bluuebunny/crossref_metadata_2025 huggingface dataset:
Aplikasi Pupuk Organik Cair Berbahan Baku Urin Ternak Terhadap Pertumbuhan Tanaman Pakcoy (Brassica rapa L.)
Authors: Rosyadi Imron , Karmanah Karmanah , Sargo Sugiarto
Published: October 2021

Abstrak Pupuk organik bentuk cair berbahan urin dari ternak adalah salah satu alternatif pupuk ramah lingkungan yang dapat meningkatkan produksi dan pertumbuhan pakcoy. Berdasarkan hal tersebut, peneliti terdorong melaksanakan kajian dengan tujuan mengetahui dampak pemberian pupuk organik cair berbahan urin ternak terhadap perkembangan tumbuhan pakcoy (Brassica rapa L.). Percobaan lima perlakuan memakai Rancangan Acak Lengkap (RAL) yang merupakan pemberian tipe pupuk organik cair hasil ternak urin kambing, urin sapi dan urin kelinci, pupuk kimia AB Mix sebagai pembanding dan tanpa pemupukan (kontrol). Pengamatan dilakukan terhadap tinggi tanaman, kuantitas daun, berat kering dan berat basah panen. Data  dianalisis menggunakan software SPSS serta diuji  Duncan Multiple Range Test (DMRT). Hasil kajian yaitu pada semua pupuk organik cair terjadi peningkatan kandungan unsur P, penurunan unsur K dan pH setelah difermentasi pH berkisar 6,85–8,45 dan sesuai dengan peraturan Menteri Pertanian No. 70/Permentan/SR.140/10/2011 tentang pupuk organik, pupuk hayati, dan pembenah tanah. Pupuk organik cair berbahan urin ternak mampu meningkatkan jumlah daun dan tinggi tanaman pakcoy yang secara sig nifikan berbeda dibandingkan pupuk kimia.  Aplikasi pupuk organik cair urin kambing menghasilkan berat kering dan berat basah panen pakcoy yang serupa dengan pupuk kimia.  AbstractLiquid organic fertilizer made from urine from livestock is an alternative to environmentally friendly fertilizers that can increase pakcoy production and growth. Based on this, researchers are interested in conducting research to determine the effect of liquid organic fertilizer made from livestock urine on the growth of pakcoy (Brassica rapa L.). The experiment was carried out with five treatments using a completely randomized design (CRD), namely the application of liquid organic fertilizer from goat urine, cow urine and rabbit urine, chemical fertilizer AB Mix as a comparison, and without fertilization (control). Observations were made on plant height, a number of leaves, dry weight and wet weight of harvest. Data were analyzed using SPSS software and further tested with Duncan Multiple Range Test (DMRT). The results of the study were that in all liquid organic fertilizers there was an increase in the content of P elements, a decrease in K elements, and pH after fermentation. 70/Permentan/SR.140/10/2011 concerning organic fertilizers, biological fertilizers, and soil enhancers. Liquid organic fertilizer made from livestock urine is able to increase the number of leaves and plant height of pakcoy which is significantly different from chemical fertilizers. The application of goat urine liquid organic fertilizer resulted in the same dry weight and wet weight of pakcoy harvest as chemical fertilizers.
A Common Formal Framework for Factorial and Probabilistic Topic Modelling Techniques
Authors: Gibert Karina , Hernandez-Potiomkin Yaroslav
Published: October 2021

Topic modelling is nowadays one of the most popular techniques used to extract knowledge from texts. There are several families of methods related to this problem, among them 1) Factorial methods, 2) Probabilistic methods and 3) Natural Language Processing methods. In this paper a common conceptual framework is provided for Factorial and probabilistic methods by identifying common elements and describing them with common and homogeneous notation and 7 different methods are described accordingly. Under a common notation it is easy to make a comparative analysis and see how flexible or more or less realistic assumptions are made by the different methods. This is the first step to a wider analysis where all families can be related to this common conceptual framework and to go in depth in the understanding of stengths and weakenesses of each method and ellaboration of general guidelines to provide application criteria. The paper ends with a discussion comparing the presented methods and future research lines.
Affective State-Based Framework for e-Learning Systems
Authors: Rodríguez Juan Antonio , Comas Joaquim , Binefa Xavier
Published: October 2021

Virtual learning and education have become crucial during the COVID-19 pandemic, which has forced a rethink by teachers and educators into designing online content and the indirect interaction with students. In an face-to-face class, some visual cues help the teacher recognize the engagement level of students, while the main weakness of the online approach is the lack of feedback that the teacher has about the learning process of the students. In this paper, we introduce a novel framework able to track the learning states, or LS, of the students while they are watching a piece of knowledge-based content. Specifically, we extract four learning states: Interested, Bored, Confused or Distracted. Finally, to demonstrate the system’s capability, we collected a reduced database to analyze the affective state of the subjects. From these preliminary results, we observe abrupt changes in the LS of the audience when there are abrupt changes in the narrative of the video, indicating that well-structured and bounded information is strongly related with the learning behaviour of the students.
The question of metrological traceability of COOMET reference materials. Pt. 1. International practice on traceability establishment of reference materials’ certified values
Authors: Medvedevskikh Sergey V. , Sobina Egor P. , Kremleva Olga N. , Medvedevskikh Мaria Yu. , Sobina Alena V. , Taraeva Nataliya S.
Published: October 2021

The multiplication of national units transfer instruments with established values of metrological traceability in international organisations is one of the most actual development directions for a large number of countries, inasmuch as this direction contributes to the solution of a global problem of measurement results comparability which were received for various objects in different times in different parts of the world as well as indicates the high quality of measuring capabilities of an organisation or a country. The paper contains issues of establishment of metrological traceability of results of physicochemical measurements. The international practice on traceability establishment of reference materials’ certified values is described in the work. The authors also provided a brief overview of internationally accepted fundamental concepts of reference materials metrological traceability demonstration.
Marketing de prensa en tiempos de COVID-19: Comparativa de los patrones de consumo de prensa nativa y digital
Authors: Crespo Pereira Verónica , Vaca Tapia Ana , Martínez Fernández Valentín
Published: October 2021

El contexto de excepcionalidad que ha provocado el COVID-19 ha tenido conse­cuencias en la prensa de todo el mundo. El confinamiento ha visto crecer el hábito de leer la prensa en su versión digital. Esta situación permite formular muchas preguntas en torno al futuro de las tiradas en papel y el tipo de consumo informativo pospande­mia. En este sentido, se ha llevado a cabo una investigación aproximativa, enmarcada en el ámbito de Ecuador, con el objetivo de identificar patrones de comportamiento de los consumidores de productos informativos a través de ediciones digitales que permitan determinar las bases de un nuevo modelo de acceso a y consumo de este tipo de medios, que todavía, en el espacio sociogeográfico estudiado, se encuentra en una fase inicial de transformación. Esta cuestión constituye uno de los principales aportes de la investigación, pues no puede obviarse la sensibilidad de países como Ecuador a la incidencia de crisis sanitarias o catástrofes naturales, en que el acceso a la información es esencial. La investigación se ha llevado a cabo en el momento más crí­tico de la pandemia, por suponer un punto de inflexión en el consumo habitual de pe­riódicos. Se ha analizado la evolución de indicadores de relevancia para los modelos digitales de negocios, como el engagement de diecisiete diarios ecuatorianos durante los meses prepandemia (febrero) y confinamiento (marzo a mayo).
Exoneration Clausula In The Goods Delivery Agreement Throughdelivery Service
Authors: Kironowarni Shinta Fawzia
Published: October 2021

Research entitled "Exoneration Clause in the Goods Delivery Agreement through the Delivery Service", due to the Exoneration Clause, it can harm consumers. Issues discussed regarding the form of exoneration clauses in goods delivery agreements through shipping services and legal protection for owners of goods that are harmed due to exoneration clauses. The study uses a normative approach and a concept approach, a conclusion is obtained as follows. The form of the exoneration clause in the goods delivery agreement via the shipping service is the contents of the exoneration clause that has binding power for the parties involved in it, the contents of the exoneration clause that do not have binding power for the parties involved in it. The exoneration clause has binding power for the parties involved in it as signed. Regarding the location, form and disclosure of standard clauses, it can also be seen from the intention of the business actor, that the obligation of the business actor is in good faith in carrying out his business activities. Legal protection for the owner of the goods that is harmed by the exoneration clause is a protection given to legal subjects in the form of legal instruments both preventive and responsive, both written and unwritten. If something happens to the goods sent, such as lost or damaged, it would be better if between the shipping service and the consumer together to resolve the case by way of peace first. Consumers can submit a claim first after that the freight forwarder can process the loss in accordance with the agreement and does not need to involve the court or the Dispute Settlement Agency (BPSK).
Ефективність взаємодії педагогічного працівника з колективом та керівництвом закладу вищої освіти: аналіз, методи та шляхи досягнення
Authors: Несправа Микола
Published: October 2021

Вища школа як один з найважливіших соціокультурних інститутів суспільства зобов’язана підготувати нове покоління до активної участі в усіх суспільних процесах. Перед викладачами закладів вищої освіти постає надзвичайно відповідальне завдання: взяти юнаків і дівчат з їхніми задатками, інтересами, особливостями пізнавальних та емоційно-вольових процесів і підготувати їх до рівня висококваліфікованих фахівців, здатних реалізувати набуті знання, практичні уміння, знайти своє місце у професії.Розглянуто питання взаємовідносин педагогічного працівника зі співробітниками та керівництвом закладу вищої освіти. На основі зібраних даних щодо виникнення та подолання конфліктних ситуацій на рівні «викладач», створено базу даних для дослідження системи міжособистісних конфліктів у закладі вищої школи. Використовуючи метод статистичного аналізу й метод аналітико-синтетичної обробки інформації, охарактеризовано та наведено найбільш типові конфлікти, визначаючи об’єкт і особливості протидіючих сторін, узагальнено характер і причини їх появи. Наголошено, що конфлікт, це явище суспільного життя, суть виникнення та вирішення якого залежить від множинності факторів нашого існування. За своєю природою конфлікти в освітніх організаціях є переважно міжособистісними. Основою таких конфліктів може бути, зазвичай, матеріальне або ціннісне протиріччя. Підсумовано, що частину конфліктів можна ефективно вирішити, налагодивши попереджувальні заходи або зробивши все для швидкого розв’язання конфліктної ситуації. Однак тривалі нерозв’язані конфлікти здатні дуже негативно впливати на міжособистісні стосунки, соціально-психологічний клімат у колективі, емоційні стани і настрій. Визначивши, що найкращим методом налагодження ефективної взаємодії педагогічного працівника з колективом та керівництвом закладу вищої освіти є уникнення конфліктів, сформульовано шляхи забезпечення запобігання, виявлення та врегулювання конфліктних ситуацій. Запропоновано також методи їх попередження та вирішення. Зазначено, що такі напрацювання в перспективі можуть теоретичним підґрунтям для формування внутрішньо-інституційного нормативного документа.
Ключові слова: конфліктна ситуація, конфлікт, педагог, керівник, заклад вищої освіти, причина конфлікту, об’єкт конфлікту, методи вирішення.
Особливості життєдіяльності відповідно до сприйняття часу особистістю
Authors: Лич Оксана
Published: October 2021

У статті розглядається проблема усвідомлення, використання діяльного наповнення часу у літньому віці, оскільки особливістю похилого віку є конфронтація з часом. Час одночасно поєднує у собі дві взаємовиключні позиції – безкінечність та завершеність, розуміння цього посилюється на останніх етапах життєвого циклу. За часом стоять переживання, вчинки, дії, взагалі життєвий шлях особистості, поєднуючи минуле, теперішнє та майбутнє. Час об’єднує та розрізняє усіх людей, бо люди різних вікових категорій живуть немов у різних часових вимірах, з різним життєвим темпом.
У статті аналізуються також джерела безвідповідального ставлення до часу у молодому віці, з тенденцію відкладати або не поспішати втілювати у життя плани. Розглядаються негативні наслідки оманливих тенденцій безкінечності часу та технологій швидкого задоволення потреб, що відволікають від справжнього сенсу життя та можливостей з користю використати час.
Обґрунтовується звʼязок особливостей життєдіяльності з використанням часу у літньому віці. Аналізуються причини свідомого застрягання у минулому часі, у минулих спогадах, що спричинюються психологічними захисними механізмами. Розглядаються ідея настання психологічної старості через вичерпність резервуару часу, по-суті, через відсутність мотивації, цілепокладання. Зникнення планів на майбутнє, мрій та задумів спричиняють відсутність у фактичній потребі часу. Адже час є цінністю не сам по собі, а лише з огляду на те, що саме може бути реалізовано в його інтервалах. Час зупиняється у ситуації бездіяльності, тому він слідує за намірами особистості діяти. І коли потреби діяти не виникає, то й час, а разом із ним і життя, стають безцільними та порожніми, особливо це стає актуальним у літньому віці.
Пропонуються життєві стратегії літнього віку, в основі яких прояви рівнів життєстійкості та особистісних характеристик. Описується також значення внутрішніх переживань та екзистенційних тривог, що впливають на життєдіяльність людини. Підкреслюється важливість психологічного супроводу літніх осіб, що можна розглядати як зовнішній ресурс.
Ключові слова: час, життєдіяльність, життєстійкість, життєві стратегії, людина похилого віку.
Особливості перебігу смисложиттєвих орієнтацій та самоактуалізації працівників сфери управління
Authors: Родченкова Ірина , Завацька Наталія , Башинська Яна , Болдирєва Алла
Published: October 2021

У статті розкрито особливості перебігу смисложиттєвих орієнтацій та самоактуалізації працівників сфери управління. Показано, що проблема смисложиттєвих орієнтацій висвітлювалися у контексті смислової сфери особистості, що віддзеркалює її спрямованість, цілі, надає усвідомленості процесу здійснення вибору у різних життєвих і професійних ситуаціях. При цьому смисложиттєві орієнтації є складною цілісною динамічною системою, що утворюється за принципом ієрархії, а її складові взаємопов’язані й залучають до себе усвідомленість життя й часову локалізацію, види смислів й суб’єкт-об’єктні орієнтації і взаємопов’язані, зокрема, з професійною діяльністю, міжособистісними взаєминами, гендерними взаємовідносинами. Наголошується, що смисложиттєві орієнтації є вагомим чинником самоактуалізації, проявом суб’єктної активності у відповідній діяльності, зокрема, в управлінській, а якісним рівнем самоактуалізації виступають показники продуктивності життєвого шляху та успішності професійної діяльності загалом.
Емпірично досліджено смисложиттєві орієнтації працівників сфери управління залежно від рівня їх самоактуалізації та здійснено порівняльний аналіз зазначеного звʼязку. Визначено, що загальними компонентами, які сприяють самоактуалізації працівників сфери управління є: ставлення до себе, особливості локусу контролю, задоволеності життям та власної ролі. Показано, що провідним критерієм, який уособлює смисложиттєві орієнтації працівників сфери управління, є просоціальна ціннісна спрямованість особистості; натомість егоїстичній спрямованості, що протидіє смисложиттєвим орієнтаціям управлінців. Серед чинників, які впливають на смисложиттєві орієнтації працівників сфери управління визначено самоактуалізаційний, що поєднує пізнавальні потреби,орієнтацію у часі, самоприйняття, креативність, гнучкість поведінки; ціннісно-рефлексивний, що поєднує контактність, спонтанність, сенситивність, гнучкість поведінки; діяльнісно-адаптативний, що поєднує синергію, локус-контролю-Я, локус контролю – життя, процес життя; організаційний, що поєднує результативність життя, ціннісні орієнтації,уявлення про природу людини, прийняття агресії.
Більш самоактуалізованими виявилися працівники сфери управління високого рангу та управлінці середньої ланки зі стажем професійної діяльності від 5-ти до 10-ти років, у порівнянні з працівниками сфери управління середньої ланки зі стажем професійної діяльності до 5-ти років.
Ключові слова: особистість, смисложиттєві орієнтації, самоактуалізація, професійна діяльність, працівники сфери управління.
Features of socialization і individual expectation features
Authors: Zavatska Natalia , Bilianska Alina , Ryndina Lilia , Shona Valentina
Published: October 2021

The article considers the features of socialization and individual expectations of the individual as components of its spheres of life. It is shown that the peculiarities of the subject's self-attitude determine the attitudes to life. Transforming, creative activity is one pole. The opposite pole - passivity, expectations, dependence. The result of psychological "tightness" is a feeling of failure. To solve the corrective tasks of forming an active life position, it is important that this transformative, corrective process begins with the analysis and work with self-assessment judgments. Individuals who have, in general, a fairly positive experience of social adaptation and self-realization will tend to form positive, flexible, realistic and concrete expectations. At the same time, individuals who have experienced numerous disappointments and conflicts in the past will be more likely to have negative, rigid, unrealistic and diffuse expectations in their respective fields of activity. Accordingly, the selected indicators are expressed in the features of the expectations of the individual in such areas as significant interpersonal relationships, ideas about their own potential and prediction of the future. The role of individual expectations (as components of cognitive development), as well as their relationship with the process of self-determination of the individual, which provides an opportunity to develop new, more effective programs of socio-psychological adaptation of the younger generation.
Key words: specialty, socialization, examination, life.
Психологічні особливості прояву самооцінки молодших школярів у процесі навчальної діяльності
Authors: Бохонкова Юлія , Бугайова Наталія , Сербін Юрій , Бугайова Ольга
Published: October 2021

Стаття присвячена теоретико-методологічному розгляду психологічних особливостей прояву самооцінки молодших школярів в процесі навчальної діяльності. У статті зроблено аналіз досліджень і публікацій з зазначеної проблематики. Розглянуто особливості розвитку самосвідомості дитини молодшого шкільного віку. Надано характеристику соціальної ситуації розвитку особистості у молодшому шкільному віці. Розглянуто чинники впливу соціального середовища (сім’ї, шкільного колективу тощо), оцінок успішності навчання, спілкування з дорослими та однолітками на формування самооцінки молодших школярів. Надано визначення поняттю «самооцінка». З’ясовано основні функції самооцінки в навчальній діяльності молодших школярів. Проаналізовано основні новоутворення молодшого шкільного віку та з’ясовано особливості їх впливу на формування самооцінки дитини. Розглянуто особливості формування самооцінки учнів молодшого шкільного віку, визначено її прояв в процесі навчальної діяльності.Відзначається, що на формування самооцінки в молодшому шкільному віці впливають особливості соціально-особистісної позиції учня в навчальному процесі, зняття негативного впливу зовнішніх оцінок, зміна системи відносин, що складаються між учителем і учнем, прилучення учнів до оцінної діяльності процесу і результату своєї навчальної діяльності.
Ключові слова: самооцінка, особистість, молодший шкільний вік, самосвідомість, навчальна діяльність, виховання, поведінка, оцінка, позитивне ставлення, шкільна успішність, саморегуляція, комунікативні навички, конфліктність, мотивація, неуспішність.
Iron Containing Nanocomposites Based on Humic Substances
Authors: Mametova A. , Zharkynbaeva R. , Gafforova Kh. , Abdullaeva Zh.
Published: October 2021

Research relevance is the study of iron-containing nanocomposites based on humic substances is their special properties, composition, structure and applications. Materials and research methods: the article was compiled using a literature review of publications on iron-containing nanocomposites based on humic substances. Research objectives: determination of the structure and types of iron-containing nanocomposites based on humic substances and their field of application in medicine. Research results: Iron oxide nanoparticles are applicable in the development of nanomedicine due to their adaptable functions. Humic substances are composed of supramolecular heteropolymers, which include natural objects. Conclusions: Iron-containing nanocomposites can be used in biomedicine as diagnostic and therapeutic tools. Humic substances are organic macromolecules with multiple properties and high structural complexity.
Radioecological Assessment of Uranium Tails Deposits (Sumsar, Shekaftar, Terek-Sai)
Authors: Zhakypbekova A. , Kulchinova G. , Abdymomunova B.
Published: October 2021

The article presents the results of radio ecological studies of the territories of uranium tailings in Kyrgyzstan (Sumsar, Shekaftar and Terek-Sai), as well as their current state and assessment of the radioactive contamination’s potential risks. The ore field of this region is characterized as an extremely complex structure and covers about 30 ore occurrences of lead and rare metals. Starting from the Precambrian period both applicative and disjunctive disturbances within its boundaries have been widely developing and being manifested many times throughout the history of geological development. Oxidized and sulfide ores have been developed within the deposit. Unfortunately, serious miscalculations were made. As result of natural disasters; such as earthquakes, landslides, mudflows, etc., several uranium tailing dumbs have been damaged. Day by day, the risk of destruction and the threat of radioactive contamination of the Kyrgyz Republic territory are increasing. There are eight tailing dumps on the territory of Shekaftar uranium natural-technogenic province, the total volume of which is 1194 thousand m3 of radioactive waste. There are 15 mountain dumps of substandard ore with an ore volume of 4585.6 thousand m3 hour, in local areas it exceeds 500 μR/h.
Biochemical Study of Soils of the Southwestern Part of Absheron
Authors: Manafova F. , Aslanova G.
Published: October 2021

This article presents data designating the direction of pedogenic processes, which are combination of various chemical, physical and biological phenomena occurring in soils and determining a particular composition and properties of the soil mass. The differences between soils are defined by the diversity of vegetation, microorganisms and soil fauna, which serves as a source of enzymes.
Study of the Source Material of Tomatoes, Obtaining Pure Lines and Organizing the Primary Seed Breeding
Authors: Adigozalov M.
Published: October 2021

Tomato occupies a leading place, which, with a wide variety of crops grown in the republic, are of great importance in human nutrition. The research was carried out within the framework of the draft State Program the approved National Strategy “Conservation and rational use of genetic resources of cultivated plants” for 2017–2020 in the Republic of Azerbaijan, as in other branches of agriculture, is of great importance in the selection work carried out in the field of vegetable growing. Tomato, which occupies a leading place among a wide variety of vegetable crops grown in the republic, possesses great importance in human nutrition. Zoned varieties of tomatoes that differ in taste and aroma were threatened with extinction under the environmental impact factors, for a number of objective and subjective reasons, currently there are very few genetic variations of these varieties in farms or they are on the verge of extinction. The National Genbank stores the seeds of these tomato varieties, which are currently very valuable in tomato breeding as donor samples adapted to local conditions. In breeding, the gene pool is considered an indispensable material. An important task facing breeders in our time is the effective use of this invaluable “golden fund” in the creation of new, high-quality, locally adapted varieties and hybrids. The article deals with the use of samling and sorting operations in the selection programs by establishing pure lines for the recovery of vitality and life cycle of seeds of regional, high quality and productive tomato varieties protected in the National Gene Bank established under the National Academy of Sciences Institute of Genetics.
Alcohol Use Disorders and Their Harmful Effects on the Contractility of Skeletal, Cardiac and Smooth Muscles
Authors: Alleyne Jerusalem , Dopico Alex M.
Published: October 2021

Alcohol misuse has deleterious effects on personal health, family, societal units, and global economies. Moreover, alcohol misuse usually leads to several diseases and conditions, including alcoholism, which is a chronic condition and a form of addiction. Alcohol misuse, whether as acute intoxication or alcoholism, adversely affects skeletal, cardiac and/or smooth muscle contraction. Ethanol (ethyl alcohol) is the main effector of alcohol-induced dysregulation of muscle contractility, regardless of alcoholic beverage type or the ethanol metabolite (with acetaldehyde being a notable exception). Ethanol, however, is a simple and “promiscuous” ligand that affects many targets to mediate a single biological effect. In this review, we firstly summarize the processes of excitation-contraction coupling and calcium homeostasis which are critical for the regulation of contractility in all muscle types. Secondly, we present the effects of acute and chronic alcohol exposure on the contractility of skeletal, cardiac, and vascular/ nonvascular smooth muscles. Distinctions are made between in vivo and in vitro experiments, intoxicating vs. sub-intoxicating ethanol levels, and human subjects vs. animal models. The differential effects of alcohol on biological sexes are also examined. Lastly, we show that alcohol-mediated disruption of muscle contractility, involves a wide variety of molecular players, including contractile proteins, their regulatory factors, membrane ion channels and pumps, and several signaling molecules. Clear identification of these molecular players constitutes a first step for a rationale design of pharmacotherapeutics to prevent, ameliorate and/or reverse the negative effects of alcohol on muscle contractility.
Insight to Gene Expression From Promoter Libraries With the Machine Learning Workflow Exp2Ipynb
Authors: Liebal Ulf W. , Köbbing Sebastian , Netze Linus , Schweidtmann Artur M. , Mitsos Alexander , Blank Lars M.
Published: October 2021

Metabolic engineering relies on modifying gene expression to regulate protein concentrations and reaction activities. The gene expression is controlled by the promoter sequence, and sequence libraries are used to scan expression activities and to identify correlations between sequence and activity. We introduce a computational workflow calledExp2Ipynbto analyze promoter libraries maximizing information retrieval and promoter design with desired activity. We appliedExp2Ipynbto seven prokaryotic expression libraries to identify optimal experimental design principles. The workflow is open source, available as Jupyter Notebooks and covers the steps to 1) generate a statistical overview to sequence and activity, 2) train machine-learning algorithms, such as random forest, gradient boosting trees and support vector machines, for prediction and extraction of feature importance, 3) evaluate the performance of the estimator, and 4) to design new sequences with a desired activity using numerical optimization. The workflow can perform regression or classification on multiple promoter libraries, across species or reporter proteins. The most accurate predictions in the sample libraries were achieved when the promoters in the library were recognized by a single sigma factor and a unique reporter system. The prediction confidence mostly depends on sample size and sequence diversity, and we present a relationship to estimate their respective effects. The workflow can be adapted to process sequence libraries from other expression-related problems and increase insight to the growing application of high-throughput experiments, providing support for efficient strain engineering.
Establishment of a Pre-vascularized 3D Lung Cancer Model in Fibrin Gel—Influence of Hypoxia and Cancer-Specific Therapeutics
Authors: Kniebs Caroline , Luengen Anja Elisabeth , Guenther Daniel , Cornelissen Christian Gabriel , Schmitz-Rode Thomas , Jockenhoevel Stefan , Thiebes Anja Lena
Published: October 2021

Lung cancer is the most frequently diagnosed cancer worldwide and the one that causes the highest mortality. In order to understand the disease and to develop new treatments, in vitro human lung cancer model systems which imitate the physiological conditions is of high significance. In this study, a human 3D lung cancer model was established that features the organization of a tumor with focus on tumor angiogenesis. Vascular networks were formed by co-culture of human umbilical vein endothelial cells and adipose tissue-derived mesenchymal stem cells (ASC) for 14 days in fibrin. A part of the pre-vascularized fibrin gel was replaced by fibrin gel containing lung cancer cells (A549) to form tri-cultures. This 3D cancer model system was cultured under different culture conditions and its behaviour after treatment with different concentrations of tumor-specific therapeutics was evaluated. The evaluation was performed by measurement of metabolic activity, viability, quantification of two-photon laser scanning microscopy and measurement of the proangiogenic factor vascular endothelial growth factor in the supernatant. Hypoxic conditions promoted vascularization compared to normoxic cultured controls in co- and tri-cultures as shown by significantly increased vascular structures, longer structures with a higher area and volume, and secretion of vascular endothelial growth factor. Cancer cells also promoted vascularization. Treatment with 50 µM gefitinib or 50 nM paclitaxel decreased the vascularization significantly. VEGF secretion was only reduced after treatment with gefitinib, while in contrast secretion remained constant during medication with paclitaxel. The findings suggest that the herein described 3D lung cancer model provides a novel platform to investigate the angiogenic potential of cancer cells and its responses to therapeutics. Thus, it can serve as a promising approach for the development and patient-specific pre-selection of anticancer treatment.
TAK1: A Molecular Link Between Liver Inflammation, Fibrosis, Steatosis, and Carcinogenesis
Authors: Wang Weijun , Gao Wenkang , Zhu Qingjing , Alasbahi Afnan , Seki Ekihiro , Yang Ling
Published: October 2021

Chronic insult and persistent injury can cause liver inflammation, fibrosis, and carcinogenesis; it can also be associated with metabolic disorders. Identification of critical molecules that link the process of inflammation and carcinogenesis will provide prospective therapeutic targets for liver diseases. Rapid advancements in gene engineering technology have allowed the elucidation of the underlying mechanism of transformation, from inflammation and metabolic disorders to carcinogenesis. Transforming growth factor-β-activated kinase 1 (TAK1) is an upstream intracellular protein kinase of nuclear factor kappa-B (NF-κB) and c-Jun N-terminal kinases, which are activated by numerous cytokines, growth factors, and microbial products. In this study, we highlighted the functional roles of TAK1 and its interaction with transforming growth factor-β, WNT, AMP-activated protein kinase, and NF-κB signaling pathways in liver inflammation, steatosis, fibrosis, and carcinogenesis based on previously published articles.
Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression
Authors: Poggio Pietro , Sorge Matteo , Seclì Laura , Brancaccio Mara
Published: October 2021

HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.
Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
Authors: Matsuura Ruka , Nakajima Tatsuro , Ichihara Saya , Sado Takashi
Published: October 2021

Non-coding Xist RNA plays an essential role in X chromosome inactivation (XCI) in female mammals. It coats the X chromosome in cis and mediates the recruitment of many proteins involved in gene silencing and heterochromatinization. The molecular basis of how Xist RNA initiates chromosomal silencing and what proteins participate in this process has been extensively studied and elucidated. Its involvement in the establishment and maintenance of the X-inactivated state is, however, less understood. The XistIVS allele we previously reported is peculiar in that it can initiate XCI but fails to establish the inactive state that is stably maintained and, therefore, may provide an opportunity to explore how Xist RNA contributes to establish a robust heterochromatin state. Here we demonstrate that ectopic splicing taking place to produce XistIVS RNA disturbs its function to properly establish stable XCI state. This finding warrants the potential of XistIVS RNA to provide further insight into our understanding of how Xist RNA contributes to establish sustainable heterochromatin.
The miRNA Profile of Inflammatory Colorectal Tumors Identify TGF-β as a Companion Target for Checkpoint Blockade Immunotherapy
Authors: Bartlett Bjarne , Gao Zitong , Schukking Monique , Menor Mark , Khadka Vedbar S. , Fabbri Muller , Fei Peiwen , Deng Youping
Published: October 2021

Extrinsic factors such as expression of PD-L1 (programmed dealth-ligand 1) in the tumor microenvironment (TME) have been shown to correlate with responses to checkpoint blockade therapy. More recently two intrinsic factors related to tumor genetics, microsatellite instability (MSI), and tumor mutation burden (TMB), have been linked to high response rates to checkpoint blockade drugs. These response rates led to the first tissue-agnostic approval of any cancer therapy by the FDA for the treatment of metastatic, MSI-H tumors with anti-PD-1 immunotherapy. But there are still very few studies focusing on the association of miRNAs with immune therapy through checkpoint inhibitors. Our team sought to explore the biology of such tumors further and suggest potential companion therapeutics to current checkpoint inhibitors. Analysis by Pearson Correlation revealed 41 total miRNAs correlated with mutation burden, 62 miRNAs correlated with MSI, and 17 miRNAs correlated with PD-L1 expression. Three miRNAs were correlated with all three of these tumor features as well as M1 macrophage polarization. No miRNAs in any group were associated with overall survival. TGF-β was predicted to be influenced by these three miRNAs (p = 0.008). Exploring miRNA targets as companions to treatment by immune checkpoint blockade revealed three potential miRNA targets predicted to impact TGF-β. M1 macrophage polarization state was also associated with tumors predicted to respond to therapy by immune checkpoint blockade.
Wnt1 Role in the Development of the Habenula and the Fasciculus Retroflexus
Authors: Company Verónica , Moreno-Cerdá Ana , Andreu-Cervera Abraham , Murcia-Ramón Raquel , Almagro-García Francisca , Echevarría Diego , Martínez Salvador , Puelles Eduardo
Published: October 2021

Wnt1 is one of the morphogenes that controls the specification and differentiation of neuronal populations in the developing central nervous system. The habenula is a diencephalic neuronal complex located in the most dorsal aspect of the thalamic prosomere. This diencephalic neuronal population is involved in the limbic system and its malfunction is related with several psychiatric disorders. Our aim is to elucidate the Wnt1 role in the habenula and its main efferent tract, the fasciculus retroflexus, development. In order to achieve these objectives, we analyzed these structures development in a Wnt1 lack of function mouse model. The habenula was generated in our model, but it presented an enlarged volume. This alteration was due to an increment in habenular neuroblasts proliferation rate. The fasciculus retroflexus also presented a wider and disorganized distribution and a disturbed final trajectory toward its target. The mid-hindbrain territories that the tract must cross were miss-differentiated in our model. The specification of the habenula is Wnt1 independent. Nevertheless, it controls its precursors proliferation rate. Wnt1 expressed in the isthmic organizer is vital to induce the midbrain and rostral hindbrain territories. The alteration of these areas is responsible for the fasciculus retroflexus axons misroute.
Privately Protected Areas: Missing Pieces of the Global Conservation Puzzle
Authors: Bingham Heather C. , Fitzsimons James A. , Mitchell Brent A. , Redford Kent H. , Stolton Sue
Published: October 2021

Protected areas are an essential component of global conservation efforts. Although extensive information is available on the location of protected areas governed by governments, data on privately protected areas remain elusive at the global level. These are areas governed by private individuals and groups—ranging from families to religious institutions to companies—that meet IUCN's definition of a protected area: a clearly defined geographical space, recognised, dedicated and managed, through legal or other effective means, to achieve the long-term conservation of nature with associated ecosystem services and cultural values. As the world's governments prepare to adopt a new post-2020 global biodiversity framework to guide conservation over the next decade, we argue that, without complete data on privately protected areas, they do so without a vital piece of the puzzle.
Higher Blood Lead Level Is Associated With Increased Likelihood of Abdominal Aortic Calcification
Authors: Qin Zheng , Li Hancong , Xu Yingfei , Li Jiameng , Su Baihai , Liao Ruoxi
Published: October 2021

Aims: This study aimed to evaluate the association between blood lead level (BLL) and abdominal aortic calcification (AAC) in US adults aged ≥40 years.

Methods: We obtained data from 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Participants missing the data of BLL and AAC scores were excluded. BLL was measured using inductively coupled plasma mass spectrometry directly. AAC scores were quantified by Kauppila score system, and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between BLL with AAC score and severe AAC.

Results: A total of 1,530 participants were included with the mean BLL of 1.45 ± 1.31 ng/dl and mean AAC score of 1.40 ± 3.13. The prevalence of severe AAC was 7.98% overall, and participants in higher BLL quartile showed higher prevalence of severe AAC (Quartile 1: 3.55%, Quartile 2: 7.28%, Quartile 3: 9.88%, Quartile 4: 12.58%, P < 0.0001). BLL was positively associated with higher AAC score (β = 0.15, 95% CI: 0.02, 0.27, P = 0.021) and increased risk of severe AAC (OR = 1.11; 95% CI: 1.00–1.22; P = 0.047). Subgroup analysis and interaction test indicated that the association between BLL and AAC was similar in different population settings.

Conclusions: Higher BLL was associated with higher AAC score and increased risk of severe AAC. Lead burden should be considered for people with AAC in clinical settings.
Study of Sexual Dimorphism in Metatarsal Bones: Geometric and Inertial Analysis of the Three-Dimensional Reconstructed Models
Authors: Liu Yaming , Antonijević Djorde , Li Ruining , Fan Yuxuan , Dukić Ksenija , Mićić Milutin , Yu Genyu , Li Zhiyu , Djurić Marija , Fan Yifang
Published: October 2021

The aim of the present paper is to determine the sex of the individual using three-dimensional geometric and inertial analyses of metatarsal bones. Metatarsals of 60 adult Chinese subjects of both sexes were scanned using Aquilion One 320 Slice CT Scanner. The three-dimensional models of the metatarsals were reconstructed, and thereafter, a novel software using the center of mass set as the origin and the three principal axes of inertia was employed for model alignment. Eight geometric and inertial variables were assessed: the bone length, bone width, bone height, surface-area-to-volume ratio, bone density, and principal moments of inertia around the x, y, and z axes. Furthermore, the discriminant functions were established using stepwise discriminant function analysis. A cross-validation procedure was performed to evaluate the discriminant accuracy of functions. The results indicated that inertial variables exhibit significant sexual dimorphism, especially principal moments of inertia around the z axis. The highest dimorphic values were found in the surface-area-to-volume ratio, principal moments of inertia around the z axis, and bone height. The accuracy rate of the discriminant functions for sex determination ranged from 88.3% to 98.3% (88.3%–98.3% cross-validated). The highest accuracy of function was established based on the third metatarsal bone. This study showed for the first time that the principal moment of inertia of the human bone may be successfully implemented for sex estimation. In conclusion, the sex of the individual can be accurately estimated using a combination of geometric and inertial variables of the metatarsal bones. The accuracy should be further confirmed in a larger sample size and be tested or independently developed for distinct population/age groups before the functions are widely applied in unidentified skeletons in forensic and bioarcheological contexts.
Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
Authors: Zhang Yu-Sheng , Zheng Yan-Dan , Yuan Yan , Chen Shi-Chun , Xie Bao-Cheng
Published: October 2021

Purpose

Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients.

Methods

Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium–glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas.

Results

One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58–13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04–0.93) and voglibose (RR 0.03; 0–0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32–2.1), follow-up duration (0.79; 0.27–1.64), and sex distribution (0.63; 0.15–1.56).

Conclusions

We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients.

Systematic Review Registration

This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
Forecasting of Steam Coal Price Based on Robust Regularized Kernel Regression and Empirical Mode Decomposition
Authors: Fu Xiangwan , Tang Mingzhu , Xu Dongqun , Yang Jun , Chen Donglin , Wang Ziming
Published: October 2021

Aiming at the problem of difficulties in modeling the nonlinear relation in the steam coal dataset, this article proposes a forecasting method for the price of steam coal based on robust regularized kernel regression and empirical mode decomposition. By selecting the polynomial kernel function, the robust loss function and L2 regular term to construct a robust regularized kernel regression model are used. The polynomial kernel function does not depend on the kernel parameters and can mine the global rules in the dataset so that improves the forecasting stability of the kernel model. This method maps the features to the high-dimensional space by using the polynomial kernel function to transform the nonlinear law in the original feature space into linear law in the high-dimensional space and helps learn the linear law in the high-dimensional feature space by using the linear model. The Huber loss function is selected to reduce the influence of abnormal noise in the dataset on the model performance, and the L2 regular term is used to reduce the risk of model overfitting. We use the combined model based on empirical mode decomposition (EMD) and auto regressive integrated moving average (ARIMA) model to compensate for the error of robust regularized kernel regression model, thus making up for the limitations of the single forecasting model. Finally, we use the steam coal dataset to verify the proposed model and such model has an optimal evaluation index value compared to other contrast models after the model performance is evaluated as per the evaluation index such as RMSE, MAE, and mean absolute percentage error.