bluuebunny/crossref_metadata_2025 huggingface dataset:
DISEÑO GRÁFICO Y PATRIMONIO
Authors: Lazo-Galán Juan
Published: February 2022

El diseño gráfico profesional en Ecuador se ha convertido en una carrera que tiene una enorme aceptación en el país con  más de 24 universidades que tienen la carrera. Es una profesión que utiliza signos y símbolos arraigados en el inconsciente colectivo para generar comunicación. En un importante movimiento en los últimos años, los diseñadores gráficos han estado buscando referentes dentro del patrimonio ecuatoriano para generar propuestas con características propias, en algunos casos volviendo la mirada al pasado y en otras buscando en la cultura popular y en la naturaleza aquello que nos caracteriza. Este artículo analiza el diseño gráfico generado en los últimos 50 años y su relación con el patrimonio histórico, cultural y natural del país.

Palabras Clave: Cultura popular, precolombino, naturaleza, identidad, expresión visual

AbstractProfessional graphic design has become a career with a huge acceptance in Ecuador, with more than 24 universities offering it as a program of study. It’s a profession that uses signs and symbols rooted in the collective subconscious to producecommunication. In an important movement over the last few years, graphic designers have been searching for references within Ecuadorean culture to generate proposals with their own unique characteristics, in some cases, looking at the past andin others, searching within popular culture and in nature all that characterizes us. This article analyzes graphic design generated in the last 50 years and its relationship with the country’s historical, cultural and natural heritage.

Keywords: Popular culture, pre-Columbian, nature, identity, visual expression.
SEM TETO E OS DIREITOS HUMANOS: UM ESTUDO SOBRE O ALCANCE DAS POLÍTICAS PÚBLICAS NAS CLASSES MAIS VULNERÁVEIS DA SOCIEDADE
Authors: Vescovi Luiz Fernando , Souza Grobe Lara
Published: February 2022

O presente estudo visa trazer informações à luz dos direitos humanos, referentes a situação das camadas mais vulnerabilizadas da sociedade: a população em situação de rua. Por meio da evolução da sociedade brasileira, o texto objetiva demonstrar as desigualdades sociais como fato intrínseco do desenvolvimento do Brasil, vez que ela existe desde o descobrimento, pelos povos europeus, e que, posteriormente, influenciou na formação das favelas e no grande contingente de pessoas nas ruas. Mesmo com o progresso histórico das políticas públicas e dos programas sociais até os dias de hoje, ainda que, com reconhecimento internacional, as camadas na extrema pobreza não recebem toda a ajuda necessária, ficando em situações de dificuldade, não possuindo itens básicos para a sobrevivência, como alimentação, água potável, etc., vez que não possuem moradia, e os que possuem, não contam com uma estrutura adequada para uma vida entendida como digna. Desta forma, a pesquisa busca investigar quais seriam as razões para que elas não abarquem os que realmente precisam, deixando-os ficar em situações degradantes e indignas.
ABSTRACT
This study aims to bring information to the light of human rights, regarding the situation of the most vulnerable layers of society: the street population. Through the evolution of Brazilian society, the text aims to demonstrate social inequalities as an intrinsic fact of the development of Brazil, since it exists since the discovery, by the European people, and which later influenced the formation of slums and the large contingent of people on the streets. Even with the historical progress of public policies and social programs until today, even though, with international recognition, the layers in extreme poverty do not receive all the necessary help, staying in situations of difficulty, not having basic items for survival, such as food, drinking water, etc., since they do not have housing, and those who do, do not have an adequate structure for a life understood as worthy. This way, the research seeks to investigate what would be the reasons for them not to embrace those who really need it, leaving them in degrading and unworthy situations.
Keywords: Human Rights. Homeless. Public Policies. Social Programs.
COMBATE À CORRUPÇÃO E O COMPLIANCE NA AMÉRICA LATINA
Authors: Martarelli Fernandes Felipe Diego
Published: February 2022

O instituto do compliance está intrinsicamente ligado ao combate da corrupção, trata-se de um instrumento interno da pessoa jurídica em parceria com as autoridades estatais a fim de evitar a corrupção corporativa, como a lavagem de dinheiro, subornos e fraudes em licitações, tal instituto tem aplicação recente na América Latina, onde deve ser estudado de maneira internacional a fim de abranger todos os países da região.
PALAVRAS CHAVE: Compliance. Corrupção. América Latina. Direito Internacional. Lavagem de Dinheiro. Suborno.
ABSTRACT
The compliance institute is intrinsically linked to the fight against corruption; it is an internal legal entity instrument in partnership with state authorities to prevent corporate corruption, such as money laundering, bribery and fraud in biddings, such an institute has a recent application in Latin America, where it must be studied in order to cover all the countries of the region.
Keywords: Compliance. Corruption. Latin America. International right. Money laundry.
REFLEXÕES SOBRE O PAPEL DAS FAKE NEWS NA DEMOCRACIA BRASILEIRA
Authors: Bonin Joel Cezar , Portes Suzana Miranda , Faoro Angela
Published: February 2022

Nos últimos anos, ganhou destaque a questão da manipulação de notícias inverídicas em cadeia nacional, nas redes sociais especialmente, para fins políticos, com o intento de prejudicar ou favorecer pessoas públicas. No Brasil, ocorre uma investigação do Supremo Tribunal Federal nominada por inquérito das Fake News desde 2019. O inquérito visa compreender de que modo e com qual alcance essa prática influenciou as eleições presidenciais de 2018 e em que medida a prática das fake news acabou por perpetuar uma visão deturpada da vida pública de pessoas ligadas ao universo público brasileiro. Assim, questiona-se, por meio deste artigo, se estas formas de comunicação estariam ofendendo princípios democráticos com o intuito deliberado de macular a imagem de algumas pessoas e de enaltecer outras, com base em informações inventadas e veiculadas por meio das redes sociais. Para isso, tomou-se como referência documentos públicos do inquérito em trâmite, notícias falsas encontradas na internet e principalmente leituras sobre o tema a partir de uma revisão bibliográfica e documental. Ao final, ao se falar sobre a disseminação de notícias fraudulentas, reflete-se sobre a educação digital e a necessária verificação de notícias em busca de um jornalismo intelectual de qualidade que combata a informação desvirtuada, sustentando o sistema democrático e não distorcendo-o.
Pelatihan Pembuatan Vermikompos di Desa Lokasi Baru Kecamatan Air Periukan Kabupaten Seluma
Authors: Trisusilo Agung , Cahyadinata Indra
Published: February 2022

This activity aims to increase the awareness of the people of Lokasi Baru Village to make animal manure into compost using the vermicomposting method. The method used in this activity is a combination of counseling and structured training. The result of this activity is that participants are able to see the potential resources they have in the form of animal manure and process it into vermicompost fertilizer which is more useful and has economic value. In practice, participants experienced problems at the stage of preparation of developmental media, hatching of worm eggs, and the composting process. Although in the implementation process the participants faced several obstacles, with assistance from the service team they were able to resolve these obstacles independently. After participating in this series of activities, the participants learned that the livestock waste they produce has economic value if managed properly. Therefore, at this time they have been practicing the knowledge gained independently. Keywords: shit livestock; Lumbricus sp.; vermicompost
Vitamin D Deficiency Presenting as Proximal Myopathy: An Overlooked Diagnosis - A Case Series and Review of the Literature
Authors: Rajkumar Venkatraman
Published: February 2022

The prevalence of vitamin D deficiency is ubiquitous. Severe disease can present very dramatically and can be misleading to the treating physician, resulting in mismanagement. A high index of suspicion in vulnerable patients should help circumvent this problem, including a thorough history and physical examination to lead the clinician in the right direction. Insidious onset and progressive proximal pelvic girdle myopathy, in the absence of other neurological findings, in the appropriate patient should prompt the physician to test for serum 25 hydroxyvitamin D levels.

The literature on endocrine myopathy does not highlight this condition as much as it does the thyroid, parathyroid, and adrenal aetiologies. Testing for vitamin D deficiency is simple, and treatment is available all over the world. The following article presents three patients, in different scenarios, with the condition. In all three patients, incapacitating pelvic girdle weakness resolved and quality of life improved dramatically with timely intervention. Most importantly, the correct approach prevented misdiagnosis and mismanagement.
THE WAYS TO STRENGTHEN COOPERATION BETWEEN CHINA AND RUSSIA IN THE FIELD OF LOW-CARBON ENERGY (IN THE CONTEXT OF THE GLOBAL TREND OF “CARBON NEUTRALITY”)
Authors:   Inner Mongolia Technological University of China, Hoh-Hot, Inner Mongolia, People’s Republic of China, HAOLEI HAN , LING CHU
Published: February 2022

Against the background of the rapid evolution of the current international energy landscape and special attention to global climate management, the main interested participants in this process have started a new round of games around the key issue of “carbon neutrality”. In the face of both opportunities and challenges, China and Russia should accelerate the implementation of “carbon neutrality” through cooperation in the field of low-carbon energy, which can be considered as an effort to jointly stabilize the overall situation in the energy sector and strengthen international trust. Both countries strongly support the “green” development of energy and work together to promote global “green” and low-carbon transformation, fully demonstrating the strong responsibility of the powers. The article points out ways to strengthen cooperation between China and Russia in the field of low - carbon energy: the creation of a mechanism for cooperation in the field of low-carbon energy, deepening cooperation in the field of capacity-building within the framework of the interface of the EAEU and the “One Belt, One Road” project, strengthening bilateral exchanges and cooperation in the field of low-carbon energy technologies, the use of multilateral organizations to perform a coordinating role between China and Russia.
CRIMINAL LAW REGULATION OF ROBOTICS: RESULTS OF A SOCIOLOGICAL STUDY
Authors:   Kazan Innovative University named after V.G. Timiryasov, Kazan, Russian Federation, BEGISHEV ILDAR
Published: February 2022

The purpose of the research. In order to establish approaches to the definition of the concept of “robot”, to understand the technological and legal essence of robotics, to form a model of legal regulation of robotics, to study the issues of criminal liability for socially dangerous acts complicated by the use of robotic devices, to describe the robot as a subject of criminal encroachment and to develop a promising mechanism for applying the criminal law in the event of harm in the course of functioning of autonomous robots, a survey (questionnaire) of respondents (N = 305) was conducted using modern digital technologies and an interactive method of collecting information. Results. The results of the conducted sociological survey almost completely confirm the reliability and correctness of the author’s previous scientific research, unequivocally prove their relevance and relevance in society.
YOUTH PUBLIC ORGANIZATIONS AS A POLITICAL ACTOR
Authors:   Kazan (Volga Region) Federal University, Kazan, Russian Federation, GARIPOV RUSLAN , IGONIN DENIS
Published: February 2022

The purpose of this scientific article is to determine the characteristics of youth socio-political organizations that act as an actor in public policy. The authors established the arachaism of the approach that differentiates youth associations according to the territorial criterion. The article analyzes such a significant feature as the influence of youth organizations on political processes, including the processes of making government decisions. Conclusions. In the political science sense, a youth organization as a participant in political relations at the domestic or international levels has certain properties. The authors refer to them as: representing the interests of youth groups; availability of a resource base; participation in political communication; the desire to influence government decisions. But the differences between youth organizations are limited to the scale of influence and to the subject of political relations. The authors state that the presence or absence of resources is not a determining criterion for the recognition of a public organization as an actor of public policy. In this interpretation, the ability of a public association to formulate and express its own interests, and not the implementation of the will of another political actor (for example, a political party or state), acquires significance.
THE LEGAL DOCTRINE OF JOHN WILLIAM SALMOND AS THE EVOLUTION OF THE ANGLO-AMERICAN LEGAL POSITIVIST TRADITION
Authors:   Moscow State Institute of International Relations (University) MFA Russia, Moscow, Russian Federation, KORZHENYAK ANASTASIA , MIKHAILOV ANTON
Published: February 2022

The purpose of the research. This article examines the key ideas underlying the legal teachings of the New Zealand lawyer, civil servant and judge John William Salmond (1862-1924), who, as the authors of this study demonstrate, was one of the first critics of the “command theory of law” of the founder of the school of analytical jurisprudence John Austin (1790-1859). By analyzing and interpreting Salmond’s legal doctrine the authors refute the view, entrenched in Russian jurisprudence, that the central representative of the 20th century neo-positivism Herbert Lionel Adolphus Hart (1907-1992) is considered a pioneer in this field who initiated the criticism of Austin’s legal understanding. The authors advocate the position that Hart’s critique of the command conception and understanding of law in his teachings is largely based on Salmond’s ideas. As a result of this study the authors conclude that there are certain similarities between J.W. Salmond’s idea of “ultimate legal principles” and H.L.A. Hart’s legal doctrine on the “rule of recognition”.
CROSS-BORDER TRANSFER OF PRISONERS IN THE LIGHT OF THE CASE-LAW OF THE COURT OF JUSTICE OF THE EUROPEAN UNION
Authors:   Matej Bel University, Banská Bystrica, Slovak Republic, KLIMEK LIBOR
Published: February 2022

A set of cases of the Court of Justice of the European Union have been adopted, supplementing the Framework Decision 2008/909/JHA on mutual recognition of custodial sentences and deprivation of liberty. In five sections the paper analyses relevant cases. In each case at the outset a reference for a preliminary ruling is mentioned. Further, dispute in the main proceedings and the question(s) referred for a preliminary ruling are analysed. The most important parts of analyses are considerations by the Court of Justice and its rulings.
PROTEST ACTIVITY OF THE POPULATION AND ITS DEPENDENCE ON THE STANDARD OF LIVING: INSTITUTIONAL AND SOCIOCULTURAL ASPECT
Authors:   Market Economy Institute of RAS, Moscow, Russian Federation, DUDIN MIKHAIL
Published: February 2022

Within the framework of this article, an attempt has been made to study the protest activity of the population of the Russian Federation from the point of view of the existing institutionally, dimorphism of development, social and cultural contradictions. The article shows that the growth of protest activity is not directly related to the low standard of living of the population. On the contrary, high protest activity can be traced in those social strata, in those countries and states where the standard of living, quality of life, or the level of well-being of the population is relatively high, which allows protesting active citizens to openly and publicly express their position of disagreement with the policy of the state, with the actions of economic or other actors. Based on the generalization of materials and statistical data, the article proposes three patterns of protest behavior that have developed among Russian citizens: condemnation of the protest and its avoidance; solidarity with the protest; open support for the protest and active protest behavior. Each behavioral pattern is given its own sociocultural description, built into the established institutional context. It is shown that resistance to change can be directly associated with condemnation of protest, while the philosophy of economic and social freedom, globalization and open borders, technologization of life can be associated with solidarity with protest or its open and public expression. The results obtained can be used for further research in the field of institutional and sociocultural features of the protest behavior of Russian citizens.
POPULISM AS A POLITICAL PHENOMENON
Authors:   Stavropol Branch, RANEPA, Stavropol, Russian Federation, PIMENOVA OLGA
Published: February 2022

The purpose of the study. The article examines populism as a political phenomenon, and also raises questions of populism as a strategy for the activities of political parties. As part of the analysis of the activities of political parties, the phenomenon of populism is analyzed at three levels: classification, description, warning/admonition. The role of the political leader is also analyzed. The article outlines the prospects for further research on populism as a social phenomenon, which seems to be very important and relevant.
CHINA AND THE EU COOPERATION IN THE CONTEXT OF COVID-19 PANDEMIC
Authors:   Peter the Great Saint Petersburg Polytechnic University, Saint Petersburg, Russian Federation, VOVENDA ALEKSEI
Published: February 2022

Purpose. The article deals with the key areas of cooperation between the PRC and the EU in the context of modern international relations, characterized by crisis processes associated with the COVID-19 pandemic. The purpose of the study is to identify the features of interaction between China and the European Union at the present stage within the framework of the “One Belt, One Road” initiative and the “16 + 1” format aimed at strengthening partnership relations between China and the countries of Central and Eastern Europe. Results. The “PRC-EU Investment Agreement” signed in 2020 demonstrated the partners’ desire to reach a consensus on investment policy, market openness, mainly Chinese, fair competition, sustainable development, minimizing the risks of rapid entry of Chinese companies into the European market and reducing the trade imbalance in partner relations. During the online meeting of the leaders of the PRC and the EU in September 2021, the partners, despite the existing contradictions, confirmed their readiness to strengthen partnership in the current crisis conditions associated with the COVID-19 pandemic.
REGIONAL FEATURES OF THE DEVELOPMENT OF ECONOMIC ZONES OF WATERSHEDS: COMPARISON OF INTERNATIONAL EXPERIENCE
Authors:   Sichuan Academy of Social Sciences, Sichuan, China, SHIQING LIU ,   Peter the Great Saint Petersburg Polytechnic University, Saint Petersburg, Russian Federation, JUNTAO WANG , LYUBINA DARIA
Published: February 2022

The article examines various forms of regional models of management of economic zones of catchment basins on the example of the experience of the United States of America, Great Britain, Canada and other countries. The purpose of the study is to analyze and compare models of economic management of watersheds, as well as to identify the features of development and models of basin management. Results. The search for effective mechanisms for watershed management was an incentive to create unified mechanisms for watershed management and predetermined the direction of reforms in this area. However, in regional international practice, there are disagreements about specific methods for implementing a unified management model. The USA offers the most centralized management model. The UK practices a market-based approach to solving this issue, and the experience of Australia is the least centralized management model, although it fully takes into account the interests of representatives of various classes and plays a positive role in public life.
XINJIANG HUMAN RIGHT VIOLATION AND RADICALISM ISSUES : A DEVELOPMENT INEQUALITY FRAMING
Authors: Ahmad Amiruddin Tennang Andi Ismira
Published: February 2022

This Article aiming to discuss about recent Human Right Situation of Uyghur People in Xinjiang Province and the logic of powerful and structural effort by Beijing’s Authority to push “De-Extrimification” through “Strike Hard” program. A situation where, non-Chinese societies being forced to conform to Chinese culture, particularly that of the ethnic Han majority. The policies, politically seems like a will to annihilate identity of a society to determine their destiny, and to re-establish themselves in future generations. This writing also eager to examine, what was the driving factor the radicalism acts which has been occur in Xinjiang since over centuries, that this Radicalis has dragging the Chinese government to put the Policies on stage and seems not going to be downwarded. Using, Descriptive Analityc methods, this article analize the Uyghur and Xinjiang situation with geo-politic, development inequality and human security concepts.
MAPAS DE USO E COBERTURA DO SOLO DO MATOPIBA, EM 2008 E 2018
Authors: Lima Temísticles Pacheco , Silva Daniel de Paiva , Da Silva Anderson Rodrigo
Published: February 2022

Produção técnica resultado de dissertação defendida em 2020 no PPG-CRENAC/IFGoiano.
ECM Mechanoregulation in Malignant Pleural Mesothelioma
Authors: Panzetta Valeria , Musella Ida , Fusco Sabato , Netti Paolo A.
Published: February 2022

Malignant pleural mesothelioma is a relatively rare, but devastating tumor, because of the difficulties in providing early diagnosis and effective treatments with conventional chemo- and radiotherapies. Patients usually present pleural effusions that can be used for diagnostic purposes by cytological analysis. This effusion cytology may take weeks or months to establish and has a limited sensitivity (30%–60%). Then, it is becoming increasingly urgent to develop alternative investigative methods to support the diagnosis of mesothelioma at an early stage when this cancer can be treated successfully. To this purpose, mechanobiology provides novel perspectives into the study of tumor onset and progression and new diagnostic tools for the mechanical characterization of tumor tissues. Here, we report a mechanical and biophysical characterization of malignant pleural mesothelioma cells as additional support to the diagnosis of pleural effusions. In particular, we examined a normal mesothelial cell line (Met5A) and two epithelioid mesothelioma cell lines (REN and MPP89), investigating how malignant transformation can influence cellular function like proliferation, cell migration, and cell spreading area with respect to the normal ones. These alterations also correlated with variations in cytoskeletal mechanical properties that, in turn, were measured on substrates mimicking the stiffness of patho-physiological ECM.
Glucose-Derived Raspberry Ketone Produced via Engineered Escherichia coli Metabolism
Authors: Masuo Shunsuke , Saga Chisa , Usui Kurumi , Sasakura Yuma , Kawasaki Yukie , Takaya Naoki
Published: February 2022

The demand for raspberry ketone (RK) as a plant-based natural flavoring agent is high, but natural RK is one of the most expensive flavor compounds due to its limited content in plants. Here, we produced RK de novo from simple carbon sources in Escherichia coli. We genetically engineered E. coli metabolism to overproduce the metabolic precursors tyrosine and p-coumaric acid and increase RK production. The engineered E. coli produced 19.3- and 1.9 g/L of tyrosine and p-coumaric acid from glucose, respectively. The p-coumaric acid CoA ligase from Agrobacterium tumefaciens and amino acid substituted benzalacetone synthase of Rhemu palmatum (Chinese rhubarb) were overexpressed in E. coli overproducing p-coumaric acid. The overexpression of fabF, encoding β-ketoacyl-acyl carrier protein synthetase II increased intracellular malonyl-CoA, the precursor of benzalacetone synthase for RK biosynthesis, and improved RK production. Fed-batch cultures given glucose as a carbon source produced 62 mg/L of RK under optimized conditions. Our production system is inexpensive and does not rely on plant extraction; thus, it should significantly contribute to the flavor and fragrance industries.
Cysteine Substitution and Calcium-Binding Mutations in FBN1 cbEGF-Like Domains Are Associated With Severe Ocular Involvement in Patients With Congenital Ectopia Lentis
Authors: Zhang Min , Chen Zexu , Chen Tianhui , Sun Xiaodong , Jiang Yongxiang
Published: February 2022

Purpose: To investigate the clinical manifestations of congenital ectopia lentis (CEL) in patients with fibrillin (FBN1) calcium-binding epidermal growth factor (cbEGF)-like mutations.

Design: Retrospective cohort study.

Methods: Consecutive 68 CEL probands with FBN1 cbEGF-like mutations were recruited, mostly comprising Marfan syndrome (MFS) patients. Patients were classified into the cysteine group (n = 43), calcium (Ca2+)-binding group (n = 13) or the others (n = 12) according to their genotypes. Ocular biometrics, morbidities and visual performance were compared among different mutation groups. Linear regression was used to evaluate the risk factors for axial length (AL) elongation.

Results: With age-adjustment, cysteine substitution and Ca2+-binding mutations positively contributed to AL elongation (standardized coefficient: 0.410 and 0.367, p = 0.008 and 0.017, respectively). In addition, cataract formation was more frequently detected in patients with Ca2+-binding mutations (observed n = 3, expected n = 1.0; p = 0.036). Patients with cysteine substitutions had the poorest preoperative visual acuity among the three groups (p = 0.012) and did not recover as well as other patients. More MFS diagnoses were made in patients with cysteine substitutions (observed n = 16, expected n = 12.6), while ectopia lentis syndrome was detected more often in patients with cbEGF-like mutations out of the functional regions (observed n = 6, expected n = 2.5; p = 0.023).

Conclusion: Compared with patients with cbEGF-like mutations out of functional regions, patients with cysteine substitutions or Ca2+-binding mutations had longer ALs with age adjustment, poorer ocular involvement, visual performance, and systematic manifestations.
Identification of DDX31 as a Potential Oncogene of Invasive Metastasis and Proliferation in PDAC
Authors: Xie Yongjie , Liu Yang , Ding Jinsheng , Li Guangming , Ni Bo , Pang Huifang , Hu Xin , Wu Liangliang
Published: February 2022

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors worldwide and has poor prognosis. DEAD box proteins31 (DDX31) participate in cellular processes involving RNA secondary structure changes. However, the functions of DDX31 in PDAC remain to be elucidated.

Methods: The key gene DDX31 was identified using a combination of a risk model and weighted gene co-expression network analysis (WGCNA) with R software. The biological functions of DDX31 in PDAC were investigated through bioinformatics analysis and in vitro experiments.

Results: Combining with WGCNA and risk model, DDX31 was identified as a potential factor of the invasive metastasis properties of PDAC, and its expression was closely related to the malignant differentiation of PDAC. The results of gene set enrichment analysis (GSEA) showed that DDX31 was correlated with cell invasive metastasis and proliferation by activating MAPK signaling pathway. The inhibition of DDX31 inhibited the invasion and migration of PDAC cells. Survival analysis showed that DDX31 expression was negatively associated with the poor prognosis in patients with PDAC.

Interpretation:DDX31 may be a potential factor for PDAC. The inhibition of DDX31 may be a potential way to treat PDAC.
Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases
Authors: Park Kihyoun , Lee Myung-Shik
Published: February 2022

Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organismin vivo, dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.
Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies
Authors: Kusuma Gina D. , Li Anqi , Zhu Dandan , McDonald Hannah , Inocencio Ishmael M. , Chambers Daniel C. , Sinclair Kenneth , Fang Haoyun , Greening David W. , Frith Jessica E. , Lim Rebecca
Published: February 2022

Therapeutic benefits of mesenchymal stem cells (MSCs) are now widely believed to come from their paracrine signalling, i.e. secreted factors such as cytokines, chemokines, and extracellular vesicles (EVs). Cell-free therapy using EVs is an active and emerging field in regenerative medicine. Typical 2D cultures on tissue culture plastic is far removed from the physiological environment of MSCs. The application of 3D cell culture allows MSCs to adapt to their cellular environment which, in turn, influences their paracrine signalling activity. In this study we evaluated the impact of 3D MSCs culture on EVs secretion, cargo proteome composition, and functional assessment in immunomodulatory, anti-inflammatory and anti-fibrotic properties.

MSC-EVs from 2D and 3D cultures expressed classical EV markers CD81, CD63, and CD9 with particle diameter of <100 nm. There were distinct changes in immunomodulatory potencies where 3D cultures exhibited reduced indoleamine 2,3-dioxygenase (IDO) activity and significantly reduced macrophage phagocytosis. Administration of 2D and 3D EVs following double dose bleomycin challenge in aged mice showed a marked increase of bodyweight loss in 3D group throughout days 7–28. Histopathological observations of lung tissues in 3D group showed increased collagen deposition, myofibroblast differentiation and leukocytes infiltrations. Assessment of lung mechanics showed 3D group did not improve lung function and instead exhibited increased resistance and tissue damping. Proteome profiling of MSC-EV composition revealed molecular enrichment of EV markers (compared to parental cells) and differential proteome between EVs from 2D and 3D culture condition associated with immune-based and fibrosis/extracellular matrix/membrane organization associated function.

This study provides insight into distinct variation in EV protein composition dependent on the cellular microenvironment of the parental cells, which could have implications in their therapeutic effect and potency. Overall, this work suggests that EVs produced from 3D MSC cultures did not enhance typical MSC-EV properties expected from 2D cultures (immunomodulation, anti-fibrotic, anti-inflammatory). The outcome highlights critical differences between MSC-EVs obtained from different culture microenvironments, which should be considered when scaling up MSC culture for clinical manufacturing.
Overexpression of MUC1 Induces Non-Canonical TGF-β Signaling in Pancreatic Ductal Adenocarcinoma
Authors: Bose Mukulika , Grover Priyanka , Sanders Alexa J. , Zhou Ru , Ahmad Mohammad , Shwartz Sophia , Lala Priyanka , Nath Sritama , Yazdanifar Mahboubeh , Brouwer Cory , Mukherjee Pinku
Published: February 2022

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human cancers. Transforming Growth Factor Beta (TGF-β) is a cytokine that switches from a tumor-suppressor at early stages to a tumor promoter in the late stages of tumor development, by yet unknown mechanisms. Tumor associated MUC1 is aberrantly glycosylated and overexpressed in >80% of PDAs and is associated with poor prognosis. MUC1 expression is found in the early stages of PDA development with subsequent increase in later stages. Analysis of human PDA samples from TCGA database showed significant differences in gene expression and survival profiles between low and high MUC1 samples. Further, high MUC1 expression was found to positively correlate to TGF-βRII expression and negatively correlate to TGF-βRI expression in PDA cell lines. We hypothesized that MUC1 overexpression induces TGF-β mediated non-canonical signaling pathways which is known to be associated with poor prognosis. In this study, we report that MUC1 overexpression in PDA cells directly activates the JNK pathway in response to TGF-β, and leads to increased cell viability via up-regulation and stabilization of c-Myc. Conversely, in low MUC1 expressing PDA cells, TGF-β preserves its tumor-suppressive function and inhibits phosphorylation of JNK and stabilization of c-Myc. Knockdown of MUC1 in PDA cells also results in decreased phosphorylation of JNK and c-Myc in response to TGF-β treatment. Taken together, the results indicate that overexpression of MUC1 plays a significant role in switching the TGF-β function from a tumor-suppressor to a tumor promoter by directly activating JNK. Lastly, we report that high-MUC1 PDA tumors respond to TGF-β neutralizing antibody in vivo showing significantly reduced tumor growth while low-MUC1 tumors do not respond to TGF-β neutralizing antibody further confirming our hypothesis.
Drug/Lead Compound Hydroxymethylation as a Simple Approach to Enhance Pharmacodynamic and Pharmacokinetic Properties
Authors: Santos Soraya S. , Gonzaga Rodrigo V. , Scarim Cauê B. , Giarolla Jeanine , Primi Marina C. , Chin Chung M. , Ferreira Elizabeth I.
Published: February 2022

Hydroxymethylation is a simple chemical reaction, in which the introduction of the hydroxymethyl group can lead to physical–chemical property changes and offer several therapeutic advantages, contributing to the improved biological activity of drugs. There are many examples in the literature of the pharmaceutical, pharmacokinetic, and pharmacodynamic benefits, which the hydroxymethyl group can confer to drugs, prodrugs, drug metabolites, and other therapeutic compounds. It is worth noting that this group can enhance the drug’s interaction with the active site, and it can be employed as an intermediary in synthesizing other therapeutic agents. In addition, the hydroxymethyl derivative can result in more active compounds than the parent drug as well as increase the water solubility of poorly soluble drugs. Taking this into consideration, this review aims to discuss different applications of hydroxymethyl derived from biological agents and its influence on the pharmacological effects of drugs, prodrugs, active metabolites, and compounds of natural origin. Finally, we report a successful compound synthesized by our research group and used for the treatment of neglected diseases, which is created from the hydroxymethylation of its parent drug.
Huoshanmycins A‒C, New Polyketide Dimers Produced by Endophytic Streptomyces sp. HS-3-L-1 From Dendrobium huoshanense
Authors: Zhu Youjuan , Kong Yichao , Hong Yu , Zhang Ling , Li Simin , Hou Shurong , Chen Xiabin , Xie Tian , Hu Yang , Wang Xiachang
Published: February 2022

Three new polyketide dimers named huoshanmycins A‒C (1–3) were isolated from a plant endophytic Streptomyces sp. HS-3-L-1 in the leaf of Dendrobium huoshanense, which was collected from the Cultivation base in Jiuxianzun Huoshanshihu Co., Ltd. The dimeric structures of huoshanmycins were composed of unusual polyketides SEK43, SEK15, or UWM4, with a unique methylene linkage. Their structures were elucidated through comprehensive 1D-/2D-NMR and HRESIMS spectroscopic data analysis. The cytotoxicity against MV4-11 human leukemia cell by the Cell Counting Kit-8 (CCK8) method was evaluated using isolated compounds with triptolide as positive control (IC50: 1.1 ± 0.4 μM). Huoshanmycins A and B (1, 2) displayed moderate cytotoxicity with IC50 values of 32.9 ± 7.2 and 33.2 ± 6.1 μM, respectively.
Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease
Authors: Wang Haiying , Han Yijun , Li Shenwei , Chen Yunan , Chen Yafen , Wang Jing , Zhang Yuqing , Zhang Yawen , Wang Jingsuo , Xia Yong , Yuan Jinxiang
Published: February 2022

Mitochondria is a ubiquitous, energy-supplying (ATP-based) organelle found in nearly all eukaryotes. It acts as a “power plant” by producing ATP through oxidative phosphorylation, providing energy for the cell. The bioenergetic functions of mitochondria are regulated by nuclear genes (nDNA). Mitochondrial DNA (mtDNA) and respiratory enzymes lose normal structure and function when nuclear genes encoding the related mitochondrial factors are impaired, resulting in deficiency in energy production. Massive generation of reactive oxygen species and calcium overload are common causes of mitochondrial diseases. The mitochondrial depletion syndrome (MDS) is associated with the mutations of mitochondrial genes in the nucleus. It is a heterogeneous group of progressive disorders characterized by the low mtDNA copy number. TK2, FBXL4, TYPM, and AGK are genes known to be related to MDS. More recent studies identified new mutation loci associated with this disease. Herein, we first summarize the structure and function of mitochondria, and then discuss the characteristics of various types of MDS and its association with cardiac diseases.
Experimental Study on Strength and Permeability Characteristics of Cemented Rock-Tailings Backfill
Authors: Qiu Huafu , Zhang Fushun , Sun Weibo , Liu Lang , Zhao Yujiao , Huan Chao
Published: February 2022

To study the strength and permeability characteristics of cemented tailings backfill with different cement–sand ratios and different waste rock contents, uniaxial compression strength test and permeability test were carried out respectively. The porosity of cemented tailings backfills after solidification was observed by scanning electron microscope. The effects of cement–sand ratio and waste rock content on the internal porosity and overall permeability of cemented tailings backfill were studied. The test results showed that the cement–sand ratio and waste rock content have certain effects on the strength and permeability of the backfill body. When the cement–sand ratio was fixed, the uniaxial compressive strength and permeability of the backfill body increased first and then decreased with the increase of waste rock content. When the waste rock content was 10%, the uniaxial compressive strength of the backfill body reached the maximum, and when the waste rock content was 30%, the permeability reached the maximum. Due to the increase of the area of waste rock particles in the cross-section, the area of gas passing rapidly decreased, resulting in the decrease of the permeability growth rate. When the waste stone content was fixed, with the decrease of cement–sand ratio, due to the decrease of cementitious materials, more micro-cracks were produced in the curing process of backfill body, resulting in the decrease of uniaxial compressive strength and the increase of permeability.
Teachers’ Emotion Regulation in the Team-Taught Classroom: Insights Into Teachers’ Perspectives on How to Regulate and Communicate Emotions With Regard to the Team Teaching Partner
Authors: Muehlbacher Franziska , Hagenauer Gerda , Keller Melanie M.
Published: February 2022

An important facet of teachers’ competence is their ability to regulate their emotions in the classroom in an adaptive manner. Recently, the advantages of teacher collaboration have sparked novel educational practices, such as team teaching, where two teachers are responsible for classroom teaching. Within this setting of complex interactions, not only students but also partner teachers are additional sources of teachers’ emotions and ensuing emotion regulation strategies. How team teachers choose to regulate and communicate their emotions, triggered by their team partners, may have significant consequences for collaborative practices and teacher well-being. Based on the process model on emotion regulation and the concepts of co- and shared regulation, the present study aimed to enhance our understanding of team teachers’ perspectives on how to regulate and communicate emotions. To this end, a qualitative interview study was conducted among 30 Austrian team teachers teaching in lower secondary schools. The results of a structuring qualitative content analysis revealed that team teaching is an educational practice that requires high amounts of emotion regulation. It was shown that team teachers regularly use strategies such as attentional deployment or reappraisal to prevent the experience of negative emotions. Team teachers’ rules regarding displays of emotion stipulated that positive emotions can be authentically shown, while negative emotions must be suppressed in front of students. Engaging in discussion with the partner teacher after class is frequently used to handle negative experiences. By making use of co- and shared regulation of emotions (e.g., situation modification), teachers also exploit the potential of team teaching concerning emotional support and workload relief. Encouragement, (shared) praise, and shared humor were also considered to be useful strategies to maintain positive emotions in order to foster successful collaboration. Implications concerning adaptive emotion regulation to foster fruitful team teaching practices are discussed.
RETRACTED: Bone Age Assessment Based on Deep Convolutional Features and Fast Extreme Learning Machine Algorithm
Authors: Guo Longjun , Wang Juan , Teng Jiaqi , Chen Yukun
Published: February 2022

Bone age is an important metric to monitor children’s skeleton development in pediatrics. As the development of deep learning DL-based bone age prediction methods have achieved great success. However, it also faces the issue of huge computation overhead in deep features learning. Aiming at this problem, this paper proposes a new DL-based bone age assessment method based on the Tanner-Whitehouse method. This method extracts limited and useful regions for feature learning, then utilizes deep convolution layers to learn representative features in these interesting regions. Finally, to realize the fast computation speed and feature interaction, this paper proposes to use an extreme learning machine algorithm as the basic architecture in the final bone age assessment study. Experiments based on publicly available data validate the feasibility and effectiveness of the proposed method.
Investigation of Cutter–Woodchip Contact Pressure in a New Biomass Comminution System
Authors: Lin Lianshan , Lanning David , Keiser James R. , Qu Jun
Published: February 2022

A Crumbler® rotary shear system was recently developed to process fuel-grade woodchips into feedstocks having more uniform particle sizes for improved flowability and higher thermochemical output yield than a traditional hammer mill. It represents a significant innovation in the state of the art of biomass comminution equipment. However, the milling unit has experienced significant abrasive wear of the feeding teeth and cutters when processing hard and dusty feedstocks, such as logging residue and corn stover. Here, we present initial simulation results from a finite-element stress analysis of the rotary shear, which is used to investigate the dynamics of interaction between the cutters and woodchips. This is the first step for optimizing the cutter design to improve the system lifetime and processing efficiency, thus reducing downtime and improving overall productivity.
Revisiting the Green City Concept in the Tropical and Global South Cities Context: The Case of Indonesia
Authors: Zain Alinda F. M. , Pribadi Didit O. , Indraprahasta Galuh S.
Published: February 2022

Urban areas play a key role in reaching global sustainability as they produce a high amount of waste and emissions, consume a lot of resources, and perform as the prime mover of the global economy. Unsustainable urbanization will generate multidimensional impacts on the earth’s socio-ecological system that is nearly impossible to be managed. As a preemptive action, urban sustainability has been considered as one of the most important targets in the Sustainable Development Goals. Within this context, the green city has emerged as a widely adopted concept around the globe. In the Global North, the concept of a green city has been incrementally developed as efforts to mainstream green infrastructure and nature-based solutions approaches in supporting ecosystem services. Quite the contrary, in the Global South cities, due to their rapid and vast urbanization process, the green city has been fragmentally adopted. Previous studies have proposed three factors, i.e., urbanization, biophysics, and governance, underlying the different approaches of green city development between cities in the Global North and South. Still, more studies are needed to explicate these factors and how these will in turn shape a particular green city trajectory in Global South cities. This study aims to respond to these questions based on green city experimentation in Indonesia. An exploratory study was done based on a literature review and participant observation. The results exhibit that the green city program in Indonesia largely focused on the development of green open spaces which has ultimately failed to improve the urban environment and sustainability. Incorporating local socio-ecological aspects coupled with integrated multi-level and multi-actors’ governance is recommended to increase the green city performances.