bluuebunny/crossref_metadata_2025 huggingface dataset:
Current State and Perspectives of Legal Support for Digital Transformation of the State Audit Office of Ukraine
Authors: Borets L. V. , Ruda V. O.
Published: November 2021

Improving the efficiency of the State Audit Office of Ukraine in exercising public financial control is largely determined by the success of the digital transformation of such activities. The legal support of such a process is important. The authors of the article outline the current state and perspectives of legal regulation of digital transformation of the State Audit Service of Ukraine for public financial control, identifies problems of legal regulation of digitalization of this service and ways to solve these problems. In particular, it is noted that one of the important issues is the legal regulation of the automated integrated information database on the status and results of state control over the management and use of state and local resources of the State Audit Service and other state control agencies, as well as databases and registers, the operation of which is financed from the state budget. Given the interdepartmental nature and the fact that the maintenance of some state registers is determined at the level of laws, the need to adopt a relevant law is not excluded. At the same time, appropriate amendments should be made to the Law of Ukraine "On Basic Principles of Public Financial Control in Ukraine", Regulations on the State Audit Office, Procedures for Inspection and Public Financial Audits, Inspection and Monitoring of Public Procurement, which should be supplemented by state financial control entities, in the order of information interaction or by direct access to them. In addition, it is impossible to solve the issue of digital transformation of the State Audit Office without raising the level of knowledge and appropriate training of its employees.
Standartization of Forensic Activities and Certification of Expert Laboratories as a Factor for the Development of Forensic Examination
Authors: Kuchynska I. V.
Published: November 2021

The author has carried out the analysis of the perspectives for certification of domestic forensic laboratories for the compliance with international standards, which would contribute to the creation of an effective legal mechanism for the transition to a new level of development of forensic technologies. The main factors of administrative and legal regulation in the field of standardization have been studied. In accordance with the requirements of DSTU ISO / IEC 17025 the principles of organization and implementation of the quality management system (QMS) into forensic laboratories have been determined.

It has been established that the execution of the DSTU ISO / IEC 17025 requirements needs significant resources and financial costs from the laboratory. The author has provided clarification to the main stages of preparation for certification, which include measures on developing management documentation (Guidelines, Regulations on forensic laboratory, Accreditation Area), on inventory of existing equipment, metrological support of laboratory activities, preparation and submission of applications to the accreditation agency. It has been noted that certified forensic laboratories should use certified expert methods within their activities that can ensure reliable results during the research. Methodologies should be tested in other reputable organizations or validated directly in the laboratory. Considerable attention has been paid to the quality of standard samples, reagents and materials. The emphasis has been placed on the need to participate in proficiency testing programs based on the results of interlaboratory comparative tests as an effective way to monitor the activities of the forensic laboratory.

The author has substantiated the conclusion that the standardization processes of forensic activity and certification of forensic laboratories are aimed at increasing the level of metrological work to protect citizens and the national economy of Ukraine from the consequences of unreliable measurement results.
An Intersectional Analysis of the English-Competency Experiences of International Teaching Assistants
Authors: Agrawal Ashish , McNair Lisa
Published: November 2021

International graduate students serving as teaching assistants constitute a major component of the teaching of undergraduate students at US universities, particularly in engineering. Prior literature on these international teaching assistants (ITAs) generally characterizes their linguistic experiences as challenges. This characterization can be attributed to an institutional environment that is reluctant to accommodate diverse ways of speaking English. This study applies an intersectionality framework to explore the variations in ITAs’ English-language experiences and the influence of the academic context on these experiences using semi-structured interviews and weekly reflections collected from seven engineering ITAs over a semester. Results of data analysis suggest that ITAs’ English proficiency varies based on their prior exposure to English in their home countries, and their English competence improves through their teaching experiences in the US. Participants’ experiences also highlight a perceived expectation to not only use English while teaching but also adapt to American English.
РОЛЬ ГАЗЕТНОГО ДИСКУРСУ РЕЛІГІЙНОЇ ПРОБЛЕМАТИКИ В ДЕРЖАВОТВОРЧИХ ПРОЦЕСАХ СУЧАСНОЇ УКРАЇНИ (НА МАТЕРІАЛАХ ПУБЛІКАЦІЙ ЗАХІДНОУКРАЇНСЬКОЇ РЕГІОНАЛЬНОЇ ПРЕСИ)
Authors: ГРЕСЬКІВ Ольга
Published: November 2021

Стаття присвячена дослідженню ролі дискурсу релігійної проблематики західноукраїнської регіональ- ної преси в процесах національного відродження та державотворення в Україні в період здобуття й утвер- дження незалежності. Встановлено, що специфіка державотворчого контексту окресленого дискурсу була зумовлена регіональними особливостями релігійної ситуації і знайшла своє вираження в кількох площинах. По-перше, публіцистичні матеріали щодо минулого та сучасного національних церковних структур, які тра- диційно пов’язані з українським націєтворенням, формували простір незалежної ідейної державницької аль- тернативи. По-друге, світоглядна, етична та виховна спрямованість публікацій зміцнювали ідейне підґрунтя для становлення громадянського суспільства. По-третє, релігійна тематика стала об’єктом експлуатації різних політичних сил у боротьбі за електоральні симпатії. Загалом, такі публікації, виступаючи засобом по- літичної боротьби, безпосередньо впливали на становлення політичної системи української держави.
Determining the integral coefficient of psychological comfort of rural school education
Authors:   Vyatka State University, Korshunova Olga V. , Baiborodova Lyudmila V. ,   Yaroslavl State Pedagogical University named after K. D. Ushinsky, Bykova Svetlana S. ,   Vyatka State University
Published: November 2021

Significance of the study. The modern global digital world often represents a threat to human security which is directly associated with psychological comfort. In this context, the research aimed at assessing psychological comfort of the educational environment in rural schools seems to be particularly relevant. The objective of the study is to study the state of psychological comfort of education in a rural school. Methods. The methods of theoretical content analysis, comparative analysis, methods of mathematical processing were used (calculations by formulas for the indicator of attitude to the educational environment, the index of satisfaction with the characteristics of the environment, the index of security in accordance with the method of I.A. Baeva), Google-forms. The Google survey involved 3223 respondents from 10 regions of the Russian Federation; meta-analysis of 217366 empirical facts was performed. Research results. The main characteristic was the integral coefficient of the psychological comfort of education in rural school, which, according to the modernized methodology of I.A. Bayeva, is determined on the basis of three indicators. The integral coefficient of the psychological comfort of education in rural school was determined, which consisted of three indicators. The integral indicator of attitude to the educational environment is recorded as a percentage and is characterized by medium and high levels of satisfaction with the environment on the part of teachers, students and their parents (from 61% to 80%). The index of satisfaction with significant characteristics of the educational environment (an ordinal scale from 1 to 5 is used) shows that in 9 out of 10 regions a higher level of satisfaction was recorded for teachers and parents (high integral indicator – 3-3.9) compared with students (average integral indicator – 2-2.9). The index of psychological safety of the educational environment of school shows a higher degree of protection of parents (high integral indicator – 3-3.9) compared with children and teachers (integral indicator is below average – 1-1.9). Research significance. The results obtained can be useful for heads of educational institutions, teachers and parents interested in creating and maintaining a psychologically comfortable environment in rural school.
The mediating effect of basic vocational competency in the effect of self-esteem on job search skills of Korean middle-aged job seekers
Authors:   Hanseo University, Kim Yun-Jeong
Published: November 2021

Introduction. Middle-aged Koreans are constantly looking for jobs in order to re-employ, despite the insecurity of declining job quality and wage levels. In order to be re-employed, it is necessary to improve job-search skills. As a way to improve job search skills, the focus was on job-seekers' self-esteem and basic vocational competency. The purpose of this study is to investigate the mediating effect of vocational competency in the effect of self-esteem on job search skills. Study participants and methods. The participants in this study were 357 middle-aged job seekers aged 40 to 64 years old. 56.9% were women, 52.9% were in their 50s and 60s, and 46.2% were college graduates. 69.2% were married and 53.2% lived in small and medium-sized cities. By utilizing SPSS Win. 25.0 and PROCESS macro 3.5, descriptive statistics analysis, reliability analysis, correlation analysis, and mediating effect were analyzed. Results. First, the higher the self-esteem, the higher the basic vocational competency (r=.438, p<.001) and the job search skills (r=.497, p<.001). The higher the basic vocational competency, the job search skills (r=. 699, p<.001) was high. Second, the effect of self-esteem on job search skills was .516(p<.001), but in the model with additional basic vocational competency, it was reduced to .245(p<.001). Therefore, the mediating effect of basic vocational competency was verified. Practical significance. It was revealed that self-esteem and basic job skills are important to improve the job-search skills of middle-aged adults. Therefore, in order to support customized career design at the national level, it is suggested that vocational education programs should include not only certification courses, but also content for improving basic vocational competency and counseling for improving self-esteem.
ВЕРБАЛІЗАЦІЯ КОНЦЕПТУ “HOUSING” АНГЛІЙСЬКИМИ НЕОЛОГІЗМАМИ
Authors: Жулінська Майя
Published: November 2021

Стаття присвячена аналізу неологізмів концепту “HOUSING”, сформованих внаслідок змін у суспільному житті, і причин їх виникнення в наші дні. Об’єктом вивчення даного дослідження стали лексичні інновації, що з’явилися в англійській мові протягом останнього року. Подано короткий огляд теоретичних підходів до проблеми вивчення неологізмів. Описано роль неологічних процесів у сучасній англійській мові. Окреслено причини, які зумовлюють потребу в необхідності дослідження нової лексики з позицій когнітивної лінгвістики. Визначено поняття концепту як базового в когнітивній лінгвістиці. Звернуто увагу на розуміння концепту в сучасній науці. У статті наголошено на універсальності концепту “HOUSING”, наведено варіанти перекладу лексеми “housing” на українську мову згідно з аналізом відомих словників. В результаті розподілу лексичних інновацій відповідно до змістових ознак цього концепту виокремлено п’ять основних і додаткових концептуальних характеристик: будівля для проживання чи інших цілей; параметри і розмір; прибудинкова територія; будівельний матеріал та житлові відносини. Подано приклади найцікавіших нових слів та їх першоджерела; тлумачення досліджуваних неологізмів, оскільки вони ще не мають перекладу на українську мову; приклади їх уживання в сучасних англомовних виданнях. Проаналізовано зміни конструкторської і дизайнерської думки, які трансформуються в нові стилі в архітектурі, вплив прагнень сучасної людини на облаштування власної оселі і відповідно зміни в лексичному складі мови у зв’язку з необхідністю нової номінації. Проведено статистичний аналіз неологізмів за способом утворення, в ході якого словоскладання і телескопія виділені як найбільш продуктивні способи утворення неологізмів концепту “HOUSING”. Встановлено основні причини появи нових слів: нові об’єкти номінації, економія мовних засобів, гра слів. У роботі обґрунтовано необхідність опису когнітивних основ породження нових слів, фіксації уваги на цілі їх використання в мові і, найголовніше, необхідність дослідження закономірних взаємозв’язків між змінами, що відбуваються в житті суспільства і постійним оновленням лексичної системи.
ОБЛІК НЕМАТЕРІАЛЬНИХ АКТИВІВ ЗГІДНО НАЦІОНАЛЬНИХ ТА МІЖНАРОДНИХ СТАНДАРТІВ: ШЛЯХИ ВДОСКОНАЛЕННЯ
Authors: Овсюк Ніна , Лесько Марія
Published: November 2021

У науковій статті розглянуто важливі питання, які виникають під час здійснення українськими підприємствами операцій, пов'язаних з обліком нематеріальних активів. Проаналізовано останні дослідження та публікації науковців, присвячені організації обліку нематеріальних активів. Вивчено поняття «нематеріальні активи» відповідно до українських національних та міжнародних стандартів. Здійснено огляд відмінностей щодо визначення поняття «нематеріальні активи». Автори статті запропонували власне бачення сутності нематеріальних активів, яке ґрунтується на дослідженні нормативно-правових актів та працях науковців. У цій статті досліджено класифікаційні ознаки нематеріальних активів, а також особливості обліку операцій з нематеріальних активів, що здійснюються іноземними країнами.
МЕХАНІЗМ УПРАВЛІННЯ КОНКУРЕНТОСПРОМОЖНІСТЮ УНІВЕРСИТЕТУ НА РИНКУ ОСВІТНІХ ПОСЛУГ
Authors: Кобідзе Нонна
Published: November 2021

У статті досліджено проблему управління конкурентоспроможністю університету, визначено можливі напрями її підвищення та розроблено механізм управління конкурентоспроможністю університету на ринку освітніх послуг. Визначено, що механізм управління конкурентоспроможністю університету повинен включати в себе наступні структурні елементи: цілі управління, фактори управління, організаційну структуру управління, ресурси управління, методи впливу на фактори (напрями, інструменти) та результати управління. Використання механізму дозволяє визначити рівень конкуренції на ринку освітніх послуг, провести аналіз впливу внутрішніх та зовнішніх чинників на рівень конкурентоспроможності університету, виявити основні напрямки підвищення рівня його конкурентоспроможності, оцінити ефективність запропонованих заходів.
Development of Learning Materials for Multicultural-Based Civic Education to Improve Students’ Learning Achievements
Authors: Kurniawan Kurniawan , Wachidi Wachidi , Turdjai Turdjai , Wasidi Wasidi
Published: November 2021

The research objective is to produce learning materials for multicultural-based Civic Education to improve students’ learning achievements. The development of this learning material applies the ADDIE model. The subjects of this study were four experts as validators, and at the evaluation stage, a quasi-experiment was carried out with a sample of 90 students. The population of quasi-experiment is students of Teacher Education of Elementary School Study Program of State Islamic Institute of (IAIN) Curup. The sample was selected through a purposive technique. The research instruments are validation sheets, practicality sheets, and achievement tests. The achievement test data were analyzed using covariate analysis (ANCOVA). The data analysis results state that multicultural-based Civic Education learning materials have met a high level of validity based on expert reviews and empirical tests. It has also met a high level of practicality. The multicultural-based Civic Education learning materials have met a high level of effectiveness, and the learning achievements of students who are taught with these learning materials are better than the learning achievements of students who are taught conventionally.
KİTAP İNCELEMESİ HUKUK DEVLETİNİN SONU OLAĞANÜSTÜ HALDEN DİKTATÖRLÜĞE TERÖRLE MÜCADELE
Authors: AKMAN Kaan
Published: November 2021

Paye hukuk devleti ve olağanüstü hal dönemleri arasındaki ilişkiyi hukuksal, siyasal, ekonomik ve yönetsel düzlemde olay ve olgulara dayalı olarak irdeleyerek hukuk devletinin geleceği hakkında düşündürmeyi başarmıştır. Ayrıca hukuk devletinin temel ilkelerindeki dönüşümlerin bireysel yaşantımızda nelerin değişimine yol açacağının da ilk izlerini göstermiştir. Dijitalleşmenin sunduğu imkânların yanında neoliberalizm temel kavramlarından biri olan yönetişim aracılığıyla toplum yönetimdeki aktörlerin farklılaşması, hukuk devleti üzerine tartışmaların zaman içerisinde yoğunlaşmasına neden olacaktır. Paye’nin bu kitabı siyasal sistem analizinden, ekonomik düzene, hukuksal yapıdan, güvenlik politikalarına geniş bir çerçevede bu tartışmaların zemini oluşturulma niteliğini taşıdığı için alanında önemlidir.
Comprometidos con el subdesarrollo: una visión alternativa para el desarrollo económico de América Latina y el Caribe
Authors: Morillo Martínez Oscar Esteban
Published: November 2021

El desarrollo en América Latina y el Caribe debe pensarse como un problema de restricción externa, donde se han impuesto discursos que impiden cualquier proceso de convergencia con las economías desarrolladas. Por esto, se hace necesario cuestionar los fundamentos teóricos de tales discursos, demostrando que, en su mayoría, han sido controvertidos y declarados inconsistentes; transformando tales posturas en ideológicas y nunca coherentes. Así pues, en este artículo se busca afrontar los desafíos del desarrollo que enfrenta la región a partir de un análisis teórico alternativo que nos acerque a una concepción global de los conflictos socio-económicos del desarrollo y nos permita sostener postulados normativos para contribuir al debate por el desarrollo de nuestras naciones, abogando siempre por políticas de industrialización y de crecimiento vía demanda efectiva.
SISTEM INFORMASI MANAJEMEN PENELITIAN DAN PENGABDIAN MASYARAKAT DI BAGIAN P3M (STUDI KASUS: STMIK HANG TUAH PEKANBARU)
Authors: Melyanti Rika , Iqbal Muhammad , Muhardi Muhardi
Published: November 2021

Sistem informasi manajemen data penelitian dan pengabdian masyarakat (P3M) pada bagian P3M (studi kasus: STMIK Hang Tuah Pekanbaru) masih menggunakan sistem manual. Dimana dosen yang akan melakukan kegiatan P3M, harus mencetak proposal P3M, dimana penggunaan proposal dalam bentuk hardcopy ini kurang efisien untuk diterapkan ditengah kemajuan teknologi komputer saat ini. dan proses pendistribusian proposal calon pendaftar dosen ini dirasa kurang efisien dikarenakan harus berpindah tangan untuk per aktivitas sehingga memakan waktu lama. Kepala P3M STMIK Hang Tuah membutuhkan suatu sistem yang baru agar sistem yang lama dapat diperbaiki. Adapun pendekatan sistem yang dilakukan penulis adalah pendekatan object  oriented dengan metode pengembangan sistem menggunakan metode waterfall, serta alat bantu analisis dan perancangan dengan menggunakan Unified Modelling Language (UML). Sedangkan untuk implementasinya digunakan beberapa perangkat lunak (software) diantaranya menggunakan framework laravel, code editor menggunakan Atom, paket PHP menggunakan XAMPP version 3.2.4 (PHP 7.3.9, web server Apache 2.4.7 serta database MySQLi versi 5.0.12) dan yang terakhir web browser dengan menggunakan Google Chrome. Sehingga aplikasi dapat memfasilitasi dosen dengan unit P3M dan reviewer secara efektif dan membantu unit P3M dalam manajemen kegiatan penelitian dan pengabdian masyarakat.
Penerapan Metode Profile Matching Dalam Sistem Pendukung Keputusan Pemilihan Karyawan Terbaik Pada CV. Karya Alam
Authors: Nisa Khoirunnisa , TPY Tri Puji Yuliani , Natasha Putri Dian
Published: November 2021

Karyawan adalah aset terpenting dalam sebuah perusahaan, karena tanpa karyawan perusahaan tidak akan bertahan lama dan akan mengalami kemunduran. Untuk mendapatkan karyawan yang berkualitas dan kompeten bagian sumber daya manusia (SDM), harus benar-benar melakukan tugasnya dengan baik. Di CV. Karya Alam proses Penentuan karyawan terbaik masih dilakukan dengan cara manual atau musyawarah, karena hanya didasarkan pada penilaian manager operasional dan tidak didasarkan pada kriteria tertentu untuk proses pemilihan karyawan terbaik sehingga menyebabkan ketidakadilan antara satu karyawan dengan karyawan lainnya. Ada beberapa Kriteria Pemilihan karyawan terbaik di Cv. Karya Alam yaitu Aspek Displin, Aspek Integritas dan Aspek Kecerdasan. Metode yang akan digunakan untuk merumuskan sistem keputusan pemilihan karyawan terbaik adalah Metode Profile matching yang merupakan metode penelitian yang dapat digunakan dalam sistem pendukung keputusan, proses evaluasi kompetensi dilakukan dengan membandingkan satu profil nilai (nilai kebutuhan kompetensi) dengan beberapa profil nilai kompetensi lainnya, sehingga hasil perbedaan antara kebutuhan kompetensi dapat diketahui.  Dengan menggunakan metode profile matching. maka Cv. Karya Alam dapat mengetahui karyawan terbaik berdasarkan rangking.
DATA MINING DENGAN 2 (DUA) MODEL KLASIFIKASI UNTUK PREDIKSI KINERJA MAHASISWA
Authors: Sabna Eka
Published: November 2021

Berlimpahnya data mahasiswa pada perguruan tinggi dapat digunakan secara maksimal sesuai dengan kebutuhan dan mampu diolah menjadi informasi yang bermanfaat sehingga dapat mengetahui hubungan antara atribut data yang di dalamnya dapat dianalisis dan diharapkan memiliki keluaran berupa kinerja mahasiswa yang berhubungan Hasil Belajar (IPK). Metode yang digunakan mengunakan metode CRISP-DM yang terdiri dari 6 tahapan. Ada 2 (dua) metode klasifikasi yang digunakan yaitu Naïve Bayes Classifier dan Decision Tree Algoritma C4.5 untuk dilakukan perbandingan algoritma mana yang lebih baik untuk memprediksi kinerja mahasiswa. Hasil dari implementasi data mining dengan menggunakan software Rapidminer, dilakukan terhadap dua model algoritma klasifikasi yaitu C4.5 dan NBC kemudian memasukan dataset sebagai bahan uji untuk kedua model tersebut yang di dalamnya terdapat data latih dan data uji. Berdasarkan nilai akurasi terbaik pada model algoritma Naive Bayes Classifier (NBC) adalah 80% sedangkan  berdasarkan nilai akurasi terbaik  pada model algoritma C4.5 adalah 60 %.

Keywords: C4.5, NBC, IPK, kinerja, mahasiswa
Identifying Retrofitting Strategies for Access to Energy Efficient Building Design in Existing Buildings
Authors: Salah Fadi , Tuna Kayılı Merve
Published: November 2021

Reducing the energy needs of existing buildings has a significant place in reducing global energy demands. High energy savings can be achieved with passive renovation suggestions in existing buildings. In this study, the effect of the proposed renovation suggestions for an educational structure in Safranbolu on the heating and cooling demands of the building was determined with a simulation program. Energy improvements of up to 70 percent have been achieved through passive improvement designs in orientation and insulation material. The highest energy saving (69.31%) was realized in the scenario of rearranging spaces from the north side to the south side where the number of users is relatively high, and selecting a 20 cm aerogel thermal insulation material. While, the fact that the heating and cooling load in accordance with the definition of a zero-energy building could not be reached in this scenario, the study however showed the importance of holistic decisions taken in the design phase of the building with respect to energy efficient building design.
INTERNATIONAL AND GLOBAL LANGUAGES: CRITERIA, RATINGS, FORECASTS
Authors:   O. O. Potebnia Institute of Linguistics of the National Academy of Sciences of Ukraine, SELIHEY P. O. 
Published: November 2021

The article examines the criteria on the basis of which ratings of international languages are compiled and their future is predicted. Language’s chances of becoming international are not highly dependent on its demographic power, structural advantages or ease of learning. What matters most is the influence that speakers of the language have on other peoples. The criteria of «internationality» of the language actually coincide with the criteria of its influence, communicative value, social prestige, sociolinguistic weight. The ratings of the influence of national languages are based on various criteria: state status, communicative potential, economic power, the number of people studying it as a foreign language. These ratings reveal more essential criteria of an international language: prevalence on several continents, the status of an official language in international organizations, value as a source of modern knowledge, a large number of its speakers as a second. A specific feature that brings the international language to the class of world languages should be recognized as its worldwide prevalence. This language is used all over the world, it is spoken (as the first or second) by the majority of the world’s population, its world status is recognized in all countries. The composition of the club of leading languages is constantly changing: some languages come to it, others decrease — depending on the military-political, demographic, economic and cultural success of their speakers. Although the number of speakers of English as a second language is growing steadily, its dominance should be considered as temporary. A new hierarchy of languages may emerge in the middle of 21st century, with other major languages — Chinese, Spanish, Arabic, Hindi/Urdu, competing equally with English in their respective regions. Although state status of the Ukrainian language creates favorable preconditions for its development, it could spread much faster due to its informational value, intellectual power, cultural attractiveness and economic success of Ukraine.
Turismo enfocado a campos de concentración: el caso de Auschwitz-Birkenau. Recordar la historia para no repetirla
Authors: Ramón Fernández Francisca
Published: November 2021

La visita a lugares vinculados con tragedias, dolor y sufrimiento se ha convertido en un atractivo turístico para un perfil de turista que por curiosidad o morbo desea conocer dichos lugares. Uno de los más visitados es el del campo de concentración Auschwitz-Birkenau, en Polonia. El comportamiento del turista difiere de la realidad de lo que visita, de ahí el interés en realizarse selfies en la puerta de entrada, barracones, cámaras de gas. Lejos de constituir un “Lugar de la memoria” se exhiben sin ningún tipo de límites ni de ética, ni pudor, ni respeto por las víctimas toda suerte de objetos personales, partes del cuerpo humano, e imágenes de las personas que sufrieron el Holocausto. La comercialización del lugar, con una evidente finalidad lucrativa lo aleja de ser considerado como un homenaje, y de remover conciencias.
Topography of Power: Venice and the Eastern Adriatic Cities in the Century Following the Fourth Crusade
Authors: Benyovsky Latin Irena
Published: November 2021

In the thirteenth century, in the aftermath of the Fourth Crusade, Venice became an important power in the Mediterranean, which caused profound change in its political, territorial and economic ambitions. The main strategy of Venice was to maintain the sea route from the northernmost point in the Adriatic to the Levant, and therefore it was crucial to dominate politically over the Eastern Adriatic: the cities there could serve as points of departure or safe harbours in which Venetian vessels could be sheltered and supplied with merchandise, food, water, and manpower. One of the ways to incorporate the Eastern Adriatic cities into a common area of governance was to construct recognizable public buildings, and to introduce and standardize a legal and administrative order that was mainly adapted to the central political entity, but also served the local urban communities. This paper follows the changes that were directly or indirectly mirrored in the urban structure of the cities during the thirteenth century: primarily the design of urban spaces (especially public ones) and the construction of public buildings linked to governance, defence, trade or administration. During the thirteenth century, one can follow the development of Venetian ambitions and their focus on particular areas or activities (economic, military) in the state, as well as the activities of Venetian patricians holding the governor’s offi ce. Naturally, the local circumstances and the local population had a crucial impact on the formation of urban space, but this paper focuses primarily on the role of the Venetian administration in this respect.
Cerebral Vasculature Influences Blast-Induced Biomechanical Responses of Human Brain Tissue
Authors: Subramaniam Dhananjay Radhakrishnan , Unnikrishnan Ginu , Sundaramurthy Aravind , Rubio Jose E. , Kote Vivek Bhaskar , Reifman Jaques
Published: November 2021

Multiple finite-element (FE) models to predict the biomechanical responses in the human brain resulting from the interaction with blast waves have established the importance of including the brain-surface convolutions, the major cerebral veins, and using non-linear brain-tissue properties to improve model accuracy. We hypothesize that inclusion of a more detailed network of cerebral veins and arteries can further enhance the model-predicted biomechanical responses and help identify correlates of blast-induced brain injury. To more comprehensively capture the biomechanical responses of human brain tissues to blast-wave exposure, we coupled a three-dimensional (3-D) detailed-vasculature human-head FE model, previously validated for blunt impact, with a 3-D shock-tube FE model. Using the coupled model, we computed the biomechanical responses of a human head facing an incoming blast wave for blast overpressures (BOPs) equivalent to 68, 83, and 104 kPa. We validated our FE model, which includes the detailed network of cerebral veins and arteries, the gyri and the sulci, and hyper-viscoelastic brain-tissue properties, by comparing the model-predicted intracranial pressure (ICP) values with previously collected data from shock-tube experiments performed on cadaver heads. In addition, to quantify the influence of including a more comprehensive network of brain vessels, we compared the biomechanical responses of our detailed-vasculature model with those of a reduced-vasculature model and a no-vasculature model for the same blast-loading conditions. For the three BOPs, the predicted ICP values matched well with the experimental results in the frontal lobe, with peak-pressure differences of 4–11% and phase-shift differences of 9–13%. As expected, incorporating the detailed cerebral vasculature did not influence the ICP, however, it redistributed the peak brain-tissue strains by as much as 30% and yielded peak strain differences of up to 7%. When compared to existing reduced-vasculature FE models that only include the major cerebral veins, our high-fidelity model redistributed the brain-tissue strains in most of the brain, highlighting the importance of including a detailed cerebral vessel network in human-head FE models to more comprehensively account for the biomechanical responses induced by blast exposure.
Incorporation of Bone Morphogenetic Protein-2 and Osteoprotegerin in 3D-Printed Ti6Al4V Scaffolds Enhances Osseointegration Under Osteoporotic Conditions
Authors: Wang Xianggang , Li Zhengyan , Wang Zhonghan , Liu He , Cui Yutao , Liu Yuzhe , Ren Ming , Zhan Hongsheng , Li Zuhao , Wu Minfei , Wang Jincheng
Published: November 2021

Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.
Nanomedicine for the Diagnosis and Therapy of COVID-19
Authors: Wang Yingruo , Hao Yuanping , Fa Shunxin , Zheng Weiping , Yuan Changqing , Wang Wanchun
Published: November 2021

The coronavirus disease-2019 (COVID-19) pandemics caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading around the world due to its high infection rate, long incubation period, as well as lack of effective diagnosis and therapy or vaccines, which is tearing global health systems apart. It is an urgent demand for point-of-care diagnosis and effective treatment to prevent the spread of COVID-19. Currently, based on the rapid development of functional materials with unique physicochemical features through advanced fabrication and chemical modification, nanomaterials provide an emerging tool to detect SARS-CoV-2, inhibit the interplay in the virus and host cell interface, and enhance host immune response. In our manuscript, we summarized recent advances of nanomaterials for the diagnosis and therapy of COVID-19. The limitation, current challenges, and perspectives for the nano-diagnosis and nano-therapy of COVID-19 are proposed. The review is expected to enable researchers to understand the effect of nanomaterials for the diagnosis and therapy of COVID-19 and may catalyze breakthroughs in this area.
A Rapid Dual-Responsive Releasing Nano-Carrier by Decomposing the Copolymer and Reversing the Core Dissolution
Authors: Liu Sen , Shen Can , Qian Cheng , Wang Jianquan , Wang Zhihao , Tang Xuecong , Zhang Qiuyang , Pan Changjiang , Ye Wei
Published: November 2021

The accumulation of nanotechnology-based drugs has been realized in various ways. However, the concentration of drugs encapsulated by nanomaterials is not equal to the concentration of effective drugs; often, the drugs become effective only when they are released from the nanomaterials as free drugs. This means only when the drugs are rapidly released after the accumulated drug-encapsulating nanomaterials can they truly achieve the purpose of increasing the concentration of drugs in the tumor. Therefore, we herein report a dual-response nano-carrier of glutathione and acid to achieve the rapid release of encapsulated drug and increase the effective drug concentration in the tumor. The nano-carrier was constructed using a dual-responsive amphiphilic copolymer, composed of polyethylene glycol and hydrophobic acetylated dextran and connected by a disulfide bond. In the tumor microenvironment, disulfide bonds could be biodegraded by glutathione that is overexpressed in the tumor, exposing the core of nano-carrier composed of acetylated dextran. Then the acidic environment would induce the deacetylation of acetylated dextran into water-soluble dextran. In this way, the nano-carrier will degrade quickly, realizing the purpose of rapid drug release. The results showed that the drug release rate of dual-responsive nano-carrier was much higher than that of glutathione or acid-responsive nano-carrier alone. Furthermore, both in vitro and in vivo experiments confirmed that dual-responsive nano-carrier possessed more efficient anti-tumor effects. Therefore, we believe that dual-responsive nano-carriers have better clinical application prospects.
An Eye in the Replication Stress Response: Lessons From Tissue-Specific Studies in vivo
Authors: Matos-Rodrigues Gabriel E. , Martins Rodrigo A. P.
Published: November 2021

Several inherited human syndromes that severely affect organogenesis and other developmental processes are caused by mutations in replication stress response (RSR) genes. Although the molecular machinery of RSR is conserved, disease-causing mutations in RSR-genes may have distinct tissue-specific outcomes, indicating that progenitor cells may differ in their responses to RSR inactivation. Therefore, understanding how different cell types respond to replication stress is crucial to uncover the mechanisms of RSR-related human syndromes. Here, we review the ocular manifestations in RSR-related human syndromes and summarize recent findings investigating the mechanisms of RSR during eye developmentin vivo. We highlight a remarkable heterogeneity of progenitor cells responses to RSR inactivation and discuss its implications for RSR-related human syndromes.
ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress
Authors: Gámez-García Andrés , Bolinaga-Ayala Idoia , Yoldi Guillermo , Espinosa-Gil Sergio , Diéguez-Martínez Nora , Megías-Roda Elisabet , Muñoz-Guardiola Pau , Lizcano Jose M.
Published: November 2021

Autophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to overcome the hostile tumor microenvironment. Thus, pharmacological activation or inhibition of autophagy is emerging as a novel antitumor strategy. ERK5 is a novel member of the MAP kinase family that is activated in response to growth factors and different forms of stress. Recent work has pointed ERK5 as a major player controlling cancer cell proliferation and survival. Therefore small-molecule inhibitors of ERK5 have shown promising therapeutic potential in different cancer models. Here, we report for the first time ERK5 as a negative regulator of autophagy. Thus, ERK5 inhibition or silencing induced autophagy in a panel of human cancer cell lines with different mutation patterns. As reported previously, ERK5 inhibitors (ERK5i) induced apoptotic cancer cell death. Importantly, we found that autophagy mediates the cytotoxic effect of ERK5i, since ATG5ˉ/ˉ autophagy-deficient cells viability was not affected by these compounds. Mechanistically, ERK5i stimulated autophagic flux independently of the canonical regulators AMPK or mTORC1. Moreover, ERK5 inhibition resulted in ER stress and activation of the Unfolded Protein Response (UPR) pathways. Specifically, ERK5i induced expression of the ER luminal chaperone BiP (a hallmark of ER stress), the UPR markers CHOP and ATF4, and the spliced form of XBP1. Pharmacological inhibition of UPR with chemical chaperone TUDC, or ATF4 silencing, resulted in impaired ERK5i-mediated UPR, autophagy and cytotoxicity. Overall, our results suggest that ERK5 inhibition induces autophagy-mediated cancer cell death by activating ER stress. Since ERK5 inhibition sensitizes cancer cells and tumors to chemotherapy, future work will determine the relevance of UPR and autophagy in the combined use of chemotherapy and ERK5i to tackle Cancer.
Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer
Authors: Sankarasubramanian Sushmitha , Pfohl Ulrike , Regenbrecht Christian R. A. , Reinhard Christoph , Wedeken Lena
Published: November 2021

Pancreatic cancer is one of the deadliest cancers and remains a major unsolved health problem. While pancreatic ductal adenocarcinoma (PDAC) is associated with driver mutations in only four major genes (KRAS, TP53, SMAD4, and CDKN2A), every tumor differs in its molecular landscape, histology, and prognosis. It is crucial to understand and consider these differences to be able to tailor treatment regimens specific to the vulnerabilities of the individual tumor to enhance patient outcome. This review focuses on the heterogeneity of pancreatic tumor cells and how in addition to genetic alterations, the subsequent dysregulation of multiple signaling cascades at various levels, epigenetic and metabolic factors contribute to the oncogenesis of PDAC and compensate for each other in driving cancer progression if one is tackled by a therapeutic approach. This implicates that besides the need for new combinatorial therapies for PDAC, a personalized approach for treating this highly complex cancer is required. A strategy that combines both a target-based and phenotypic approach to identify an effective treatment, like Reverse Clinical Engineering® using patient-derived organoids, is discussed as a promising way forward in the field of personalized medicine to tackle this deadly disease.
Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma
Authors: Lin Xiandong , Wang Steven , Lin Keyu , Zong Jingfeng , Zheng Qianlan , Su Ying , Huang Tao
Published: November 2021

Non-coding RNAs have been shown to play important regulatory roles, notably in cancer development. In this study, we investigated the role of microRNAs and circular RNAs in Nasopharyngeal Carcinoma (NPC) by constructing a circRNA-miRNA-mRNA co-expression network and performing differential expression analysis on mRNAs, miRNAs, and circRNAs. Specifically, the Epstein-Barr virus (EBV) infection has been found to be an important risk factor for NPC, and potential pathological differences may exist for EBV+ and EBV- subtypes of NPC. By comparing the expression profile of non-cancerous immortalized nasopharyngeal epithelial cell line and NPC cell lines, we identified differentially expressed coding and non-coding RNAs across three groups of comparison: cancer vs. non-cancer, EBV+ vs. EBV- NPC, and metastatic vs. non-metastatic NPC. We constructed a ceRNA network composed of mRNAs, miRNAs, and circRNAs, leveraging co-expression and miRNA target prediction tools. Within the network, we identified the regulatory ceRNAs of CDKN1B, ZNF302, ZNF268, and RPGR. These differentially expressed axis, along with other miRNA-circRNA pairs we identified through our analysis, helps elucidate the genetic and epigenetic changes central to NPC progression, and the differences between EBV+ and EBV- NPC.
Increasing Superstructure Optimization Capacity Through Self-Learning Surrogate Models
Authors: Granacher Julia , Kantor Ivan Daniel , Maréchal François
Published: November 2021

Simulation-based optimization models are widely applied to find optimal operating conditions of processes. Often, computational challenges arise from model complexity, making the generation of reliable design solutions difficult. We propose an algorithm for replacing non-linear process simulation models integrated in multi-level optimization of a process and energy system superstructure with surrogate models, applying an active learning strategy to continuously enrich the database on which the surrogate models are trained and evaluated. Surrogate models are generated and trained on an initial data set, each featuring the ability to quantify the uncertainty with which a prediction is made. Until a defined prediction quality is met, new data points are continuously labeled and added to the training set. They are selected from a pool of unlabeled data points based on the predicted uncertainty, ensuring a rapid improvement of surrogate quality. When applied in the optimization superstructure, the surrogates can only be used when the prediction quality for the given data point reaches a specified threshold, otherwise the original simulation model is called for evaluating the process performance and the newly obtained data points are used to improve the surrogates. The method is tested on three simulation models, ranging in size and complexity. The proposed approach yields mean squared errors of the test prediction below 2% for all cases. Applying the active learning approach leads to better predictions compared to random sampling for the same size of database. When integrated in the optimization framework, simpler surrogates are favored in over 60% of cases, while the more complex ones are enabled by using simulation results generated during optimization for improving the surrogates after the initial generation. Significant time savings are recorded when using complex process simulations, though the advantage gained for simpler processes is marginal. Overall, we show that the proposed method saves time and adds flexibility to complex superstructure optimization problems that involve optimizing process operating conditions. Computational time can be greatly reduced without penalizing result quality, while the continuous improvement of surrogates when simulation is used in the optimization leads to a natural refinement of the model.
Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy
Authors: Peng Xiaoyao , Luo Zhixuan , He Shuang , Zhang Luhua , Li Ying
Published: November 2021

As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.