bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of direct numerical simulations to the budget and modelling of the transport equations for passive scalar turbulent fields with wall scalar fluctuations
Authors: Chaouat Bruno
Published: May 2023

We perform direct numerical simulations (DNS) of the fully developed turbulent channel flow with a passive scalar subjected to constant time-averaged scalar fluxes at the wall. The first case (case I) considers a constant time-averaged scalar flux

$\left \langle q_w \right \rangle$

along with the specific condition of a non-fluctuating scalar

$\theta _w$

imposed at the wall implying zero wall scalar fluctuation

$\theta '_w=0$

and zero variance (isoscalar boundary condition) whereas the second case (case II) accounts for a constant instantaneous scalar flux

$q_w$

in time and space leading to zero gradient of scalar fluctuation along the normal to the wall

$(\partial \theta '/ \partial x_n)_w = 0$

(isoflux boundary condition) implying a non-zero variance. The friction Reynolds number takes on the value

$R_\tau =395$

and the molecular Prandtl numbers considered are

$P_r=0.01$

, 0.1, 1 and 10. The purpose is to investigate the effect of the wall scalar fluctuations on the scalar field. Emphasis is put on the mean passive scalar

$\left \langle \theta \right \rangle$

, the half-scalar variance

$k_\theta$

, the turbulent scalar fluxes

$\tau _{i \theta }$

, the correlation coefficients

$R_{i \theta }$

, the passive scalar to dynamic time-scale ratio

$\mathcal {R}$

, the turbulent Prandtl number

$Pr_t$

and higher-order scalar statistics. Systematic comparisons between these two scalar fields are undertaken. As a result of interest, it is found that the mean scalar remains almost the same whatever the type of the boundary layer condition but not the scalar variance. The budgets of transport equations for the half-scalar variance and turbulent fluxes reveal that some scalar quantities such as the dissipation-rate and the molecular diffusion terms are highly modified in the near-wall region but not really the production, diffusion and the scalar-pressure gradient correlation terms in a first approximation. Visualization of the instantaneous scalar fields indicates that the topology of the structures is strongly modified as the Prandtl number increases from

$P_r=0.01$

up to

$10$

. Finally, it is shown how to use this DNS database to devise and calibrate scalar flux equation models in the framework of both first and second moment closures. This study suggests that accounting for wall scalar fluctuations should be considered in the simulation of turbulent flows involving fluid and solid combinations at the interface and provides a useful high resolution DNS database.
General kernel estimates of Schrödinger-type operators with unbounded diffusion terms
Authors: Caso Loredana , Kunze Markus , Porfido Marianna , Rhandi Abdelaziz
Published: May 2023

We first prove that the realization $A_{\mathrm {min}}$ of $A:={\operatorname {\mathrm {div}}}(Q\nabla )-V$ in $L^2({\mathbb {R}}^d)$ with unbounded coefficients generates a symmetric sub-Markovian and ultracontractive semigroup on $L^2({\mathbb {R}}^d)$ which coincides on $L^2({\mathbb {R}}^d)\cap C_b({\mathbb {R}}^d)$ with the minimal semigroup generated by a realization of $A$ on $C_b({\mathbb {R}}^d)$. Moreover, using time-dependent Lyapunov functions, we prove pointwise upper bounds for the heat kernel of $A$ and deduce some spectral properties of $A_{\min }$ in the case of polynomially and exponentially growing diffusion and potential coefficients.
The potential conservation value of anthropogenically modified habitat for the Endangered moor macaque Macaca maura in Sulawesi, Indonesia
Authors: Riley Erin P. , Albani Alessandro , Zak Alison A. , Germani Lavinia , Rothman Jessica M. , Carosi Monica , Ngakan Putu Oka
Published: May 2023

Human-induced land-use change has resulted in substantial loss and degradation of habitat for forest-dwelling wildlife. The moor macaque Macaca maura, an Endangered primate endemic to Sulawesi, Indonesia, has been observed in a wide array of habitats, including heavily modified areas, but little is known about the quality of these habitats. Here we compared the habitat quality of two areas occupied by moor macaque populations: a previously human-modified karst forest now located within a national park and a heavily modified forest located in an unprotected area. We assessed habitat quality by measuring specific indicators of potential food availability derived from vegetation data and quantified the nutritional environment based on macronutrient analysis of fruit samples collected at the two sites. Although the species richness, diversity and overall stem density of macaque food trees were greater in the protected area forest, total basal area and mean diameter at breast height were greater in the heavily modified forest. Mean metabolizable energy concentrations of fruits eaten by macaques were similar between forests, as were the proportions of protein, lipids and total non-structural carbohydrates. These results provide further support for the notion that heavily modified habitats should not be overlooked for their potential conservation value. To further augment their value, conservation efforts should focus on forest restoration, specifically the planting of fast-growing species that are utilized by both wildlife and people.
Emerging trends: Risks 3.0 and proliferation of spyware to 50,000 cell phones
Authors: Church Kenneth Ward , Chandrasekar Raman
Published: May 2023

Our last emerging trend article introduced Risks 1.0 (fairness and bias) and Risks 2.0 (addictive, dangerous, deadly, and insanely profitable). This article introduces Risks 3.0 (spyware and cyber weapons). Risks 3.0 are less profitable, but more destructive. We will summarize two recent books, Pegasus: How a Spy in Your Pocket Threatens the End of Privacy, Dignity, and Democracy and This is How They Tell Me the World Ends: The Cyberweapons Arms Race. The first book starts with a leak of 50,000 phone numbers, targeted by spyware named Pegasus. Pegasus uses a zero-click exploit to obtain root access to your phone, taking control of the microphone, camera, GPS, text messages, etc. The list of 50,000 numbers includes journalists, politicians, and academics, as well as their friends and family. Some of these people have been murdered. The second book describes the history of cyber weapons such as Stuxnet, which is described as crossing the Rubicon. In the short term, it sets back Iran’s nuclear program for less than the cost of conventional weapons, but it did not take long for Iran to build the fourth-biggest cyber army in the world. As spyware continues to proliferate, we envision a future dystopia where everyone spies on everyone. Nothing will be safe from hacking: not your identity, or your secrets, or your passwords, or your bank accounts. When the endpoints (phones) have been compromised, technologies such as end-to-end encryption and multi-factor authentication offer a false sense of security; encryption and authentication are as pointless as closing the proverbial barn door after the fact. To address Risks 3.0, journalists are using the tools of their trade to raise awareness in the court of public opinion. We should do what we can to support them. This paper is a small step in that direction.
Die Komplexität in der Sturzprävention und Mobilität bei älteren Menschen
Authors: Freiberger Ellen
Published: May 2023

Zusammenfassung: Für ältere Menschen ist ein Sturzereignis oft ein einschneidendes Erlebnis. Trotz positiver Entwicklung in der Sturzprävention über die letzten 20 Jahre steigt die Anzahl der Stürze bei älteren Menschen immer noch. Festzuhalten ist aber auch, dass das Sturzrisiko je nach Setting schwankt: Bei selbstständig lebenden älteren Menschen über 65 Jahren sind es ca. 33%, die mindestens einmal pro Jahr stürzen, während es im Pflegeheimbereich bereits über 60% sind. Auch die Sturzraten für das Setting Krankenhaus sind höher. Stürze sind in den seltensten Fällen nur einem Risikofaktor zu zuordnen. Die Komplexität der zusammenwirkenden Risikofaktoren reicht über biologische, sozio-ökonomische und umweltbedingte bis hin zu verhaltensbedingten Risikofaktoren. Der folgende Artikel befasst sich mit dieser Komplexität und der dynamischen Interaktion der Sturzrisiken. Dabei wird besonders auf die verhaltensbedingten und umweltbedingten Risikofaktoren und ein effektives Screening und Assessment eingegangen werden, die auch in den neuen Empfehlungen der «World Falls Guidelines (WFG)»-Taskforce thematisiert werden.
Relevanz der Neuropsychologie bei der Beurteilung der Fahreignung nach Schlaganfall
Authors: Schwind Marc
Published: May 2023

Zusammenfassung: Mobilität ist für viele Menschen unter normalen Umständen eine Selbstverständlichkeit. Nach einer erworbenen Hirnschädigung wird sie plötzlich zu einer existenziellen Frage, nicht zuletzt wegen der gesellschaftlichen Teilhabe. Die Fahreignung wird häufig mit Autonomie, Freiheit und Lebensqualität assoziiert und als selbstverständlich angesehen. Nach einem Schlaganfall wird diese Autonomie von einem Augenblick auf den anderen von externen Behandlern infrage gestellt, und für die Patienten sind dann nicht mehr die somatischen oder kognitiven Probleme zentral, sondern ihre «genommene Freiheit». Nicht selten kommt es zu einer Schuldzuweisung gegenüber dem Behandler. Je nach Ätiologie der Hirnschädigung sind die Patienten einsichtig und zeigen Verständnis für eine Fahrkarenz, oder sie sind überrascht und reagieren gereizt bis aggressiv und haben kein Störungsbewusstsein. Da eine auferlegte Fahrkarenz für viele Patienten überraschend und nicht immer nachvollziehbar ist, sind eine gute Aufklärung und ein gemeinsames Festlegen des weiteren Vorgehens besonders wichtig. Für die Sicherheit im Strassenverkehr ist es notwendig und eine Pflicht, die Fahreignung bei Patienten mit erworbener Hirnschädigung eingehend zu prüfen.
Increased Biogenic Calcification and Burial Under Elevated pCO2 During the Miocene: A Model‐Data Comparison
Authors: Si Weimin , Herbert Timothy , Wu Mengxi , Rosenthal Yair
Published: May 2023

Ocean acidification due to anthropogenic CO2 emission reduces ocean pH and carbonate saturation, with the projection that marine calcifiers and associated ecosystems will be negatively affected in the future. On longer time scale, however, recent studies of deep‐sea carbonate sediments suggest significantly increased carbonate production and burial in the open ocean during the warm Middle Miocene. Here, we present new model simulations in comparison to published Miocene carbonate accumulation rates to show that global biogenic carbonate production in the pelagic environment was approximately doubled relative to present‐day values when elevated atmospheric pCO2 led to substantial global warming ∼13–15 million years ago. Our analysis also finds that although high carbonate production was associated with high dissolution in the deep‐sea, net pelagic carbonate burial was approximately 30%–45% higher than modern. At the steady state of the long‐term carbon cycle, this requires an equivalent increase in riverine carbonate alkalinity influx during the Middle Miocene, attributable to enhanced chemical weathering under a warmer climate. Elevated biogenic carbonate production resulted in a Miocene ocean that had carbon (dissolved inorganic carbon) and alkalinity (total alkalinity) inventories similar to modern values but was poorly buffered and less saturated in both the surface and the deep ocean relative to modern.
Quantifying 3D Gravity Wave Drag in a Library of Tropical Convection‐Permitting Simulations for Data‐Driven Parameterizations
Authors: Sun Y. Qiang , Hassanzadeh Pedram , Alexander M. Joan , Kruse Christopher G.
Published: May 2023

Atmospheric gravity waves (GWs) span a broad range of length scales. As a result, the un‐resolved and under‐resolved GWs have to be represented using a sub‐grid scale (SGS) parameterization in general circulation models (GCMs). In recent years, machine learning (ML) techniques have emerged as novel methods for SGS modeling of climate processes. In the widely used approach of supervised (offline) learning, the true representation of the SGS terms have to be properly extracted from high‐fidelity data (e.g., GW‐resolving simulations). However, this is a non‐trivial task, and the quality of the ML‐based parameterization significantly hinges on the quality of these SGS terms. Here, we compare three methods to extract 3D GW fluxes and the resulting drag (Gravity Wave Drag [GWD]) from high‐resolution simulations: Helmholtz decomposition, and spatial filtering to compute the Reynolds stress and the full SGS stress. In addition to previous studies that focused only on vertical fluxes by GWs, we also quantify the SGS GWD due to lateral momentum fluxes. We build and utilize a library of tropical high‐resolution (Δx = 3 km) simulations using weather research and forecasting model. Results show that the SGS lateral momentum fluxes could have a significant contribution to the total GWD. Moreover, when estimating GWD due to lateral effects, interactions between the SGS and the resolved large‐scale flow need to be considered. The sensitivity of the results to different filter type and length scale (dependent on GCM resolution) is also explored to inform the scale‐awareness in the development of data‐driven parameterizations.
FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth
Authors: Wei Wenxia , Qin Baifu , Wen Weijie , Zhang Boyu , Luo Haidan , Wang Yuzhi , Xu Hui , Xie Xiaoshan , Liu Sicheng , Jiang Xin , Wang Mengan , Tang Qin , Zhang Jiayu , Yang Runxiang , Fan Zongmin , Lyu Haiwen , Lin Junzhong , Li Kai , Lee Mong-Hong
Published: May 2023

Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor. FBXW7 is a highly mutated gene in CRC, but its biological functions in cancer are not fully characterized. Here, we report that FBXW7β, a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC, is an E3 ligase of fatty acid synthase (FASN). Cancer-specific FBXW7β mutations that could not degrade FASN can lead to sustained lipogenesis in CRC. COP9 signalosome subunit 6 (CSN6), an oncogenic marker of CRC, increases lipogenesis via interacting with and stabilizing FASN. Mechanistic studies show that CSN6 associates with both FBXW7β and FASN, and antagonizes FBXW7β’s activity by enhancing FBXW7β autoubiquitination and degradation, which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation, thereby regulating lipogenesis positively. Both CSN6 and FASN are positively correlated in CRC, and CSN6-FASN axis, regulated by EGF, is responsible for poor prognosis of CRC. The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab. Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC. Thus, CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.
Radiation-induced tumor immune microenvironments and potential targets for combination therapy
Authors: Guo Siyu , Yao Yihan , Tang Yang , Xin Zengfeng , Wu Dang , Ni Chao , Huang Jian , Wei Qichun , Zhang Ting
Published: May 2023

As one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.
Novel insights into the METTL3-METTL14 complex in musculoskeletal diseases
Authors: Xu Yeqiu , Zhang Yuanzhuang , Luo Yinzhou , Qiu Guanzhen , Lu Jie , He Ming , Wang Yong
Published: May 2023

N6-methyladenosine (m6A) modification, catalyzed by methyltransferase complexes (MTCs), plays many roles in multifaceted biological activities. As the most important subunit of MTCs, the METTL3-METTL14 complex is reported to be the initial factor that catalyzes the methylation of adenosines. Recently, accumulating evidence has indicated that the METTL3-METTL14 complex plays a key role in musculoskeletal diseases in an m6A-dependent or -independent manner. Although the functions of m6A modifications in a variety of musculoskeletal diseases have been widely recognized, the critical role of the METTL3-METTL14 complex in certain musculoskeletal disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis and osteosarcoma, has not been systematically revealed. In the current review, the structure, mechanisms and functions of the METTL3-METTL14 complex and the mechanisms and functions of its downstream pathways in the aforementioned musculoskeletal diseases are categorized and summarized.
Unidirectional rotation of micromotors on water powered by pH-controlled disassembly of chiral molecular crystals
Authors: Carmeli Itai , Bounioux Celine M. , Mickel Philip , Richardson Mark B. , Templeman Yael , Scofield Joel M. P. , Qiao Greg G. , Rosen Brian Ashley , Yusupov Yelena , Meshi Louisa , Voelcker Nicolas H. , Diéguez Oswaldo , Miloh Touvia , Král Petr , Cohen Hagai , Richter Shachar E.
Published: May 2023

Biological and synthetic molecular motors, fueled by various physical and chemical means, can perform asymmetric linear and rotary motions that are inherently related to their asymmetric shapes. Here, we describe silver-organic micro-complexes of random shapes that exhibit macroscopic unidirectional rotation on water surface through the asymmetric release of cinchonine or cinchonidine chiral molecules from their crystallites asymmetrically adsorbed on the complex surfaces. Computational modeling indicates that the motor rotation is driven by a pH-controlled asymmetric jet-like Coulombic ejection of chiral molecules upon their protonation in water. The motor is capable of towing very large cargo, and its rotation can be accelerated by adding reducing agents to the water.
Long-wave infrared transparent sulfur polymers enabled by symmetric thiol cross-linker
Authors: Lee Miyeon , Oh Yuna , Yu Jaesang , Jang Se Gyu , Yeo Hyeonuk , Park Jong-Jin , You Nam-Ho
Published: May 2023

Infrared (IR) transmissive polymeric materials for optical elements require a balance between their optical properties, including refractive index (n) and IR transparency, and thermal properties such as glass transition temperature (Tg). Achieving both a high refractive index (n) and IR transparency in polymer materials is a very difficult challenge. In particular, there are significant complexities and considerations to obtaining organic materials that transmit in the long-wave infrared (LWIR) region, because of high optical losses due to the IR absorption of the organic molecules. Our differentiated strategy to extend the frontiers of LWIR transparency is to reduce the IR absorption of the organic moieties. The proposed approach synthesized a sulfur copolymer via the inverse vulcanization of 1,3,5-benzenetrithiol (BTT), which has a relatively simple IR absorption because of its symmetric structure, and elemental sulfur, which is mostly IR inactive. This strategy resulted in approximately 1 mm thick windows with an ultrahigh refractive index (nav > 1.9) and high mid−wave infrared (MWIR) and LWIR transmission, without any significant decline in thermal properties. Furthermore, we demonstrated that our IR transmissive material was sufficiently competitive with widely used optical inorganic and polymeric materials.
A map of single-phase high-entropy alloys
Authors: Chen Wei , Hilhorst Antoine , Bokas Georgios , Gorsse Stéphane , Jacques Pascal J. , Hautier Geoffroy
Published: May 2023

High-entropy alloys have exhibited unusual materials properties. The stability of equimolar single-phase solid solution of five or more elements is supposedly rare and identifying the existence of such alloys has been challenging because of the vast chemical space of possible combinations. Herein, based on high-throughput density-functional theory calculations, we construct a chemical map of single-phase equimolar high-entropy alloys by investigating over 658,000 equimolar quinary alloys through a binary regular solid-solution model. We identify 30,201 potential single-phase equimolar alloys (5% of the possible combinations) forming mainly in body-centered cubic structures. We unveil the chemistries that are likely to form high-entropy alloys, and identify the complex interplay among mixing enthalpy, intermetallics formation, and melting point that drives the formation of these solid solutions. We demonstrate the power of our method by predicting the existence of two new high-entropy alloys, i.e. the body-centered cubic AlCoMnNiV and the face-centered cubic CoFeMnNiZn, which are successfully synthesized.
Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank
Authors: Zeleznik Oana A. , Kang Jae H. , Lasky-Su Jessica , Eliassen A. Heather , Frueh Lisa , Clish Clary B. , Rosner Bernard A. , Elze Tobias , Hysi Pirro , Khawaja Anthony , Wiggs Janey L. , Pasquale Louis R. ,   UK Biobank Eye and Vision Consortium
Published: May 2023

Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses’ Health Studies, and Health Professionals’ Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.
ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy
Authors: Xiao Xiangling , Shi Jie , He Chuan , Bu Xia , Sun Yishuang , Gao Minling , Xiang Bolin , Xiong Wenjun , Dai Panpan , Mao Qi , Xing Xixin , Yao Yingmeng , Yu Haisheng , Xu Gaoshan , Li Siqi , Ren Yan , Chen Baoxiang , Jiang Congqing , Meng Geng , Lee Yu-Ru , Wei Wenyi , Freeman Gordon J. , Xie Conghua , Zhang Jinfang
Published: May 2023

The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1. Mechanistically, USP5 interacts with PD-1, leading to deubiquitination and stabilization of PD-1. Moreover, extracellular signal-regulated kinase (ERK) phosphorylates PD-1 at Thr234 and promotes PD-1 interaction with USP5. Conditional knockout of Usp5 in T cells increases the production of effector cytokines and retards tumor growth in mice. USP5 inhibition in combination with Trametinib or anti-CTLA-4 has an additive effect on suppressing tumor growth in mice. Together, this study describes a molecular mechanism of ERK/USP5-mediated regulation of PD-1 and identifies potential combinatorial therapeutic strategies for enhancing anti-tumor efficacy.
Independent rediploidization masks shared whole genome duplication in the sturgeon-paddlefish ancestor
Authors: Redmond Anthony K. , Casey Dearbhaile , Gundappa Manu Kumar , Macqueen Daniel J. , McLysaght Aoife
Published: May 2023

Whole genome duplication (WGD) is a dramatic evolutionary event generating many new genes and which may play a role in survival through mass extinctions. Paddlefish and sturgeon are sister lineages that both show genomic evidence for ancient WGD. Until now this has been interpreted as two independent WGD events due to a preponderance of duplicate genes with independent histories. Here we show that although there is indeed a plurality of apparently independent gene duplications, these derive from a shared genome duplication event occurring well over 200 million years ago, likely close to the Permian-Triassic mass extinction period. This was followed by a prolonged process of reversion to stable diploid inheritance (rediploidization), that may have promoted survival during the Triassic-Jurassic mass extinction. We show that the sharing of this WGD is masked by the fact that paddlefish and sturgeon lineage divergence occurred before rediploidization had proceeded even half-way. Thus, for most genes the resolution to diploidy was lineage-specific. Because genes are only truly duplicated once diploid inheritance is established, the paddlefish and sturgeon genomes are thus a mosaic of shared and non-shared gene duplications resulting from a shared genome duplication event.
Universal quantum control of an atomic spin qubit on a surface
Authors: Wang Yu , Haze Masahiro , Bui Hong T. , Soe We-hyo , Aubin Herve , Ardavan Arzhang , Heinrich Andreas J. , Phark Soo-hyon
Published: May 2023

Scanning tunneling microscopy (STM) enables the bottom-up fabrication of tailored spin systems on a surface that are engineered with atomic precision. When combining STM with electron spin resonance (ESR), these single atomic and molecular spins can be controlled quantum-coherently and utilized as electron-spin qubits. Here we demonstrate universal quantum control of such a spin qubit on a surface by employing coherent control along two distinct directions, achieved with two consecutive radio-frequency (RF) pulses with a well-defined phase difference. We first show transformations of each Cartesian component of a Bloch vector on the quantization axis, followed by ESR-STM detection. Then we demonstrate the ability to generate an arbitrary superposition state of a single spin qubit by using two-axis control schemes, in which experimental data show excellent agreement with simulations. Finally, we present an implementation of two-axis control in dynamical decoupling. Our work extends the scope of STM-based pulsed ESR, highlighting the potential of this technique for quantum gate operations of electron-spin qubits on a surface.
Calibration of a serum reference standard for Group B streptococcal polysaccharide conjugate vaccine development using surface plasmon resonance
Authors: Esadze Alexandre , Grube Christopher D. , Wellnitz Sabine , Singh Suddham , Nguyen Ha H. , Gaylord Michelle A. , Zhu Aiping , Gribenko Alexey , Tan Charles Y. , Anderson Annaliesa S. , Simon Raphael
Published: May 2023

Group B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality worldwide. Development of a maternal vaccine to protect newborns through placentally transferred antibody is considered feasible based on the well-established relationship between anti-GBS capsular polysaccharide (CPS) IgG levels at birth and reduced risk of neonatal invasive GBS. An accurately calibrated serum reference standard that can be used to measure anti-CPS concentrations is critical for estimation of protective antibody levels across serotypes and potential vaccine performance. For this, precise weight-based measurement of anti-CPS IgG in sera is required. Here, we report an improved approach for determining serum anti-CPS IgG levels using surface plasmon resonance with monoclonal antibody standards, coupled with a direct Luminex-based immunoassay. This technique was used to quantify serotype-specific anti-CPS IgG levels in a human serum reference pool derived from subjects immunized with an investigational six-valent GBS glycoconjugate vaccine.
Rapid and efficient ambient temperature X-ray crystal structure determination at Turkish Light Source
Authors: Gul Mehmet , Ayan Esra , Destan Ebru , Johnson J. Austin , Shafiei Alaleh , Kepceoğlu Abdullah , Yilmaz Merve , Ertem Fatma Betül , Yapici İlkin , Tosun Bilge , Baldir Nilüfer , Tokay Nurettin , Nergiz Zeliş , Karakadioğlu Gözde , Paydos Seyide Seda , Kulakman Cahine , Ferah Cengiz Kaan , Güven Ömür , Atalay Necati , Akcan Enver Kamil , Cetinok Haluk , Arslan Nazlı Eylül , Şabanoğlu Kardelen , Aşci Bengisu , Tavli Serra , Gümüsboğa Helin , Altuntaş Sevde , Otsuka Masami , Fujita Mikako , Teki̇n Şaban , Çi̇ftçi̇ Halilibrahim , Durdaği Serdar , Karaca Ezgi , Kaplan Türköz Burcu , Kabasakal Burak Veli , Kati Ahmet , DeMi̇rci̇ Hasan
Published: May 2023

High-resolution biomacromolecular structure determination is essential to better understand protein function and dynamics. Serial crystallography is an emerging structural biology technique which has fundamental limitations due to either sample volume requirements or immediate access to the competitive X-ray beamtime. Obtaining a high volume of well-diffracting, sufficient-size crystals while mitigating radiation damage remains a critical bottleneck of serial crystallography. As an alternative, we introduce the plate-reader module adapted for using a 72-well Terasaki plate for biomacromolecule structure determination at a convenience of a home X-ray source. We also present the first ambient temperature lysozyme structure determined at the Turkish light source (Turkish DeLight). The complete dataset was collected in 18.5 min with resolution extending to 2.39 Å and 100% completeness. Combined with our previous cryogenic structure (PDB ID: 7Y6A), the ambient temperature structure provides invaluable information about the structural dynamics of the lysozyme. Turkish DeLight provides robust and rapid ambient temperature biomacromolecular structure determination with limited radiation damage.
Information load dynamically modulates functional brain connectivity during narrative listening
Authors: Mastrandrea Rossana , Cecchetti Luca , Lettieri Giada , Handjaras Giacomo , Leo Andrea , Papale Paolo , Gili Tommaso , Martini Nicola , Latta Daniele Della , Chiappino Dante , Pietrini Pietro , Ricciardi Emiliano
Published: May 2023

Narratives are paradigmatic examples of natural language, where nouns represent a proxy of information. Functional magnetic resonance imaging (fMRI) studies revealed the recruitment of temporal cortices during noun processing and the existence of a noun-specific network at rest. Yet, it is unclear whether, in narratives, changes in noun density influence the brain functional connectivity, so that the coupling between regions correlates with information load. We acquired fMRI activity in healthy individuals listening to a narrative with noun density changing over time and measured whole-network and node-specific degree and betweenness centrality. Network measures were correlated with information magnitude with a time-varying approach. Noun density correlated positively with the across-regions average number of connections and negatively with the average betweenness centrality, suggesting the pruning of peripheral connections as information decreased. Locally, the degree of the bilateral anterior superior temporal sulcus (aSTS) was positively associated with nouns. Importantly, aSTS connectivity cannot be explained by changes in other parts of speech (e.g., verbs) or syllable density. Our results indicate that the brain recalibrates its global connectivity as a function of the information conveyed by nouns in natural language. Also, using naturalistic stimulation and network metrics, we corroborate the role of aSTS in noun processing.
Molecular and biochemical characterization of rice developed through conventional integration of nDart1-0 transposon gene
Authors: Jalil Sanaullah , Ali Qurban , Khan Asad Ullah , Nazir Muhammad Mudassir , Ali Sharafat , Zulfiqar Faisal , Javed Muhammad Arshad , Jin Xiaoli
Published: May 2023

Mutations, the genetic variations in genomic sequences, play an important role in molecular biology and biotechnology. During DNA replication or meiosis, one of the mutations is transposons or jumping genes. An indigenous transposonnDart1-0was successfully introduced into local indica cultivar Basmati-370 from transposon-tagged line viz., GR-7895 (japonica genotype) through conventional breeding technique, successive backcrossing. Plants from segregating populationsshowed variegated phenotypes were tagged asBM-37mutants. Blast analysis of the sequence data revealed that the GTP-binding protein, located on the BAC clone OJ1781_H11 of chromosome 5, contained an insertion of DNA transposonnDart1-0. ThenDart1-0has “A” at position 254 bp, whereasnDart1homologs have “G”, which efficiently distinguishesnDart1-0from its homologs. The histological analysis revealed that the chloroplast of mesophyll cells inBM-37was disrupted with reduction in size of starch granules and higher number of osmophillic plastoglobuli, which resulted in decreased chlorophyll contents and carotenoids, gas exchange parameters (Pn, g, E, Ci), and reduced expression level of genes associated with chlorophyll biosynthesis, photosynthesis and chloroplast development. Along with the rise of GTP protein, the salicylic acid (SA) and gibberellic acid (GA) and antioxidant contents(SOD) and MDA levels significantly enhanced, while, the cytokinins (CK), ascorbate peroxidase (APX), catalase (CAT), total flavanoid contents (TFC) and total phenolic contents (TPC) significantly reduced in BM-37 mutant plants as compared with WT plants. These results support the notion that GTP-binding proteins influence the process underlying chloroplast formation. Therefore, it is anticipated that to combat biotic or abiotic stress conditions, thenDart1-0tagged mutant (BM-37) of Basmati-370 would be beneficial.
Evaluation of rosuvastatin-induced QT prolongation risk using real-world data, in vitro cardiomyocyte studies, and mortality assessment
Authors: Koo Yeryung , Hyun Sung-Ae , Choi Byung Jin , Kim Yujeong , Kim Tae Young , Lim Hong-Seok , Seo Joung-Wook , Yoon Dukyong
Published: May 2023

Drug-induced QT prolongation is attributed to several mechanisms, including hERG channel blockage. However, the risks, mechanisms, and the effects of rosuvastatin-induced QT prolongation remain unclear. Therefore, this study assessed the risk of rosuvastatin-induced QT prolongation using (1) real-world data with two different settings, namely case–control and retrospective cohort study designs; (2) laboratory experiments using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM); (3) nationwide claim data for mortality risk evaluation. Real-world data showed an association between QT prolongation and the use of rosuvastatin (OR [95% CI], 1.30 [1.21–1.39]) but not for atorvastatin (OR [95% CI], 0.98 [0.89–1.07]). Rosuvastatin also affected the sodium and calcium channel activities of cardiomyocytes in vitro. However, rosuvastatin exposure was not associated with a high risk of all-cause mortality (HR [95% CI], 0.95 [0.89–1.01]). Overall, these results suggest that rosuvastatin use increased the risk of QT prolongation in real-world settings, significantly affecting the action potential of hiPSC-CMs in laboratory settings. Long-term rosuvastatin treatment was not associated with mortality. In conclusion, while our study links rosuvastatin use to potential QT prolongation and possible influence on the action potential of hiPSC-CMs, long-term use does not show increased mortality, necessitating further research for conclusive real-world applications.
The effect of decellularization protocols on characterizations of thermoresponsive and light-curable corneal extracellular matrix hydrogels
Authors: Yazdanpanah Ghasem , Jalilian Elmira , Shen Xiang , Anwar Khandaker N. , Jiang Yizhou , Jabbehdari Sayena , Rosenblatt Mark I. , Pan Yayue , Djalilian Ali R.
Published: May 2023

To compare the effects of two decellularization protocols on the characteristics of fabricated COrnea Matrix (COMatrix) hydrogels. Porcine corneas were decellularized with Detergent (De) or Freeze–Thaw (FT)-based protocols. DNA remnant, tissue composition and α-Gal epitope content were measured. The effect of α-galactosidase on α-Gal epitope residue was assessed. Thermoresponsive and light-curable (LC) hydrogels were fabricated from decellularized corneas and characterized with turbidimetric, light-transmission and rheological experiments. The cytocompatibility and cell-mediated contraction of the fabricated COMatrices were assessed. Both protocols reduced the DNA content to < 0.1 µg/mg (native, > 0.5 µg/mg), and preserved the collagens and glycosaminoglycans. The α-Gal epitope remnant decreased by > 50% following both decellularization methods. We observed more than 90% attenuation in α-Gal epitope after treatment with α-galactosidase. The thermogelation half-time of thermoresponsive COMatrices derived from De-Based protocol (De-COMatrix) was 18 min, similar to that of FT-COMatrix (21 min). The rheological characterizations revealed significantly higher shear moduli of thermoresponsive FT-COMatrix (300.8 ± 22.5 Pa) versus De-COMatrix 178.7 ± 31.3 Pa, p < 0.01); while, this significant difference in shear moduli was preserved after fabrication of FT-LC-COMatrix and De-LC-COMatrix (18.3 ± 1.7 vs 2.8 ± 2.6 kPa, respectively, p < 0.0001). All thermoresponsive and light-curable hydrogels have similar light-transmission to human corneas. Lastly, the obtained products from both decellularization methods showed excellent in vitro cytocompatibility. We found that FT-LC-COMatrix was the only fabricated hydrogel with no significant cell-mediated contraction while seeded with corneal mesenchymal stem cells (p < 0.0001). The significant effect of decellularization protocols on biomechanical properties of hydrogels derived from porcine corneal ECM should be considered for further applications.
Bioinformatic analysis and experimental validation of the potential gene in the airway inflammation of steroid-resistant asthma
Authors: Wei Chaochao , Wang Yang , Hu Chengping
Published: May 2023

Steroid-resistant asthma is a troublesome clinical problem in public health. The pathogenesis of steroid-resistant asthma is complex and remains to be explored. In our work, the online Gene Expression Omnibus microarray dataset GSE7368 was used to explore differentially expressed genes (DEGs) between steroid-resistant asthma patients and steroid-sensitive asthma patients. Tissue-specific gene expression of DEGs was analyzed using BioGPS. The enrichment analyses were performed using GO, KEGG, and GSEA analysis. The protein–protein interaction network and key gene cluster were constructed using STRING, Cytoscape, MCODE, and Cytohubba. A steroid-resistant neutrophilic asthma mouse model was established using lipopolysaccharide (LPS) and ovalbumin (OVA). An LPS-stimulated J744A.1 macrophage model was prepared to validate the underlying mechanism of the interesting DEG gene using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 66 DEGs were identified, most of which were present in the hematologic/immune system. Enrichment analysis displayed that the enriched pathways were the IL-17 signaling pathway, MAPK signal pathway, Toll-like receptor signaling pathway, and so on. DUSP2, as one of the top upregulated DEGs, has not been clearly demonstrated in steroid-resistant asthma. In our study, we observed that the salubrinal administration (DUSP2 inhibitor) reversed neutrophilic airway inflammation and cytokine responses (IL-17A, TNF-α) in a steroid-resistant asthma mouse model. We also found that salubrinal treatment reduced inflammatory cytokines (CXCL10 and IL-1β) in LPS-stimulated J744A.1 macrophages. DUSP2 may be a candidate target for the therapy of steroid-resistant asthma.
YB1 modulates the DNA damage response in medulloblastoma
Authors: McSwain Leon F. , Pillsbury Claire E. , Haji-Seyed-Javadi Ramona , Rath Sandip Kumar , Chen Victor , Huang Tiffany , Shahab Shubin W. , Kunhiraman Haritha , Ross James , Price Gabrielle A. , Dey Abhinav , Hambardzumyan Dolores , MacDonald Tobey , Yu David S. , Porter Christopher C. , Kenney Anna M.
Published: May 2023

Y-box binding protein 1 (YBX1 or YB1) is a therapeutically relevant oncoprotein capable of RNA and DNA binding and mediating protein–protein interactions that drive proliferation, stemness, and resistance to platinum-based therapies. Given our previously published findings, the potential for YB1-driven cisplatin resistance in medulloblastoma (MB), and the limited studies exploring YB1-DNA repair protein interactions, we chose to investigate the role of YB1 in mediating radiation resistance in MB. MB, the most common pediatric malignant brain tumor, is treated with surgical resection, cranio-spinal radiation, and platinum-based chemotherapy, and could potentially benefit from YB1 inhibition. The role of YB1 in the response of MB to ionizing radiation (IR) has not yet been studied but remains relevant for determining potential anti-tumor synergy of YB1 inhibition with standard radiation therapy. We have previously shown that YB1 drives proliferation of cerebellar granular neural precursor cells (CGNPs) and murine Sonic Hedgehog (SHH) group MB cells. While others have demonstrated a link between YB1 and homologous recombination protein binding, functional and therapeutic implications remain unclear, particularly following IR-induced damage. Here we show that depleting YB1 in both SHH and Group 3 MB results not only in reduced proliferation but also synergizes with radiation due to differential response dynamics. YB1 silencing through shRNA followed by IR drives a predominantly NHEJ-dependent repair mechanism, leading to faster γH2AX resolution, premature cell cycle re-entry, checkpoint bypass, reduced proliferation, and increased senescence. These findings show that depleting YB1 in combination with radiation sensitizes SHH and Group 3 MB cells to radiation.
Accurate drusen segmentation in optical coherence tomography via order-constrained regression of retinal layer heights
Authors: Morelle Olivier , Wintergerst Maximilian W. M. , Finger Robert P. , Schultz Thomas
Published: May 2023

Drusen are an important biomarker for age-related macular degeneration (AMD). Their accurate segmentation based on optical coherence tomography (OCT) is therefore relevant to the detection, staging, and treatment of disease. Since manual OCT segmentation is resource-consuming and has low reproducibility, automatic techniques are required. In this work, we introduce a novel deep learning based architecture that directly predicts the position of layers in OCT and guarantees their correct order, achieving state-of-the-art results for retinal layer segmentation. In particular, the average absolute distance between our model’s prediction and the ground truth layer segmentation in an AMD dataset is 0.63, 0.85, and 0.44 pixel for Bruch's membrane (BM), retinal pigment epithelium (RPE) and ellipsoid zone (EZ), respectively. Based on layer positions, we further quantify drusen load with excellent accuracy, achieving 0.994 and 0.988 Pearson correlation between drusen volumes estimated by our method and two human readers, and increasing the Dice score to 0.71 ± 0.16 (from 0.60 ± 0.23) and 0.62 ± 0.23 (from 0.53 ± 0.25), respectively, compared to a previous state-of-the-art method. Given its reproducible, accurate, and scalable results, our method can be used for the large-scale analysis of OCT data.
Endometriosis increases the risk of gestational diabetes: a meta-analysis stratified by mode of conception, disease localization and severity
Authors: Salmeri Noemi , Li Piani Letizia , Cavoretto Paolo Ivo , Somigliana Edgardo , Viganò Paola , Candiani Massimo
Published: May 2023

To review the current evidence on the risk of gestational diabetes mellitus (GDM) in women with endometriosis, taking into account relevant confounders such as the higher frequency of Assisted Reproductive Technologies (ART) conceptions. Database searches on PubMed, Medline, Embase and Scopus through June 2022, using combinations of relevant keywords. A total of 18 studies, involving N = 4,600,885 women, were included. The overall risk of GDM in endometriosis patients was significantly higher than in controls (OR, 1.23; 95% CI 1.07–1.51). This significant association persisted in natural pregnancies (OR, 1.08; 95% CI 1.04–1.12) but not in pregnancies conceived through ART (OR, 0.93;95% CI 0.70–1.24). Based on the limited number of studies that examined this association in relation to endometriosis phenotype, an increased risk was found in more severe stages (OR, 3.20; 95% CI 1.20–8.54) but independently from localization of the lesions. Endometriosis increases the risk of GDM, with a possible progressive effect in more advanced stages of the disease. Although the effect magnitude may be limited in some subgroups, this finding has a clinically relevant impact due to both the strong biological plausibility and to the relatively high incidence of both endometriosis and GDM.
Bidirectional meta-Kronecker factored optimizer and Hausdorff distance loss for few-shot medical image segmentation
Authors: Kim Yeongjoon , Kang Donggoo , Mok Yeongheon , Kwon Sunkyu , Paik Joonki
Published: May 2023

To increase the accuracy of medical image analysis using supervised learning-based AI technology, a large amount of accurately labeled training data is required. However, the supervised learning approach may not be applicable to real-world medical imaging due to the lack of labeled data, the privacy of patients, and the cost of specialized knowledge. To handle these issues, we utilized Kronecker-factored decomposition, which enhances both computational efficiency and stability of the learning process. We combined this approach with a model-agnostic meta-learning framework for the parameter optimization. Based on this method, we present a bidirectional meta-Kronecker factored optimizer (BM-KFO) framework to quickly optimize semantic segmentation tasks using just a few magnetic resonance imaging (MRI) images as input. This model-agnostic approach can be implemented without altering network components and is capable of learning the learning process and meta-initial points while training on previously unseen data. We also incorporated a combination of average Hausdorff distance loss (AHD-loss) and cross-entropy loss into our objective function to specifically target the morphology of organs or lesions in medical images. Through evaluation of the proposed method on the abdominal MRI dataset, we obtained an average performance of 78.07% in setting 1 and 79.85% in setting 2. Our experiments demonstrate that BM-KFO with AHD-loss is suitable for general medical image segmentation applications and achieves superior performance compared to the baseline method in few-shot learning tasks. In order to replicate the proposed method, we have shared our code on GitHub. The corresponding URL can be found:https://github.com/YeongjoonKim/BMKFO.git.