bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in Turkish patients with type 2 diabetes mellıtus.
Authors: Agachan B , Yilmaz H , Ergen HA , Karaali ZE , Isbir T
Published: June 2022

Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the low density lipoproteins (LDL) from oxidative modifications. Because diabetic patients are at greater risk of oxidative stress, we investigated the effect of PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B) polymorphisms on oxidant-antioxidant system in 213 individuals with type 2 diabetes mellitus and 116 non-diabetic control subjects from Turkish population were included in the study. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS), conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM genotypes had higher TBARS, conjugated dienes levels and lower GSH levels, whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene levels and higher GSH level than other genotypes. We thus conclude that PON1 192 BB and PON1 55 LL alleles have protective effect against oxidative stress.
Follicular fluid levels of vascular endothelial growth factor and leptin are associated with pregnancy outcome of normal women participating in intracytoplasmic sperm injection cycles.
Authors: Asimakopoulos B , Nikolettos N , Papachristou DN , Simopoulou M , Al-Hasani S , Diedrich K
Published: June 2022

Cytokines play a critical and multifarious role in follicular maturation. Consequently, they may influence the pregnancy outcome in cycles of assisted reproduction. The aim of this study was to measure the levels of tumor necrosis factor-alpha (TNFalpha), vascular endothelial growth factor (VEGF) and leptin in serum and follicular fluids (FFs) from women undergoing controlled ovarian hyperstimulation (COH) for intracytoplasmic sperm injection cycles (ICSI). We tried to investigate their interrelationships and to evaluate them as predictive markers for the cycle's outcome. Seventeen women participated in this study. Male factor infertility was the only indication for ICSI cycles. For COH, the long agonist protocol with triptorelin and recombinant FSH was employed. Cytokines levels were evaluated by ELISA. Serum cytokine levels did not differ between pregnant and non-pregnant women. FF-VEGF levels were significantly elevated in non-pregnant women (722.2+/-1093.2 pg/ml) as compared to pregnant women (290.3+/-259.8 pg/ml). Leptin concentrations were also significantly higher in FFs of non-pregnant women (682.6+/-625.1 ng/ml) than those of pregnant women (231.6+/-286.5 ng/ml). There were significant positive correlations between FF-leptin and age, as well as between FF-leptin and FF-VEGF concentrations. It was concluded that elevated FF-leptin and VEGF levels are associated with failure of conception in IVF cycles and may serve as markers in clinical practice.
ANALYSIS OF STUDENTS ERROR IN CLASS VIII A MTs DARUL HIKMAH IN SOLVING PROBLEMS ON THE RELATION AND FUNCTIONS MATERIALS
Authors: Nurwahyuni Sisi , Marnis Eli
Published: June 2022

This research aims to know the students' mistakes on MTs Darul Hikmah Pekanbaru in solving questions relations and functions materials. This research was conduted in MTs Darul Hikmah Pekanbaru in the odd semester of Academic Year 2020/2021. This research uses a descriptive method with research form is a case study. Subjects in the study were four students. The analysis was made with the interview and discussion. Based on the results of research, it can be concluded that’s is types of student errors are  in facts, concepts, and procedures.
DEVELOPMENT OF MATHEMATICS LEARNING MEDIA USING KAHOOT APPLICATION
Authors: Rahmi Afra Yunisa , Ariawan Rezi
Published: June 2022

Learning in the Industrial Age 4.0 is currently expected to produce quality human resources to face these global developments and competition. The implication of this is that it is expected that teachers will be creative and active in designing and conducting creative and innovative learning. Based on this, the researcher aims to produce mathematics learning media using the Kahoot application, tested for validity. This research was conducted in the even semester of the 2020/2021 academic year. The type of research used in this research is research and development with ADDIE development design. The validation sheet is a data collection instrument used in this study. The non-test technique was used to obtain data from this study by asking for responses from 4 expert validators. The data obtained were analyzed using quantitative descriptive techniques. Based on the analysis of the data obtained information that the resulting mathematics learning media using the Kahoot application that has been tested for validity with very valid criteria or with a percentage of 82.78%.
GENERATING STUDENTS’ CONFIDENCE IN LEARNING MATHEMATICS THROUGH THE EVERYONE IS A TEACHER HERE STRATEGY ON LINEAR PROGRAMMING MATERIAL AT SMAN 5 PINRANG
Authors: Anggreni Dewi , Buhaerah  , Usman
Published: June 2022

The purposed of this study were: (1) determine the self-confidence of students in class XI at SMAN 5 Pinrang; (2) determine learning mathematics through the everyone is a teacher here strategy in class XI at SMAN 5 Pinrang; and (3) determine the everyone is a teacher here strategy can generate confidence students of class XI in learning mathematics in the Linear Program material at SMAN 5 Pinrang. The type of this research was pre-experimental research with data collection instruments using learning implementation observation sheets, student activity observation sheets, and questionnaire sheets. The data analysis technique wa using descriptive analysis and non-parametric statistical analysis with the Wilcoxon formula. Wilcoxon test results obtained Zcount = 4.847 and Ztable = 1.96 so that Zcount > Ztable. Thus, H1 is accepted and H0 is rejected. So the research shows that students' self-confidence can be raised through the everyone is a teacher here strategy. This was indicated by (1) the activities of students in accordance with learning through the everyone is a teacher here strategy increased because the percentage that met the aspects > 70%; (2) the percentage value of the implementation of learning was 72.2% and included in the "High" category; and (3) the percentage of students' self-confidence questionnaire responses increased by 14.3% and was included in the self-confidence category.
DEVELOPMENT OF MATHEMATICS LEARNING DEVICES BASED ON PROBLEM BASED LEARNING MODELS ON THE MATERIAL OF POLYHEDRON TO FACILITATE MATHEMATICS PROBLEM-SOLVING ABILITY FOR SMP/MTS STUDENTS
Authors: Putri Shania Uthami , Atma Murni
Published: June 2022

This research is to produce a product in the form of mathematical learning devices using the Problem-Based Learning model on Three-Dimensional Shapes material to facilitate students Mathematics Problem-Solving Ability. The development model used is the ADDIE model, namely Analysis, Design, Development, and Evaluation. The research instrument used is validity instrument and practicality. The validity instrument is in the form of a validation sheet to assess the validity of the learning tools, namely the Syllabus, Lesson Plans, and LKPD. The practical instrument in the form of student response questionnaires to assess the usability and ease of use of LKPD. Learning Tools developed will be validated by three validators and revised according to the validator's suggestions. Next, a small group trial was conducted with six students. The results of the average validation score for the Syllabus are 3.84, RPP 3.75, and LKPD 3.64, so the learning tools are categorized as very valid. The result of the average percentage of the practicality of LKPD is 91.15%, with a very practical category. Based on the results of data analysis, it was concluded that this study produced a product in the form of a mathematical learning device based on the Problem Based Learning model on the material of Three-Dimensional Shapes that was valid for Syllabus, RPP, and LKPD and practical for LKPD.
APPLICATION OF THE DISCOVERY LEARNING MODEL TO IMPROVE MATHEMATICS LEARNING OUTCOMES OF CLASS XI MIA 1 BABUSSALAM SENIOR HIGH SCHOOL PEKANBARU
Authors: Nanda Silvi , Armis
Published: June 2022

The purpose of this study is to improve the mathematics learning process and student performance by applying the Discovery learning model. is composed. This exploration is an excellent case study with two rounds. The tools for this study are instructional tools (syllabus, Lesson Plans, and worksheets), data collection tools (teacher and student observation sheets), and student math tests. The data collection methods of this study are the observation method and test method. The observation papers were analyzed in the descriptive type, and the students' math test was analyzed in the statistical narrative type. The data analysis of this study is the analysis of observation data of teachers and students and the analysis of student learning performance data in mathematics. The teacher and student observation data analysis revealed that the curriculum improved after completing the behaviour (first and second cycle). Research of data about student performance shows that student performance has improved in math. The number of students in the "very high" and "high" ranges increases. On the other hand, the number of students in the “very low”, “low” and “medium” segments is declining. Based on the results of this study, it can be concluded that the implementation of the Discovery learning model can improve the mathematics curriculum and student performance in the XI MIA 1 SMA Babussalam Pekanbaru classroom.
THE EFFECT OF IMPLEMENTING A DIRECT LEARNING MODEL WITH GEOGEBRA SOFTWARE TOWARD STUDENTS’ MATHEMATIC CONCEPT COMPREHENSION ABILITY DERIVED FROM THEIR SELF-EFFICACY
Authors: Suhartini  , Nufus Hayatun
Published: June 2022

This research aimed to know the effect of implementing a direct learning model with Geogebra on students' mathematic concept comprehension ability derived from their self-efficacy. It was an experimental research with a factorial experimental design. All the eleventh-grade students of pharmacy major at vocational High school of Ikasari Pekanbaru in the academic Year of 2019-2020 were the population of this research. The samples of this research were the eleventh-grade students of Pharmacy 6 as the Experimental group and the students of Pharmacy 2 as the Control group. The Cluster Random Sampling technique was used in this research. The data collection techniques were a test, questionnaire, observation, and documentation. The data collection instruments were the teacher and student observation sheets, mathematic concept comprehension ability pretest and posttest: self-efficacy questionnaire, and documentation. The technique of analyzing the data was two-way ANOVA. Based on the data analysis, it could be concluded that 1) there was a difference in mathematic concept comprehension ability between students taught by using Direct learning model with Geogebra software and those who were taught by using Conventional learning, 2) there was a difference in mathematic concept comprehension ability among students having high, medium, and low self-efficacy, 3) there was no interaction between learning model and self-efficacy toward student mathematic concept comprehension ability. So it could be concluded that implementing the Direct learning model with Geogebra software was affected by students' mathematic concept comprehension ability derived from their self-efficacy.
STUDENTS’ MATHEMATICAL CONNECTION ABILITY IN TERMS OF SELF-CONFIDENCE
Authors: Risdayati Anisa Hilmia , Nurdin Erdawati , Kurniati Annisah
Published: June 2022

The connection was needed to solve mathematics problems. In connecting some concepts existing in mathematics to other fields of science, student self-confidence was required to solve the encountered problems.  It was qualitative research, and this research aimed at knowing and describing students’ mathematical connection ability derived from their self-confidence in quadrilateral and triangle materials.  The subjects of this research were the seventh-grade students at Junior High School of Juara Pekanbaru.  The purposive sampling technique was used in this research.  The instruments used in this research were the self-confidence questionnaire, mathematical connection ability test question, and interview guideline.  All data were analyzed in three steps—data reduction, data display, and concluding.  The research findings and data analyses showed that students’ self-confidence at Junior High School of Juara Pekanbaru differed.  Overall, student mathematical connection ability was in enough category with 71.7%.  Students with high self-confidence owned very good mathematical connection ability category, students with moderate self-confidence owned enough mathematical connection ability category, and students with low self-confidence owned very poor mathematical connection ability category.
DEVELOPMENT OF LEARNING DEVICES BASED ON PROBLEM BASED LEARNING MODELS ON THE MATERIAL OF SOCIAL ARITHMETIC TO FACILITATE MATHEMATICS COMMUNICATION SKILL FOR CLASS VII SMP/MTs STUDENTS
Authors: Putri Novalina Okta Dwi , Sakur
Published: June 2022

This research is motivated by teachers who still have difficulty designing learning tools based on the 2013 curriculum. This study aims to produce mathematical learning tools based on a problem-based learning model to facilitate students' valid and practical mathematical communication skills. Learning tools are developed in the form of a syllabus, lesson plan (RPP), and student worksheets (LAS). The development model used is the 4-D model, in which stages are defined, designed, developed, and disseminate. The test subjects in this study were 6 class VII students. The test instrument used was a validity instrument in the form of a validation sheet to assess the appropriateness of the learning device and a practicality instrument in the form of a student response questionnaire to assess the practicality of using LAS. Based on the validation data analysis results, it is concluded that this mathematics learning tool is very valid, with the average rating for the syllabus being 3,84, for RPP is 3,76, and for LAS being 3,72. Based on the practicality data analysis results, the student response questionnaire showed a very practical category with an average assessment of 3,61.
DEVELOPMENT OF MATHEMATICS LEARNING DEVICES WITH PROBLEM BASED LEARNING ON SOCIAL ARITHMETIC MATERIALS FOR STUDENTS OF CLASS VII SMP/MTs
Authors: Saputra Ronny , Saragih Sehatta
Published: June 2022

This research produces mathematics learning tools in the form of syllabus, lesson plans (RPP), and student worksheets (LKPD) based on the Problem Based Learning model of social arithmetic material for seventh-grade junior high school students. This study uses a 4-D development model which includes four stages, namely: (1) define (define); (2) design (planning); (3) develop (development); and (4) spread (spread). The research instrument used is the instrument of validity and practicality. The validity instrument is in the form of a validation sheet to assess the feasibility of the syllabus, lesson plans, and LKPD. The practicum instrument is in the form of a student response questionnaire to use LKPD. The learning tools that have been compiled are then validated by three validators and revised according to suggestions from the validators. The valid learning tools were then tested in the readability test with four seventh grade junior high school students and a small group trial with nine junior high school class VII students as the subject. Based on the data analysis and discussion results, mathematics learning tools in the form of syllabus, lesson plans, and LKPD based on Problem-Based Learning models on social arithmetic material are considered very valid and practical to be used by class VII junior high school students.
DEVELOPMENT OF MATHEMATICAL LEARNING DEVICES USING PROBLEM SOLVING STRATEGY IN STAD-TYPE COOPERATIVE LEARNING MODEL ON PYTHAGORAS THEOREM MATERIAL
Authors: Romi Pirdaus
Published: June 2022

This research produces a product in the form of a mathematics learning device using the STAD type cooperative learning model on the Pythagorean Theorem material using problem solving strategies. The development model used is a 4-D model, namely Define, Design, Develop, and disseminate. The research instrument used is instrument validity and practicality. The validity instrument is in the form of a validation sheet to assess the validity of the learning tools, namely the syllabus, lesson plans, and LAS. The practicum instrument is a student response questionnaire to assess the usefulness and ease of use of LAS. The Learning Toolkit developed will be validated by three validators and revised according to the validator's suggestions. Subsequently, a small group trial was conducted with six students. The average value of syllabus validation is 3.76, lesson plans are 3.82, and LAS is 3.63, so the learning tools are categorized as very valid. The average result of the practicality of LAS is 85.95% in the very practical category. Based on the results of data analysis, it was concluded that this study produced a product in the form of mathematics learning tools using problem solving strategies with the STAD Type Cooperative learning model on the valid Pythagorean Theorem for Syllabus, RPP, and LAS. and practical for LAS.
WRITTEN MATHEMATIC COMMUNICATION ABILITY DESCRIPTION ON MATHEMATICS LEARNING FOR CLASS VIII STUDENT SMPN 8 PAREPARE
Authors: Cahyani Ainun Dwi , Ahsan Muhammad , Buhaerah
Published: June 2022

This study aims to produce a description of the written mathematical communication skills of SMP class VIII students on the subject matter of patterns and number sequences. The research method used by the researcher is descriptive qualitative research. Sources of data are taken from primary data and secondary data. Data collection techniques consist of observation, interviews, and documentation. The data obtained by the researcher was analyzed using analytical methods with the steps of data reduction, data presentation, and conclusions and verification. Based on the study results, the written mathematical communication skills of class VIII students at SMPN 8 Parepare, the subject matter of patterns and number sequences, seen from the four indicators, were classified as average. This is evidenced by the results of the data presentation of indicators where indicators 3 and 4 are combined as follows: 1). Presenting and rewriting the description of a given picture or pattern using their written language is considered not good; 2). Declaring the picture into a mathematical model and completing it is considered good; 3). Declaring mathematical situations or everyday events into mathematical models in writing and connecting mathematical ideas with relevant images and solving them is considered good.
PANDEMİ DÖNEMİNDE EBEVEYNLERİN UYKU KALİTESİ VE YORGUNLUK DÜZEYLERİNİN İNCELENMESİ
Authors: ATAMAN Neşe , DEMİR Aylin
Published: June 2022

Dünya Sağlık Örgütü (DSÖ) tarafından 30 Ocak 2020’de “uluslararası boyutta halk sağlığı acil durumu” olarak ilan edilen pandemi sürecinde ebeveynlerin uyku kalitesi ve yorgunluk düzeylerinin incelenmesinin amaçlandığı tanımlayıcı tipte ve etik izni alınmış bu çalışma, 205 gönüllü ebeveyn ile yürütülmüştür. Araştırmada veriler kişisel bilgi formu, Pittsburgh Uyku Kalite İndeksi (PUKİ) ve Yorgunluk Şiddeti Ölçeği (YŞÖ) kullanılarak toplandı. Katılımcıların %70.2'sinin kadınlardan oluştuğu çalışmada, yaş ortalaması 34.35±8.05'tir. Bu bireylerin %18'inin gelir durumu kötü, %11.2'sinin çocuğu uzaktan eğitim almakta olup %10.7'sinin evde bakmakla yükümlü olduğu birey bulunmaktadır. Kadın katılımcıların %16.6'sı 16.04.2021 tarihli “10 yaş altı çocuğu bulunan kadın personel idari izinli sayılacak” genelgesinden faydalanmıştır. Ebeveynlerin PUKİ toplam puan ortalaması 6.43±3.64; YŞÖ 4.43±4.55'tir. Mesleği işçi olan ve eğitim seviyesi okuryazar olan kadınların, evde bakmakla yükümlü birey olanların, geniş ailede yaşayanların ve uyumadan önce kafein kullananların PUKİ puan ortalaması (p<0,05); kadın katılımcılardan geliri az olanların PUKİ ve YŞÖ puan ortalamaları anlamlı düzeyde yüksek bulunmuştur. Yine uzaktan eğitim alan çocuğa sahip katılımcıların YŞÖ puan ortalaması anlamlı düzeyde yüksektir (p<0,05). Korelasyon analizi sonucuna göre her iki ölçek arasındaki ilişki pozitif yönlüdür (p<0.001).
MACAO’S NONGAMING ENTERTAINMENT, CULTURE AND CITY BRANDING
Authors: Siu Lam Carlos , Jamieson Lynn
Published: June 2022

Although entertainment can be a pull-factor to attract tourists in their trips, it can be easily duplicated in other jurisdictions. Focused on the non-gaming entertainment by the gaming concessionaires in Macao, this paper examines the entertainment development, and explores how these concessionaires identify the right entertainment for patrons and the challenges associated with such entertainment offerings. Despite Macao’s wealth of East-West culture, this study analyzes the use of such culture in Macao’s entertainment, and the creation of its unique branding. The integration of culture into such entertainment, when coupled with Macao’s smallness, may represent the essential factors to satisfy tourists’ multiple needs for entertainment products, thereby leading to Macao’s renewed branding as a center of tourism and leisure from its strong gaming image. This study is one of a few that focuses on the merger of culture and entertainment, and is exploratory and qualitative in nature. Semi-structured in-depth interviews with executives in Macao’s entertainment segment were utilized. Such interview findings were analyzed using the Miles and Huberman (1994) framework, along with the data from the annual reports of the concessionaires and the Macao Census and Statistics Service. The findings may be useful for gaming destinations planning to alter their branding.
POSITIONING SPICES AS A TOURISM PRODUCT FOR FOREIGNERS: A STUDY FROM THE INDIAN PERSPECTIVE
Authors: Datta Bivek
Published: June 2022

Spice Tourism is an emerging sector in tourism majorly focusing on the impact of spices on tourism choices, growth, and distinctiveness. Because of the fascinating role of spices in tourism growth and diversification in new emerging economies, there is an increased demand for the promotion and growth of spice tourism in many developing economies like India and Sri Lanka. However, a comprehensive investigation is lacking pertaining to spice tourism. In this situation, the present research attempts to bring together and discuss the role of spices as an instrument to entice foreign tourists visiting India. A structured survey instrument in the form of a questionnaire was used for data collection from 400 inbound foreign tourists at the Indira Gandhi International (IGI) Airport, New Delhi. This study has provided directions to the practitioners and academicians in uncovering a diversity of perspectives on the emerging spice tourism market. It also suggests the role of spices as a tactical tool to recreate the destination image of India as a spice tourism destination. The research can also be utilized to examine the foreign tourist’s spice preferences in India, which can be used by stakeholders and practitioners to entice and enhance their revisit to India.
Heparanase 1 Upregulation Promotes Tumor Progression and Is a Predictor of Low Survival for Oral Cancer
Authors: Rodrigues André A. Nimtz , Lopes-Santos Lucilene , Lacerda Pammela A. , Juste Mariana F. , Mariz Bruno Augusto , Cajazeiro Débora C. , Giacobbe Victoria , Borges Rafael , Casarim André , Callegari Giovanna De Sanctis , Claret Arcadipane Fernando Antônio M. , Aprahamian Ivan , Salo Tuula Anneli , De Oliveira Carine Ervolino , Coletta Ricardo D. , Augusto Taize M. , Cervigne Nilva K.
Published: June 2022

Background: Oral cavity cancer is still an important public health problem throughout the world. Oral squamous cell carcinomas (OSCCs) can be quite aggressive and metastatic, with a low survival rate and poor prognosis. However, this is usually related to the clinical stage and histological grade, and molecular prognostic markers for clinical practice are yet to be defined. Heparanase (HPSE1) is an endoglycosidase associated with extracellular matrix remodeling, and although involved in several malignancies, the clinical implications of HPSE1 expression in OSCCs are still unknown.

Methods: We sought to investigate HPSE1 expression in a series of primary OSCCs and further explore whether its overexpression plays a relevant role in OSCC tumorigenesis. mRNA and protein expression analyses were performed in OSCC tissue samples and cell lines. A loss-of-function strategy using shRNA and a gain-of-function strategy using an ORF vector targeting HPSE1 were employed to investigate the endogenous modulation of HPSE1 and its effects on proliferation, apoptosis, adhesion, epithelial–mesenchymal transition (EMT), angiogenesis, migration, and invasion of oral cancer in vitro.

Results: We demonstrated that HPSE1 is frequently upregulated in OSCC samples and cell lines and is an unfavorable prognostic indicator of disease-specific survival when combined with advanced pT stages. Moreover, abrogation of HPSE1 in OSCC cells significantly promoted apoptosis and inhibited proliferation, migration, invasion, and epithelial–mesenchymal transition by significantly decreasing the expression of N-cadherin and vimentin. Furthermore, a conditioned medium of HPSE1-downregulated cells resulted in reduced vascular endothelial growth.

Conclusion: Our results confirm the overexpression of HPSE1 in OSCCs, suggest that HPSE1 expression correlates with disease progression as it is associated with several important biological processes for oral tumorigenesis, and can be managed as a prognostic marker for patients with OSCC.
Rad5 and Its Human Homologs, HLTF and SHPRH, Are Novel Interactors of Mismatch Repair
Authors: Miller Anna K. , Mao Guogen , Knicely Breanna G. , Daniels Hannah G. , Rahal Christine , Putnam Christopher D. , Kolodner Richard D. , Goellner Eva M.
Published: June 2022

DNA mismatch repair (MMR) repairs replication errors, and MMR defects play a role in both inherited cancer predisposition syndromes and in sporadic cancers. MMR also recognizes mispairs caused by environmental and chemotherapeutic agents; however, in these cases mispair recognition leads to apoptosis and not repair. Although mutation avoidance by MMR is fairly well understood, MMR-associated proteins are still being identified. We performed a bioinformatic analysis that implicated Saccharomyces cerevisiae Rad5 as a candidate for interacting with the MMR proteins Msh2 and Mlh1. Rad5 is a DNA helicase and E3 ubiquitin ligase involved in post-replicative repair and damage tolerance. We confirmed both interactions and found that the Mlh1 interaction is mediated by a conserved Mlh1-interacting motif (MIP box). Despite this, we did not find a clear role for Rad5 in the canonical MMR mutation avoidance pathway. The interaction of Rad5 with Msh2 and Mlh1 is conserved in humans, although each of the Rad5 human homologs, HLTF and SHPRH, shared only one of the interactions: HLTF interacts with MSH2, and SHPRH interacts with MLH1. Moreover, depletion of SHPRH, but not HLTF, results in a mild increase in resistance to alkylating agents although not as strong as loss of MMR, suggesting gene duplication led to specialization of the MMR-protein associated roles of the human Rad5 homologs. These results provide insights into how MMR accessory factors involved in the MMR-dependent apoptotic response interact with the core MMR machinery and have important health implications into how human cells respond to environmental toxins, tumor development, and treatment choices of tumors with defects in Rad5 homologs.
Conserved Amino Acids Residing Outside the Voltage Field Can Shift the Voltage Sensitivity and Increase the Signal Speed and Size of Ciona Based GEVIs
Authors: Sepehri Rad Masoud , Cohen Lawrence B. , Baker Bradley J.
Published: June 2022

To identify potential regions of the voltage-sensing domain that could shift the voltage sensitivity of Ciona intestinalis based Genetically Encoded Voltage Indicators (GEVIs), we aligned the amino acid sequences of voltage-gated sodium channels from different organisms. Conserved polar residues were identified at multiple transmembrane/loop junctions in the voltage sensing domain. Similar conservation of polar amino acids was found in the voltage-sensing domain of the voltage-sensing phosphatase gene family. These conserved residues were mutated to nonpolar or oppositely charged amino acids in a GEVI that utilizes the voltage sensing domain of the voltage sensing phosphatase from Ciona fused to the fluorescent protein, super ecliptic pHluorin (A227D). Different mutations shifted the voltage sensitivity to more positive or more negative membrane potentials. Double mutants were then created by selecting constructs that shifted the optical signal to a more physiologically relevant voltage range. Introduction of these mutations into previously developed GEVIs resulted in Plos6-v2 which improved the dynamic range to 40% ΔF/F/100 mV, a 25% increase over the parent, ArcLight. The onset time constant of Plos6-v2 is also 50% faster than ArcLight. Thus, Plos6-v2 appears to be the GEVI of choice.
Ultra-Tough Polylactide/Bromobutyl Rubber-Based Ionomer Blends via Reactive Blending Strategy
Authors: Zhang Xingfang , Lu Xu , Huang Dong , Ding Yingli , Li Jinshan , Dai Zhenyu , Sun Liming , Li Jin , Wei Xiaohui , Wei Jie , Li Yang , Zhang Kunyu
Published: June 2022

A series of ultra-toughened sustainable blends were prepared from poly(lactic acid) (PLA) and bromobutyl rubber-based ionomers (i-BIIRs) via reactive blending, in which dicumyl peroxide (DCP) and Joncryl®ADR-4440 (ADR) were used as reactive blending additives. The miscibility, phase morphology and mechanical property of the PLA/i-BIIRs blends were thoroughly investigated through DMA, SEM, tensile and impact tests. The influence of different ionic groups and the effects of DCP and ADR on the compatibility between the phases, phase structure and mechanical properties were analyzed. The introduction of the imidazolium-based ionic groups and the reactive agents enable the i-BIIRs play multiple roles as effective compatibilizers and toughening agents, leading to improved interfacial compatibility and high toughness of the blends. The mechanical properties test showed that the PLA/i-BIIRs blends exhibit excellent toughness: impact strength and the elongation at break of AR-OH(30)+AD reached 95 kJ/m2 and 286%, respectively. The impact fracture surface showed the large-scale plastic deformation of the PLA matrix in the blends, resulting in greatly absorbing the impact energy. The results proved that simultaneously applying reactive blend and multiple intermolecular interactions methods is an effective toughening strategy for toughening modification of the PLA blends.
Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism
Authors: Wen Long , Shi Lei , Kong Xiang-Long , Li Ke-Yu , Li Hui , Jiang Di-Xuan , Zhang Fan , Zhou Zhi-Guo
Published: June 2022

Backgrounds and Purpose

The theory of “entero-pulmonary axis” proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia.

Methods

Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism.

Results

Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism.

Conclusions

FMT restored the Treg/Th17 cells’ balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder.
Exploring the Mechanism of Hawthorn Leaves Against Coronary Heart Disease Using Network Pharmacology and Molecular Docking
Authors: Ding Jie , Wu Jun , Wei Haoran , Li Sui , Huang Man , Wang Yan , Fang Qin
Published: June 2022

Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.
Increased BMI and Blood Lipids Are Associated With a Hypercoagulable State in the Moli-sani Cohort
Authors: de Laat-Kremers Romy , Di Castelnuovo Augusto , van der Vorm Lisa , Costanzo Simona , Ninivaggi Marisa , Cerletti Chiara , Huskens Dana , De Curtis Amalia , Gialluisi Alessandro , Bai Cuicui , de Gaetano Giovanni , Yin Dongmei , Donati Maria Benedetta , de Laat Bas , Iacoviello Licia ,   The Moli-sani Investigators
Published: June 2022

The coagulation system can be assessed by the thrombin generation (TG) assay, and increased TG peak height, endogenous thrombin potential (ETP), and velocity index are associated with an increased risk of thrombosis. Obesity had been reported to increase TG and is associated with dyslipidemia, which also predisposes to atherosclerotic cardiovascular disease (CVD). However, the effect of the blood lipid profile on TG has not been studied extensively. To gain more insight into the associations of TG, body mass index (BMI) and lipid profile, we studied TG in relation to these parameters in a large Italian population cohort, the Moli-sani study (N = 22,546; age ≥ 35 years; 48% men). TG was measured in plasma samples collected at the enrollment of subjects in the Moli-sani study. TG was triggered with 1 or 5 pM tissue factor, and TG parameters lag time, peak, ETP, time-to-peak (TTP) and velocity index (VI). Additionally, thrombomodulin was added to assess the function of the activated protein C system during TG. In both women and men, overweight (BMI 25–30 kg/m2) and obesity (BMI > 30 kg/m2) were significantly associated with higher ETP, peak and VI (all p < 0.001). High total cholesterol, triglycerides and LDL-cholesterol levels were significantly associated with increased ETP and peak (all p < 0.001). Linear regression analysis revealed that the ETP is positively associated with both plasma LDL and HDL cholesterol levels, whereas the velocity index is positively associated with HDL cholesterol. Additionally, ETP, peak and VI were significantly associated with the plasma triglycerides content. In conclusion, our study shows significant associations of high BMI and blood lipid levels with increased TG parameters, and this hypercoagulability may partly explain the increased risk of CVD in individuals with obesity and/or dyslipidemia.
DFT Study on the Compatibility Between Bentonite Clay Mineral and Hydration Products With the Polycarboxylate Water Reducer in the Cement Hydration Process
Authors: Teng Huang , He Zhihao , Meiben Gao , Zhang Jiaxing
Published: June 2022

As one of the most used grouting materials, cement has the characteristics of low price and a wide resource of raw material. With the in-depth research and application of cement admixture, the compatibility between different water-reducing agents and clay has become one of the critical factors that affects the cement hydration process. Due to the adsorption of clay on cement additives, the dispersion efficiency of the water reducer will be reduced, also the strength and impermeability of hydration products will be adversely affected. This paper studies the adsorption characteristics of different PCE superplasticizers on bentonite clay minerals and hydration products using a molecular simulation technique. Results showed that there is competitive adsorption between the clay and hydration products when the admixture participates in the hydration reaction, the additives are likely to adsorb on the CH rather than the clay minerals, while the adsorption energy of the hydration product C-S-H is the highest, thus the preferential adsorption order and compatibility between clay minerals and hydration products on admixtures could also be obtained. PDOS (partial density of states) analysis concluded that some new characteristic peaks and rearrangement of the bonding orbitals may appear after the adsorption, with the peak value of the minerals higher than that of jennite, which is also consistent with the adsorption energy. This study aims to reveal the interaction mechanism and compatibility between the hydration product and clay minerals, hoping to fully utilize the advantages of both clay minerals and admixtures in the cement hydration process.
Limestone Sea Stacks (Rauks) Record Past Sea Levels and Rocky Coast Evolution in the Baltic Sea (Gotland and Fårö Islands, Sweden)
Authors: Strzelecki Mateusz C. , Duszyński Filip , Tyszkowski Sebastian , Zbucki Łukasz
Published: June 2022

In this article, we explore the potential for sea-level change and rocky coastal evolution reconstruction hidden in one of the most intriguing rocky coastal landforms in the Baltic Sea region—rauks. Those unique limestone sea stacks are preserved along the coasts of a number of Swedish islands, with Gotland and Fårö as primary locations. We contributed to the long-standing debate on their origin and attempted to investigate the modern geomorphological processes operating on rauks using novel approaches in rock coast studies, including Schmidt hammer rock tests (SHRT)—to characterize zonation in the degree of coastal landforms weathering; traversing micro-erosion meters (TMEM)—to calculate shore platform downwearing rates; and terrestrial laser scanning (TLS) to monitor coastal abrasion and detect sea-level markers (notches) and describe their size and shapes. Our study shows the dominance of mesoscale changes in the shore platform morphology (erosion scars, spalling, and block erosion) over the microscale downwearing carried out by abrasion. We argue that the preservation of rauks along the modern coast of Baltic islands is a result of a favorable sequence of events including the rapid land uplift and their lithological resistance, significantly higher than observed on surrounding platforms and cliffs formed in different types of limestone. Our findings prove that the microrelief of rauks in the form of well-preserved notches records the sea-level changes from at least the late Ancylus Lake period. Finally, we incorporate the results of our observations into the classic notions of rauk formation and highlight the effect of cutting off sea stacks from the operation of littoral processes as a consequence of land uplift and dominance of subaerial weathering over the wave action.
What Counts as Evidence in the Understanding of School Exclusion in England?
Authors: Daniels Harry , Porter Jill , Thompson Ian
Published: June 2022

Exclusion from school can be regarded as a seemingly simple but in fact a rather complex intervention in response to the “wicked problem” of behavior in schools. This manuscript will discuss what counts as evidence that may used to inform policy and judgments on practices of exclusion. The role of evidence, and how this is measured, has long been an issue of contention in educational research. This is particularly true for research that focuses on educational inequality and inclusion or exclusion. In this manuscript we will discuss issues concerning evidence with respect to two aspects of exclusion in England. Firstly, we will focus on questions concerning the scale of the problem, examining both the statistical evidence of official exclusions and data concerning the myriad of ways in which children may experience other forms of exclusion. Taken together, this indicates an under-estimate of the numbers of young people missing an education. We then move to a consideration of the evaluation of means of reducing exclusion, arguing for a shift from an individual to a systemic in context account that recognizes the role of cultural transmission and cultural historical theory.
Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
Authors: Zhu Feng , Zhou Min , Deng Xiuling , Li Yujuan , Xiong Jing
Published: June 2022

Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic–pituitary–gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of NR0B1 at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the NR0B1 gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene NR0B1. Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic–pituitary–gonadal axis.
An Ontology-Based Dynamic Attack Graph Generation Approach for the Internet of Vehicles
Authors: Hou Shuning , Chen Xiuzhen , Ma Jin , Zhou Zhihong , Yu Haiyang
Published: June 2022

With the development of automobile intelligence, the security of the Internet of Vehicles has become a key factor that affects the development of intelligent vehicles. However, existing security risk analysis methods for the IoV either focus only on certain levels, such as the component level, or perform only a static analysis. This paper proposes a dynamic attack graph generation method for the IoV to identify and visually display the security risks caused by the associated vulnerabilities in an IoV system. First, using the actual architecture of the IoV, this paper shows how to model the security elements and their relationships in the IoV system and proposes a network security ontology model for this system. Second, it shows how to construct a reasoning rule base according to the causal relationship between the vulnerabilities using the Semantic Web Rule Language Finally, in view of the rapid change in the network topology of the IoV, a dynamic attack graph generation algorithm based on an ontology reasoning engine is proposed, which can effectively reduce the overhead caused by the changes in the attack graph. The effectiveness of the algorithm is demonstrated through an actual security event scenario and a constructed scenario. The experimental results show that the algorithm can dynamically and accurately display the network attack graph of the IoV. The proposed method is helpful in globally analyzing the threat caused by the combined exploitation of the vulnerabilities in an IoV system and risk management.