bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine facilitates endoplasmic reticulum stress and apoptosis of hepatocytes by suppressing ERO1α expression via cooperation between DNMT1 and G9a
Authors: Shen Jiangyong , Jiao Yun , Ding Ning , Xie Lin , Ma Shengchao , Zhang Hui , Yang Anning , Zhang Huiping , Jiang Yideng
Published: March 2022

Endoplasmic reticulum (ER) stress and apoptosis play a critical role in liver injury. Endoplasmic reticulum oxidoreductase 1α (ERO1α) is an oxidase that exists in the luminal side of the ER membrane, participating in protein folding and secretion and inhibiting apoptosis, but the underlying mechanism on liver injury induced by homocysteine (Hcy) remains obscure. In this study, hyperhomocysteinemia (HHcy) mice model was established in cbs+/− mice by feeding a high‐methionine diet for 12 weeks; and cbs+/− mice fed with high‐methionine diet exhibited more severe liver injury compared to cbs+/+ mice. Mechanistically, we found that Hcy promoted ER stress and apoptosis of hepatocytes and thereby aggravated liver injury through inhibiting ERO1α expression; accordingly, overexpression of ERO1α remarkably alleviated ER stress and apoptosis of hepatocytes induced by Hcy. Epigenetic modification analysis revealed that Hcy significantly increased levels of DNA methylation and H3 lysine 9 dimethylation (H3K9me2) on ERO1α promoter, which attributed to upregulated DNA methyltransferase 1 (DNMT1) and G9a, respectively. Further study showed that DNMT1 and G9a cooperatively regulated ERO1α expression in hepatocytes exposed to Hcy. Taken together, our work demonstrates that Hcy activates ER stress and apoptosis of hepatocytes by downregulating ERO1α expression via cooperation between DNMT1 and G9a, which provides new insight into the mechanism of Hcy‐induced ER stress and apoptosis of hepatocytes in liver injury.
Structural Phase Transitions and Magnetic Superexchange in MIAgIIF3 Perovskites at High Pressure**
Authors: Wolański Łukasz , Metzelaars Marvin , van Leusen Jan , Kögerler Paul , Grochala Wojciech
Published: March 2022

Pressure‐induced phase transitions of MIAgIIF3 perovskites (M=K, Rb, Cs) have been predicted theoretically for the first time for pressures up to 100 GPa. The sequence of phase transitions for M=K and Rb consists of a transition from orthorhombic to monoclinic and back to orthorhombic, associated with progressive bending of infinite chains of corner‐sharing [AgF6]4− octahedra and their mutual approach through secondary Ag⋅⋅⋅F contacts. In stark contrast, only a single phase transition (tetragonal→triclinic) is predicted for CsAgF3; this is associated with substantial deformation of the Jahn–Teller‐distorted first coordination sphere of AgII and association of the infinite [AgF6]4− chains into a polymeric sublattice. The phase transitions markedly decrease the coupling strength of intra‐chain antiferromagnetic superexchange in MAgF3 hosts lattices.
Crime data optimization using neutrosophic logic based game theory
Authors: Remani Naga Venkata Jagan Mohan , Naresh Vankamamidi S. , Reddi Sivaranjani , Kumar Kadali Dileep
Published: March 2022

The significance of prisoner's dilemma in making two completely rational individuals might not cooperate even their best interest to do so. Every criminal investigation is strongly reliant on crime data classification and optimization. In this work, we extended prisoners' dilemma for crime data classification and its optimization. A confusion matrix‐based optimization technique for crime data with game theory model in order to identify the person involvement in crime is to be predicted and clustered them into confess, not confessed, and indeterministic states based on the neutrosophic logic principle. In this technique, first we map neutrosophic logic into crime system to break the uncertainties in crime clustering. Next, we preliminary cluster the crime data pairs that indicates two offenders neutrosophic values into three clusters. However, some pairs lie in intersections of two or three clusters. So we optimize the clustering into disjoint clusters will be done based on the ratio of intra‐cluster and inter‐cluster distances. We have implemented the proposed method. The experimental result shows that the quality of proposed method based on accuracy, precision, and recall parameters, observed more than 90% accuracy.
Optimal seed node selection method for LTIS model
Authors: Devi Kalyanee , Tripathi Rohit
Published: March 2022

The problem of seed node selection to maximize the influence diffusion is one of the most pivotal problems related to applications like marketing campaigns, spreading awareness, and so forth. Most of the existing work focuses on single‐step influence diffusion where the seed nodes are selected in one go to trigger the diffusion process, and the influence spread is mostly studied under progressive models. This article proposes a new model named the LTIS model, where the diffusion process can take place in multiple steps. In this model, a node that gets influenced in one step can again go to an uninfluenced state in subsequent steps. This article also proposes an optimal seed node selection method named advantage‐of‐seed‐node method to find the seed node‐set. This proposed method accurately computes the advantage of the seed node to find the influence spread of each node. A comparative analysis of the proposed method in terms of activated nodes from a selected seed node‐set under the proposed LTIS model outperforms many existing seed set selection schemes.
Power‐efficient optimized clustering method with intelligent fog computing for wireless sensor networks
Authors: Jain Abhishek , Bhardwaj Amit Kumar
Published: March 2022

One of the most essential characteristics that is taken into consideration while dealing with wireless sensor networks (WSNs) is to optimize energy consumption during the transmission of data packets. Routing algorithms must provide optimal solutions to reduce the amount of energy consumed during the process. In wireless sensor networks, the end devices layer comprises of clustering of sensor nodes using ant lion optimization (ALO) which is followed by fog layer consisting of k‐means clustering technique. When nature inspired optimization solution is implemented, the accuracy majorly depends upon complexity and number of parameters. The algorithm proposed majorly focuses on the bottom layer and not on the fog layer. The results of the proposed algorithm were proved to significantly better than the conventional algorithms used for the very same purpose. The proposed algorithm focuses on ALO only on the bottom layer and not on the fog layer. To evaluate the performance of the proposed algorithm, the results are compared with the findings of several traditional algorithms, such as energy‐efficient cross‐layer‐sensing clustering method, Distributed and Morphological Operation‐based Data Collection Algorithm, and trust‐based secure routing. Comparative results showed that the proposed algorithm presented significant improvement.
Acute haemodynamic impact of transcatheter aortic valve implantation in patients with severe aortic stenosis
Authors: Graziani Francesca , Cialdella Pio , Lillo Rosa , Locorotondo Gabriella , Genuardi Lorenzo , Ingrasciotta Gessica , Cangemi Stefano , Nesta Marialisa , Bruno Piergiorgio , Aurigemma Cristina , Romagnoli Enrico , Calabrese Michele , Giambusso Nicole , Lombardo Antonella , Burzotta Francesco , Trani Carlo
Published: March 2022

Aims

There are limited data about the intraprocedural haemodynamic study performed immediately before and after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). We aimed to evaluate the acute haemodynamic impact of TAVI in patients with severe AS and to investigate invasive and non‐invasive parameters predicting all‐cause mortality.

Methods and results

A total of 245 consecutive AS patients (43% male, mean age 80.3 ± 7.3 years) undergoing TAVI were enrolled. Intraprocedural left heart catheterization (LHC) and echocardiogram before and after TAVI were performed. The clinical endpoint was the death for any cause. LHC after TAVI revealed significant changes in aortic and left ventricular (LV) pressures, including indexes of intrinsic myocardial contractility and diastolic function such as positive dP/dT (1128.9 ± 398.7 vs. 806.3 ± 247.2 mmHg/s, P ˂ 0.001) and negative dP/dT (1310.7 ± 431.1 vs. 1075.1 ± 440.8 mmHg/s, P ˂ 0.001). Post‐TAVI echo showed a significant reduction in LV end‐diastolic (P = 0.036) and end‐systolic (P ˂ 0.001) diameters, improvement in LV ejection fraction (from 55 ± 12% to 57.2 ± 10.5%, P ˂ 0.001), and pulmonary artery systolic pressure (42.1 ± 14.2 vs. 33.1 ± 10.7 mmHg, P < 0.001). After a mean follow‐up time interval of 24 months, 47 patients died. Post‐TAVI significant aortic regurgitation at echocardiography was the only independent predictor of mortality (hazard ratio 5.592, confidence interval 1.932–16.184, P = 0.002).

Conclusions

Left heart catheterization performed immediately before and after prosthesis release offers a unique insight in the assessment of LV adaptation to severe AS and the impact of TAVI on LV, catching changes in indexes of intrinsic contractility and myocardial relaxation. Aortic regurgitation assessed by echocardiography was the only independent predictor of mortality in patients undergoing TAVI.
Monolithic three‐dimensional hollow nanoporous CuxO encapsulated mesoporous Cu heterostructures with superior Li storage properties
Authors: Yan Xiaomeng , Kang Hong , Cheng Peng , Zhang Shichao , Shi Sanqiang , Liu Wenbo
Published: March 2022

Drastic volume expansion and low conductivity are critical factors leading to severe capacity decay of transition metal oxides (TMOs) as anodes for lithium‐ion batteries (LIBs). An effective strategy to overcome this challenge is to engineer freestanding 3D hollow architectures integrated with nanostructured metals to boost their structural stability and electrical conductivity simultaneously. Inspired by cowpea configuration beneficial to improve the transport of rich water in arid environment, herein, a novel monolithic 3D hollow nanoporous CuxO encapsulated mesoporous Cu heterostructure (3D‐HNP CuxO@m‐Cu) is delicately designed and fabricated via a simple three‐step approach. Compared to other CuxO‐based electrodes with different structure designs in published reports, the unique 3D‐HNP CuxO@m‐Cu as a binder‐free integrated anode for LIBs shows superior Li storage properties with first reversible capacity of 2.02 mAh cm−2 and good cycling stability with 76.2% capacity retention and 99.9% coulombic efficiency after 200 cycles. This can be largely attributed to the unique 3D nanoporous heterostructure design with a synergistic effect between interconnected hollow CuxO nanotubes with bidirectional mechanical stress buffer and internal mesoporous Cu network with enhanced electrical conductivity. We believe that this work provides a brand‐new strategy for rational design and fabrication of next‐generation high‐performance TMOs‐based anodes toward advanced LIBs.

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Dynamic branch pruning aided low switching fixed complexity sphere decoding for small scale and massive MIMO detection
Authors: Chakraborty Sourav , Sinha Nirmalendu Bikas , Mitra Monojit
Published: March 2022

In this article, we have proposed a dynamic branch pruning aided low switching fixed complexity sphere decoding (LSFSD) algorithm that can reduce the number of node visits in conventional fixed‐complexity sphere decoder (FSD) or imbalanced fixed‐complexity sphere decoder (IFSD) detector dynamically based on the channel condition. Further, we propose a low complexity QR‐based FSD ordering scheme in the real domain that requires half of the number of real arithmetic operations in the conventional case. As a case study, we have simulated the proposed algorithm for and MIMO system with 64‐QAM modulation. The simulation results show that the proposed algorithm can reduce approximately 50% of node visits to achieve a BER of . Additionally, a low complexity solution of the soft bit information generation method is also proposed. The concept is further extended to massive MIMO applications where the number of receiving antenna to transmit antenna ratio is close to one. A smaller node extension parameter is defined for the proposed detector to reduce the complexity in massive MIMO detection. Simulation results demonstrate that the proposed detection algorithm has significantly lower computational complexity than other recent state‐of‐the‐art detection algorithms for massive MIMO and large MIMO systems.
Exploring wait time variations in a prostate cancer patient pathway—A qualitative study
Authors: Valbekmo Anne Grete , Mo Lise , Gjøsund Gudveig , Håland Erna , Melby Line
Published: March 2022

Norwegian health authorities emphasise that all citizens should have equal access to healthcare and implement cancer patient pathways (CPPs) to ensure medical care for all patients within the same time frame and to avoid unwanted variation. Statistics regarding prostate cancer indicate longer wait times for patients from a local hospital compared to patients from a university hospital. This study describes which health system‐related factors influence variations in wait times. Eighteen healthcare workers participated in qualitative individual interviews conducted using a semi‐structured interview guide. Transcripts were analysed by systematic text condensation, which is a cross‐case method for the thematic analysis of qualitative data. The analysis unveiled four categories describing possible health system‐related factors causing variation in times spent on diagnostics for patients in the local hospital and in university hospital, respectively: (a) capacity and competence, (b) logistics and efficiency, (c) need for highly specialised investigations, and (d) need for extra consultations. Centralisation of surgical treatment necessitated the transfer of patients, with extra steps indicated in the CPP for patients transferring from the local hospital to the university hospital for surgery. The local hospital seemed to lack capacity more frequently than the university hospital. Possible factors explaining variations in wait time between the two hospitals concern both internal conditions at the hospitals in organising CPPs and the implications of transferring patients between hospitals. Differences in hospitals' capacity can cause variations in wait time. The extra steps involved in transferring patients between hospitals can lead to additional time spent in CPP.
Conservative solute transport processes and associated transient storage mechanisms: Comparing streams with contrasting channel morphologies, land use and land cover
Authors: Emanuelson Karin , Covino Tim , Ward Adam S. , Dorley Jancoba , Gooseff Michael
Published: March 2022

Land use within a watershed impacts stream channel morphology and hydrology and, therefore, in‐stream solute transport processes and associated transient storage mechanisms. This study evaluated transport processes in two contrasting stream sites where channel morphology was influenced by the surrounding land use, land cover, climate and geologic controls: Como Creek, CO, a relatively undisturbed, high gradient, forested stream with a gravel bed and complex channel morphology, and Clear Creek, IA, an incised, low‐gradient stream with low‐permeability substrate draining an agricultural landscape. We performed conservative stream tracer injections at these sites to address the following questions: (1) How does solute transport vary between streams with differing morphologies? and (2) How does solute transport at each stream site change as a function of discharge? We analysed in‐stream tracer time series data and compared results quantifying solute attenuation in surface and subsurface transient storage zones. Significant trends were observed in these metrics with varying discharge conditions at the forested site but not at the agricultural site. There was a broad range of transport mechanisms and evidence of substantial exchange with both surface and hyporheic transient storage in the relatively undisturbed, forested stream. Changing discharge conditions activated or deactivated different solute transport mechanisms in the forested site and greatly impacted advective travel time. Conversely in the simplified agricultural stream, there was a narrow range of solute transport behaviour across flows and predominantly surface transient storage at all measured discharge conditions. These results demonstrate how channel simplification inhibits available solute transport mechanisms across varying discharge conditions.
UK professional accounting bodies (PAB): Members’ unethical behaviors and exclusion
Authors: Adelopo Ismail , Meier Florian
Published: March 2022

Although previous studies have explored the disciplinary procedures and sanctions by PABs, the focus of these studies has often been generalized to all forms of infringements. This has prevented specific attention on the most severe ethical breaches by PAB members, that is, offences leading to exclusion. Consequently, we do not know their prevalence, the features of these behaviors or the motivating factors for their perpetration by members of the UK's PABs. Clarity on these issues is in the public interest given the centrality of the role of the accounting profession to the efficient functioning of the financial system. We used the fraud triangle theory to shed light on these issues. Our analysis is based on the entire population of 141 serious cases that led to members’ exclusion. We developed an analytical framework that focused on the nature of the infringements, their prevalence amongst the PABs, and the variety of explanations provided by the culprits. Our analysis shows that criminal convictions and breach of ethical guidance are the two major causes of exclusion. Our findings have implications for the PABs in their attempts to ensure their members’ ethical behavior and the adequacy of their disciplinary process.
Case report: A novel cause of acute liver failure in children: A combination of human herpesvirus‐6 infection and homozygous mutation in NBAS gene
Authors: Cheng Ying , Xia Zhi , Huang Chengjiao , Xu Hui
Published: March 2022

Etiologies of acute liver failure in children can be multiple factors including virus infection, drug‐induced damage, and different pathogens. Next‐generation sequencing (NGS) is an emerging method for pan‐pathogen screening. Here we reported a case of acute liver failure in a 15‐month‐old male, using NGS and gene sequencing to determine the cause of acute liver failure may be caused by pathogens, drug‐induction and pathogenic variant gene.
TLR4 polymorphisms as potential predictors of atopic dermatitis in Chinese Han children
Authors: Shi Jianrong , He Lin , Tao Ran , Zheng Huiwen , Li Wei , Huang Shuangshuang , Li Yunling , Shang Shiqiang
Published: March 2022

Background

Toll‐like receptor 4 (TLR4) is considered to be involved in the pathogenesis and progression of atopic dermatitis (AD). In the present study, we evaluated the relationship between TLR4 gene polymorphisms and the susceptibility or severity of AD among Chinese Han children.

Methods

A total of 132 AD patients and 100 healthy controls were enrolled in this study. Four single‐nucleotide polymorphisms (rs19277914, rs11536891, rs7869402, and rs11536889) of the TLR4 gene were genotyped by multiplex PCR combined with next‐generation sequencing.

Results

Our results showed that a significantly reduced risk for AD was associated with C allele [p = 0.008; odds ratio (OR) = 0.41, C vs. T], TC genotype (p = 0.022; OR = 0.41, TC vs. TT), and TC + CC genotype (p = 0.010; OR = 0.39, TC + CC vs. TT) of TLR4 rs11536891. The frequency of the haplotype GCCG (rs1927914–rs11536891–rs7869402–rs11536889) in AD patients was lower than that in the controls (p = 0.010; OR = 0.38). Moreover, the results indicated that a higher risk of severe AD was related to the T allele (p = 0.019; OR = 2.97, T vs. C) and the TC genotype (p = 0.021; OR = 3.34, TC vs. CC) of TLR4 rs7869402. A risk haplotype of TLR4 (GTTG) was found in severe AD patients (p = 0.010; OR = 5.26).

Conclusions

Our data suggested that TLR4 rs11536891 polymorphism was associated with the susceptibility to AD in Chinese Han children. And TLR4 rs7869402 might confer the severity of pediatric AD patients.
The Japanese adaptation and validation of the COVID‐19 Phobia Scale (C19P‐S)
Authors: Özdemir Şevket , Baloğlu Mustafa , Şahin Rukiye
Published: March 2022

There exists a significant need of screening, measuring, and assessing phobic reactions to the negative effects and consequences of coronavirus disease 2019 (COVID‐19) across the world. For this purpose, the C19P‐S has b een developed and adapted to several languages and cultures including Turkish, Russian, Arabic, English, Korean, and soforth. This study aimed to adapt the scale into Japanese. Convenience sampling was used in the recruitment of the participants. The sample involved 310 Japanese‐speaking natives from different prefectures of the country (MeanAGE = 49.97; SD = 13.07). The scale is a self‐report instrument, which includes 20, 5‐point Likert‐type items. The scale assesses the levels of COVID‐19 phobia in four areas: Psychological, Somatic, Economic, and Social. The validity (content, construct, convergent, and discriminant) and reliability (internal consistency) analyses were conducted. Multivariate analysis of variance (MANOVA) was used for group comparisons. MANOVA results show that women scored statistically higher in the psychological area. Furthermore, the participants with a lower educational level scored higher than those with a higher level in the somatic area. Among other scales measuring fear and anxiety, the C19P‐S Japanese (C19P‐SJ) is the first measurement tool specifically designed and adapted for evaluating coronaphobia. It is suggested that the individuals with psychiatric diagnoses be included to measure and support the construct validity of the scale.
Downregulation of STK25 promotes autophagy via the Janus kinase 2/signal transducer and activator of transcription 3 pathway in colorectal cancer
Authors: Chen Jiangbo , Gao Pin , Peng Lin , Liu Tianqi , Wu Fan , Xu Kai , Chen Lei , Tan Fei , Xing Pu , Wang Zaozao , Di Jiabo , Jiang Beihai , Su Xiangqian
Published: March 2022

Autophagy plays a crucial role in colorectal cancer (CRC) development. Our previous study suggested that serine/threonine protein kinase 25 (STK25) regulates aerobic glycolysis in CRC cells. Glycolysis modulates cellular autophagy during tumor growth; however, the role of STK25 in autophagy remains unclear. In this study, we found that STK25 expression was decreased in CRC tissues and CRC patients with high STK25 expression had a favorable prognosis. Functional assays suggested that STK25 inhibition promoted autophagy in CRC cells. Overexpression of STK25 exhibited the opposite effects. Moreover, the results of western blot demonstrated that silencing STK25 induced autophagy by activating the JAK2/STAT3 pathway. Therefore, STK25 could be a potential indicator for therapies targeting the JAK2/STAT3 pathway in CRC.
General and bladder‐related quality of life: A focus on women living with spinal cord injury
Authors: Dekalo Ann , Myers Jeremy B. , Kennelly Michael , Welk Blayne
Published: March 2022

Objective

To compare bladder symptoms, and urinary and overall quality of life (QOL) among women and men after Spinal cord injury (SCI), and to describe specific aspects of QOL among women with SCI.

Methods

We used data from a prospective, multi‐center, and cross‐sectional study that was carried out from May 2019 to September 2020. Clinical and demographic details were obtained and participants completed two patient reported outcomes: the neurogenic bladder symptoms score‐short form (NBSS‐SF, which measures bladder symptoms and QOL) and the SF‐12 (which measures overall physical and mental health QOL).

Results

Our cohort included 135 women and 210 men with SCI. Among the women, the median age was 50, and 40% had a cervical SCI. For general QOL, women with SCI had physical functioning scores similar to men, but lower mental health scores on the SF‐12 (46.85 vs. 49.76, p = 0.01). Women had significantly worse overall NBSS (10.76 vs. 9.08, p < 0.001) and NBSS continence domain scores (4.71 vs. 3.66, p < 0.001) compared to men. There were significant differences between overall QOL measures, and bladder symptoms based on bladder management techniques among the women. NBSS‐SF symptom scores were better among women who used overactive bladder medications compared to women who did not (8.43 vs. 11.9, p = 0.02) and NBSS‐SF QOL domain scores were significantly better among women who underwent surgery and those that used overactive bladder medications.

Conclusions

Women have more bladder symptoms (specifically incontinence) compared to men. Symptom burden and overall QOL vary among women who use different bladder management techniques and treatments.
Newsprint microcrystalline fibers reinforced styrene butadiene rubber as a low thermal conducting material: Effect of electron beam irradiation and fiber content
Authors: El‐Nemr Khaled F. , Ali Magdy A. , Gad Yasser H. , Gabr Eman M.
Published: March 2022

The present study focuses on utilizing polystyrene emulsion treated newsprint microcrystalline fibers (NPMCF). These treated fibers were then added to styrene‐butadiene rubber (SBR) at different concentrations, namely, 3, 6, 9, and 12 phr (part per hundred part of rubber). Mixing of ingredients was carried out on a rubber roll mill and afterward molded as a thin film on a hot press, then, exposed to electron beam irradiation doses up to 200 kGy so as to enhance the treatment of the composites. Mechanical properties of the composites, such as tensile strength, elongation at break, tensile modulus, and cross‐link density were enhanced by adding the treated fiber to SBR and by irradiation, and this enhancement was obtained at 6 phr fiber at 100 kGy. Measurements of scanning electron microscopy (SEM) proved the adhesion of the treated fibers to SBR. The thermal conductivity was measured for the prepared composites as a function of electron beam irradiation and fiber content. It was found that the thermal conductivity decreases according to fiber loading (up to 6 phr fiber) and irradiation dose.
Molecular Inclusion of Small Aging Products into the Hexanitrohexaazaisowurtzitane (CL‐20) Lattice: Part II, Polymorph Dependence
Authors: Beste Ariana
Published: March 2022

In Part I of this two‐part series, we conducted accelerated aging studies of β CL‐20 thin films deposited on glass surfaces in different environments (N2, air, air/water) and analyzed the samples with attenuated total reflectance infrared (ATR‐IR) spectroscopy. We observed a polymorph transformation to α CL‐20, accompanied by lattice incorporation of water and other small guest molecules when samples were aged in air/water. Comparison to simulated IR spectra identified NO2 (possibly interacting with a carbon species), HNCO, N2O, and CO2 as potential molecular inclusions. For these molecules, we assessed the thermodynamic feasibility of lattice incorporation into α, β, and ϵ CL‐20 and the accompanying local stress due to lattice expansion in Part II, reported here. We found that the insertion of guest molecules (with the exception of water), into β and ϵ CL‐20 is thermodynamically and kinetically unfavorable, explaining the absence of ATR‐IR features corresponding to molecular inclusions in β CL‐20 prior to polymorph conversion. We hypothesize that water facilitates the transformation to α CL‐20, which allows the insertion of small degradation products into the CL‐20 lattice. We predict a larger stability of ϵ CL‐20 compared to β CL‐20 towards polymorph transformation to α CL‐20, including in the presence of water.
Identification of the metabolites of methylophiopogonanone A by ultra‐high‐performance liquid chromatography combined with high‐resolution mass spectrometry
Authors: Wu Xiaowen , Sun Shuai , Wu Xiaoyi , Sun Zengxian
Published: March 2022

Rationale

Methylophiopogonanone A (MOA) is a naturally occurring homoisoflavonoid from the Chinese herb Ophiopogon japonicus, which has been demonstrated to attenuate myocardial apoptosis. However, the metabolism of MOA remains unknown. The goal of the present work was to investigate the in vitro metabolism of MOA using liver microsomes and hepatocytes.

Methods

The metabolites were generated by incubating MOA with rat, monkey and human liver microsomes or hepatocytes. The resulting samples were analyzed by using a quadrupole‐orbitrap high‐resolution mass spectrometer. The metabolites were identified through the measurements of the exact mass, elemental composition and product ions.

Results

A total of 15 metabolites were detected and identified. Among these metabolites, M7 (demethylenation) was the most abundant metabolite in liver microsomes, while M6 (hydroxylation) was the predominant metabolite in hepatocytes, and glucuronidation metabolites (M9 and M10) were also the main metabolites in hepatocytes. The metabolic pathways of MOA included hydroxylation, demethylenation, glucuronidation, methylation, sulfation and glutathione conjugation.

Conclusions

This study for the first time provides valuable data on the metabolites of MOA, which will be of great importance for a better understanding of its disposition and to predict human pharmacokinetics.
Learning methods for structural damage detection via entropy‐based sensors selection
Authors: Smarra Francesco , Tjen Jimmy , D'Innocenzo Alessandro
Published: March 2022

In this article the problem of data‐driven structural damage detection is considered exploiting historical data collected from a structure. First, a novel technique based on Kalman filtering and on a combination of regression trees theory from machine learning and auto‐regressive system identification from control theory is derived to build switching models that can be used to detect structural damages. A technique is also proposed leveraging principal component analysis together with the poly‐exponential approach to create nonlinear models to be used for structural damage detection. Finally, a novel sensors selection algorithm based on the notions of entropy and information gain from information theory is developed to reduce the number of sensors without affecting or even improving, as it happens in our experimental setup, the model accuracy. The presented techniques are validated on three independent experimental datasets, showing that the proposed algorithms outperform previous and classical approaches, improving the prediction accuracy and the damage detection sensitivity while reducing the number of sensors.
Deep learning for the dynamic prediction of multivariate longitudinal and survival data
Authors: Lin Jeffrey , Luo Sheng
Published: March 2022

The joint model for longitudinal and survival data improves time‐to‐event predictions by including longitudinal outcome variables in addition to baseline covariates. However, in practice, joint models may be limited by parametric assumptions in both the longitudinal and survival submodels. In addition, computational difficulties arise when considering multiple longitudinal outcomes due to the large number of random effects to be integrated out in the full likelihood. In this article, we discuss several recent machine learning methods for incorporating multivariate longitudinal data for time‐to‐event prediction. The presented methods use functional data analysis or convolutional neural networks to model the longitudinal data, both of which scale well to multiple longitudinal outcomes. In addition, we propose a novel architecture based on the transformer neural network, named TransformerJM, which jointly models longitudinal and time‐to‐event data. The prognostic abilities of each model are assessed and compared through both simulation and real data analysis on Alzheimer's disease datasets. Specifically, the models were evaluated based on their ability to dynamically update predictions as new longitudinal data becomes available. We showed that TransformerJM improves upon the predictive performance of existing methods across different scenarios.
Three Birds with One Stone: An Integrated Cathode–Electrolyte Structure for High‐Performance Solid‐State Lithium–Oxygen Batteries
Authors: Li Chao‐Le , Huang Gang , Yu Yue , Xiong Qi , Yan Jun‐Min , Zhang Xin‐Bo
Published: March 2022

Constructing solid‐state lithium–oxygen batteries (SSLOBs) holds a great promise to solve the safety and stability bottlenecks faced by lithium–oxygen batteries (LOBs) with volatile and flammable organic liquid electrolytes. However, the realization of high‐performance SSLOBs is full of challenges due to the poor ionic conductivity of solid electrolytes, large interfacial resistance, and limited reaction sites of cathodes. Here, a flexible integrated cathode–electrolyte structure (ICES) is designed to enable the tight connection between the cathode and electrolyte through supporting them on a 3D SiO2 nanofibers (NFs) framework. The intimate cathode–electrolyte structure and the porous SiO2 NFs scaffold combination are favorable for decreasing interfacial resistance and increasing reaction sites. Moreover, the 3D SiO2 NFs framework can also behave as an efficient inorganic filler to enhance the ionic conductivity of the solid polymer electrolyte and its ability to inhibit lithium dendrite growth. As a result, the elaborately designed ICES can simultaneously tackle the issues that limit the performance liberation of SSLOBs, making the batteries deliver a high discharge capacity and a long lifetime of 145 cycles with a cycling capacity of 1000 mAh g−1 at 60 °C, much superior to coventional SSLOBs (50 cycles).
Air‐Processed Carbon‐Based Cs0.5FA0.5PbI3–Cs4PbI6 Heterostructure Perovskite Solar Cells with Efficiency Over 16%
Authors: Huang Zhaoshuai , Li Lingcong , Rao Huashang , Pan Zhenxiao , Zhong Xinhua
Published: March 2022

The preparation of low‐cost, high‐stability cell devices is the primary trend in the future development of perovskite solar cells (PSCs). The hole transport layer (HTL)‐free carbon electrode‐based PSCs (C‐PSCs) based on methylamine (MA) free perovskites prepared in the ambient air environment is expected to realize this goal. In MA‐free perovskites represented by CsxFA1–xPbI3, although the increase of Cs content increases the bandgap, CsxFA1–xPbI3 with high Cs content has superior stability. Herein, a hot flow‐assisted (HFA) spin‐coating method to prepare Cs0.5FA0.5PbI3 films in the ambient air environment with a wide relative humidity operation window is proposed. Compared with the traditional antisolvent method that requires a dry processing environment, the HFA method can easily prepare high‐quality Cs0.5FA0.5PbI3 films in a high‐humidity ambient air environment. In addition, it is found that the presence of trace amount of Cs4PbI6 can not only passivate the defects of Cs0.5FA0.5PbI3 but also suppress the undesired phase transition. As a result, the in situ formed Cs0.5FA0.5PbI3–Cs4PbI6 heterostructure film corresponds to better stability and higher photovoltaic performance than the plain Cs0.5FA0.5PbI3 film. The efficiency of the assembled champion C‐PSCs is up to 16.30%, which is currently the highest efficiency for MA‐ and HTL‐free low‐temperature C‐PSCs.
Toward Understanding the Short‐Circuit Current Loss in Perovskite Solar Cells with 2D Passivation Layers
Authors: Herterich Jan , Baretzky Clemens , Unmüssig Moritz , Maheu Clément , Glissmann Nico , Gutekunst Jeremias , Loukeris Georgios , Mayer Thomas , Kohlstädt Markus , Hofmann Jan P. , Würfel Uli
Published: March 2022

Herein, a strong short‐circuit current density (JSC) loss is observed when using phenetylammonium iodide (PEAI) as n‐side passivation in p–i–n perovskite solar cells. Comparing experiments with drift–diffusion simulations, different hypotheses for the origin of the JSC loss are presented and evaluated. Whereas the optical properties of the investigated cell stack remain unchanged, the internal quantum efficiency of the PEAI‐based devices decreases drastically. Strong bulk doping and interface traps are ruled out as the origin of the charge extraction limitation. High‐spatial resolution photoluminescence (PL) spectroscopy directly images the inhomogeneity of the PEAI‐based quasi‐2D perovskite wide‐bandgap interlayer, which is found to be crucial for the observed JSC loss. A 2D drift–diffusion model implemented with mobile ions and an inhomogeneous electron transport layer reproduces the experimental behavior accurately. The ionic space charge distribution under short circuit reduces the effective charge‐carrier diffusion length, hindering charge transport toward those domains in the perovskite–electron transport layer interface where electrons can be extracted efficiently. A longer charge‐carrier lifetime reduces the JSC loss, highlighting the importance of suppressed non‐radiative bulk recombination, not only for achieving high open‐circuit voltages, but also for efficient charge extraction.
Lower Aeronian (Llandovery, Silurian) graptolites of the generaRastritesandStavrites: systematics, biostratigraphy and palaeobiogeography
Authors: Sun Zongyuan , Štorch Petr , Fan Junxuan , Melchin Michael J. , Suyarkova Anna
Published: March 2022

The lower Aeronian graptolite speciesRastrites longispinus longispinusPerner,R. approximatusPerner,R. peregrinusBarrande,R.? norilskensisObut & Sobolevskaya, andStavrites rossicusObut & Sobolevskaya have been revised using material from China, the Czech Republic, Siberia, Canada and Spain, together with published data.Rastrites longispinus chenxuisubsp. nov. is recognized as a new biogeographical subspecies known only from China and Canada.Rastrites guizhouensisMuet al.,R. confertusChen & Lin andStavrites laticellatusObut & Sobolevskaya, are all considered to be junior synonyms ofS. rossicus.Rastrites geinitziiTörnquist is regarded as a junior synonym ofR. longispinus longispinus; andR. orbitusChurkin & Carter andR. hemigyratusChen & Lin are considered to be junior synonyms ofR.? norilskensis. We propose that a distinctR.? norilskensisBiozone can be recognized between a lowest AeronianDemirastrites triangulatusorD. triangulatus – D. pectinatusBiozone in Siberia and northern Canada (possibly in South China, with future work) and the overlyingLituigraptus convolutusBiozone. Cluster analysis of the palaeogeographical distribution of species ofRastritesandStavritessupports the hypothesis that two graptolite palaeobiographical provinces can be defined in the early Aeronian: a low‐latitude Circumequatorial Province including northern Laurentia, South China, Siberia and peri‐Siberian terranes; and a largely mid‐latitude Rheic – West Gondwana Province comprising Avalonian Britain, the Baltic area, central Europe, western and southern Europe, and cratonic North Africa. None of our studied taxa exhibits a cosmopolitan distribution. Our systematic revision has a significant impact on our palaeogeographical interpretations.
To scan or not to scan? Efficacy of transthoracic ultrasonography for ovine pulmonary adenocarcinoma screening in a large commercial UK sheep flock
Authors: Davies Peers , Strugnell Ben , Waine Katie , Wessels Mark , Cousens Chris , Willison Isobel
Published: March 2022

Background

Transthoracic ultrasonography (TTUS) is currently the only widely used method to diagnose preclinical or subclinical ovine pulmonary adenocarcinoma (OPA) in the live sheep. However, little is known about the test characteristics of TTUS.

Methods

One thousand and seventy‐four breeding ewes in a flock with evidence of low OPA prevalence underwent TTUS by an experienced operator. Fifty‐one sheep were diagnosed with OPA and underwent gross postmortem examination (PME).

Results

Lesions consistent with OPA were found in only 24% (12/51) of the culled ewes. Thirty‐five percent (18/51) of culled ewes had gross lesions consistent with other pulmonary disease and 41% (21/51) had no detectable gross lesions on PME. Histopathology and immunohistochemistry confirmed OPA in only the 12 animals identified with OPA lesions from PME.

Conclusion

Great caution should be exercised when deciding if TTUS is an appropriate screening test in groups of sheep where OPA prevalence may be anticipated to be low. TTUS is a subjective test and thus individual operator ability will influence the sensitivity and specificity of TTUS for OPA diagnosis while the underlying prevalence influences the eventual positive predictive value.
HOLL: Program Synthesis for Higher Order Logic Locking
Authors: Takhar Gourav , Karri Ramesh , Pilato Christian , Roy Subhajit
Published: March 2022

Logic locking “hides” the functionality of a digital circuit to protect it from counterfeiting, piracy, and malicious design modifications. The original design is transformed into a “locked” design such that the circuit reveals its correct functionality only when it is “unlocked” with a secret sequence of bits—the key bit-string. However, strong attacks, especially the SAT attack that uses a SAT solver to recover the key bit-string, have been profoundly effective at breaking the locked circuit and recovering the circuit functionality.

We lift logic locking to Higher Order Logic Locking (HOLL) by hiding a higher-order relation, instead of a key of independent values, challenging the attacker to discover this key relation to recreate the circuit functionality. Our technique uses program synthesis to construct the locked design and synthesize a corresponding key relation. HOLL has low overhead and existing attacks for logic locking do not apply as the entity to be recovered is no more a value. To evaluate our proposal, we propose a new attack (SynthAttack) that uses an inductive synthesis algorithm guided by an operational circuit as an input-output oracle to recover the hidden functionality. SynthAttack is inspired by the SAT attack, and similar to the SAT attack, it is verifiably correct, i.e., if the correct functionality is revealed, a verification check guarantees the same. Our empirical analysis shows that SynthAttack can break HOLL for small circuits and small key relations, but it is ineffective for real-life designs.
A New Approach for Active Automata Learning Based on Apartness
Authors: Vaandrager Frits , Garhewal Bharat , Rot Jurriaan , Wißmann Thorsten
Published: March 2022

We present $$L^{\#}$$

L
#

, a new and simple approach to active automata learning. Instead of focusing on equivalence of observations, like the $$L^{*}$$

L

∗

algorithm and its descendants, $$L^{\#}$$

L
#

takes a different perspective: it tries to establish apartness, a constructive form of inequality. $$L^{\#}$$

L
#

does not require auxiliary notions such as observation tables or discrimination trees, but operates directly on tree-shaped automata. $$L^{\#}$$

L
#

has the same asymptotic query and symbol complexities as the best existing learning algorithms, but we show that adaptive distinguishing sequences can be naturally integrated to boost the performance of $$L^{\#}$$

L
#

in practice. Experiments with a prototype implementation, written in Rust, suggest that $$L^{\#}$$

L
#

is competitive with existing algorithms.
Learning Realtime One-Counter Automata
Authors: Bruyère Véronique , Pérez Guillermo A. , Staquet Gaëtan
Published: March 2022

We present a new learning algorithm for realtime one-counter automata. Our algorithm uses membership and equivalence queries as in Angluin’s $${L}^*$$

L

∗

algorithm, as well as counter value queries and partial equivalence queries. In a partial equivalence query, we ask the teacher whether the language of a given finite-state automaton coincides with a counter-bounded subset of the target language. We evaluate an implementation of our algorithm on a number of random benchmarks and on a use case regarding efficient JSON-stream validation.
Scalable Anytime Algorithms for Learning Fragments of Linear Temporal Logic
Authors: Raha Ritam , Roy Rajarshi , Fijalkow Nathanaël , Neider Daniel
Published: March 2022

Linear temporal logic (LTL) is a specification language for finite sequences (called traces) widely used in program verification, motion planning in robotics, process mining, and many other areas. We consider the problem of learning formulas in fragments of LTL without the $$\mathbf {U}$$
U
-operator for classifying traces; despite a growing interest of the research community, existing solutions suffer from two limitations: they do not scale beyond small formulas, and they may exhaust computational resources without returning any result. We introduce a new algorithm addressing both issues: our algorithm is able to construct formulas an order of magnitude larger than previous methods, and it is anytime, meaning that it in most cases successfully outputs a formula, albeit possibly not of minimal size. We evaluate the performances of our algorithm using an open source implementation against publicly available benchmarks.
NeuReach: Learning Reachability Functions from Simulations
Authors: Sun Dawei , Mitra Sayan
Published: March 2022

We present , a tool that uses neural networks for predicting reachable sets from executions of a dynamical system. Unlike existing reachability tools, computes areachability functionthat outputs an accurate over-approximation of the reachable set foranyinitial set in a parameterized family. Such reachability functions are useful for online monitoring, verification, and safe planning. implements empirical risk minimization for learning reachability functions. We discuss the design rationale behind the optimization problem and establish that the computed output is probably approximately correct. Our experimental evaluations over a variety of systems show promise. can learn accurate reachability functions for complex nonlinear systems, including some that are beyond existing methods. From a learned reachability function, arbitrary reachtubes can be computed in milliseconds. is available athttps://github.com/sundw2014/NeuReach.
Kmclib: Automated Inference and Verification of Session Types from OCaml Programs
Authors: Imai Keigo , Lange Julien , Neykova Rumyana
Published: March 2022

Theories and tools based on multiparty session types offer correctness guarantees for concurrent programs that communicate using message-passing. These guarantees usually come at the cost of an intrinsically top-down approach, which requires the communication behaviour of the entire program to be specified as a global type.

This paper introduces : an OCaml library that supports the development of correct message-passing programs without having to write any types. The library utilises the meta-programming facilities of OCaml to automatically infer the session types of concurrent programs and verify their compatibility (k-MC [15]). Well-typed programs, written with , do not lead to communication errors and cannot get stuck.
Better Counterexamples for Dafny
Authors: Chakarov Aleksandar , Fedchin Aleksandr , Rakamarić Zvonimir , Rungta Neha
Published: March 2022

Dafny is a verification-aware programming language used at Amazon Web Services to develop critical components of their access management, storage, and cryptography infrastructures. The Dafny toolchain provides a verifier that can prove an implementation of a method satisfies its specification. When the underlying SMT solver cannot establish a proof, it generates a counterexample. These counterexamples are hard to understand and their interpretation is often a bottleneck in the proof debugging process. In this paper, we introduce an open-source tool that transforms counterexamples generated by the SMT solver to a more user-friendly format that maps to the Dafny syntax and is suitable for further processing. This new tool allows the Dafny developers to quickly identify the root cause of a problem with their proof, thereby speeding up the development of Dafny projects.