bluuebunny/crossref_metadata_2025 huggingface dataset:
Deformation characteristics of solid-state benzene as a step towards understanding planetary geology
Authors: Zhang Wenxin , Zhang Xuan , Edwards Bryce W. , Zhong Lei , Gao Huajian , Malaska Michael J. , Hodyss Robert , Greer Julia R.
Published: December 2022

Small organic molecules, like ethane and benzene, are ubiquitous in the atmosphere and surface of Saturn’s largest moon Titan, forming plains, dunes, canyons, and other surface features. Understanding Titan’s dynamic geology and designing future landing missions requires sufficient knowledge of the mechanical characteristics of these solid-state organic minerals, which is currently lacking. To understand the deformation and mechanical properties of a representative solid organic material at space-relevant temperatures, we freeze liquid micro-droplets of benzene to form ~10 μm-tall single-crystalline pyramids and uniaxially compress them in situ. These micromechanical experiments reveal contact pressures decaying from ~2 to ~0.5 GPa after ~1 μm-reduction in pyramid height. The deformation occurs via a series of stochastic (~5-30 nm) displacement bursts, corresponding to densification and stiffening of the compressed material during cyclic loading to progressively higher loads. Molecular dynamics simulations reveal predominantly plastic deformation and densified region formation by the re-orientation and interplanar shear of benzene rings, providing a two-step stiffening mechanism. This work demonstrates the feasibility of in-situ cryogenic nanomechanical characterization of solid organics as a pathway to gain insights into the geophysics of planetary bodies.
A pH-responsive T1-T2 dual-modal MRI contrast agent for cancer imaging
Authors: Lu Hongwei , Chen An , Zhang Xindan , Wei Zixiang , Cao Rong , Zhu Yi , Lu Jingxiong , Wang Zhongling , Tian Leilei
Published: December 2022

Magnetic resonance imaging (MRI) is a non-invasive imaging technology to diagnose health conditions, showing the weakness of low sensitivity. Herein, we synthesize a contrast agent, SPIO@SiO2@MnO2, which shows decreased T1 and T2 contrast intensity in normal physiological conditions. In the acid environment of tumor or inflamed tissue, the manganese dioxide (MnO2) layer decomposes into magnetically active Mn2+ (T1-weighted), and the T1 and T2 signals are sequentially recovered. In addition, both constrast quenching-activation degrees of T1 and T2 images can be accurately regulated by the silicon dioxide (SiO2) intermediate layer between superparamagnetic iron oxide (SPIO) and MnO2. Through the “dual-contrast enhanced subtraction” imaging processing technique, the contrast sensitivity of this MRI contrast agent is enhanced to a 12.3-time difference between diseased and normal tissue. Consequently, SPIO@SiO2@MnO2 is successfully applied to trace the tiny liver metastases of approximately 0.5 mm and monitor tissue inflammation.
Diverse monogenic subforms of human spermatogenic failure
Authors: Nagirnaja Liina , Lopes Alexandra M. , Charng Wu-Lin , Miller Brian , Stakaitis Rytis , Golubickaite Ieva , Stendahl Alexandra , Luan Tianpengcheng , Friedrich Corinna , Mahyari Eisa , Fadial Eloise , Kasak Laura , Vigh-Conrad Katinka , Oud Manon S. , Xavier Miguel J. , Cheers Samuel R. , James Emma R. , Guo Jingtao , Jenkins Timothy G. , Riera-Escamilla Antoni , Barros Alberto , Carvalho Filipa , Fernandes Susana , Gonçalves João , Gurnett Christina A. , Jørgensen Niels , Jezek Davor , Jungheim Emily S. , Kliesch Sabine , McLachlan Robert I. , Omurtag Kenan R. , Pilatz Adrian , Sandlow Jay I. , Smith James , Eisenberg Michael L. , Hotaling James M. , Jarvi Keith A. , Punab Margus , Rajpert-De Meyts Ewa , Carrell Douglas T. , Krausz Csilla , Laan Maris , O’Bryan Moira K. , Schlegel Peter N. , Tüttelmann Frank , Veltman Joris A. , Almstrup Kristian , Aston Kenneth I. , Conrad Donald F.
Published: December 2022

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human “knockouts”, and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.
Constraints on the martian crust away from the InSight landing site
Authors: Li Jiaqi , Beghein Caroline , McLennan Scott M. , Horleston Anna C. , Charalambous Constantinos , Huang Quancheng , Zenhäusern Géraldine , Bozdağ Ebru , Pike W. T. , Golombek Matthew , Lekić Vedran , Lognonné Philippe , Bruce Banerdt W.
Published: December 2022

The most distant marsquake recorded so far by the InSight seismometer occurred at an epicentral distance of 146.3 ± 6.9o, close to the western end of Valles Marineris. On the seismogram of this event, we have identified seismic wave precursors, i.e., underside reflections off a subsurface discontinuity halfway between the marsquake and the instrument, which directly constrain the crustal structure away (about 4100−4500 km) from the InSight landing site. Here we show that the Martian crust at the bounce point between the lander and the marsquake is characterized by a discontinuity at about 20 km depth, similar to the second (deeper) intra-crustal interface seen beneath the InSight landing site. We propose that this 20-km interface, first discovered beneath the lander, is not a local geological structure but likely a regional or global feature, and is consistent with a transition from porous to non-porous Martian crustal materials.
Permafrost in the Cretaceous supergreenhouse
Authors: Rodríguez-López Juan Pedro , Wu Chihua , Vishnivetskaya Tatiana A. , Murton Julian B. , Tang Wenqiang , Ma Chao
Published: December 2022

Earth’s climate during the last 4.6 billion years has changed repeatedly between cold (icehouse) and warm (greenhouse) conditions. The hottest conditions (supergreenhouse) are widely assumed to have lacked an active cryosphere. Here we show that during the archetypal supergreenhouse Cretaceous Earth, an active cryosphere with permafrost existed in Chinese plateau deserts (astrochonological age ca. 132.49–132.17 Ma), and that a modern analogue for these plateau cryospheric conditions is the aeolian–permafrost system we report from the Qiongkuai Lebashi Lake area, Xinjiang Uygur Autonomous Region, China. Significantly, Cretaceous plateau permafrost was coeval with largely marine cryospheric indicators in the Arctic and Australia, indicating a strong coupling of the ocean–atmosphere system. The Cretaceous permafrost contained a rich microbiome at subtropical palaeolatitude and 3–4 km palaeoaltitude, analogous to recent permafrost in the western Himalayas. A mindset of persistent ice-free greenhouse conditions during the Cretaceous has stifled consideration of permafrost thaw as a contributor of C and nutrients to the palaeo-oceans and palaeo-atmosphere.
Altered sulfation status of FAM20C-dependent chondroitin sulfate is associated with osteosclerotic bone dysplasia
Authors: Koike Toshiyasu , Mikami Tadahisa , Tamura Jun-Ichi , Kitagawa Hiroshi
Published: December 2022

Raine syndrome, a lethal osteosclerotic bone dysplasia in humans, is caused by loss-of-function mutations in FAM20C; however, Fam20c deficiency in mice does not recapitulate the human disorder, so the underlying pathoetiological mechanisms remain poorly understood. Here we show that FAM20C, in addition to the reported casein kinase activity, also fine-tunes the biosynthesis of chondroitin sulfate (CS) chains to impact bone homeostasis. Specifically, FAM20C with Raine-originated mutations loses the ability to interact with chondroitin 4-O-sulfotransferase-1, and is associated with reduced 4-sulfation/6-sulfation (4S/6S) ratio of CS chains and upregulated biomineralization in human osteosarcoma cells. By contrast, overexpressing chondroitin 6-O-sulfotransferase-1 reduces CS 4S/6S ratio, and induces osteoblast differentiation in vitro and higher bone mineral density in transgenic mice. Meanwhile, a potential xylose kinase activity of FAM20C does not impact CS 4S/6S ratio, and is not associated with Raine syndrome mutations. Our results thus implicate CS 4S/6S ratio imbalances caused by FAM20C mutations as a contributor of Raine syndrome etiology.
Observation of enhanced nanoscale creep flow of crystalline metals enabled by controlling surface wettability
Authors: Xiang Jun-Xiang , Liu Ze
Published: December 2022

Understanding and controlling interface friction are central to many science and engineering applications. However, frictional sliding is closely related to adhesion, surface roughness, surface chemistry, mechanical deformation of contact solids, which poses the major challenge to experimental studying and theoretical modeling of friction. Here, by exploiting the recent developed thermomechanical nanomolding technique, we present a simple strategy to decouple the interplay between surface chemistry, plastic deformation, and interface friction by monitoring the nanoscale creep flow of metals in nanochannels. We show that superhydrophobic nanochannels outperforming hydrophilic nanochannels can be up to orders of magnitude in terms of creep flow rate. The comparative experimental study on pressure and temperature dependent nanomolding efficiency uncovers that the enhanced creep flow rate originates from diffusion-based deformation mechanism as well as the superhydrophobic surface induced boundary slip. Moreover, our results reveal that there exists a temperature-dependent critical pressure below which the traditional lubrication methods to reduce friction will break down. Our findings not only provide insights into the understanding of mechanical deformation and nanotribology, but also show a general and practical technique for studying the fundamental processes of frictional motion. Finally, we anticipate that the increased molding efficiency could facilitate the application of nanoimprinting/nanomolding.
Arabidopsis γ-H2A.X-INTERACTING PROTEIN participates in DNA damage response and safeguards chromatin stability
Authors: Fan Tianyi , Kang Huijia , Wu Di , Zhu Xinyu , Huang Lin , Wu Jiabing , Zhu Yan
Published: December 2022

Upon the occurrence of DNA double strand breaks (DSB), the proximal histone variant H2A.X is phosphorylated as γ-H2A.X, a critical signal for consequent DSB signaling and repair pathways. Although γ-H2A.X-triggered DNA damage response (DDR) has been well-characterized in yeast and animals, the corresponding pathways in plant DDR are less well understood. Here, we show that an Arabidopsis protein γ-H2A.X-INTERACTING PROTEIN (XIP) can interact with γ-H2A.X. Its C-terminal dual-BRCT-like domain contributes to its specific interaction with γ-H2A.X. XIP-deficient seedlings display smaller meristems, inhibited growth, and higher sensitivity to DSB-inducing treatment. Loss-of-function in XIP causes transcriptome changes mimicking wild-type plants subject to replicative or genotoxic stresses. After genotoxic bleomycin treatment, more proteins with upregulated phosphorylation modifications, more DNA fragments and cell death were found in xip mutants. Moreover, XIP physically interacts with RAD51, the key recombinase in homologous recombination (HR), and somatic HR frequency is significantly reduced in xip mutants. Collectively, XIP participates in plant response to DSB and contributes to chromatin stability.
Large-scale genotyping and phenotyping of a worldwide winter wheat genebank for its use in pre-breeding
Authors: Schulthess Albert W. , Kale Sandip M. , Zhao Yusheng , Gogna Abhishek , Rembe Maximilian , Philipp Norman , Liu Fang , Beukert Ulrike , Serfling Albrecht , Himmelbach Axel , Oppermann Markus , Weise Stephan , Boeven Philipp H. G. , Schacht Johannes , Longin C. Friedrich H. , Kollers Sonja , Pfeiffer Nina , Korzun Viktor , Fiebig Anne , Schüler Danuta , Lange Matthias , Scholz Uwe , Stein Nils , Mascher Martin , Reif Jochen C.
Published: December 2022

Plant genetic resources (PGR) stored at genebanks are humanity’s crop diversity savings for the future. Information on PGR contrasted with modern cultivars is key to select PGR parents for pre-breeding. Genotyping-by-sequencing was performed for 7,745 winter wheat PGR samples from the German Federal ex situ genebank at IPK Gatersleben and for 325 modern cultivars. Whole-genome shotgun sequencing was carried out for 446 diverse PGR samples and 322 modern cultivars and lines. In 19 field trials, 7,683 PGR and 232 elite cultivars were characterized for resistance to yellow rust - one of the major threats to wheat worldwide. Yield breeding values of 707 PGR were estimated using hybrid crosses with 36 cultivars - an approach that reduces the lack of agronomic adaptation of PGR and provides better estimates of their contribution to yield breeding. Cross-validations support the interoperability between genomic and phenotypic data. The here presented data are a stepping stone to unlock the functional variation of PGR for European pre-breeding and are the basis for future breeding and research activities.
Trends of kidney cancer burden from 1990 to 2019 in European Union 15 + countries and World Health Organization regions
Authors: Jani Chinmay , Abdallah Nour , Mouchati Christian , Jani Ruchi , Sharma Rajesh , Bhatt Padmanabh , Hanbury Georgina , Salciccioli Justin , Singh Harpreet , Shalhoub Joseph , McKay Rana R. , Marshall Dominic C.
Published: December 2022

In recent decades, variability in the incidence and mortality of kidney cancer (KC) has been reported. This study aimed to compare trends in incidence, mortality, and disability-adjusted life years (DALY) of KC between the European Union (EU) 15 + countries and 6 World Health Organization (WHO) regions. The data of KC Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs were extracted from the Global Burden of Disease database. Joinpoint regression was employed to examine trends. From 1990 to 2019, the ASIR increased in most countries except for Luxembourg (males), the USA (females) and Austria and Sweden (both sexes). ASIR increased across all 6 WHO regions for both sexes except for females in Americas. The ASMR increased in 10/19 countries for males and 9/19 for females as well across most WHO regions. The mortality-to-incidence ratio (MIR) decreased in all countries and WHO regions. Trends in DALYs were variable across countries and WHO regions. While the incidence and mortality from KC rose in most EU15 + countries and WHO regions from 1990 to 2019, the universal drop in MIR suggests an overall improvement in KC outcomes. This is likely multifactorial, including earlier detection of KC and improved treatments.
Longitudinal change of reticular pseudodrusen area in ultrawide-field imaging
Authors: Yoon Je Moon , Choi Young Joo , Ham Don-Il
Published: December 2022

This study aimed to investigate the longitudinal change in the reticular pseudodrusen (RPD) area in the fundus and its association with late age-related macular degeneration (AMD). 91 RPD eyes (55 patients; age 67.9 ± 7.3 years) with > 5 years’ follow-up (6.8 ± 0.9 years) from a single medical center were enrolled. Ultrawide-field photography images were analyzed using the concentric rings method, and the RPD area was semi-quantitatively classified according to the affected segment number into central, intermediate, and extensive types. Correlations of longitudinal changes in the RPD area and late AMD risk were investigated. RPD area increased significantly during the follow-up (p < 0.001). The increase rate correlated with age (r = 0.207; p = 0.048), RPD area at first visit (r = − 0.222; p = 0.035), and the decrease rate of subfoveal choroidal thickness (SFCT) (r = 0.217; p = 0.039). Many central (18/49, 36.7%) and intermediate (15/23, 65.2%) types switched to the more advanced type during the follow-up. Macular neovascularization and geographic atrophy developed in 12.3% and 18.7% of patients by 7 years. Late AMD incidence was significantly higher in eyes with large than in those with small RPD areas (p = 0.002). Larger RPD area at baseline, faster increase in RPD area, thinner SFCT, rapid decrease in SFCT, and the presence of late AMD on fellow eye were associated with late AMD. All RPD areas progressively increase over time. The regular assessment of RPD area may help to predict late AMD risk in RPD eyes.
Brain parenchymal and leptomeningeal metastasis in non-small cell lung cancer
Authors: Li Qing , Lin Zhen , Hong Ye , Fu Yang , Chen Yueyun , Liu Ting , Zheng Yue , Tian Jiangfang , Liu Chunhua , Pu Wei , Ding Zhenyu , Wang Chun
Published: December 2022

Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p < 0.0001). The median time to the onset of PM and LM from the diagnosis of advanced NSCLC was 0 months and 8.3 months, respectively. Patients with LM had a statistically shorter over survival (OS) compared to either No-BM or PM patients (p < 0.0001). Based on independent predictive variables, two nomogram models were constructed to predict the development of PM and LM in advanced NSCLC patients, and the C-indexes were 0.656 and 0.767, respectively. Although both considered as BM, PM and LM had different clinical characteristics. And the nomogram showed good performance in predicting LM development, but not PM.
Spatially structured multi-wave-mixing induced nonlinear absorption and gain in a semiconductor quantum well
Authors: Panchadhyayee Pradipta , Dutta Bibhas Kumar
Published: December 2022

We have studied two-dimensional absorption and gain spectrum in an asymmetric semiconductor triple-coupled-quantum-well (TCQW) nanostructure. Four subband transitions are coupled by using four coherent fields in a close-loop configuration to introduce cross-Kerr effect and four-wave-mixing (FWM) induced nonlinearity in achieving nonlinear absorption and gain profiles. Position-dependent absorption and gain are obtained by applying one, or two coherent fields in a variety of standing wave configurations including superposed field configuration in the standing-wave regime. In addition to the control parameters like Rabi frequency and detuning, the specialty of the model is to employ double-controlled spatial phase-coherence guided by the FWM-induced phase and the phases introduced by the standing wave formation. Our results highlight the high-precision electron localization in spatial domain. The evolution of spatially modulated gain without inversion may be a substitute for obtaining gain from a traditional quantum cascade laser. The importance of the present work is to find its application in designing electro-optic modulators in semiconductor nanostructures in near future.
Ultrahigh evaporative heat transfer measured locally in submicron water films
Authors: Wang Xiaoman , Ghaffarizadeh S. Arman , He Xiao , McGaughey Alan J. H. , Malen Jonathan A.
Published: December 2022

Thin film evaporation is a widely-used thermal management solution for micro/nano-devices with high energy densities. Local measurements of the evaporation rate at a liquid-vapor interface, however, are limited. We present a continuous profile of the evaporation heat transfer coefficient ($$h_{\text {evap}}$$

h
evap

) in the submicron thin film region of a water meniscus obtained through local measurements interpreted by a machine learned surrogate of the physical system. Frequency domain thermoreflectance (FDTR), a non-contact laser-based method with micrometer lateral resolution, is used to induce and measure the meniscus evaporation. A neural network is then trained using finite element simulations to extract the $$h_{\text {evap}}$$

h
evap

profile from the FDTR data. For a substrate superheat of 20 K, the maximum $$h_{\text {evap}}$$

h
evap

is $$1.0_{-0.3}^{+0.5}$$

1
.

0

-
0.3

+
0.5

 MW/$$\text {m}^2$$

m
2

-K at a film thickness of $$15_{-3}^{+29}$$

15

-
3

+
29

 nm. This ultrahigh $$h_{\text {evap}}$$

h
evap

value is two orders of magnitude larger than the heat transfer coefficient for single-phase forced convection or evaporation from a bulk liquid. Under the assumption of constant wall temperature, our profiles of $$h_{\text {evap}}$$

h
evap

and meniscus thickness suggest that 62% of the heat transfer comes from the region lying 0.1–1 μm from the meniscus edge, whereas just 29% comes from the next 100 μm.
Perioral secretions enable complex social signaling in African mole-rats (genus Fukomys)
Authors: Caspar Kai R. , Stopka Pavel , Issel Daniel , Katschak Kristin H. , Zöllner Till , Zupanc Sina , Žáček Petr , Begall Sabine
Published: December 2022

Subterranean common mole-rats of the genus Fukomys (family Bathyergidae) live in large, cooperatively-breeding families. Odor cues have been hypothesized to play an important role in mediating social behaviors in the underground ecotope, but only little is known about the role of olfactory signaling in burrowing mammals. Here we characterize the so far neglected perioral glands of Fukomys and other African mole-rats as an important source of olfactory social information. Histology demonstrates these structures to be derived sebaceous glands that are developed regardless of sex and reproductive status. However, gland activity is higher in Fukomys males, leading to sexually dimorphic patterns of stain and clotting of the facial pelage. Behavioral assays revealed that conspecifics prefer male but not female perioral swabs over scent samples from the back fur and that male sebum causes similar attraction as anogenital scent, a known source of social information in Fukomys. Finally, we assessed volatile compounds in the perioral sebum of the giant mole-rat (Fukomys mechowii) via GCxGC-MS-based metabolomic profiling. Volatiles display pronounced sex-specific signatures but also allow to differentiate between intrasexual reproductive status groups. These different lines of evidence suggest that mole-rat perioral glands provide complex odor signals which play a crucial role in social communication.
Effect of learning on slow gamma propagation between hippocampus and cortex in the wild-type and AD mice
Authors: Blinowska Katarzyna J. , Kamiński Maciej , Macrez Nathalie , Marighetto Aline , Meyrand Pierre , Bem Tiaza
Published: December 2022

Slow gamma oscillations (20–50 Hz) have been suggested to coordinate information transfer between brain structures involved in memory formation. Whereas the involvement of slow gamma in memory processing was studied by means of correlation between the gamma power and the occurrence of a given event (sharp wave ripples (SWRs), cortical transients), our approach consists of the analysis of the transmission of slow gamma itself. We use the method based on Granger causality principle—direct Directed Transfer Function, which allows to determine directed propagation of brain activity, including bidirectional flows. Four cortical sites along with CA1 ipsi- and contralateral were recorded in behaving wild-type and APP/PS1 mice before and after learning session of a spatial memory task. During slow wave sleep propagation of slow gamma was bidirectional, forming multiple loops of interaction which involved both CA1 and some of cortical sites. In episodes coincident with SWRs the number and strength of connectivity pathways increased in both groups compared to episodes without SWRs. The effect of learning was expressed only in APP/PS1 mice and consisted in strengthening of the slow gamma transmission from hippocampus to cortex as well as between both CA1 which may serve more efficient transmission of information from impaired CA1.
Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis
Authors: Stø Kristine , Valeur Jørgen , Ueland Thor , Malmstrøm Gunn Helen , Bjerkeli Vigdis , Trøseid Marius , Hov Johannes R. , Holm Kristian , Vestad Beate , Halvorsen Bente , Skjelland Mona , Skagen Karolina R.
Published: December 2022

The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.
Derivation of harmonised high-level safety requirements for self-driving cars using railway experience
Authors: Filip Aleš , Capua Roberto , Neri Alessandro , Rispoli Francesco
Published: December 2022

The development and manufacture of self-driving cars (SDCs) have triggered unprecedented challenges among car manufacturers and smart road operators to accelerate awareness and implementation of innovative technologies for cooperative, connected and automated mobility (CCAM), especially those with a high level of automation and safety. Safety improvement is a pre-requisite to justify and unleashing a mass deployment of connected and driverless cars to reach the goal of zero-accident in 2050 set by the European Commission. Behind these motivations a well-justified and widely acceptable high-level safety target for SDCs is mandatory. The aim of this article is to contribute to the derivation of an harmonised high-level safety target for SDCs, starting from the safety requirements and the state of the art achieved by train and airplane operations. The novelty of our approach is to leverage the Common Safety Method-Design Targets (CSM-DT) already adopted and widely accepted by the railway community. According to this approach, the derived, justified and harmonised high-level design safety target for SDCs, defined as the average probability of a dangerous failure PFSDC per 1 h, should be 1 × 10−7/h. An example of PFSDC allocation to individual SDC safety functions, including position determination based on Global Navigation Satellite System (GNSS), is described using a fault tree. The proposed methodology can speed up the validation and certification process needed to authorise the SDCs, by capitalising the know-how and best practices in use since many years for the train management.
A new strategy for the early detection of alzheimer disease stages using multifractal geometry analysis based on K-Nearest Neighbor algorithm
Authors: Elgammal Yasmina M. , Zahran M. A. , Abdelsalam Mohamed M.
Published: December 2022

Alzheimer's Disease (AD) is considered one of the most diseases that much prevalent among elderly people all over the world. AD is an incurable neurodegenerative disease affecting cognitive functions and were characterized by progressive and collective functions deteriorating. Remarkably, early detection of AD is essential for the development of new and invented treatment strategies. As Dementia causes irreversible damage to the brain neurons and leads to changes in its structure that can be described adequately within the framework of multifractals. Hence, the present work focus on developing a promising and efficient computing technique to pre-process and classify the AD disease especially in the early stages using multifractal geometry to extract the most changeable features due to AD. Then, A machine learning classification algorithm (K-Nearest Neighbor) has been implemented in order to classify and detect the main four early stages of AD. Two datasets have been used to ensure the validation of the proposed methodology. The proposed technique has achieved 99.4% accuracy and 100% sensitivity. The comparative results show that the proposed classification technique outperforms is recent techniques in terms of performance measures.
Multi-centre discriminating concentration determination of broflanilide and potential for cross-resistance to other public health insecticides in Anopheles vector populations
Authors: Portwood Natalie M. , Shayo Magreth F. , Tungu Patrick K. , Mbewe Njelembo J. , Mlay George , Small Graham , Snetselaar Janneke , Kristan Mojca , Levy Prisca , Walker Thomas , Kirby Matthew J. , Kisinza William , Mosha Franklin W. , Rowland Mark , Messenger Louisa A.
Published: December 2022

Novel insecticides are urgently needed to control insecticide-resistant populations of Anopheles malaria vectors. Broflanilide acts as a non-competitive antagonist of the gamma-aminobutyric acid receptor and has shown prolonged effectiveness as an indoor residual spraying product (VECTRON T500) in experimental hut trials against pyrethroid-resistant vector populations. This multi-centre study expanded upon initial discriminating concentration testing of broflanilide, using six Anopheles insectary colonies (An. gambiae Kisumu KCMUCo, An. gambiae Kisumu NIMR, An. arabiensis KGB, An. arabiensis SENN, An. coluzzii N’Gousso and An. stephensi SK), representing major malaria vector species, to facilitate prospective susceptibility monitoring of this new insecticide; and investigated the potential for cross-resistance to broflanilide via the A296S mutation associated with dieldrin resistance (rdl). Across all vector species tested, the discriminating concentration for broflanilide ranged between LC99 × 2 = 1.126–54.00 μg/ml or LC95 × 3 = 0.7437–17.82 μg/ml. Lower concentrations of broflanilide were required to induce complete mortality of An. arabiensis SENN (dieldrin-resistant), compared to its susceptible counterpart, An. arabiensis KGB, and there was no association between the presence of the rdl mechanism of resistance and survival in broflanilide bioassays, demonstrating a lack of cross-resistance to broflanilide. Study findings provide a benchmark for broflanilide susceptibility monitoring as part of ongoing VECTRON T500 community trials in Tanzania and Benin.
Integrated metabolomics and transcriptomics analysis of roots of Bupleurum chinense and B. scorzonerifolium, two sources of medicinal Chaihu
Authors: Wan Hefang , Zhou Lei , Wu Bin , Han Wenjing , Sui Chun , Wei Jianhe
Published: December 2022

Radix Bupleuri (Chaihu in Chinese) is a traditional Chinese medicine commonly used to treat colds and fevers. The root metabolome and transcriptome of two cultivars of B. chinense (BCYC and BCZC) and one of B. scorzonerifolium (BSHC) were determined and analyzed. Compared with BSHC, 135 and 194 differential metabolites were identified in BCYC and BCZC, respectively, which were mainly fatty acyls, organooxygen metabolites. A total of 163 differential metabolites were obtained between BCYC and BCZC, including phenolic acids and lipids. Compared with BSHC, 6557 and 5621 differential expression genes (DEGs) were found in BCYC and BSHC, respectively, which were annotated into biosynthesis of unsaturated fatty acid and fatty acid metabolism. A total of 4,880 DEGs existed between the two cultivars of B. chinense. The abundance of flavonoids in B. scorzonerifolium was higher than that of B. chinense, with the latter having higher saikosaponin A and saikosaponin D than the former. Pinobanksin was the most major flavonoid which differ between the two cultivars of B. chinense. The expression of chalcone synthase gene was dramatically differential, which had a positive correlation with the biosynthesis of pinobanksin. The present study laid a foundation for further research on biosynthesis of flavonoids and terpenoids of Bupleurum L.
Proteomic profiling of a patient with cutaneous melanoma metastasis regression following topical contact sensitizer diphencyprone and immune checkpoint inhibitor treatment
Authors: Han Joseph , Agarwal Aneesh , Young Jade N. , Owji Shayan , Luu Yen , Poplausky Dina , Yassky Daniel , Estrada Yeriel , Ungar Jonathan , Krueger James G. , Gulati Nicholas
Published: December 2022

Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of advanced melanoma, but many patients do not respond to ICIs alone, and thus there is need for additional treatment options. Topical immunomodulators such as diphencyprone (DPCP) also have clinical use in advanced melanoma, particularly in the treatment of cutaneous metastases. In a previous report, we characterized the enhanced clinical response to dual agent immunotherapy with pembrolizumab and DPCP in a patient with cutaneous melanoma metastases. To improve mechanistic understanding of this response, we analyzed proteomic data using the Olink immuno-oncology panel of 96 biomarkers from tissue and serum samples of this patient throughout his treatment course. Particular attention was paid to programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) given they are all targeted by ICIs in clinical practice. These proteins were upregulated during the period of DPCP monotherapy, then downregulated during pembrolizumab monotherapy, and then robustly upregulated again during dual therapy. Although not exclusively, the induction of checkpoint inhibitor proteins in the presence of DPCP suggests potential synergy between this agent and ICIs in the treatment of cutaneous melanoma metastases. Large-scale investigation is warranted to further evaluate this potential novel combination therapeutic approach.
Coal seam in-situ inorganic analysis based on least angle regression and competitive adaptive reweighted sampling algorithm by XRF–visNIR fusion
Authors: Zhu Lei , Gu Wenzhe , Song Tianqi , Qiu Fengqi , Wang Qingya
Published: December 2022

The fusion of X-ray fluorescence spectroscopy (XRF) and visible near infrared spectroscopy (visNIR) has been widely used in geological exploration. The outer product analysis (OPA) has a good effect in the fusion. The dimension of the spectral matrix obtained by OPA is large, and the Competitive Adaptive Reweighted Sampling (CARS) cannot cover the whole spectrum. As a result, the selected variables by the method are inconsistent each time. In this paper, a new feature variable screening method is proposed, which uses the Least Angle Regression (LAR) to select the high dimensional spectral matrix first, and then uses CARS to complete the secondary selection of the spectral matrix, forming the LAR-CARS algorithm. The purpose is to make the sampling method cover all the spectral data. XRF and visNIR tests were carried out on three cores in two boreholes, and a cross-validation set, validation set and a test set were established by combining the results of wavelength dispersion X-ray fluorescence spectrometer and ITRAX Core scanner in the laboratory. The quantitative model was established with the Extreme Gradient Boosting (XGBoost) and LAR-CARS was compared to these other algorithms (LAR, Successive Projections Algorithm, Monte Carlo uninformative variables elimination and CARS). The results showed that the RMSEP values of the models established by the LAR-CARS for six rock-forming elements (Si, Al, K, Ca, Fe, Ti) were relatively small, and the RPD ranges from 1.424 to 2.514. All these results show that the high-dimensional matrix formed by XRF and visNIR integration combined with LAR-CARS can be used for quantitative analysis of rock forming elements in in-situ coal seam cores, and the analysis results can be used as the basis for judging lithology. The research will provide necessary technical support for digital mine construction.
Identification of RT-qPCR reference genes suitable for gene function studies in the pitaya canker disease pathogen Neoscytalidium dimidiatum
Authors: Wang Meng , Wang Zhouwen , Wei Shuangshuang , Xie Jun , Huang Jiaquan , Li Dongdong , Hu Wenbin , Li Hongli , Tang Hua
Published: December 2022

Neoscytalidium dimidiatum is the main causal agent of pitaya canker. Most studies of virulence and pathogenicity genes have measured expression levels using real-time quantitative polymerase chain reaction (RT-qPCR). Suitable reference genes are essential for ensuring that estimates of gene expression levels by RT-qPCR are accurate. However, no reference genes can be robustly applied across all contexts and species. No studies to date have evaluated the most effective reference genes for normalizing gene expression levels estimated by RT-qPCR in N. dimidiatum. In this study, RT-qPCR data for individual candidate reference genes were analyzed using four different methods: the delta Ct method and the geNorm, NormFinder, and BestKeeper algorithms. We evaluated the utility of eight candidate reference genes (18S rRNA, Actin (1), Actin (2), Actin, GAPDH (1), GAPDH (2), UBQ, and Tubulin) for normalizing expression levels estimated by RT-qPCR in N. dimidiatum at different developmental stages, at different temperatures, and during interaction with pitaya. All candidate reference genes were suitable for gene expression analysis except for Actin (2). Tubulin and Actin (1) were the most stably expressed reference genes under different temperatures. Actin (1) and Actin were the most stably expressed reference genes in N. dimidiatum at different developmental stages. Tubulin and UBQ were the most stably expressed reference genes during interaction with pitaya. Actin and 18s rRNA were the most stably expressed across all experimental conditions. Subsequently, Tubulin and UBQ were further investigated in analyses of pectinase expression during the pitaya–N. dimidiatum interaction. Our results provide insights that will aid future RT-qPCR studies of gene expression in N. dimidiatum.
A multiple criteria decision analysis based approach to remove uncertainty in SMP models
Authors: Yenduri Gokul , Gadekallu Thippa Reddy
Published: December 2022

Software has to be updated frequently to match the customer needs. If software maintainability is not given priority, it affects the software development life cycle and maintenance expenses, which deplete organizational assets. Before releasing software, maintainability must be estimated, as the impact of bugs and errors can affect the cost and reputation of the organization after deployment. Regardless of the programming paradigm, it’s important to assess software maintainability. Many software maintainability prediction models’ compatibilities with new programming paradigms are criticized because their limited applicability over heterogeneous datasets. Due this challenge small and medium-sized organizations may even skip the maintainability assessment, resulting in huge lose to such organizations. Motivated by this fact, we used Genetic Algorithm optimized Random Forest technique (GA) for software maintainability prediction models over heterogeneous datasets. To find optimal model for software maintainability prediction, the Technique for Order preference by Similarity to Ideal Solution (TOPSIS), a popular multiple-criteria decision-making model, is adopted. From the results, it is concluded that the GA is optimal for predicting maintainability of software developed in various paradigms.
Evolution and diversification of Mountain voles (Rodentia: Cricetidae)
Authors: Liu Shaoying , Zhou Chengran , Meng Guanliang , Wan Tao , Tang Mingkun , Yang Chentao , Murphy Robert W. , Fan Zhenxin , Liu Yang , Zeng Tao , Zhao Yun , Liu Shanlin
Published: December 2022

The systematics of the Cricetid genus Neodon have long been fraught with uncertainty due to sampling issues and a lack of comprehensive datasets. To gain better insights into the phylogeny and evolution of Neodon, we systematically sampled Neodon across the Hengduan and Himalayan Mountains, which cover most of its range in China. Analyses of skulls, teeth, and bacular structures revealed 15 distinct patterns corresponding to 15 species of Neodon. In addition to morphological analyses, we generated a high-quality reference genome for the mountain vole and generated whole-genome sequencing data for 47 samples. Phylogenomic analyses supported the recognition of six new species, revealing a long-term underestimation of Neodon diversity. We further identified positively selected genes potentially related to high-elevation adaptation. Together, our results illuminate how climate change caused the plateau to become the centre of Neodon origin and diversification and how mountain voles have adapted to the hypoxic high-altitude plateau environment.
Deep eutectic solvent-based dispersive liquid–liquid microextraction followed by smartphone digital image colorimetry for the determination of carbofuran in water samples
Authors: Zhao Luyao , Wang Min , Wang Jiadong , Wu Jing , Zhang Zhuoting , Jing Xu , Wang Xiaowen
Published: December 2022

A detection method of carbofuran in water samples was reported using deep eutectic solvent-based dispersion liquid–liquid microextraction combined with digital image colorimetry.
Photocatalytic dehydrative etherification of alcohols with a nanoporous gold catalyst
Authors: Miyauchi Masato , Hiraoka Takehiro , Raut Vivek S. , Asao Naoki
Published: December 2022

Photocatalytic dehydrative etherification proceeds by the use of localized surface plasmon resonance properties induced by nanoporous gold.
Si-rhodamine fluorescent probe for monitoring of hypochlorous acid in the brains of mice afflicted with neuroinflammation
Authors: Liang Fanghui , Jiang Jian , Yang Xinyue , Zhang Guoyang , Zhou Jiaying , Han Jiahao , Geng Yujie , Wang Zhuo
Published: December 2022

The fluorescent probe SiR-FH realized real-time monitoring of HClO in the brains of mice with LPS-induced neuroinflammation.
The high magnetoresistance performance of epitaxial half-metallic CrO2-based magnetic junctions
Authors: Zhang Zhenhua , Cheng Ming , Fan Zhiqiang , Liu Yong , Wang Dengjing , Wang Ke , Xiong Rui , Lu Zhihong
Published: December 2022

The high magnetoresistance performance of epitaxial half-metallic CrO2-based magnetic junctions is verified by systematic theoretical and experimental studies.
A DFT study of plasma-catalytic ammonia synthesis: the effect of electric fields, excess electrons and catalyst surfaces on N2 dissociation
Authors: Chen She , Wang Yulei , Li Qihang , Li Kelin , Li Mengbo , Wang Feng
Published: December 2022

The effect of electric field and surface charging on N2 adsorption and dissociation on Ru and Ni in plasma catalytic synthesis of ammonia.
Abnormal vibrational anisotropy and thermal properties of a two-dimensional GeAs semiconductor
Authors: Liu Yucheng , Yang Shuai , Sui Fengrui , Qi Ruijuan , Dong Shangwei , Yang Pingxiong , Yue Fangyu
Published: December 2022

The polarization-dependent Raman shifts in 2D GeAs also evolve periodically in different symmetries, and the temperature-dependent Raman intensities can give a uniform constant, based on which the thermal-related key parameters can be derived.
Using molecular dynamics to simulate realistic structures of nitrocellulose of different nitration levels
Authors: Gibbon Catriona , Di Pietro Poppy , Storr Mark , Broughton Duncan , Skylaris Chris-Kriton
Published: December 2022

Finding a protocol based on molecular dynamics simulations for creating realistic paracrystalline structures of nitrocellulose, and analysis of the results.
Realizing near white and warm light emission of cuprous iodide complexes by alkyl-isomerization of ligands
Authors: Shao Juan-Juan , Chen Wei-Min , Mensah Abraham , Liu Peng-Lai , Ni Jian-Ling , Chen Li-Zhuang , Wang Fang-Ming
Published: December 2022

Four luminescent cuprous iodide cluster inorganic–organic hybrids were synthesized with alkylated triethyldiamines. Modifications of the alkyl chain can effect luminescence of the complexes providing a way to achieve high-quality solid-state lighting materials.
σ-Hole interactions in organometallic catalysts: the case of methyltrioxorhenium(vii)
Authors: Calabrese Miriam , Pizzi Andrea , Daolio Andrea , Frontera Antonio , Resnati Giuseppe
Published: December 2022

Experimental and computational results prove that methyltrioxorhenium(vii), an efficient and reliable catalyst, forms σ-hole interactions with typical co-catalysts opposite to both O–Re and C–Re bonds.
Solvation regulation to mitigate the decomposition of 2,6-dihydroxyanthraquinone in aqueous organic redox flow batteries
Authors: Peng Kang , Li Yuanyuan , Tang Gonggen , Liu Yahua , Yang Zhengjin , Xu Tongwen
Published: December 2022

This communication documents the first case of a solvation regulation strategy for improving the AORFB cycling lifetime by exploiting the ion pairing and hydration effect of supporting electrolytes.
Effective strategies toward imine-linked cationic covalent organic frameworks for rapid and selective removal of 99TcO4− from water: insights from DFT and MD calculations
Authors: Zhao Chaofeng , Ma Xinjie , Wei Xin , Liu Weiwei , Sun Lu , Ai Yuejie
Published: December 2022

The dynamic behavior and anion exchange mechanism of 99TcO4− on imine-linked cationic COFs are elucidated to provide theoretical basis for developing novel cationic COFs materials for environmental remediation.
Modified cereal bran (MCB) from finger millet, kodo millet, and rice bran prevents high-fat diet-induced metabolic derangements
Authors: Devi Kirti , Kumar Vibhu , Kumar Vijay , Mahajan Neha , Kaur Jasleen , Sharma Shikha , Kumar Ajay , Khan Rehan , Bishnoi Mahendra , Kondepudi Kanthi Kiran
Published: December 2022

Metabolic complications induced by the HFD and their prevention through dietary supplementation of MCBs in a mouse model. MCBs reduces endotoxemia, prevents leaky gut, beneficially modulates selected gut bacteria, increases SCFAs levels and lowers dyslipidemia.
Heptacoordinate transition-metal-decorated metallo-borospherenes and multiple-helix metallo-boronanotubes
Authors: Ao Mei-Zhen , Zhang Fei , Ma Yuan-Yuan , Mu Yue-Wen , Li Si-Dian
Published: December 2022

Extensive first-principles theory calculations predict the possibility of a series of novel heptacoordinate Ni-decorated cage-like metallo-borospherenes and one-dimensional multiple-helix metallo-boronanotubes composed of interconnected boron double chains.