simulation results reveal that when ω2/ω1≥4, CP harmonics with opposite helicities can appear simultaneously due to the relativistic mirror effect and the related conservation laws. Meanwhile, the harmonic spectra features (including the HHG efficiency, the allowed harmonic orders, and their polarization states) can be tuned through adjusting the frequency and intensity ratio of the two driving field components. This finding might be helpful for a consummate understanding of the bi-circular HHG technique.
The influence of cross-interactions between dilute cosolutes upon liquid interfaces
Authors: Mandalaparthy Varun , Bui Pho T. , Noid W. G.
Published: October 2022

We employ a statistical mechanical dilute solution theory (DST) and lattice Monte Carlo simulations to investigate the interfacial properties of ternary solutions with a dominant solvent and two dilute cosolutes. We consider cosolutes with weak interfacial preferences in order to focus on the impact of cross-interactions between the two cosolute species. When the cross-interaction is properly balanced, the two cosolutes make independent, additive contributions to both bulk and interfacial properties. Conversely, repulsive cross-interactions slightly enhance the interfacial preference of both solutes. In contrast, attractive cross-interactions reduce interfacial preferences and can convert weak surfactants into weak depletants. We observe a particularly interesting transition in the symmetric case of two equivalent self-repelling cosolutes with attractive cross-interactions. In this regime, the major cosolute acts as a weak surfactant in order to avoid repulsive self-interactions, while the minor cosolute acts as a weak depletant in order to form attractive cross-interactions. The two equivalent cosolutes switch roles depending upon their relative concentration. DST very accurately describes the surface tension and surface excess of simulated lattice solutions up to molar concentrations. More importantly, DST provides quantitative and qualitative insight into the mechanism by which cosolute interactions modulate interfacial preferences.
One-to-one internal resonance in a symmetric MEMS micromirror
Authors: Opreni Andrea , Furlan Matteo , Bursuc Andreea , Boni Nicoló , Mendicino Gianluca , Carminati Roberto , Frangi Attilio
Published: October 2022

Resonant modal interaction is a nonlinear dynamic phenomenon observed in structures excited at large vibration amplitudes. In the present work, we report the experimental evidence of a 1:1 internal resonance in a symmetric resonant micromirror. The experiments are complemented with a reduced model obtained from the 3D finite element discretization of the device by parametrizing the system motion along a low dimensional invariant set of the phase space. The presence of coupling monomials in the governing equations makes the resulting dynamics non-linearizable. Both model and experimental data show the existence of a complex pattern of multiple stable solutions for a given value of the excitation frequency.
Ligand additivity relationships enable efficient exploration of transition metal chemical space
Authors: Arunachalam Naveen , Gugler Stefan , Taylor Michael G. , Duan Chenru , Nandy Aditya , Janet Jon Paul , Meyer Ralf , Oldenstaedt Jonas , Chu Daniel B. K. , Kulik Heather J.
Published: October 2022

To accelerate the exploration of chemical space, it is necessary to identify the compounds that will provide the most additional information or value. A large-scale analysis of mononuclear octahedral transition metal complexes deposited in an experimental database confirms an under-representation of lower-symmetry complexes. From a set of around 1000 previously studied Fe(II) complexes, we show that the theoretical space of synthetically accessible complexes formed from the relatively small number of unique ligands is significantly (∼816k) larger. For the properties of these complexes, we validate the concept of ligand additivity by inferring heteroleptic properties from a stoichiometric combination of homoleptic complexes. An improved interpolation scheme that incorporates information about cis and trans isomer effects predicts the adiabatic spin-splitting energy to around 2 kcal/mol and the HOMO level to less than 0.2 eV. We demonstrate a multi-stage strategy to discover leads from the 816k Fe(II) complexes within a targeted property region. We carry out a coarse interpolation from homoleptic complexes that we refine over a subspace of ligands based on the likelihood of generating complexes with targeted properties. We validate our approach on nine new binary and ternary complexes predicted to be in a targeted zone of discovery, suggesting opportunities for efficient transition metal complex discovery.
Sleep deprivation and hippocampal ripple disruption after one-session learning eliminate memory expression the next day
Authors: Aleman-Zapata Adrian , Morris Richard G. M. , Genzel Lisa
Published: October 2022

Memory reactivation during non–rapid-eye-movement ripples is thought to communicate new information to a systems-wide network and thus can be a key player mediating the positive effect of sleep on memory consolidation. Causal experiments disrupting ripples have only been performed in multiday training paradigms, which decrease but do not eliminate memory performance, and no comparison with sleep deprivation has been made. To enable such investigations, we developed a one-session learning paradigm in a Plusmaze and show that disruption of either sleep with gentle handling or hippocampal ripples with electrical stimulation impaired long-term memory. Furthermore, we detected hippocampal ripples and parietal high-frequency oscillations after different behaviors, and a bimodal frequency distribution in the cortical events was observed. Faster cortical high-frequency oscillations increased after normal learning, a change not seen in the hippocampal ripple-disruption condition, consistent with these having a role in memory consolidation.
Multiple traces and altered signal-to-noise in systems consolidation: Evidence from the 7T fMRI Natural Scenes Dataset
Authors: Vanasse Thomas J. , Boly Melanie , Allen Emily J. , Wu Yihan , Naselaris Thomas , Kay Kendrick , Cirelli Chiara , Tononi Giulio
Published: October 2022

The brain mechanisms of memory consolidation remain elusive. Here, we examine blood-oxygen-level-dependent (BOLD) correlates of image recognition through the scope of multiple influential systems consolidation theories. We utilize the longitudinal Natural Scenes Dataset, a 7-Tesla functional magnetic resonance imaging human study in which ∼135,000 trials of image recognition were conducted over the span of a year among eight subjects. We find that early- and late-stage image recognition associates with both medial temporal lobe (MTL) and visual cortex when evaluating regional activations and a multivariate classifier. Supporting multiple-trace theory (MTT), parts of the MTL activation time course show remarkable fit to a 20-y-old MTT time-dynamical model predicting early trace intensity increases and slight subsequent interference (
R
2
> 0.90). These findings contrast a simplistic, yet common, view that memory traces are transferred from MTL to cortex. Next, we test the hypothesis that the MTL trace signature of memory consolidation should also reflect synaptic “desaturation,” as evidenced by an increased signal-to-noise ratio. We find that the magnitude of relative BOLD enhancement among surviving memories is positively linked to the rate of removal (i.e., forgetting) of competing traces. Moreover, an image-feature and time interaction of MTL and visual cortex functional connectivity suggests that consolidation mechanisms improve the specificity of a distributed trace. These neurobiological effects do not replicate on a shorter timescale (within a session), implicating a prolonged, offline process. While recognition can potentially involve cognitive processes outside of memory retrieval (e.g., re-encoding), our work largely favors MTT and desaturation as perhaps complementary consolidative memory mechanisms.
Electrophysiological markers of memory consolidation in the human brain when memories are reactivated during sleep
Authors: Creery Jessica D. , Brang David J. , Arndt Jason D. , Bassard Adrianna , Towle Vernon L. , Tao James X. , Wu Shasha , Rose Sandra , Warnke Peter C. , Issa Naoum P. , Paller Ken A.
Published: October 2022

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10 to 20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.
Mechanism of 4-aminopyridine inhibition of the lysosomal channel TMEM175
Authors: Oh SeCheol , Stix Robyn , Zhou Wenchang , Faraldo-Gómez José D. , Hite Richard K.
Published: October 2022

Transmembrane protein 175 (TMEM175) is an evolutionarily distinct lysosomal cation channel whose mutation is associated with the development of Parkinson’s disease. Here, we present a cryoelectron microscopy structure and molecular simulations of TMEM175 bound to 4-aminopyridine (4-AP), the only known small-molecule inhibitor of TMEM175 and a broad K+channel inhibitor, as well as a drug approved by the Food and Drug Administration against multiple sclerosis. The structure shows that 4-AP, whose mode of action had not been previously visualized, binds near the center of the ion conduction pathway, in the open state of the channel. Molecular dynamics simulations reveal that this binding site is near the middle of the transmembrane potential gradient, providing a rationale for the voltage-dependent dissociation of 4-AP from TMEM175. Interestingly, bound 4-AP rapidly switches between three predominant binding poses, stabilized by alternate interaction patterns dictated by the twofold symmetry of the channel. Despite this highly dynamic binding mode, bound 4-AP prevents not only ion permeation but also water flow. Together, these studies provide a framework for the rational design of novel small-molecule inhibitors of TMEM175 that might reveal the role of this channel in human lysosomal physiology both in health and disease.
Estimating the total treatment effect in randomized experiments with unknown network structure
Authors: Yu Christina Lee , Airoldi Edoardo M. , Borgs Christian , Chayes Jennifer T.
Published: October 2022

Randomized experiments are widely used to estimate the causal effects of a proposed treatment in many areas of science, from medicine and healthcare to the physical and biological sciences, from the social sciences to engineering, and from public policy to the technology industry. Here we consider situations where classical methods for estimating the total treatment effect on a target population are considerably biased due to confounding network effects, i.e., the fact that the treatment of an individual may impact its neighbors’ outcomes, an issue referred to as network interference or as nonindividualized treatment response. A key challenge in these situations is that the network is often unknown and difficult or costly to measure. We assume a potential outcomes model with heterogeneous additive network effects, encompassing a broad class of network interference sources, including spillover, peer effects, and contagion. First, we characterize the limitations in estimating the total treatment effect without knowledge of the network that drives interference. By contrast, we subsequently develop a simple estimator and efficient randomized design that outputs an unbiased estimate with low variance in situations where one is given access to average historical baseline measurements prior to the experiment. Our solution does not require knowledge of the underlying network structure, and it comes with statistical guarantees for a broad class of models. Due to their ease of interpretation and implementation, and their theoretical guarantees, we believe our results will have significant impact on the design of randomized experiments.
Intrinsic nonlinear dynamics drive single-species systems
Authors: Werner Johannes , Pietsch Tobias , Hilker Frank M. , Arndt Hartmut
Published: October 2022

The importance of oscillations and deterministic chaos in natural biological systems has been discussed for several decades and was originally based on discrete-time population growth models (May 1974). Recently, all types of nonlinear dynamics were shown for experimental communities where several species interact. Yet, there are no data exhibiting the whole range of nonlinear dynamics for single-species systems without trophic interactions. Up until now, ecological experiments and models ignored the intracellular dimension, which includes multiple nonlinear processes even within one cell type. Here, we show that dynamics of single-species systems of protists in continuous experimental chemostat systems and corresponding continuous-time models reveal typical characteristics of nonlinear dynamics and even deterministic chaos, a very rare discovery. An automatic cell registration enabled a continuous and undisturbed analysis of dynamic behavior with a high temporal resolution. Our simple and general model considering the cell cycle exhibits a remarkable spectrum of dynamic behavior. Chaos-like dynamics were shown in continuous single-species populations in experimental and modeling data on the level of a single type of cells without any external forcing. This study demonstrates how complex processes occurring in single cells influence dynamics on the population level. Nonlinearity should be considered as an important phenomenon in cell biology and single-species dynamics and also, for the maintenance of high biodiversity in nature, a prerequisite for nature conservation.
Genome-wide chromatin accessibility analysis unveils open chromatin convergent evolution during polyploidization in cotton
Authors: Han Jinlei , Lopez-Arredondo Damar , Yu Guangrun , Wang Yankun , Wang Baohua , Wall Sarah Brooke , Zhang Xin , Fang Hui , Barragán-Rosillo Alfonso Carlos , Pan Xiaoping , Jiang Yanqin , Chen Jingbo , Zhang Hui , Zhou Bao-Liang , Herrera-Estrella Luis , Zhang Baohong , Wang Kai
Published: October 2022

Allopolyploidization, resulting in divergent genomes in the same cell, is believed to trigger a “genome shock”, leading to broad genetic and epigenetic changes. However, little is understood about chromatin and gene-expression dynamics as underlying driving forces during allopolyploidization. Here, we examined the genome-wide DNase I-hypersensitive site (DHS) and its variations in domesticated allotetraploid cotton (
Gossypium hirsutum
and
Gossypium barbadense
, AADD) and its extant AA (
Gossypium arboreum
) and DD (
Gossypium raimondii
) progenitors. We observed distinct DHS distributions between
G. arboreum
and
G. raimondii
. In contrast, the DHSs of the two subgenomes of
G. hirsutum
and
G. barbadense
showed a convergent distribution. This convergent distribution of DHS was also present in the wild allotetraploids
Gossypium darwinii
and
G. hirsutum
var.
yucatanense
, but absent from a resynthesized hybrid of
G. arboreum
and
G. raimondii
, suggesting that it may be a common feature in polyploids, and not a consequence of domestication after polyploidization. We revealed that putative
cis
-regulatory elements (CREs) derived from polyploidization-related DHSs were dominated by several families, including Dof, ERF48, and BPC1. Strikingly, 56.6% of polyploidization-related DHSs were derived from transposable elements (TEs). Moreover, we observed positive correlations between DHS accessibility and the histone marks H3K4me3, H3K27me3, H3K36me3, H3K27ac, and H3K9ac, indicating that coordinated interplay among histone modifications, TEs, and CREs drives the DHS landscape dynamics under polyploidization. Collectively, these findings advance our understanding of the regulatory architecture in plants and underscore the complexity of regulome evolution during polyploidization.
Plate motion and a dipolar geomagnetic field at 3.25 Ga
Authors: Brenner Alec R. , Fu Roger R. , Kylander-Clark Andrew R. C. , Hudak George J. , Foley Bradford J.
Published: October 2022

The paleomagnetic record is an archive of Earth’s geophysical history, informing reconstructions of ancient plate motions and probing the core via the geodynamo. We report a robust 3.25-billion-year-old (Ga) paleomagnetic pole from the East Pilbara Craton, Western Australia. Together with previous results from the East Pilbara between 3.34 and 3.18 Ga, this pole enables the oldest reconstruction of time-resolved lithospheric motions, documenting 160 My of both latitudinal drift and rotation at rates of at least 0.55°/My. Motions of this style, rate, and duration are difficult to reconcile with true polar wander or stagnant-lid geodynamics, arguing strongly for mobile-lid geodynamics by 3.25 Ga. Additionally, this pole includes the oldest documented geomagnetic reversal, reflecting a stably dipolar, core-generated Archean dynamo.
Significantly suppressing metal particle-induced surface charge accumulation of spacers in DC gas-insulated power transmission lines
Authors: Xing Yunqi , Sun Xinbo , Jiang Jinpeng , Liang Fangwei , Liang Zuodong , Zhuang Weijian , Liu Bo , Li Dege , Cao Shaohua , Li Min , He Jinliang , Li Chuanyang
Published: October 2022

In this letter, we report functions of surface roughening and fluorination on suppressing linear metal particle-induced spacer surface charge accumulation. An appropriate increase in spacer surface conductivity by short-term fluorination and roughening not only increases the metal particle lifting voltage, but also weakens the particle activation. The spacer surface charge shows reduced charge density in roughened spacer, while fluorination modification significantly suppresses the charge density on the spacer surface. For roughened and fluorinated samples, the decrease of surface charge density and the intrinsic lower electric field (due to an increase in conductivity) near the triple junction both contribute to a higher particle lifting voltage. The content in this letter provides an approach to effectively suppress the charge accumulation induced by linear metal particles.
Element analysis and its application in rotating machinery fault diagnosis
Authors: Dai Hanfang , Wang Yanxue , Wang Xuan , Liu Qi
Published: October 2022

Conventional signal processing methods make it difficult to extract the fault impulse features from the target signal, and the time-frequency representation has energy ambiguity. Thus, it is critical to develop new approaches for mechanical fault diagnostics. In this paper, the element analysis method, which was originally utilized in the marine field, is applied to the field of mechanical fault diagnosis for the first time. A de-noising technique of rotating machinery signals based on the element analysis method is proposed. The proposed method first determines the corresponding wavelet parameters according to the mechanical fault signals and constructs the element model. Then the method performs the Morse wavelet transform on the element model, and calculates the signal impulse point from the wavelet transform to obtain the signal’s fault characteristic frequency. Furthermore, the method can also reconstruct the signal by utilizing a small number of solitary points in the time or scale plane. The performance of the method is verified by analyzing simulated signals and mechanical vibration signals collected from different experimental platforms. The results demonstrate that the method has excellent signal characteristic extraction capability and successfully diagnoses different kinds of rotating machinery faults.
Size estimation of spall-like fault on rolling element bearing using an integrated approach incorporating total variation regularization and singular spectrum analysis
Authors: Patel Dhaval V , Bhojawala Vipul M , Patel Kaushik M
Published: October 2022

Spalling in rolling element bearings is a common localized defect generated during the operation of a bearing due to rolling fatigue. Size estimation of such localized defects can be helpful in determining the severity of the fault. This can be further used as an input for predicting the remaining useful life of the bearing. The popular approach for estimating the size (in terms of width) of a spall is to trace the entry and exit events of the rolling element while interacting with the fault. The time estimated between entry and exit of a rolling element from a pit-like spall can be converted to a geometric estimation of the fault size from the vibration signature. The present approach demonstrates the use of singular spectrum analysis (SSA) to accomplish this task. The vibration signal generated from the interaction of the rolling element with the localized fault is a hybrid signal consisting of a low frequency stepped response generated while the rolling element enters the fault superimposed onto the high frequency impact generated during the re-entry of the rolling element into the raceway from the spall. The signal information is enhanced via pre-processing with total variation regularization (TVR) filtration. The informative signal, which is extracted from the row temporal signal via SSA, aids in the accurate identification of entry and exit events. The proposed method integrating TVR with SSA for fault size estimation is validated using simulated signals and experimental signals from independent resources. The results show strong agreement with the accuracy level of size estimation.
Electronic and superconducting properties of hydrogenated graphene from first-principles calculations
Authors: Lu Qing , Ding Chi , Wang Xiaomeng , Chen Tong , Sun Jian
Published: October 2022

We performed first-principles calculations on two hydrogenated graphene systems with different hydrogen coverages, C8H2 and C50H2, to analyze their electronic and superconducting properties. Our results show that their electronic properties are highly correlated to the hydrogenation positions. If the two hydrogen atoms are attached to the same sublattice, the final system will be ferromagnetic. Otherwise, it will maintain nonmagnetic rather than anti-ferromagnetic. Moreover, the distance between the doped hydrogens can trigger the movement of Dirac points, and even annihilate Dirac points when the distance is close to the maximum. We further studied their superconducting properties by applying hole doping and tensile strains. The results show that the superconducting transition temperature T
c increases with more holes and reaches its maximum of about 20.2 K at the critical doping level (x
c = 0.17 holes/cell). Our results show that the superconductivity mainly originates from the coupling between the out-of-plane lattice vibration modes and the electronic p
z orbitals of carbon atoms. The increase of T
c can be attributed to the stronger coupling between the electrons and the low-frequency phonon. However, the application of biaxial and uniaxial tensile strain will depress the superconductivity because of the modulation of the low-frequency phonon. It is worthy to note that weak anharmonicity exists in the hydrogenated graphene systems. This work provides a systematic study on tuning the superconductivity of hydrogenated graphene.
New Continuum and Polarization Observations of the Cygnus Loop with FAST. II. Images and Analyses
Authors: Sun Xiao-Hui , Gao Xu-Yang , Reich Wolfgang , Jiang Peng , Li Di , Yan Huirong , Li Xiang-Hua
Published: October 2022

We present total-intensity and polarized-intensity images of the Cygnus Loop supernova remnant (SNR) observed by the Five-hundred-meter Aperture Spherical radio Telescope. The high angular-resolution and high-sensitivity images enable us to thoroughly compare the properties of the northern part with the southern part of the SNR. The central filament in the northern part and the southern part have a similar foreground rotation measure, meaning their distances are likely similar. The polarization analysis indicates that the random magnetic field is larger than the regular field in the northern part, but negligible in the southern part. The total-intensity image is decomposed into components of various angular scales, and the brightness-temperature spectral index of the shell structures in the northern part is similar to that in the southern part in the component images. All the evidence suggests that the northern and southern parts of the Cygnus Loop are situated and thus evolved in different environments of interstellar medium, while belonging to the same SNR.
Alignment-free metal ion-binding site prediction from protein sequence through pretrained language model and multi-task learning
Authors: Yuan Qianmu , Chen Sheng , Wang Yu , Zhao Huiying , Yang Yuedong
Published: October 2022

More than one-third of the proteins contain metal ions in the Protein Data Bank. Correct identification of metal ion-binding residues is important for understanding protein functions and designing novel drugs. Due to the small size and high versatility of metal ions, it remains challenging to computationally predict their binding sites from protein sequence. Existing sequence-based methods are of low accuracy due to the lack of structural information, and time-consuming owing to the usage of multi-sequence alignment. Here, we propose LMetalSite, an alignment-free sequence-based predictor for binding sites of the four most frequently seen metal ions in BioLiP (Zn2+, Ca2+, Mg2+ and Mn2+). LMetalSite leverages the pretrained language model to rapidly generate informative sequence representations and employs transformer to capture long-range dependencies. Multi-task learning is adopted to compensate for the scarcity of training data and capture the intrinsic similarities between different metal ions. LMetalSite was shown to surpass state-of-the-art structure-based methods by more than 19.7, 14.4, 36.8 and 12.6% in area under the precision recall on the four independent tests, respectively. Further analyses indicated that the self-attention modules are effective to learn the structural contexts of residues from protein sequence. We provide the data sets, source codes and trained models of LMetalSite at https://github.com/biomed-AI/LMetalSite.
Comprehensive characterization of elevated tau PET signal in the absence of amyloid-beta
Authors: Weigand Alexandra J , Edwards Lauren , Thomas Kelsey R , Bangen Katherine J , Bondi Mark W ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2022

Recently proposed biomarker-only diagnostic frameworks propose that amyloid-beta is necessary for placement on the Alzheimer’s disease continuum, whereas tau in the absence of amyloid-beta is considered to be a non-Alzheimer’s disease pathologic change. Similarly, the pathologic designation of tau in the absence of amyloid-beta is characterized as primary age-related tauopathy and separable from Alzheimer’s disease. Our study sought to identify an early-to-moderate tau stage with minimal amyloid-beta using PET imaging and characterize these individuals in terms of clinical, cognitive and biological features. Seven hundred and three participants from the Alzheimer’s Disease Neuroimaging Initiative were classified into one of the four groups (A−/T−, A−/T+, A+/T− and A+/T+) based on PET positivity or negativity for cortical amyloid-beta (A−/A+) and early-to-moderate stage (i.e. meta-temporal) tau (T−/T+). These groups were then compared on demographic and clinical features, vascular risk, multi-domain neuropsychological performance, multi-domain subjective cognitive complaints, apolipoprotein E epsilon-4 carrier status and cortical thickness across Alzheimer’s disease-vulnerable regions. The proportion of participants classified in each group was as follows: 47.23% A−/T−, 13.51% A−/T+, 12.23% A+/T− and 27.03% A+/T+. Results indicated that the A−/T+ and A+/T+ groups did not statistically differ on age, sex, depression levels, vascular risk and cortical thickness across temporal and parietal regions. Additionally, both A−/T+ and A+/T+ groups showed significant associations between memory performance and cortical thickness of temporal regions. Despite the different pathologic terminology used for A−/T+ and A+/T+, these groups did not statistically differ on a number of clinical, cognitive and biomarker features. Although it remains unclear whether A−/T+ reflects a pathologic construct separable from Alzheimer’s disease, our results provide evidence that this group typically characterized as ‘non-Alzheimer’s pathologic change’ or ‘primary age-related tauopathy’ should be given increased attention, given some similarities in cognitive and biomarker characteristics to groups traditionally considered to be on the Alzheimer’s continuum.
Adult-onset KMT2B-related dystonia
Authors: Monfrini Edoardo , Ciolfi Andrea , Cavallieri Francesco , Ferilli Marco , Soliveri Paola , Pedace Lucia , Erro Roberto , Del Sorbo Francesca , Valzania Franco , Fioravanti Valentina , Cossu Giovanni , Pellegrini Maria , Salviati Leonardo , Invernizzi Federica , Oppo Valentina , Murgia Daniela , Giometto Bruno , Picillo Marina , Garavaglia Barbara , Morgante Francesca , Tartaglia Marco , Carecchio Miryam , Di Fonzo Alessio
Published: October 2022

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic findings of a series of subjects affected by adult-onset dystonia, hearing loss or intellectual disability carrying rare heterozygous KMT2B variants. Twelve cases from five unrelated families carrying four rare KMT2B missense variants predicted to impact protein function are described. Seven affected subjects presented with adult-onset focal or segmental dystonia, three developed isolated progressive hearing loss, and one displayed intellectual disability and short stature. Genome-wide DNA methylation profiling allowed to discriminate these adult-onset dystonia cases from controls and early-onset DYT-KMT2B patients. These findings document the relevance of KMT2B variants as a potential genetic determinant of adult-onset dystonia and prompt to further characterize KMT2B carriers investigating non-dystonic features.