bluuebunny/crossref_metadata_2025 huggingface dataset:
Nontriplet feature of genetic code in
Euplotes
ciliates is a result of neutral evolution
Authors: Gaydukova Sofya A. , Moldovan Mikhail A. , Vallesi Adriana , Heaphy Stephen M. , Atkins John F. , Gelfand Mikhail S. , Baranov Pavel V.
Published: May 2023

The triplet nature of the genetic code is considered a universal feature of known organisms. However, frequent stop codons at internal mRNA positions in
Euplotes
ciliates ultimately specify ribosomal frameshifting by one or two nucleotides depending on the context, thus posing a nontriplet feature of the genetic code of these organisms. Here, we sequenced transcriptomes of eight
Euplotes
species and assessed evolutionary patterns arising at frameshift sites. We show that frameshift sites are currently accumulating more rapidly by genetic drift than they are removed by weak selection. The time needed to reach the mutational equilibrium is several times longer than the age of
Euplotes
and is expected to occur after a several-fold increase in the frequency of frameshift sites. This suggests that
Euplotes
are at an early stage of the spread of frameshifting in expression of their genome. In addition, we find the net fitness burden of frameshift sites to be noncritical for the survival of
Euplotes
. Our results suggest that fundamental genome-wide changes such as a violation of the triplet character of genetic code can be introduced and maintained solely by neutral evolution.
Apple-shaped obesity: A risky soil for cytokine-accelerated severity in COVID-19
Authors: Hosoya Tadashi , Oba Seiya , Komiya Yoji , Kawata Daisuke , Kamiya Mari , Iwai Hideyuki , Miyamoto Sho , Kataoka Michiyo , Tobiume Minoru , Kanno Takayuki , Ainai Akira , Sato Hiroyuki , Hirakawa Akihiro , Mitsui Yuichi , Satoh Takashi , Wakabayashi Kenji , Yamada Tetsuya , Otomo Yasuhiro , Miyazaki Yasunari , Hasegawa Hideki , Suzuki Tadaki , Yasuda Shinsuke
Published: May 2023

Obesity has been recognized as one of the most significant risk factors for the deterioration and mortality associated with COVID-19, but the significance of obesity itself differs among ethnicity. Multifactored analysis of our single institute–based retrospective cohort revealed that high visceral adipose tissue (VAT) burden, but not other obesity-associated markers, was related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients. To elucidate the mechanisms how VAT-dominant obesity induces severe inflammation after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we infected two different strains of obese mice, C57BL/6JHamSlc-ob/ob (ob/ob), C57BLKS/J-db/db (db/db), genetically impaired in the leptin ligand and receptor, respectively, and control C57BL/6 mice with mouse-adapted SARS-CoV-2. Here, we revealed that VAT-dominant ob/ob mice were extremely more vulnerable to SARS-CoV-2 due to excessive inflammatory responses when compared to SAT-dominant db/db mice. In fact, SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased cytokine production including interleukin (IL)-6. Both an anti-IL-6 receptor antibody treatment and the prevention of obesity by leptin replenishment improved the survival of SARS-CoV-2-infected ob/ob mice by reducing the viral protein burden and excessive immune responses. Our results have proposed unique insights and clues on how obesity increases the risk of cytokine storm and death in patients with COVID-19. Moreover, earlier administration of antiinflammatory therapeutics including anti-IL-6R antibody to VAT-dominant patients might improve clinical outcome and stratification of the treatment for COVID-19, at least in Japanese patients.
Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration
Authors: Lavrsen Kirstine , Rajendraprasad Girish , Leda Marcin , Eibes Susana , Vitiello Elisa , Katopodis Vasileios , Goryachev Andrew B. , Barisic Marin
Published: May 2023

To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and a contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton and asymmetric distribution of regulatory molecules. However, what triggers and maintains this asymmetry during cell migration remains largely elusive. Here, we established a micropatterning-based 1D motility assay to investigate the molecular basis of symmetry breaking required for directed cell migration. We show that microtubule (MT) detyrosination drives cell polarization by directing kinesin-1-based transport of the adenomatous polyposis coli (APC) protein to cortical sites. This is essential for the formation of cell's leading edge during 1D and 3D cell migration. These data, combined with biophysical modeling, unveil a key role for MT detyrosination in the generation of a positive feedback loop linking MT dynamics and kinesin-1-based transport. Thus, symmetry breaking during cell polarization relies on a feedback loop driven by MT detyrosination that supports directed cell migration.
Quantification of gallium cryo-FIB milling damage in biological lamellae
Authors: Lucas Bronwyn A. , Grigorieff Nikolaus
Published: May 2023

Cryogenic electron microscopy (cryo-EM) can reveal the molecular details of biological processes in their native, cellular environment at atomic resolution. However, few cells are sufficiently thin to permit imaging with cryo-EM. Thinning of frozen cells to <500 nm lamellae by focused-ion-beam (FIB) milling has enabled visualization of cellular structures with cryo-EM. FIB milling represents a significant advance over prior approaches because of its ease of use, scalability, and lack of large-scale sample distortions. However, the amount of damage it causes to a thinned cell section has not yet been determined. We recently described an approach for detecting and identifying single molecules in cryo-EM images of cells using 2D template matching (2DTM). 2DTM is sensitive to small differences between a molecular model (template) and the detected structure (target). Here, we use 2DTM to demonstrate that under the standard conditions used for machining lamellae of biological samples, FIB milling introduces a layer of variable damage that extends to a depth of 60 nm from each lamella surface. This layer of damage limits the recovery of information for in situ structural biology. We find that the mechanism of FIB milling damage is distinct from radiation damage during cryo-EM imaging. By accounting for both electron scattering and FIB milling damage, we estimate that FIB milling damage with current protocols will negate the potential improvements from lamella thinning beyond 90 nm.
Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation
Authors: Li Yunlong , Majumdar Soneya , Treen Ryan , Sharma Manjuli R. , Corro Jamie , Gamper Howard B. , Manjari Swati R. , Prusa Jerome , Banavali Nilesh K. , Stallings Christina L. , Hou Ya-Ming , Agrawal Rajendra K. , Ojha Anil K.
Published: May 2023

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease–dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle.
Stem cell decoupling underlies impaired lymphoid development during aging
Authors: Jang Geunhyo , Contreras Castillo Stephania , Esteva Eduardo , Upadhaya Samik , Feng Jue , Adams Nicholas M. , Richard Elodie , Awatramani Rajeshwar , Sawai Catherine M. , Reizis Boris
Published: May 2023

Mammalian aging is associated with multiple defects of hematopoiesis, most prominently with the impaired development of T and B lymphocytes. This defect is thought to originate in hematopoietic stem cells (HSCs) of the bone marrow, specifically due to the age-dependent accumulation of HSCs with preferential megakaryocytic and/or myeloid potential (“myeloid bias”). Here, we tested this notion using inducible genetic labeling and tracing of HSCs in unmanipulated animals. We found that the endogenous HSC population in old mice shows reduced differentiation into all lineages including lymphoid, myeloid, and megakaryocytic. Single-cell RNA sequencing and immunophenotyping (CITE-Seq) showed that HSC progeny in old animals comprised balanced lineage spectrum including lymphoid progenitors. Lineage tracing using the aging-induced HSC marker
Aldh1a1
confirmed the low contribution of old HSCs across all lineages. Competitive transplantations of total bone marrow cells with genetically marked HSCs revealed that the contribution of old HSCs was reduced, but compensated by other donor cells in myeloid cells but not in lymphocytes. Thus, the HSC population in old animals becomes globally decoupled from hematopoiesis, which cannot be compensated in lymphoid lineages. We propose that this partially compensated decoupling, rather than myeloid bias, is the primary cause of the selective impairment of lymphopoiesis in older mice.
First encounters
Authors: Morar Florin-Stefan
Published: May 2023

This article examines the earliest extant translations from Chinese in the period of the first systematic
encounters between Chinese and Europeans in the sixteenth and seventeenth centuries. It argues that agents of the Spanish and
Portuguese empires in the context of early modern colonialism devised practical and effective social and linguistic approaches for
translating Chinese. The article investigates three such approaches: the use of Chinese interpreters who learned European
languages; the use of oral translation in the collaboration between Chinese and European interpreters; and the use of Europeans
fluent in Chinese translating themselves.
Small lipid droplets are rigid enough to indent a nucleus, dilute the lamina, and cause rupture
Authors: Ivanovska Irena L. , Tobin Michael P. , Bai Tianyi , Dooling Lawrence J. , Discher Dennis E.
Published: May 2023

The nucleus in many cell types is a stiff organelle, but fat-filled lipid droplets (FDs) in cytoplasm are seen to indent and displace the nucleus. FDs are phase-separated liquids with a poorly understood interfacial tension γ that determines how FDs interact with other organelles. Here, micron-sized FDs remain spherical as they indent peri-nuclear actomyosin and the nucleus, while causing local dilution of Lamin-B1 independent of Lamin-A,C and sometimes triggering nuclear rupture. Focal accumulation of the cytosolic DNA sensor cGAS at the rupture site is accompanied by sustained mislocalization of DNA repair factors to cytoplasm, increased DNA damage, and delayed cell cycle. Macrophages show FDs and engulfed rigid beads cause similar indentation dilution. Spherical shapes of small FDs indicate a high γ, which we measure for FDs mechanically isolated from fresh adipose tissue as ∼40 mN/m. This value is far higher than that of protein condensates, but typical of oils in water and sufficiently rigid to perturb cell structures including nuclei.
Modeling analysis and experiments of a novel hydro-pneumatic suspension with piezoelectric energy harvester
Authors: Wang Yulong , Wu Tianliang , Ran Zonghui , Lv Baozhan , Wang Shuang
Published: May 2023

With the rapid development of the semiconductor field, the application of micro-electro-mechanical systems embedded in smart devices and driverless vehicles is gradually widespread, and the problem of the self-powered of devices has gradually been attention. Hence, this study propose a novel hydro-pneumatic suspension system by embedding piezoelectric energy harvester into hydro-pneumatic suspensions, which makes the suspension structure simple and achieves the effect of self-powered for the monitoring and the diagnostics of a vehicle or its subsystems. The mathematical model of intermediate fixed piezoelectric energy harvester with hydro-pneumatic suspension was established. The influence of hydraulic component and exitation parameters of suspension system on damping force and power is analyzed. Numerical simulation proves that the novel hydro-pneumatic suspension with piezoelectric energy harvester is justified to achieve self-powered. The bench test proves the accuracy of some of the conclusions of the simulation and the feasibility of the structure.
Structural, elastic, and thermodynamic properties of BaXCl3 (X = Li, Na) perovskites under pressure effect: ab initio exploration
Authors: Chaba Mouna Sara , Radjai Missoum , Bouhemadou Abdelmadjid , Houatis Djamel , Allali Djamel , Sâad Essaoud Saber , Bin-Omran Saad
Published: May 2023

In this study, we employed the ab initio pseudopotential plane wave approach, utilizing the GGA-PBEsol exchange-correlation functional, to investigate the structural, elastic, and thermodynamic properties of BaXCl3 (X = Li, Na) perovskites under hydrostatic pressures ranging from 0 to 18 GPa. Apart from utilizing the GGA-PBEsol functional, this study also employed the GGA-PBE, GGA-WC, and LDA functionals to simulate the exchange-correlation interactions for computing the structural parameters. Our results show that the optimized lattice parameters are in good agreement with previously predicted values. Based on the calculated elastic moduli of a single crystal, we found that both BaLiCl3 and BaNaCl3 perovskites retain mechanical stability under hydrostatic pressures of up to 18 GPa. Furthermore, we calculated several other important parameters that describe the polycrystalline aggregates of these compounds, including the modulus of compressibility, the shear modulus, the Poisson’s ratio, Young’s modulus, the speeds of sound, and the Debye temperature. Additionally, we examined the temperature and pressure dependencies of the thermal coefficients of the perovskites using the quasi-harmonic approximation. Notably, all of the results presented in this study are reported for the first time and require further confirmation through experimental investigations. We hope that our findings contribute to a more comprehensive understanding of the structural and thermodynamic properties of BaXCl3 (X = Li, Na) perovskites under pressure.
DFT investigations of optoelectronic and electronic transport properties of Li-based double perovskites for energy storage applications
Authors: Mahmood Asif , Al-Masry Waheed , Ramay Shahid Mahmood
Published: May 2023

Because of their non-toxicity as well as environmental stability, Li-based double perovskites are an excellent choice for energy storage, optoelectronic, as well as thermoelectric uses. This density functional theory (DFT) study looks at the physical attributes of the Li2AgBiY6(Y = Cl, Br, I), which might benefit thermal and optoelectronics uses. The Born stability criteria, tolerance factor, and formation energy are calculated for structural stability in the cubic phase. The computed indirect band gaps for Li2AgBiY6(Y = Cl, Br, and I) ensure maximum UV and visible spectrum absorption. As a result, all of the double perovskites investigated are often utilized in optoelectronic purposes like solar cells, photo-catalysts, and LED. The electrical conductivity, thermal conductivity, and the Seebeck coefficient are used to investigate transport qualities. Li2AgBiY6(Y = Cl, Br, and I) compounds double perovskites having ZT indices 0.57 and 0.56, respectively, highlighting their importance for thermoelectric devices.
Light-sheet fluorescent microscopy: fundamentals, developments and applications
Authors: Kafian Hosein , Mozaffari-Jovin Sina , Bagheri Mohammad , Mousavi Shaegh Seyed Ali
Published: May 2023

Deep volumetric microscopy of live objects plays a critical role in biology and medicine. To this end, development of rapid and non-invasive optical methods for 3-dimensional (3D) imaging is still demanding. In this way, light-sheet fluorescence microscopy (LSFM) has emerged as a volumetric microscopy method having high spatial-temporal resolution for imaging of samples within dimensions from submicron to few centimeters with minimum induced photo damaging. Unique features of LSFM allow for its modification and deployments in various fields including developmental biology, pathology, and microfluidics. Considering the wide spectrum of LSFM users, this tutorial review article explains basic concepts and design considerations of LSFM and provides a detailed analysis of various optical configurations of LSFM. Major developments of LSFM for adoption in both research and clinical applications including tissue imaging, diagnostics, and cytometry are also explained. In addition, various designs of light-sheet fluorescent microscopes for use as a stand-alone microscopy unit and an add-on device are discussed.
On the study of the higher-order and multiple lump/rogue waves to the (3+1)-dimensional variable-coefficient Kadomtsev-Petviashvili equation
Authors: Tian Yi-Lin , Zhao Yi-Kang , Zhang Rui-Gang , Cui Ji-Feng
Published: May 2023

In the text, rational solutions to a (3 + 1)-dimensional variable-coefficient Kadomtsev-Petviashvili equation in determinant form are solved by means of the Kadomtsev-Petviashvili hierarchy reduction method and Hirota’s bilinear form. The first-order, higher-order, multi-lump waves and multi-rogue waves on the basis of the solution in Gramian are presented in graphs. Periodic and parabolic line rogue waves are obtained by choosing different dispersion coefficient functions. The second-order rogue waves are also depicted, which can be seen as the composition of two first-order rogue waves. For multiple rogue waves, taking the periodic and parabolic line rogue waves as examples, it can be observed the change tendency of amplitudes of the intersection region is different from that in branches of line rogue waves. Besides, propagation of the first-order lump wave, interaction between one-lump-soliton and one-rogue-wave, and two kinds of collisions of two lump waves, i.e., elastic and inelastic, are also shown in the

x
−
t

plane.
Strange stars within bosonic and fermionic admixed dark matter
Authors: Lopes Luiz L. , Das H.C.
Published: May 2023

In this work, we study dark matter (DM) admixed strange quark stars exploring the different possibilities about the nature of the DM and their effects on the macroscopic properties of strange stars, such as maximum masses, radii, as well the dimensionless tidal parameter. We observe that the DM significantly affects the macroscopic properties that depend on its mass, type, and fraction inside the star.
Peculiarities of exciton formation in 2D semiconductor nanostructures induced by quantum electromagnetic field under nonlinear self-phase modulation
Authors: Tereshchenko I A , Tikhonova O V
Published: May 2023

Specific features of the excitation of a 2D semiconductor nanosystem by non-classical light in a solid state micro-resonator are found under the impact of the Kerr phase nonlinearity in the cavity. Different regimes of excitation are revealed in dependence on the efficiency of the nonlinearity. A negative impact of the nonlinear self-phase modulation on the excitation is found to be compensated by proper choice of the field frequency detuning. The possibility to controllably enhance a certain excitation channel by varying field frequency detuning is demonstrated and the value of the optimal detuning is found analytically. The effect of transfer of non-classical features from the field to the electronic subsystem is revealed. The formation of the photon-like non-classical excitonic states is demonstrated. The obtained results seem to be a basis for the creation of the light–matter interface and development of quantum information algorithms in solid state nanosystems.
A Data-driven Method for Realistic Covariance Prediction of Space Object with Sparse Tracking Data
Authors: Liu Hong-Kang , Li Bin , Zhang Yan , Sang Ji-Zhang
Published: May 2023

Covariance of the orbital state of a resident space object (RSO) is a necessary requirement for various space situational awareness tasks, like the space collision warning. It describes an accuracy envelope of the RSO's location. However, in current space surveillance, the tracking data of an individual RSO is often found insufficiently accurate and sparsely distributed, making the predicted covariance (PC) derived from the tracking data and classical orbit dynamic system usually unrealistic in describing the error characterization of orbit predictions. Given the fact that the tracking data of an RSO from a single station or a fixed network share a similar temporal and spatial distribution, the evolution of PC could share a hidden relationship with that data distribution. This study proposes a novel method to generate accurate PC by combining the classical covariance propagation method and the data-driven approach. Two popular machine learning algorithms are applied to model the inconsistency between the orbit prediction error and the PC from historical observations, and then this inconsistency model is used for the future PC. Experimental results with the Swarm constellation satellites demonstrate that the trained Random Forest models can capture more than 95% of the underlying inconsistency in a tracking scenario of sparse observations. More importantly, the trained models show great generalization capability in correcting the PC of future epochs and other RSOs with similar orbit characteristics and observation conditions. Besides, a deep analysis of generalization performance is carried out to describe the temporal and spatial similarities of two data sets, in which the Jaccard similarity is used. It demonstrates that the higher the Jaccard similarity is, the better the generalization performance will be, which may be used as a guide to whether to apply the trained models of a satellite to other satellites. Further, the generalization performance is also evaluated by the classical Cramer von Misses test, which also shows that trained models have encouraging generalization performance.
Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina
Authors: Zhuo Shun-Yi , Gong Hai-Qing , Li Guo-Feng , Qiu Wei-Bao , Zheng Hai-Rong , Liang Pei-Ji
Published: May 2023

Objective. Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question. Approach. Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (I
SPTA 0.5 W cm−2) ultrasound stimulation. Main results. We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynaptic N-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity. Significance. Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.
A data acquisition and reconstruction software for SAMPA-SRS integration
Authors: de Souza G.G.A. , Abelha T.S. , Saramela T.B. , Cortez A.F.V. , da Luz H.N. , Penteado C.G. , Bregant M.
Published: May 2023

In this work we present the latest developments in the SAMPA-SRS integration. A
software was developed to improve the acquisition configuration, acquisition, and decoding of the data. The complete framework was tested using a triple GEM-based position sensitive detector for X-rays. The detector was operated in Ar/CO2 (70/30) in continuous flow, at atmospheric pressure and made use of a 1 dimension strip readout (200 μm wide strips at a pitch of 400 μm) for charge collection. With this detector a position resolution of better than 833 μm was obtained, with an energy resolution of 14.2 % (σ/E) for 5.9 keV.
THC in breath aerosols collected with an impaction filter device before and after legal-market product inhalation—a pilot study
Authors: Jeerage Kavita M , Beuning Cheryle N , Friss Adam J , Bidwell L Cinnamon , Lovestead Tara M
Published: May 2023

An accurate cannabis breathalyzer based on quantitation of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) could be an important tool for deterring impaired driving. Such a device does not exist. Simply translating what is known about alcohol breathalyzers is insufficient because ethanol is detected as a vapor. THC has extremely low volatility and is hypothesized to be carried in breath by aerosol particles formed from lung surfactant. Exhaled breath aerosols can be recovered from electrostatic filter devices, but consistent quantitative results across multiple studies have not been demonstrated. We used a simple-to-use impaction filter device to collect breath aerosols from participants before and after they smoked a legal market cannabis flower containing ∼25% Δ9-tetrahydrocannabinolic acid. Breath collection occurred at an intake session (baseline-intake) and four weeks later in a federally-compliant mobile laboratory 15 min before (baseline-experimental) and 1 h after cannabis use (post-use). Cannabis use was in the participant’s residence. Participants were asked to follow a breathing maneuver designed to increase aerosol production. Breath extracts were analyzed by liquid chromatography with tandem mass spectrometry with multiple reaction monitoring of two transitions for analytes and their deuterated internal standards. Over more than 1 yr, 42 breath samples from 18 participants were collected and analyzed in six batches. THC was quantified in 31% of baseline-intake, 36% of baseline-experimental, and 80% of 1 h post-use breath extracts. The quantities observed 1 h post-use are compared to those reported in six other pilot studies that sampled breath at known intervals following cannabis use and are discussed with respect to participant characteristics and breath sampling protocols. Larger studies with verified abstinence and more post-use timepoints are necessary to generate statistically significant data to develop meaningful cannabis breathalyzer technology.
Computationally effective estimation of supersonic flow field around airfoils using sparse convolutional neural network
Authors: Wu Ming-Yu , Peng Jiang-Zhou , Qiu Zhi-Ming , Chen Zhi-Hua , Li Yu-Bai , Wu Wei-Tao
Published: May 2023

This work proposes an innovative approach for supersonic flow field modeling around airfoils based on sparse convolutional neural networks (SCNNs) and Bézier generative adversarial network (GAN), where (1) the SCNN model is built to end-to-end predict supersonic compressible physical flow fields around airfoils from spatially-sparse geometries and (2) the trained Bézier-GAN is utilized to generate plenty of smooth airfoils as well as the latent codes representing airfoils. The spatially-sparse positions of airfoil geometry are represented using signed distance function (SDF). Particularly, the latent codes are merged with the SDF matrix and the Mach number to form the input of the SCNN model, effectively making the SCNN model possess more robust geometric adaptability to different flow conditions. The most significant contribution compared to the regular convolutional neural network is that SCNN introduces sparse convolutional operations to process spatially-sparse input matrix, specifically, which only focuses on the local area with flow information when performing convolution, eventually saving memory usage and improving the network’s attention on the flow area. Further, the testing results show that the SCNN model can more accurately predict supersonic flow fields with a mean absolute error lower than 5% and save 40% of graphics processing unit memory. These results indicate that the proposed SCNN model can capture the shock wave features of supersonic flow fields and improve learning efficiency and computing efficiency.
The Intersections of Resistance and Health
Authors: Essex Ryan
Published: May 2023

Resistance refers to a range of actions such as marches, strikes, and civil disobedience. It also refers to less visible and even hidden acts like sabotage. Perhaps more subtly, it refers to discourse and knowledge; how issues are thought or spoken about could be an act of resistance. While the concept of resistance is far from settled, it is a concept that has broad applications and has been applied to better understand a range of actions and struggles. Its relationship to health, however, has often been overlooked or taken for granted. This is despite resistance having an influential role in securing a number of important health related gains and pushing back against powers that would otherwise harm health. Resistance has also been triggered by concerns about health, or framed around issues related to health. The intersections of resistance and health, however, are far more complex. Resistance has challenged and shaped health related knowledge and practice, and health in itself has been used as an act of resistance. Charting the intersections of health and resistance is not only important in itself; it also sheds light on how disruption, dispute, and opposition can shape health and well-being.
The Tree of Life, Health, and Risk Through the Lens of Biblical Wisdom
Authors: Gregory Bradley C
Published: May 2023

As a way forward in assessing how the Old Testament wisdom tradition might speak to decisions in a modern medical context, in this paper, I propose exploring the iconographic function of the “tree of life” in the Old Testament, which is consistently associated with both wisdom as well as life and health, in order to tease out two-related issues that can help in providing a Christian theological framework for thinking about the problem of the medicalization of risk: first, how should the natural and good human desire for health and long life be framed in terms of the pursuit of wisdom? And, second, how might a sapientially formed character approach risk and uncertainty in making medical decisions? The answers to these questions help establish a framework in which more specific questions related to the medicalization of risk can be assessed. As such, this paper is deliberately programmatic and perspectival rather than prescriptive.
NF1gene inactivation acts as a tumor driver inRET/RAS-negative medullary thyroid carcinomas
Authors: Ciampi Raffaele , Ramone Teresa , Romei Cristina , Casalini Roberta , Matrone Antonio , Prete Alessandro , Gambale Carla , Minardi Simone Paolo , Caparezza Giovanni , Pierotti Marco Alessandro , Torregrossa Liborio , Ugolini Clara , Materazzi Gabriele , Elisei Rossella
Published: May 2023

Objective

About 20% of sporadic medullary thyroid carcinomas (MTC) have no RET/RAS somatic alterations or other known gene alterations. The aim of this study was to investigate RET/RAS-negative MTC for the presence of NF1 alterations.

Methods

We studied 18 sporadic RET/RAS-negative MTC cases. Next-generation sequencing (NGS) of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene. The effect of NF1 alterations on the transcripts was characterized by reverse transcriptase–polymerase chain reaction (RT–PCR), and the loss of heterozygosity (LOH) of the other NF1 allele was investigated with Multiplex Ligation-dependent Probe Amplification (MLPA).

Results

Two cases showed biallelic inactivation of NF1 with a prevalence of about 11% of RET/RAS-negative cases. In a patient affected by neurofibromatosis, there was a somatic intronic point mutation determining the transcript alteration in 1 allele and a germline LOH in the other. In a second patient, we described that both the point mutation and the LOH were somatic events; this latter finding shows, for the first time, a driver role of NF1 inactivation in MTC independent of RET/RAS alterations and the presence of neurofibromatosis.

Conclusions

About 11% of our series of sporadic RET/RAS-negative MTC harbor biallelic inactivation of the NF1 suppressor gene also regardless of neurofibromatosis status. According to our results, NF1 alterations should be searched in all RET/RAS-negative MTC as possible drivers. Moreover, this finding reduces the number of negative sporadic MTC and may have important clinical implications in the management of these tumors.
Right ventricular function is a predictor for sustained ventricular tachycardia requiring anti-tachycardic pacing in arrhythmogenic ventricular cardiomyopathy: insight into transvenous vs. subcutaneous implantable cardioverter defibrillator insertion
Authors: Honarbakhsh Shohreh , Protonotarios Alexander , Monkhouse Christopher , Hunter Ross J , Elliott Perry M , Lambiase Pier D
Published: May 2023

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients develop ventricular arrhythmias (VAs) responsive to anti-tachycardia pacing (ATP). However, VA episodes have not been characterized in accordance with the device therapy, and with the emergence of the subcutaneous implantable cardioverter defibrillator (S-ICD), the appropriate device prescription in ARVC remains unclear. Study aim was to characterize VA events in ARVC patients during follow-up in accordance with device therapy and elicit if certain parameters are predictive of specific VA events.

Methods and results

This was a retrospective single-centre study utilizing prospectively collated registry data of ARVC patients with ICDs. Forty-six patients were included [54.0 ± 12.1 years old and 20 (43.5%) secondary prevention devices]. During a follow-up of 12.1 ± 6.9 years, 31 (67.4%) patients had VA events [n = 2, 6.5% ventricular fibrillation (VF), n = 14], 45.2% VT falling in VF zone resulting in ICD shock(s), n = 10, 32.3% VT resulting in ATP, and n = 5, 16.1% patients had both VT resulting in ATP and ICD shock(s). Lead failure rates were high (11/46, 23.9%). ATP was successful in 34.5% of patients. Severely impaired right ventricular (RV) function was an independent predictor of VT resulting in ATP (hazard ratio 16.80, 95% confidence interval 3.74–75.2; P < 0.001) with a high predictive accuracy (area under the curve 0.88, 95%CI 0.76–1.00; P < 0.001).

Conclusion

VA event rates are high in ARVC patients with a majority having VT falling in the VF zone resulting in ICD shock(s). S-ICDs could be of benefit in most patients with ARVC with the absence of severely impaired RV function which has the potential to avoid consequences of the high burden of lead failure.
A Soft Power Challenge, or an Opportunity? A Big Data Analysis on Chinese Soft Power during COVID-19 Pandemic
Authors: Kim Yerin , Kim Byungjun , Park Min Hyung , Nam Woomin , Kim Jang Hyun
Published: May 2023

The Chinese government's rigorous efforts to enhance its soft power have confronted a major challenge during the COVID-19 pandemic. This study aimed to look at how the Chinese soft power changed throughout the pandemic using English news articles that covered China. The research took a data science approach to investigate the contents of articles using machine-learning-based sentiment analysis and Dirichlet-Multinomial Regression (DMR) analysis. The results show a gradual downturn in overall sentiment and that the topics related to political issues made the most significant impact. Nevertheless, the major increase in referencing Chinese social media implied that the sources of Chinese soft power have been diversified throughout the pandemic. In addition, this research has aimed to engage in major debates around soft power theory. Providing a multi-disciplinary approach for analyzing soft power, this research has tackled the difficulties in the quantitative conceptualization of soft power.
Context-dependent role of Pho binding sites in Polycomb complex recruitment in Drosophila
Authors: Brown Janet Lesley , Price Joshua D , Erokhin Maksim , Kassis Judith A
Published: May 2023

Polycomb group (PcG) proteins maintain the silenced state of key developmental genes, but how these proteins are recruited to specific regions of the genome is still not completely understood. In Drosophila, PcG proteins are recruited to Polycomb response elements (PREs) comprised of a flexible array of sites for sequence-specific DNA binding proteins, “PcG recruiters,” including Pho, Spps, Cg, and GAF. Pho is thought to play a central role in PcG recruitment. Early data showed that mutation of Pho binding sites in PREs in transgenes abrogated the ability of those PREs to repress gene expression. In contrast, genome-wide experiments in pho mutants or by Pho knockdown showed that PcG proteins can bind to PREs in the absence of Pho. Here, we directly addressed the importance of Pho binding sites in 2 engrailed (en) PREs at the endogenous locus and in transgenes. Our results show that Pho binding sites are required for PRE activity in transgenes with a single PRE. In a transgene, 2 PREs together lead to stronger, more stable repression and confer some resistance to the loss of Pho binding sites. Making the same mutation in Pho binding sites has little effect on PcG-protein binding at the endogenous en gene. Overall, our data support the model that Pho is important for PcG binding but emphasize how multiple PREs and chromatin environment increase the ability of PREs to function in the absence of Pho. This supports the view that multiple mechanisms contribute to PcG recruitment in Drosophila.
Polygenic pathogen networks influence transcriptional plasticity in the Arabidopsis–Botrytis pathosystem
Authors: Krishnan Parvathy , Caseys Celine , Soltis Nik , Zhang Wei , Burow Meike , Kliebenstein Daniel J
Published: May 2023

Bidirectional flow of information shapes the outcome of the host–pathogen interactions and depends on the genetics of each organism. Recent work has begun to use co-transcriptomic studies to shed light on this bidirectional flow, but it is unclear how plastic the co-transcriptome is in response to genetic variation in both the host and pathogen. To study co-transcriptome plasticity, we conducted transcriptomics using natural genetic variation in the pathogen, Botrytis cinerea, and large-effect genetic variation abolishing defense signaling pathways within the host, Arabidopsis thaliana. We show that genetic variation in the pathogen has a greater influence on the co-transcriptome than mutations that abolish defense signaling pathways in the host. Genome-wide association mapping using the pathogens’ genetic variation and both organisms’ transcriptomes allowed an assessment of how the pathogen modulates plasticity in response to the host. This showed that the differences in both organism's responses were linked to trans-expression quantitative trait loci (eQTL) hotspots within the pathogen's genome. These hotspots control gene sets in either the host or pathogen and show differential allele sensitivity to the host’s genetic variation rather than qualitative host specificity. Interestingly, nearly all the trans-eQTL hotspots were unique to the host or pathogen transcriptomes. In this system of differential plasticity, the pathogen mediates the shift in the co-transcriptome more than the host.
Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection
Authors: Kudelka Matthew R , Gu Wei , Matsumoto Yasuyuki , Ju Tongzhong , Barnes II Richard H , Kardish Robert J , Heimburg-Molinaro Jamie , Lehoux Sylvain , Zeng Junwei , Cohen Cynthia , Robinson Brian S , Shah Kinjal S , Chaikof Elliot L , Stowell Sean R , Cummings Richard D
Published: May 2023

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.
The clinical features and TCAP mutation spectrum in a Chinese cohort of patients with limb-girdle muscular dystrophy R7
Authors: Lv Xiaoqing , Lin Feng , Wu Wenjing , Wang Hui , Luo Yuebei , Wang Zhiqiang , Yan Chuanzhu , Lv He , Luo Sushan , Lin Pengfei
Published: May 2023

Limb-girdle muscular dystrophy R7 (LGMDR7) is an autosomal recessive hereditary muscular dystrophy caused by mutations in titin-cap (TCAP). Here, we summarized the clinical characteristics and TCAP mutations in a Chinese cohort of 30 patients with LGMDR7. The onset age of Chinese patients was 19.89 ± 6.70 years old, which is later than European and South Asian patients (P < 0.05). Clinically speaking, 20.0% of patients presented with predominant distal weakness, and 73.3% of patients presented with predominant pelvic girdle weakness. Radiological study revealed semitendinosus and magnus adductor were severely involved in Chinese LGMDR7 patients. Rectus femoris, vastus lateralis, vastus intermedius, soleus and tibialis anterior were moderately to severely involved. The most prevalent mutation in this cohort is c.26_33dupAGGTGTCG, while c.165dupG and c.110 + 5G > A are unique in Chinese population as two of the common mutations. Besides, variant c.26_33dupAGGGTGTCG might be a founder mutation in Asian patients. Internal nuclei, lobulated fibers, and scattered rimmed vacuoles were typical morphological changes in Chinese LGMDR7 patients. This is the largest LGMDR7 cohort in the Chinese population and in the world. This article also expands the clinical, pathological, mutational and radiological spectrum of patients with LGMDR7 in China and in the world.
China's rise and the reshaping of sovereign debt relief
Authors: Chen Muyang
Published: May 2023

China has become the world's largest bilateral creditor to low- and middle-income countries, and yet its participation in collective debt-relief frameworks led by western multilateral institutions—the International Monetary Fund, the World Bank and the Paris Club—has not met those institutions' expectations. Prevailing discussion perceives China's ‘reserved’ participation as free-riding on or contesting the international sovereign debt regime. This article advances ongoing discussion by drawing a historical parallel between China's current debt-relief approach and that of the United States and the multilateral institutions during and after the debt crisis of the 1980s. The article finds that towards the end of the 1980s, the US transitioned from practicing a new money approach—continued financing for existing projects—to a haircut approach—increasingly writing off debts. Around the same time, multilateral institutions started to become more acceptive of debt forgiveness. Yet China's policy banks, the main financiers of its overseas projects, have been primarily practising a commercially oriented, new money approach. China's rise has therefore revitalized an approach that western private banks once commonly practised and weakened the current international sovereign debt regime that took shape in the post-1980s decades.
An indicator-based approach for assessing marine ecosystem resilience
Authors: Flensborg L C , Maureaud A A , Bravo D N , Lindegren M
Published: May 2023

Marine ecosystems are under threat from a range of human pressures, notably climate change, overexploitation, and habitat destruction. The resulting loss of species and biodiversity can cause abrupt and potentially irreversible changes in their structure and functioning. Consequently, maximizing resilience has emerged as a key concept in conservation and management. However, despite a well-developed theory, there is an urgent need for a framework that can quantify key components promoting resilience by accounting for the role of biodiversity. In this study, we applied an indicator-based approach to assess the potential resilience of marine ecosystems using the North Sea as an illustrative case study. More specifically, we quantified and compared multiple indicators of ecological resilience, estimated based on high-resolution monitoring data on marine demersal fish species, combined with information on ecological traits. Our results show a pronounced spatial structuring of indicators, including both similarities and differences among individual metrics and indicators. This implies that high resilience cannot be achieved by maximizing all individual aspects of resilience, simply because there seems to be inherent trade-offs between these components. Our framework is generic and is therefore applicable to other systems and can inform spatial planning and management.
Spectral Multiplicity and Nodal Domains of Torus-Invariant Metrics
Authors: Cianci Donato , Judge Chris , Lin Samuel , Sutton Craig
Published: May 2023

Let a $d$-dimensional torus $\mathbb{T}$ act freely and smoothly on a closed manifold $M$ of dimension $n>d$. We show that, for a generic $\mathbb{T}$-invariant Riemannian metric $g$ on $M$, each real $\Delta _{g}$-eigenspace is an irreducible real representation of $\mathbb{T}$ and, therefore, has dimension at most two. We also show that, for the generic $\mathbb{T}$-invariant metric $g$ on $M$, if $u$ is a non-invariant real-valued $\Delta _{g}$-eigenfunction that vanishes on some $\mathbb{T}$-orbit, then the nodal set of $u$ is a connected smooth hypersurface. If $n>d+1$, we show that the complement of the nodal set has exactly two connected components. As a consequence, we obtain new examples of manifolds for which—up to a sequence of Weyl density zero—each eigenfunction has exactly two nodal domains.