bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors
Authors: Marcu Ana , Schlosser Andreas , Keupp Anne , Trautwein Nico , Johann Pascal , Wölfl Matthias , Lager Johanna , Monoranu Camelia Maria , Walz Juliane S , Henkel Lisa M , Krauß Jürgen , Ebinger Martin , Schuhmann Martin , Thomale Ulrich Wilhelm , Pietsch Torsten , Klinker Erdwine , Schlegel Paul G , Oyen Florian , Reisner Yair , Rammensee Hans-Georg , Eyrich Matthias
Published: October 2021

Background

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear which epitopes T cells might recognize on AT/RT cells.

Methods

Here, we report a comprehensive mass spectrometry (MS)-based analysis of naturally presented human leukocyte antigen (HLA) class I and class II ligands on 23 AT/RTs. MS data were validated by matching with a human proteome dataset and exclusion of peptides that are part of the human benignome. Cryptic peptide ligands were identified using Peptide-PRISM.

Results

Comparative HLA ligandome analysis of the HLA ligandome revealed 55 class I and 139 class II tumor-exclusive peptides. No peptide originated from the SMARCB1 region. In addition, 61 HLA class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas, but no concordance was found with extracranial tumors. More than 80% of AT/RT exclusive peptides were able to successfully prime CD8+T cells, whereas naturally occurring memory responses in AT/RT patients could only be detected for class II epitopes. Interestingly, >50% of AT/RT exclusive class II ligands were also recognized by T cells from glioblastoma patients but not from healthy donors.

Conclusions

These findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA class I and class II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion.
Dual checkpoint blockade of CD47 and PD-L1 using an affinity-tuned bispecific antibody maximizes antitumor immunity
Authors: Chen Shih-Hsun , Dominik Pawel K , Stanfield Jessica , Ding Sheng , Yang Wenjing , Kurd Nadia , Llewellyn Ryan , Heyen Jonathan , Wang Carole , Melton Zea , Van Blarcom Thomas , Lindquist Kevin C , Chaparro-Riggers Javier , Salek-Ardakani Shahram
Published: October 2021

Background

T cell checkpoint immunotherapies have shown promising results in the clinic, but most patients remain non-responsive. CD47-signal regulatory protein alpha (SIRPα) myeloid checkpoint blockade has shown early clinical activity in hematologic malignancies. However, CD47 expression on peripheral blood limits αCD47 antibody selectivity and thus efficacy in solid tumors.

Methods

To improve the antibody selectivity and therapeutic window, we developed a novel affinity-tuned bispecific antibody targeting CD47 and programmed death-ligand 1 (PD-L1) to antagonize both innate and adaptive immune checkpoint pathways. This PD-L1-targeted CD47 bispecific antibody was designed with potent affinity for PD-L1 and moderate affinity for CD47 to achieve preferential binding on tumor and myeloid cells expressing PD-L1 in the tumor microenvironment (TME).

Results

The antibody design reduced binding on red blood cells and enhanced selectivity to the TME, improving the therapeutic window compared with αCD47 and its combination with αPD-L1 in syngeneic tumor models. Mechanistically, both myeloid and T cells were activated and contributed to antitumor activity of αCD47/PD-L1 bispecific antibody. Distinct from αCD47 and αPD-L1 monotherapies or combination therapies, single-cell RNA sequencing (scRNA-seq) and gene expression analysis revealed that the bispecific treatment resulted in unique innate activation, including pattern recognition receptor-mediated induction of type I interferon pathways and antigen presentation in dendritic cells and macrophage populations. Furthermore, treatment increased the Tcf7+stem-like progenitor CD8 T cell population in the TME and promoted its differentiation to an effector-like state. Consistent with mouse data, the compounds were well tolerated and demonstrated robust myeloid and T cell activation in non-human primates (NHPs). Notably, RNA-seq analysis in NHPs provided evidence that the innate activation was mainly contributed by CD47-SIRPα but not PD-L1-PD-1 blockade from the bispecific antibody.

Conclusion

These findings provide novel mechanistic insights into how myeloid and T cells can be uniquely modulated by the dual innate and adaptive checkpoint antibody and demonstrate its potential in clinical development (NCT04881045) to improve patient outcomes over current PD-(L)1 and CD47-targeted therapies.
Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer
Authors: Liu Huicheng , Bai Lili , Huang Liu , Ning Na , Li Lin , Li Yijia , Dong Xuejiao , Du Qiuyang , Xia Minghui , Chen Yufei , Zhao Likun , Li Yanhu , Meng Qingwu , Wang Jing , Duan Yaqi , Ming Jie , Yuan Andy Qingan , Yang Xiang-Ping
Published: October 2021

Background

Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo.

Methods

The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells.

Results

We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model.

Conclusion

This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.
Association Between Anatomical Features and Anterior Knee Pain in a “Fit” Service Population
Authors: Hand C. J. , Spalding J. W.
Published: October 2021

Anterior knee pain and overuse sports type injuries have been associated with anatomical factors. Specific diagnosis in knee pain is difficult, most service patients are grouped together as “Patello-Femoral Stress Syndrome”. Knee pain incidence within the service population is unknown, but thought to be greater than those presenting to General Practitioners. 293 active duty service men (100 Army and 193 Royal Navy) were interviewed and examined in relation to their knees. 138 measurements were made on each subject.

118 admitted to knee problems. Six had specific diagnoses, ranging from patellar tendonitis to ACL deficiency (with marked anterior instability). The remaining 112 individuals formed the study group and examination findings were compared with the 175 without Patello-Femoral Stress Syndrome. The results have been analysed to determine normal ranges and predictors of knee pain.

Age, years in the military and results of patello-femoral compression tests were consistently significantly different between the groups.

This survey provides useful information on normal values at examination. Q angle measurement was a poor predictor of knee pain. There was no clinically detectable anatomical variant that correlated with the Patello-Femoral Stress Syndrome. There was poor correlation between Tegner activity score and the perceived limitation on sport or work, as assessed on a visual analogue scale.
Critical Care Retrieval Revisited
Authors: Bateman R. M.
Published: October 2021

In 2000, the Journal of the Royal Naval Medical Service published an account of critical care retrieval experience written by Adrian Mellor and based on his time spent with CareFlight in Sydney, Australia. Having recently completed a term with the same organisation. I wanted to reiterate the usefulness of such an attachment.

The purpose of this article is therefore to compare my experiences with those of Surgeon Commander Mellor and to provide an update on the work involved in critical care retrieval within New South Wales.
Case Report: Use of a Remifentanil Infusion with the Tri-Service Anaesthetic Apparatus
Authors: Bateman R. , Wedgwood J. , Henning J.
Published: October 2021

During a recent deployment to Iraq, it was noticed that patients’ recovery times from general anaesthesia were significantly prolonged. We postulated that this was because of a lack of nitrous oxide – thereby creating a requirement for greater concentrations of volatile agent to maintain adequate depth of anaesthesia. We chose to adopt the technique of running a remifentanil infusion with the Tri-Service apparatus in an attempt to reduce the administered volatile and thus shorten recovery times.
Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry
Authors: Ren Zeguang , Ma Gaoting , Mokin Maxim , Jadhav Ashutosh P , Jia Baixue , Tong Xu , Bauer Clayton , Liu Raynald , Wang Anxin , Zhang Xuelei , Mo Dapeng , Ma Ning , Gao Feng , Song Ligang , Sun Xuan , Huo Xiaochuan , Deng Yiming , Liu Lian , Luo Gang , Luo Xiang , Peng Ya , Gui Liqiang , Song Cunfeng , Wu Jin , Wang Leyuan , Li Chunlei , Jovin Tudor G , Wang Yilong , Wang Yongjun , Miao Zhongrong
Published: October 2021

Backgroud

The goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).

Methods

This is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.

Results

A total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes.

Conclusions

In patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.
Changes in ST segment elevation myocardial infarction hospitalisations in China from 2011 to 2015
Authors: Zhou Tianna , Li Xi , Lu Yuan , Murugiah Karthik , Bai Xueke , Hu Shuang , Gao Yan , Masoudi Frederick A , Krumholz Harlan M , Li Jing
Published: October 2021

Objective

Access to acute cardiovascular care has improved and health services capacity has increased over the past decades. We assessed national changes in (1) patient characteristics, (2) in-hospital management and (3) patient outcomes among patients presenting with ST segment elevation myocardial infarction (STEMI) in 2011–2015 in China.

Methods

In a nationally representative sample of hospitals in China, we created two random cohorts of patients in 2011 and 2015 separately. We weighted our findings to estimate nationally representative numbers and assessed changes from 2011 to 2015. Data were abstracted from medical charts centrally using standardised definitions.

Results

While the proportion of patients with STEMI among all patients with acute myocardial infarction decreased over time from 82.5% (95% CI 81.7 to 83.3) in 2011 to 68.5% (95% CI 67.7 to 69.3) in 2015 (p<0.0001), the weighted national estimate of patients with STEMI increased from 210 000 to 380 000. The rate of reperfusion eligibility among patients with STEMI decreased from 49.3% (95% CI 48.1 to 50.5) to 42.2% (95% CI 41.1 to 43.4) in 2015 (p<0.0001); ineligibility was principally driven by larger proportions with prehospital delay exceeding 12 hours (67.4%–76.7%, p<0.0001). Among eligible patients, the proportion receiving reperfusion therapies increased from 54% (95% CI 52.3 to 55.7) to 59.7% (95% CI 57.9 to 61.4) (p<0.0001). Crude and risk-adjusted rates of in-hospital death did not differ significantly between 2011 and 2015.

Conclusions

In this most recent nationally representative study of STEMI in China, the use of acute reperfusion increased, but no significant improvement occurred in outcomes. There is a need to continue efforts to prevent cardiovascular diseases, to monitor changes in in-hospital treatments and outcomes, and to reduce prehospital delay.
‘No-Barriers’ tobacco product? Selling smokeless tobacco to women, people of colour and the LGBTQ+ community in the USA
Authors: Hendlin Yogi Hale , Small Sarah , Ling Pamela M
Published: October 2021

Background

In both Sweden and the USA, smokeless tobacco (ST) is legal and used predominantly by men. Starting in the 1970s, US tobacco companies attempted to expand the ST market to women, African Americans, Hispanic Americans and lesbian, gay, bisexual, transgender, queer and other sexual orientation (LGBTQ+) people.

Design

We analysed industry documents from the Truth Tobacco Industry Documents Library triangulating findings with recent ST advertising and publicly available literature.

Findings

We found tobacco companies used design innovations such as pouched moist snuff, snus and dissolvable products to expand the market. In addition, diverse advertising campaigns targeted women, people of colour (Hispanic, African American) and LGBTQ+ communities with identity-targeted messages emphasising novelty, convenience, cleanliness and use in smoke-free environments. However, stereotypes of ST users as rural white males endured, perpetuated by continued marketing aimed at this customer base, which created cognitive dissonance and stymied marketer’s hopes that pouch products would ‘democratize’ ST.

Conclusion

These failed campaigns suggest novel products such as nicotine pouch products may provide a ‘clean slate’ to similarly target women and other low-ST-using groups. Based on this history, the risk of new tobacco and nicotine products to increase health disparities should be closely monitored.
Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2
Authors: Bassiouni Wesam , Seubert John M. , Schulz Richard
Published: October 2021

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS) – induced cell death. AIF cleavage and translocation to the cytosol is thought to be calpain-1-dependent as calpain inhibitors reduce AIF proteolysis; however, many calpain inhibitors also inhibit matrix metalloproteinase-2 (MMP-2) activity, an intracellular and extracellular protease implicated in apoptosis. Here we investigated whether MMP-2 activity is affected in response to STS and if it contributes to AIF cleavage. Human fibrosarcoma HT1080 cells were treated with STS (0.1 µM, 0.25–24 h). A significant increase in cellular MMP-2 activity was seen by gelatin zymography after a 6 h STS treatment, prior to induction of cell necrosis. Western blot showed the time-dependent appearance of two forms of AIF (∼60 and 45 kDa) in the cytosol which were significantly increased at 6 h. Surprisingly, knocking down MMP-2 or inhibiting its activity with MMP-2 preferring inhibitors ARP-100 or ONO-4817, or inhibiting calpain activity with ALLM or PD150606, did not prevent the STS-induced increase in cytosolic AIF. These results show that although STS rapidly increases MMP-2 activity, the cytosolic release of AIF may be independent of the proteolytic activities of MMP-2 or calpain.
Consensus for networked Euler–Lagrange agents with partial velocity measurements missing
Authors: Cheng Shan , Huo Lujing
Published: October 2021

This brief paper studies the consensus problems for networked Euler–Lagrange (EL) agents in which only partial EL agents’ velocity measurements are available. Based on partial EL agents’ velocity measurements, the consensus protocols which indicate the communication structure among EL agents are derived in detail. Furthermore, the networked EL agents can achieve consensus with derived protocols. The obtained results show that the consensus protocol can always be designed under the condition that at least one EL agent can measure velocity measurements for any networked EL agents. Finally, numerical simulations are given to illustrate the effectiveness of the proposed protocols.
DECENTRALIZED DONATION EXPERT SYSTEM TO BRING DOWN COVID-19
Authors: AGUILERA RICARDO CARREÑO , ORTIZ MIGUEL PATIÑO , ORTIZ JULIAN PATIÑO , LOZADA ERICK VELAZQUEZ
Published: October 2021

Due to the exponential growth in the use of systems with applications of blockchain technology, this paper develops a funding system, with donations and offers of shares, through the Ethereum platform with blockchain technology. Given the benefits that blockchain provides data protection and has high security, this paper offers a decentralized donation expert system using smart contracts that makes fully reliable donation systems to attract more funds to this urgent global health issue. Smart contracts provide faithful donations and meet the characteristics of being versatile, accessible, and sustainable to combat the COVID-19 pandemic. This expert system found the Merkle grid as an optimum method to work efficiently on the blockchain. The expert system proved to be steady and efficient by using an essential test dataset. A reliable donation system expects more donors and investors since a sustainable and reliable approach is always a milestone. The primary purpose of developing this system is to attract donors to bring down the COVID-19 pandemic by providing a faithful donation system.
EVALUATION OF MATERIAL REMOVAL RATE AND SURFACE ROUGHNESS IN WIRE ELECTRO-DISCHARGE MACHINING OF 10-WT.% ZrO2-REINFORCED AL ALLOY COMPOSITE
Authors: KARTHIKEYAN A. , ALAGARSAMY S. V. , ILAIYA PERUMAL C.
Published: October 2021

In this study, we optimize the wire electro-discharge machining (WEDM) parameters in zirconia ([Formula: see text] ceramic particulates-filled Al7075 alloy composite by using the Taguchi-combined Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method. The Al7075 alloy composite was synthesized via the stir casting route by the addition of 10[Formula: see text]wt.% of ZrO2 particulates. Scanning electron microscopy (SEM) was used to analyze the microstructure of fabricated composite. Experimental work was executed as per the [Formula: see text]([Formula: see text] orthogonal array design by considering three input machining parameters like pulse current ([Formula: see text], pulse on-time ([Formula: see text] and pulse off-time ([Formula: see text], respectively. The material removal rate (MRR) and surface roughness (SR) were chosen as the output responses for machining of the developed composite. The signal-to-noise (S/N) ratio was employed to determine the optimum levels of machining parameters for the output responses. Moreover, analysis of variance (ANOVA) was used to find the significant contribution of parameters. The main effect plot explored that [Formula: see text] of 25 A, [Formula: see text] of 115[Formula: see text][Formula: see text]s and [Formula: see text] of 60[Formula: see text][Formula: see text]s were identified as the optimum levels of machining parameters which provide the maximum MRR (0.36757[Formula: see text]g/min) and minimum SR (3.826[Formula: see text][Formula: see text]m) for the proposed composite during the WEDM process. ANOVA results revealed that [Formula: see text] was the most dominant factor regarding MRR and SR followed by [Formula: see text] with contributions of 74.05% and 14.48%, respectively.
Insiders Dissected: New Foundations and a Systematisation of the Research on Insiders
Authors: Zimmer Ephraim , Burkert Christian , Federrath Hannes
Published: October 2021

The insider threat is often cited as one of the most challenging threats for security practitioners. Even though this topic is receiving considerable attention, two main problems remain unsolved. First, research on
insider threats
is focusing on many different
insiders
without being able to actually identify and consistently entitle the key aspects of the insiders. As a result, this research can neither be identified by practitioners as being relevant for their real-world insider problems, nor can it be compared with other research targeting the same insider aspects. Second, a clear understanding of
insiders
is vital for analysing, which insider properties are responsible for the peculiarity of
insider threats
. In this article, a systematic approach to dissect the defining aspects of
insiders
is proposed, which includes specific allocatable insider characteristics. Additionally, the insider characteristics are extended toward insider types, which establish universal and unambiguous names for different insiders and which are related with each other to form a new and simple
insider taxonomy
. The new foundations on insiders allow the comparison of different insider research in a structured manner. Furthermore, the new approach facilitates the identification of specific features of insider threats in future work.
An Experiment to Design an Operation and Maintenance System Integrating Apriori Association Rules for a Telecom Platform
Authors: Li Chengfan , Liu Lan , Zhao Junjuan , Liu Yuejun
Published: October 2021

The operation and maintenance management of telecom platforms puts more emphasis on operation and alarm monitoring and less on business flow, and it is difficult to have a seamless connection between operation and maintenance and sales. To improve the cooperative efficiency and the informatization level of telecom platform operation and maintenance, a new operation and maintenance system integrating Apriori association rules for a telecom platform is proposed. In this paper, the Apriori algorithm is firstly used to analyse the fault correlation of the operation and maintenance system of the telecommunications platform to get the alarm message. Then, the fault risk of the operation and maintenance platform is evaluated intelligently by the system‐business alarm causality model. Finally, based on the fixed end and the mobile end, the dynamic presentation of the system running state and alarm monitoring, device query and positioning, and online and offline inspection are implemented and designed, respectively. Experimental results show that the proposed operation and maintenance systems integrating Apriori association rules for the telecom platform innovate the cooperative mode between the operations and sales team, and the average time reduces to 3.9 minutes from 4.7 minutes and the risk forecasting accuracy increases from 8% to 26%. The assumed method can significantly improve the operational efficiency and intelligent level of the telecom platform’s system and business.
Towards a Blended Programme for Arabic and Other Less Commonly Taught Languages (LCTLs) in the South African Higher Education Context
Authors: Mohammed Tawffeek A. S. , Saidi Mustapha , Nyingone Assam Blanche , Eldokali Elsanosi M.
Published: October 2021

Disruptive technologies are widely used in education today. They aim to develop the knowledge, skills, and competencies of students. The field of applied linguistics, in general, and foreign language teaching, in particular, have benefited immensely from the developments taking place in computer-assisted language learning (CALL) and mobile-assisted language learning (MALL). However, meaningful learning cannot be achieved by using technology indiscriminately; an understanding of educational theories and key instructional design models is urgently required. The present study argues that the adoption of established instructional design models will yield effective learning materials not only for the less commonly taught languages (LCTLs) but also for language classrooms in general. It investigates the use of ADDIE instructional design model for designing and developing a blended syllabus for teaching Arabic as a foreign language in South African institutions of higher learning. The study also deals with the attitudes of the students towards the designed blended syllabus. The proposed syllabus is based on a wide range of web-based tools and e-learning specifications such as Learning Tools Interoperability (LTI) and Shareable Content Object Reference Model (SCORM). This study serves as a guideline for developing instructional materials for teaching Arabic, as well as other languages.
Rat Bone Mesenchymal Stem Cell‐Derived Exosomes Loaded with miR‐494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury
Authors: Huang Wei , Lin Miaoman , Yang Cunheng , Wang Fumin , Zhang Meng , Gao Junxiao , Yu Xiaobing
Published: October 2021

Exosomes (Exo) exhibit numerous advantages (e.g., good encapsulation, high targeting efficiency, and easy to penetrate the blood‐brain barrier to the central nervous system). Exosomes are recognized as prominent carriers of mRNAs, siRNAs, miRNAs, proteins, and other bioactive molecules. As confirmed by existing studies, miR‐494 is important to regulate the occurrence, progression, and repair of spinal cord injury (SCI). We constructed miR‐494‐modified exosomes (Exo‐miR‐494). As indicated from related research in vitro and vivo, Exo‐miR‐494 is capable of effectively inhibiting the inflammatory response and neuronal apoptosis in the injured area, as well as upregulating various anti‐inflammatory factors and miR‐494 to protect neurons. Moreover, it can promote the regeneration of the neurofilament and improve the recovery of behavioral function of SCI rats.
High‐Temperature Properties of a Long‐Span Double‐Deck Suspension Bridge under a Tanker Fire
Authors: Yu Mengsheng , Chen Qifeng , Yao Xinyu , Guo Xiao , Hao Tianzhi , Wang Hua
Published: October 2021

This paper presents a numerical study on the high‐temperature mechanical properties of a long‐span double‐deck suspension bridge. The main focus of this paper is the behavior analysis of Wuhan Yangtze River Bridge. A three‐dimensional thermal model of the bridge was established by the Fire Dynamics software (FDS) to obtain the 3D temperature field distribution, and the thermal analysis result was then applied to the three‐dimensional finite element model of the suspension bridge. The shortest failure time of the main cable and sling was determined to obtain the rescue time of a bridge fire. According to the calculation results of the suspension bridge under a tanker fire initiated at the upper deck of the bridge, the middle lane in the upper deck of the suspension bridge was determined to be a safe lane. Thus, the tanker should be guided to go in this lane of the bridge. The numerical analysis of the experimental results shows that when the fuel tanker is located on the upper and lower floors of the bridge, the bridge structure is affected by the fire. When the oil tanker burns in the outermost lane of the upper bridge, it will have a great impact on the main cables and slings of the bridge. When the fuel tanker burns in the lower nonmotorized lane of the bridge, it will have a great impact on the upper stiffening beam steel plates and truss rods.
[Retracted] Exercise or Dietotherapy Is Not Better than Returning to a Regular Diet to Rebuild Lipid Homeostasis of Rats
Authors: Yang Yuan , Xu Nan-Jun , Li Jia-Hui , Zeng Ling-Feng , Liang Gui-Hong , Zhang Feng , Luo Ming-Hui , Pan Jian-Ke , Huang He-Tao , Han Yan-Hong , Zhao Jin-Long , Xiao Xiao , Ma Chunlian , Liu Hua , Yang Yi , Yang Wei-Yi , Liu Jun
Published: October 2021

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high‐fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high‐fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high‐fat control group, and 9 were sorted into high‐fat diet with rice vinegar group. Meanwhile, 10 were put into high‐fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T‐CHO (P < 0.001) and LDL‐C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high‐fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high‐fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.
Automatic Calibration Algorithm for English Text Translation Based on Semantic Features
Authors: Liu Fengzhen
Published: October 2021

At present, the existing methods of English article flip calibration neglect to extract English semantic features, which leads to errors in English flip results and has a great impact on the accuracy and time consumption of translation sentence calibration. Therefore, a semantic feature-based automatic text flipping calibration algorithm is proposed. According to the features of semantic information in machine translation, a semantic grammar tree is constructed to complete the machine turning of English articles. The CART decision tree attribute is obtained, and the random forest method is introduced to extract the input matrix and output matrix of the corpus feature as samples to determine the spatial attribute feature of the mistranslated sentences. Choose 10000 English sentences about human body parts as the experimental object and design the simulation experiment. The experimental results show that the minimum and maximum accuracy rates are 95.4% and 100.0%, respectively. The proposed algorithm is time-consuming, and the KSMR value is lower than that of the traditional method. It is proved that the error rate of English article flipping is significantly reduced.
Implementation of English “Online and Offline” Hybrid Teaching Recommendation Platform Based on Reinforcement Learning
Authors: Dong Danling , Wu Libo
Published: October 2021

At present, there is a serious disconnect between online teaching and offline teaching in English MOOC large-scale hybrid teaching recommendation platform, which is mainly due to the problems of cold start and matrix sparsity in the recommendation algorithm, and it is difficult to fully tap the user's interest characteristics because it only considers the user's rating but neglects the user's personalized evaluation. In order to solve the above problems, this paper proposes to use reinforcement learning thought and user evaluation factors to realize the online and offline hybrid English teaching recommendation platform. First, the idea of value function estimation in reinforcement learning is introduced, and the difference between user state value functions is used to replace the previous similarity calculation method, thus alleviating the matrix sparsity problem. The learning rate is used to control the convergence speed of the weight vector in the user state value function to alleviate the cold start problem. Second, by adding the learning of the user evaluation vector to the value function estimation of the state value function, the state value function of the user can be estimated approximately and the discrimination degree of the target user can be reflected. Experimental results show that the proposed recommendation algorithm can effectively alleviate the cold start and matrix sparsity problems existing in the current collaborative filtering recommendation algorithm and can dig deep into the characteristics of users' interests and further improve the accuracy of scoring prediction.
Identification of a Pyroptosis-Related Gene Signature for Prediction of Overall Survival in Lung Adenocarcinoma
Authors: Dong Zheng , Bian Lv , Wang Minglang , Wang Luoqing , Wang Yilian
Published: October 2021

Pyroptosis is a kind of programmed cell death that is characterized by inflammation. However, the expression of pyroptosis-related genes and their connection with prognosis in lung adenocarcinoma (LUAD) remain unknown. The aim of this study is to create and validate a LUAD prediction signature based on genes associated with pyroptosis. The TCGA and GEO were used to collect gene sequencing data and clinical information for LUAD samples. To identify patients with LUAD from the TCGA cohort, consensus clustering by pyroptosis-related genes was employed. Our prognostic model was constructed using LASSO-Cox analysis after Cox regression using differentially expressed genes. To predict patient survival, we created a seven-mRNA signature. Additionally, reliability and validity were established in the GEO cohort. To assess its diagnostic and prognostic usefulness, an integrated bioinformatics method was used. Using a risk score with varying overall survival (OS) in two cohorts (all

p
<
0.001

), a seven-gene signature was developed to categorize patients into two risk categories. The signature was shown to be an independent predictor of LUAD using multivariate regression analysis. The signature was linked to a variety of immune cell subtypes according to a study of immune cell infiltration. We constructed a signature consisting of seven genes as a robust biomarker with potential for clinical use in risk stratification and OS prediction in LUAD patients, as well as a potential indicator of immunotherapy in LUAD.
H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets
Authors: Boccellino Mariarosaria , Galasso Giovanni , Ambrosio Pasqualina , Stiuso Paola , Lama Stefania , Di Zazzo Erika , Schiavon Sonia , Vecchio Daniele , D’ambrosio Luca , Quagliuolo Lucio , Feola Antonia , Frati Giacomo , Di Domenico Marina
Published: October 2021

The association between diabetes and cardiovascular diseases is well known. Related diabetes macro‐ and microangiopathies frequently induce hypoxia and consequently energy failure to satisfy the jeopardized myocardium basal needs. Additionally, it is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity, resulting in diminished nitric oxide (NO) bioavailability and consequent endothelial cell dysfunction. In this study, we analyzed the embryonic heart‐derived H9c2 cell response to hypoxic stress after administration of a high glucose concentration to reproduce a condition often observed in diabetes. We observed that 24 h hypoxia exposure of H9c2 cells reduced cell viability compared to cells grown in normoxic conditions. Cytotoxicity and early apoptosis were increased after exposure to high glucose administration. In addition, hypoxia induced a RhoA upregulation and a Bcl‐2 downregulation and lowered the ERK activation observed in normoxia at both glucose concentrations. Furthermore, a significant cell proliferation rate increases after the 1400 W iNOS inhibitor administration was observed. Again, hypoxia increased the expression level of myogenin, a marker of skeletal muscle cell differentiation. The cardiomyocyte gene expression profiles and morphology changes observed in response to pathological stimuli, as hypoxia, could lead to improper ventricular remodeling responsible for heart failure. Therefore, understanding cell signaling events that regulate cardiac response to hypoxia could be useful for the discovery of novel therapeutic approaches able to prevent heart diseases.
Nicotine Exacerbates TAAD Formation Induced by Smooth Muscle-Specific Deletion of the TGF-β Receptor 2
Authors: Chun Changzoon , Qi Xiaoyan , Wang Fen , Madrid Kyle B. , Saldarriaga Lennon A. , Fisch Max R. , Brantly Mark L. , Upchurch Gilbert R. , Jiang Zhihua
Published: October 2021

Tobacco smoke is an established risk factor for thoracic aortic aneurysms and dissections (TAAD). However, little is known about its underlying mechanisms due to the lack of validated animal models. The present study developed a mouse model that may be utilized to investigate exacerbation of TAAD formation by mimetics of tobacco smoke. TAADs were created via inducible deletion of smooth muscle cell-specific Tgfbr2 receptors. Using this model, the first set of experiments evaluated the efficacy of nicotine salt (34.0 mg/kg/day), nicotine free base (NFB, 5.0 mg 90-day pellets), and cigarette smoke extract (0.1 ml/mouse/day). Compared with their respective control groups, only NFB pellets promoted TAAD dilation (

23
±
3
%

vs.

12
±
2
%

,

P
=
0.014

), and this efficacy was achieved at a cost of >50% acute mortality. Infusion of NFB with osmotic minipumps at extremely high, but nonlethal, doses (15.0 or 45.0 mg/kg/day) failed to accelerate TAAD dilation. Interestingly, costimulation with β-aminopropionitrile (BAPN) promoted TAAD dilation and aortic rupture at dosages of 3.0 and 45.0 mg/kg/day, respectively, indicating that BAPN sensitizes the response of TAADs to NFB. In subsequent analyses, the detrimental effects of NFB were associated with clustering of macrophages, neutrophils, and T-cells in areas with structural destruction, enhanced matrix metalloproteinase- (MMP-) 2 production, and pathological angiogenesis with attenuated fibrosis in the adventitia. In conclusion, modeling nicotine exacerbation of TAAD formation requires optimization of chemical form, route of delivery, and dosage of the drug as well as the pathologic complexity of TAADs. Under the optimized conditions of the present study, chronic inflammation and adventitial mal-remodeling serve as critical pathways through which NFB exacerbates TAAD formation.
On the Positive Operator Solutions to an Operator Equation
X
−

A

∗

X

−
t

A
=
Q
Authors: Yang Kaifan
Published: October 2021

In this paper, the positive operator solutions to operator equation

X
−

A

∗

X

−
t

A
=
Q

(t > 1) are studied in infinite dimensional Hilbert space. Firstly, the range of norm and the spectral radius of the solution to the equation are given. Secondly, by constructing effective iterative sequence, it gives some conditions for the existence of positive operator solutions to operator equation

X
−

A

∗

X

−
t

A
=
Q

(t > 1). The relations of these operators in the operator equation are given.
Blow-Up of Solutions for Wave Equation Involving the Fractional Laplacian with Nonlinear Source
Authors: Bidi Y. , Beniani A. , Alnegga M. Y. , Moumen A.
Published: October 2021

In this paper, we study the blow-up of solutions for wave equation involving the fractional Laplacian with nonlinear source.
A Clustering-based Method for Business Hall Efficiency Analysis
Authors: Huang Tianlin , Wang Ning
Published: October 2021

Excessive or insufficient business hall resources may result in unreasonable resource allocation, adversely affecting the value of an entity business hall. Therefore, proper characteristic parameters are the key factors for analyzing the business hall, which strongly affect the final analysis results. In this study, a characteristic analysis method for the economic operation of a business hall is developed and the feature engineering is established. Because of its simplicity and versatility, the

k

-means algorithm has been widely used since it was first proposed around 50 years ago. However, the classical

k

-means algorithm has poor stability and accuracy. In particular, it is difficult to achieve a suitable balance between of the centroid initialization and the clustering number

k

. We propose a new initialization (LSH-

k

-means) algorithm for

k

-means clustering. This algorithms is mainly based on locality-sensitive hashing (LSH) as an index for computing the initial cluster centroids, and it reduces the range of the clustering number. Furthermore, an empirical study is conducted. According to the load intensity and time change of the business hall, an index system reflecting the optimization analysis of the business hall is established, and the LSH-

k

-means algorithm is used to analyze the economic operation of the business hall. The results of the empirical study show that the LSH-

k

-means that the clustering method outperforms the direct prediction method, provides expected analysis results as well as decision optimization recommendations for the business hall, and serves as a basis for the optimal layout of the business hall.
Experimental Study of the Dynamic Shear Modulus Ratio and Damping Ratio of the Quaternary Sedimentary Soils in the Offshore Areas of the Yellow Sea
Authors: Fang Yi , Lv Yuejun , Xu Dandan , Peng Yanju , Zhou Xingyuan
Published: October 2021

The effects of marine and continental sedimentary environments and geological ages on the dynamic shear modulus ratio and damping ratio of the Quaternary sedimentary soils in the offshore areas of the Yellow Sea were analyzed by using a resonant column device (GCTS, USA). The results show the following: (1) The

G

max

of various marine soils increases with the depth and shows a typical linear relationship. (2) The marine transgression has significantly different effects on the dynamic shear modulus ratio versus the shear strain amplitude curves (i.e.,

G
/

G

max

~

γ

a

curves) and the damping ratio versus the shear strain amplitude curves (i.e.,

λ
~

γ

a

curves) of the different soil types in the offshore areas of the Yellow Sea. The effects of marine transgression were strong on clays, moderate on silty clays, and minor on silts. (3) The geological ages have noticeable effects on the

G
/

G

max

~

γ

a

curves of the tested marine silty clays, marine silts, and continental silty clays, but the effects of geological ages on the

λ
~

γ

a

curves are minimal. The fitting parameters and recommended empirical equations of the

G
/

G

max

~

γ

a

and

λ
~

γ

a

curves for each type of the tested soils (silty clay, clay, and silt) were obtained mirroring the effects of sedimentary environments and geological ages.
Electrochemical Determination of Triclosan Using ZIF-11/Activated Carbon Derived from the Rice Husk Modified Electrode
Authors: Luyen Nguyen Dinh , Toan Tran Thanh Tam , Trang Ha Thuy , Nguyen Vo Thang , Son Le Van Thanh , Thanh Tran Si , Thanh Nguyen Mau , Quy Phan Tu , Khieu Dinh Quang
Published: October 2021

In the present paper, the composite of zeolite imidazolate framework-11 (ZIF-11) and activated carbon derived from rice husks (RHAC) was synthesized. The obtained materials were characterized by XRD, SEM, EDX-mapping, and nitrogen adsorption/desorption isotherms. The final composite ZIF-11/RHAC exhibits an even dispersion of ZIF-11 particles on activated carbon matrix. Herein, an electrochemical sensor based on a ZIF-11/RHAC was developed for a rapid determination of triclosan (TCS). It was found that the oxidation of TCS is irreversible and involves the transfer of one electron. The linear range for TCS detection in the optimized experimental conditions was found to be 0.1-8 μM with the limit of detection of 0.076 μM. Finally, the proposed method was successfully employed to detect TCS in different personal care product samples with high accuracy, which was confirmed by a good agreement between these results and those obtained using high-performance liquid chromatography (HPLC).
GNS: Forge High Anonymity Graph by Nonlinear Scaling Spectrum
Authors: Zeng Yong , Li Yixin , Jiang Zhongyuan , Ma Jianfeng
Published: October 2021

It is crucial to generate random graphs with specific structural properties from real graphs, which could anonymize graphs or generate targeted graph data sets. The state-of-the-art method called spectral graph forge (SGF) was proposed at INFOCOM 2018. This method uses a low-rank approximation of the matrix by throwing away some spectrums, which provides privacy protection after distributing graphs while ensuring data availability to a certain extent. As shown in SGF, it needs to discard at least 20% spectrum to defend against deanonymous attacks. However, the data availability will be significantly decreased after more spectrum discarding. Thus, is there a way to generate a graph that guarantees maximum spectrum and anonymity at the same time? To solve this problem, this paper proposes graph nonlinear scaling (GNS). We firmly prove that GNS can preserve all eigenvectors meanwhile providing high anonymity for the forged graph. Precisely, the GNS scales the eigenvalues of the original spectrum and constructs the forged graph with scaled eigenvalues and original eigenvectors. This approach maximizes the preservation of spectrum information to guarantee data availability. Meanwhile, it provides high robustness towards deanonymous attacks. The experimental results show that when SGF discards only 10% of the spectrum, the forged graph has high data availability. At this time, if the distance vector deanonymity algorithm is used to attack the forged graph, almost 100% of the nodes can be identified, while when achieving the same availability, only about 20% of the nodes in the forged graph obtained from GNS can be identified. Moreover, our method is better than SGF in capturing the real graph’s structure in terms of modularity, the number of partitions, and average clustering.