bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INTERIOR DESIGN OF A MUSIC SCHOOL FOR PERSONS WITH VISION IMPAIRMENT WITH THE CONCEPT OF LANDMARK PERCEPTION IN SURAKARTA, INDONESIA
Authors: Cosynala W Ranta , Ariyanto Ahmad Fajar
Published: August 2021

The Law of the Republic of Indonesia, article 5, paragraphs 1 and 2 concerning the education system, states that every citizen has the same right to obtain a good quality education. Citizens who have physical, emotional, mental, intellectual, and social disabilities are entitled to special education, including vision impairment. One of those people with vision impairment skills is their music expertise by maximizing touch and the sense of hearing. This work aims to realize the Landmark Perception concept by applying dynamic repetition by visualizing the repetition of several elements, such as line, shapes, textures, colors, dimensional gradations, shape gradations, and circulation patterns. These work results are the interior designs for the main facilities, including vocal classrooms, guitar classrooms, Violin classrooms, drum classrooms, piano classrooms, concert halls, and some supporting facilities such as cafeterias and libraries. The results of this work can be a reference for interior designers in designing interiors in a contemporary style based on the needs of people with vision impairment.
FOREWORD, Pendhapa: Vol. XI, No. 2.
Authors: Sumarno Sumarno
Published: August 2021

History is the circumstances and events of human life in the past including previous achievements that are disclosed again. The glory, advancement, and fame of a certain nation, state, tribe or community group are often retold to educate, remember, and generate a positive spirit to build the future through various ways with various points of view in accordance with their respective fields of knowledge and passion.Jaza Chehata Hadi, in designing the interior of the Port, seeks to bring back the old Semarang atmosphere with the concept of Venice van Java, the nickname of Semarang city – Central Java Indonesia, years ago, due to many rivers in the middle of the city just like the city of Venice (Italy). The icons, documentation and knick-knacks of the past are presented to bring out the old Semarang atmosphere.The second article is Mahdi Nurcahyo's article, revealing how people with visual impairment or blindness recognize and present some aspects of convenience in the house where he lives in, as a part of giving meaning to everyday life through his sense of experience and sensitivity to arrange space according to his body's comfort. The third article by Muhammad Fadilah Fatah and his friends concerns on the design of a chair as a sitting facility which combines functions of bag, charger, as well as table by utilizing waste as its raw material to reduce environmental pollution.The existence of batik for Indonesian people is as the nation's ancestral cultural heritage. Batik covers various aspects such like philosophy, techniques or production, community economy, batik motifs, coloring, identity and other aspects. In the Edition XI, No. 2 of Pendhapa: Journal of Interior Design, Art and Culture, there are three articles related to batik. Two articles contain the results of some designs of the infrastructure facilities for the interiors to protect and develop batik. The revitalization of a noble's residence that had been neglected into a batik shop and museum in Laweyan village, Surakarta, Central Java, Indonesia, is the article of Yosafat Adi Pradipta and Raden Ersnathan Budi Prasetyo. Another article about batik is the interior design of Omah Batik in Bayat, Klaten, Central Java, Indonesia as a means of protecting and developing batik, by Annisa Isma Safitri and Joko Budiwiyanto. The last article is batik motifs as a design idea for hotel design, written by Wahyu Tri Widiyanto and Putri Sekar Hapsari.History stores a lot of knowledge, philosophy, science, wisdom, and many other things. The time span of batik work that has been going on for generations has become a part of the history of the cultural journey of the people, especially in Java. The preservation and development is a shared responsibility. The scholars, the researchers, and the academics morally have the obligation to always be sensitive to various things, especially related to phenomena in their surrounding environment.
Kill or be killed: living in fear
Authors: Orrell Katya
Published: August 2021

This article explores fear and aggression in relation to trauma. These themes are explored using the case study of a man who needs conflict, particularly around race and gender, in order to bypass feelings of fear. Faced with actually experiencing trauma, he finds himself running and keeps on running in order to not commit murder, first in reality and then later in his mind. Exploring the mechanisms involved when, after a difficult early life, he escapes from home as a young teenager and then finds himself unable to settle or maintain relationships. Instead, we see how moving from continent to continent, finding himself in violent conflict again and again, he is unable to resolve the conflict within himself. Using Freud's concepts of repetition compulsion, denial, and disavowal to think about this patient, I examine what is driving this internal destructiveness and the need to keep fear consistently at arm's length.
A strange case of gendercide: fascination, psychotic features, archaic elements, and phantasmatic metamorphosis
Authors: Spadaro Francesco , Versaggio Marzia
Published: August 2021

This is a strange case of murder: a mafia pentito, an informer, reveals after ten years that the death of a man which had been considered natural, had in fact been a murder. The victim, a loan shark associated with crime people, was the companion of his lover at the time. The strange aspect is the way in which the mobster, with a couple of hired killers and helped by the woman, organised the murder: a shot of pesticide while the man was lying in bed with the woman. This modality was suggested by a veterinarian friend of the mobster who claimed that the pesticide would not be detected. The interviewer's imagination/vision of a metamorphosis while he was interviewing the woman in a forensic setting; the dream he had immediately after the interview; the bizarre construction of the crime; the seductive abilities of the woman linked to the choice and the type of partners she had and the bonds she had created; and the almost dreamlike description of the crime itself, suggest the emergence of primitive mechanisms of mental functioning: splitting, the use of massive projections of partial aspects and projective identification. A fragile and hidden common thread is hypothesised in this work. A common thread whose core is the desire for the narcissistic realisation of a woman who, in order to achieve it, puts eros at the service of thanatos. A red thread that connects all the different events, the real and the phantasmatic ones: from seeking a role as a woman of the criminal underworld to the magic fascination of an archaic Sicily, evoking primitive mechanisms of functioning typical of psychosis.
Venus: victim or violator?
Authors: Theodorou Alexis , Ali Saima
Published: August 2021

This article explores sexual boundary violations and their clinical implications in forensic settings. In particular, the authors consider whether female professional and male patient relationship transgressions have similar clinical meanings as the inverse, or whether there is an inherent or perceived difference between genders. Furthermore, attention is brought to the problematic aspects of reductive, dichotomous interpretations of victim–violator relationships.
Composite cases of such clinical "accidents" are presented. These are set within secure environments in the United Kingdom. The scope of these cases encompasses incidents between clinician and patient, as well as inter-professional boundary violations. By discussing these vignettes, the authors demonstrate the risk of a subtle, gradual, and insidious erosion of boundaries, alongside more overt incidents of a sexual nature and abuse of power. Contemporary societal factors that may influence conscious and unconscious biases will also be considered in the post #MeToo world.
Where clinical examples are given, they are composites of cases reported in the public domain known to the authors. They are clinically accurate but do not involve actual identifiable people and cases.
HOW SPANISH SCIENCE TEACHERS PERCEIVE THE INTRODUCTION OF COMPETENCE-BASED SCIENCE TEACHING
Authors: Jiménez Antonio Mateos , Fernández Beatriz García , Bejarano Franco María Teresa
Published: August 2021

The aim of the research was to determine how teachers in Spain perceived the introduction of competence-based science teaching in the classroom. The research was carried out during the transition between the LOE and LOMCE Education Laws (academic year 2014-2015). Data were collected using an ad hoc questionnaire comprising 19 items requiring responses on a 5-point Likert scale. The sample comprised 443 science teachers in compulsory education in Spain. The results indicated that the way teachers perceived science and its scope and application in the classroom was unlikely to lead to the effective development of the scientific competence. Significant findings were discussed relating to the participating teachers’ initial training, gender, type of school and stage of education. As a final component the didactic implications of teaching scientific competence were considered. Key words: primary education, scientific competence, secondary education, teachers’ perceptions, science teachers.
Protesta y noticiero televisivo: la vuelta de lo siempre igual
Authors: Berti Silvina Beatriz , Cantú Ariadna Laura
Published: August 2021

En este artículo se presenta un análisis cuantitativo de la protesta social televisada por el noticiero local - Telediario, Canal 13 de Río Cuarto, de Córdoba - Argentina, para dar cuenta de manera general de lo que se podría llamar las presencias y las ausencias más evidentes y notorias de la “realidad” que se muestra en las pantallas; imágenes que distan de devolver, a modo de espejo, lo que sucede delante de las cámaras que registran los hechos y de los micrófonos que dejan escuchar solo algunas voces.
Корпоративный этикет и культура общения
Authors: Pestova Alina , Makogonov Alexander
Published: August 2021

Цель данной статьи – раскрыть особенности корпоративного этикета и культуры общения. В статье затрагиваются такие темы как: коммуникативная культура, показатели культуры речи в деловом общении, виды, формы и стили корпоративного общения. Особое внимание уделено навыкам, которыми человеку необходимо обладать для общения в деловых кругах. Статья посвящена актуальной на сегодняшний день проблеме корпоративному этикету и культуре общения, так как в любой ситуации необходимо иметь хороший словарный запас, грамотно поставленную речь, умение правильно выходить из трудного разговора и обладать всеми необходимыми навыками для работы и делового общения.

Ключевые слова: коммуникативная культура, этикет, общениe, собственная личность
Развитие туризма на территориях национальных парков Казахстана
Authors: Seitimova Assem , Beysembinova Ardak , Baekeyev Yernur
Published: August 2021

В статье изучены перспективы для развития туристской деятельности на особо охраняемых природных территориях, в частности государственных национальных природных парков в Республике Казахстан.  Определены сдерживающие факторы, слабые стороны для развития туризма на территориях нацпарков. Даны пути решения проблем и сдерживающих факторов в условиях пандемии для переориентации выездного туристского потока на развитие внутреннего туризма. Проведен анализ самых популярных туристских направлений среди нацпарков.

Ключевые слова: национальные природные парки, туризм, пандемия, государство
Skirtingų kineziterapijos programų poveikis kaklinės stuburo dalies skausmui ir sutrikusiai funkcinei būklei
Authors: Jankauskaitė Akvilė , Sipavičienė Saulė
Published: August 2021

Tyrimo pagrindimas. Mokslininkų teigimu, kaklo skausmas yra globalus sveikatos sutrikimas, kuris paveikia žmogaus gyvenimo kokybę. Dėl skirtingai vertinamų metodikų stinga tyrėjų nuomonės, kokia kineziterapijos intervencija yra veiksmingiausia mažinant kaklinės stuburo dalies skausmą, todėl pasirinkome palyginti tris skirtingas intervencijas.

Tikslas. Nustatyti skirtingų kineziterapijos metodų poveikį stuburo kaklinės dalies skausmui ir sutrikusiai funkcinei būklei.

Metodai. Buvo tiriami 89 asmenys, kurie skundėsi nespecifinio pobūdžio lėtiniu kaklo skausmu. Tiriamieji buvo suskirstyti į tris grupes. Pirmai grupei buvo taikomi gydomieji pratimai, antrai grupei – gydomieji pratimai ir vakuuminės taurės, trečiai grupei – gydomieji pratimai ir kinezioteipavimas. Prieš intervencijas ir po jų buvo įvertinta tiriamųjų gyvenimo kokybė, funkcinė negalia, skausmas bei kaklo judesių amplitudės.

Rezultatai. Po reabilitacijos pastebėti visų grupių tiriamųjų statistiškai reikšmingai pagerėję rodikliai. Po tyrimo skausmas sumažėjo visuose grupėse. Palyginus rodiklius tarp grupių, pastebėti geresni gydomųjų pratimų ir vakuuminių taurių grupės rodikliai, šios grupės tiriamiesiems reikšmingai sumažėjo skausmo intensyvumas, padidėjo kaklo judesių amplitudės ir pagerėjo gyvenimo kokybė (p < 0,05).

Išvada. Gydomieji pratimai su vakuuminėmis taurėmis labiau sumažino skausmo intensyvumą ir funkcinę negalią, aktyvių galvos judesių amplitudė padidėjo labiau nei taikant kitas kineziterapines programas.

Raktažodžiai: kaklo skausmas, kinezioteipavimas, vakuuminės taurės, gydomieji pratimai.
Stuburo stabilizavimo ir klubo sąnario mobilumą didinančių pratimų programos poveikis pacientams, kurie jaučia lėtinį nespecifinį apatinės nugaros dalies skausmą
Authors: Urbanavičiūtė Laura , Sipavičienė Saulė , Švedaitė Neringa
Published: August 2021

Tyrimo pagrindimas. Viena iš apatinės nugaros dalies skausmo priežasčių yra liemens raumenų silpnumas bei sutrikusi giliųjų liemens raumenų kontrolė. Norint išlaikyti juosmeninės stuburo dalies ir dubens stabilumą bei išvengti skausmo arba funkcijos sutrikimo, svarbu aktyvuoti dauginį, skersinį pilvo, vidinius įstrižinius ir didįjį sėdmens raumenis (Kim, Yim, 2020).

Tyrimo tikslas – įvertinti stuburo stabilizavimo pratimų programos ir stuburo stabilizavimo kartu su klubo sąnario mobilumą didinančiais pratimais programos poveikį skausmui bei funkcinei būklei asmenims su lėtiniu nespecifiniu apatinės nugaros dalies skausmu.

Metodai. Tyrime dalyvavo 20 pacientų, kurie skundėsi lėtiniu nespecifiniu apatinės nugaros dalies skausmu, jie atsitiktiniu būdu buvo suskirstyti į dvi grupes. Pirmos grupės tiriamųjų amžius buvo 24,90 ± 3,70 metų, antros – 30,00 ± 4,30 metų. Užsiėmimai vyko tris kartus per savaitę, šešias savaites. Buvo vertinami skausmo, funkcinės būklės ir negalios, stuburo juosmeninės dalies paslankumo, šlaunies judesių amplitudės, pilvo raumenų statinės ištvermės pokyčiai.

Rezultatai. Po tyrimo skausmas sumažėjo abiejose grupėse (p < 0,05). Juosmeninės stuburo dalies paslankumas abiejose grupėse pagerėjo (p < 0,05). Šlaunies lenkimo, tiesimo, atitraukimo ir pritraukimo judesių amplitudės pirmoje grupėje padidėjo (p < 0,05); antroje grupėje statistiškai reikšmingai nepakito. Funkcinė būklė pagerėjo abiejose grupėse (p < 0,05). Pilvo raumenų ištvermė pagerėjo abiejose grupėse (p < 0,05). Po tyrimo, statistiškai reikšmingo vertintų rodiklių skirtumo tarp grupių nebuvo.

Išvados. Taikant tiek stuburo stabilizavimo pratimus, tiek stuburo stabilizavimo pratimus kartu su klubo sąnario mobilumą didinančiais pratimais, sumažėjo nugaros skausmas, pagerėjo juosmeninės nugaros dalies stabilumas, padidėjo šlaunies judesių amplitudė, tarp programų poveikio reikšmingo skirtumo nebuvo.

Raktažodžiai: stuburo stabilizavimo pratimai, klubo sąnario mobilumą didinantys pratimai, apatinės nugaros dalies skausmas.
Robust Optimal Damper Placement of Nonlinear Oil Dampers With Uncertainty Using Critical Double Impulse
Authors: Fujita Kohei , Wataya Ryota , Takewaki Izuru
Published: August 2021

A new robust method for optimal damper placement is presented for building structures under the critical double impulse. Oil dampers are treated here as representative supplemental dampers to control the seismic response of high-rise buildings. Such oil dampers usually obey a bi-linear force-velocity relation in controlling the maximum damping force through a relief mechanism to avoid the occurrence of excessive design forces in surrounding frames. The influence of uncertainty in characteristics of those bi-linear oil dampers on building structural safety is investigated. For the efficient evaluation of dynamic performance, the resonant critical double impulse is used as the base input instead of actual earthquake ground motions. Since the critical double impulse is determined to maximize the input energy to the objective building by changing the second impulse timing, uncertainties in input ground motions can be taken into account in a robust manner. To consider these various uncertainties, the robustness function based on the Info-Gap model is used in the robust optimization to assess structural performance variations caused by various uncertainties in the structural design phase. In this paper, a new innovative objective function in the robust optimal damper placement problem is proposed to enhance the robustness of structural performance under the variation of structural parameters by comparing the robustness function of the robust design with that of an ordinary optimal damper placement without considering uncertainties. Numerical examples of the robust optimal design of linear and bi-linear oil damper placements are shown for 10-story and 20-story planar building frame models. Structural performances of the robust optimal design to the conventional design earthquake ground motions are examined to investigate the validity of using the critical double impulse in the structural design under uncertainties.
Parkinson’s Disease: A Nanotheranostic Approach Targeting Alpha-Synuclein Aggregation
Authors: Zoey Fong LaiGuan , Palanivel Mathangi , Padmanabhan Parasuraman , Gulyás Balázs
Published: August 2021

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders that is implicated in aging populations. As numerous developed nations are experiencing progressively aging populations today, there is a heightened propensity for the occurrence of PD cases. Alpha-synuclein (α-syn) aggregation has been considered to be the pivotal mechanism leading to PD pathogenesis. Thus, early diagnostic and therapeutic strategies targeting the misfolded α-syn protein can potentially improve the prognosis of PD. With rapid advancements in nanotechnology in the last decade, effective solutions to various neurodegenerative and oncological diseases have been suggested. This review will explore the current innovations in nanotechnology that target the α-syn aggregation pathway, and reinstate the promise they hold as effective early diagnostic and therapeutic solutions to PD.
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer
Authors: Yan Yilin , Cai Jinming , Huang Zhengnan , Cao Xiangqian , Tang Pengfei , Wang Zeyi , Zhang Fang , Xia Shujie , Shen Bing
Published: August 2021

Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.
How Phagocytes Acquired the Capability of Hunting and Removing Pathogens From a Human Body: Lessons Learned From Chemotaxis and Phagocytosis of Dictyostelium discoideum (Review)
Authors: Xu Xuehua , Pan Miao , Jin Tian
Published: August 2021

How phagocytes find invading microorganisms and eliminate pathogenic ones from human bodies is a fundamental question in the study of infectious diseases. About 2.5 billion years ago, eukaryotic unicellular organisms–protozoans–appeared and started to interact with various bacteria. Less than 1 billion years ago, multicellular animals–metazoans–appeared and acquired the ability to distinguish self from non-self and to remove harmful organisms from their bodies. Since then, animals have developed innate immunity in which specialized white-blood cells phagocytes- patrol the body to kill pathogenic bacteria. The social amoebaeDictyostelium discoideumare prototypical phagocytes that chase various bacteria via chemotaxis and consume them as food via phagocytosis. Studies of this genetically amendable organism have revealed evolutionarily conserved mechanisms underlying chemotaxis and phagocytosis and shed light on studies of phagocytes in mammals. In this review, we briefly summarize important studies that contribute to our current understanding of how phagocytes effectively find and kill pathogens via chemotaxis and phagocytosis.
Contributions to Polar Amplification in CMIP5 and CMIP6 Models
Authors: Hahn L. C. , Armour K. C. , Zelinka M. D. , Bitz C. M. , Donohoe A.
Published: August 2021

As a step towards understanding the fundamental drivers of polar climate change, we evaluate contributions to polar warming and its seasonal and hemispheric asymmetries in Coupled Model Intercomparison Project phase 6 (CMIP6) as compared with CMIP5. CMIP6 models broadly capture the observed pattern of surface- and winter-dominated Arctic warming that has outpaced both tropical and Antarctic warming in recent decades. For both CMIP5 and CMIP6, CO2 quadrupling experiments reveal that the lapse-rate and surface albedo feedbacks contribute most to stronger warming in the Arctic than the tropics or Antarctic. The relative strength of the polar surface albedo feedback in comparison to the lapse-rate feedback is sensitive to the choice of radiative kernel, and the albedo feedback contributes most to intermodel spread in polar warming at both poles. By separately calculating moist and dry atmospheric heat transport, we show that increased poleward moisture transport is another important driver of Arctic amplification and the largest contributor to projected Antarctic warming. Seasonal ocean heat storage and winter-amplified temperature feedbacks contribute most to the winter peak in warming in the Arctic and a weaker winter peak in the Antarctic. In comparison with CMIP5, stronger polar warming in CMIP6 results from a larger surface albedo feedback at both poles, combined with less-negative cloud feedbacks in the Arctic and increased poleward moisture transport in the Antarctic. However, normalizing by the global-mean surface warming yields a similar degree of Arctic amplification and only slightly increased Antarctic amplification in CMIP6 compared to CMIP5.
Investigation of the Thermal Conductivity, Viscosity, and Thermal Performance of Graphene Nanoplatelet-Alumina Hybrid Nanofluid in a Differentially Heated Cavity
Authors: Borode Adeola O. , Ahmed Noor A. , Olubambi Peter A. , Sharifpur Mohsen , Meyer Josua P.
Published: August 2021

This paper investigates the thermophysical properties and heat transfer performance of graphene nanoplatelet (GNP) and alumina hybrid nanofluids at different mixing ratios. The electrical conductivity and viscosity of the nanofluids were obtained at temperatures between 15–55°C. The thermal conductivity was measured at temperatures between 20–40°C. The natural convection properties, including Nusselt number, Rayleigh number, and heat transfer coefficient, were experimentally obtained at different temperature gradients (20, 25, 30, and 35°C) in a rectangular cavity. The Mouromtseff number was used to theoretically estimate all the nanofluids’ forced convective performance at temperatures between 20–40°C. The results indicated that the thermal conductivity and viscosity of water are increased with the hybrid nanomaterial. On the other hand, the viscosity and thermal conductivity of the hybrid nanofluids are lesser than that of mono-GNP nanofluids. Notwithstanding, of all the hybrid nanofluids, GNP-alumina hybrid nanofluid with a mixing ratio of 50:50 and 75:25 were found to have the highest thermal conductivity and viscosity, enhancing thermal conductivity by 4.23% and increasing viscosity by 15.79%, compared to water. Further, the addition of the hybrid nanomaterials improved the natural convective performance of water while it deteriorates with mono-GNP. The maximum augmentation of 6.44 and 10.48% were obtained for Nuaverage and haverage of GNP-Alumina (50:50) hybrid nanofluid compared to water, respectively. This study shows that hybrid nanofluids are more effective for heat transfer than water and mono-GNP nanofluid.
Participatory Qualitative Modeling to Assess the Sustainability of a Coastal Socio-Ecological System
Authors: Gourguet Sophie , Marzloff Martin Pierre , Bacher Cedric , Boudry Pierre , Cugier Philippe , Dambacher Jeffrey Mark , Desroy Nicolas , Gangnery Aline , Le Mao Patrick , Monnier Léa , Pérez Agúndez José A. , Thébaud Olivier
Published: August 2021

Assessing the sustainability of socio-ecological systems requires understanding the interactions between numerous ecological, economic and social components. Models are often used to investigate how interactions shape system feedbacks and drive the complex dynamics at play in such systems. However, building these models is a non-trivial exercise, which often neglects stakeholder knowledge and perceptions. We adopted a participatory approach that relies on conducting workshops to engage stakeholders into the development of qualitative models of system feedback. This type of participatory qualitative modeling is well suited to address the complexity of socio-ecological systems in a holistic manner, identify key stakes and feedbacks, and predict responses to perturbations. We use this approach to investigate the factors that condition sustainability of the socio-ecological system associated with shellfish aquaculture in the Normand-Breton Gulf in France. Six region-specific workshops were organized with shellfish producers, managers and other stakeholders to identify and describe key components, interactions and pressures that contribute to overall socio-ecological dynamics. Differences and commonalities in system perceptions were identified across the different regions and focus groups. We reconciled stakeholder-specific discrepancies in model structure into a synthetic representation that conciliates alternative views of the system. Next, we predicted how the system might respond to alternative scenarios of change. Overall, our participatory qualitative modeling exercise identified key drivers of the system under study that constitute effective management levers to maintain system sustainability. For instance, low social acceptability of the aquaculture industry generally appears to be a major constraint on the sustainability of shellfish aquaculture in the Normand-Breton Gulf, while reducing rearing density appears to be a key driver of sustainability.
Interpreting Immunoregulation in Lung Fibrosis: A New Branch of the Immune Model
Authors: Huaux François
Published: August 2021

Immunostimulation is recognized as an important contribution in lung fibrosis in some animal models and patient subsets. With this review, we illustrate an additional scenario covering the possible implication of immunoregulation during fibrogenesis. Available animal and human data indicate that pulmonary fibrosis also includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells (immunosuppressive macrophages and myeloid-derived suppressive cells; MDSC). They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators (mainly TGF-β1 and IL-10) that directly or indirectly stimulate fibroblasts and matrix protein deposition. The existence of this silent immunoregulatory environment sustains an alternative mechanism of fibrosis that explains why in some conditions neither pro-inflammatory cytokine deficiency nor steroid and immunosuppressive therapies limit lung fibrosis. Therefore, the persistent presence of immunoregulation is an important parameter to consider for refining therapeutical strategies in lung fibrotic disorders under non-immunostimulatory conditions.
The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?
Authors: Roberto Michela , Carconi Catia , Cerreti Micaela , Schipilliti Francesca Matilde , Botticelli Andrea , Mazzuca Federica , Marchetti Paolo
Published: August 2021

The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota’s community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.
Extracellular Vesicles in Sickle Cell Disease: Plasma Concentration, Blood Cell Types Origin Distribution and Biological Properties
Authors: Nader Elie , Garnier Yohann , Connes Philippe , Romana Marc
Published: August 2021

Prototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In addition to anemia, SCD patients may exhibit a plethora of clinical manifestations ranging from acute complications such as the frequent and debilitating painful vaso-occlusive crisis to chronic end organ damages. Several interrelated pathophysiological processes have been described, including impaired blood rheology, increased blood cell adhesion, coagulation, inflammation and enhanced oxidative stress among others. During the last two decades, it has been shown that extracellular vesicles (EVs), defined as cell-derived anucleated particles delimited by a lipid bilayer, and comprising small EVs (sEVs) and medium/large EVs (m/lEVs); are not only biomarkers but also subcellular actors in SCD pathophysiology. Plasma concentration of m/lEVs, originated mainly from RBCs and platelets (PLTs) but also from the other blood cell types, is higher in SCD patients than in healthy controls. The concentration and the density of externalized phosphatidylserine of those released from RBCs may vary according to clinical status (crisis vs. steady state) and treatment (hydroxyurea). Besides their procoagulant properties initially described, RBC-m/lEVs may promote inflammation through their effects on monocytes/macrophages and endothelial cells. Although less intensely studied, sEVs plasma concentration is increased in SCD and these EVs may cause endothelial damages. In addition, sEVs released from activated PLTs trigger PLT-neutrophil aggregation involved in lung vaso-occlusion in sickle mice. Altogether, these data clearly indicate that EVs are both biomarkers and bio-effectors in SCD, which deserve further studies.
Virulence of Cholera Toxin Gene-Positive Vibrio cholerae Non-O1/non-O139 Strains Isolated From Environmental Water in Kolkata, India
Authors: Takahashi Eizo , Ochi Sadayuki , Mizuno Tamaki , Morita Daichi , Morita Masatomo , Ohnishi Makoto , Koley Hemanta , Dutta Moumita , Chowdhury Goutam , Mukhopadhyay Asish K. , Dutta Shanta , Miyoshi Shin-Ichi , Okamoto Keinosuke
Published: August 2021

Cholera toxin (CT)-producing Vibrio cholerae O1 and O139 cause acute diarrheal disease and are proven etiological agents of cholera epidemics and pandemics. On the other hand, V. cholerae non-O1/non-O139 are designated as non-agglutinable (NAG) vibrios and are not associated with epidemic cholera. The majority of NAG vibrios do not possess the gene for CT (ctx). In this study, we isolated three NAG strains (strains No. 1, 2, and 3) with ctx from pond water in Kolkata, India, and examined their pathogenic properties. The enterotoxicity of the three NAG strains in vivo was examined using the rabbit ileal intestinal loop test. Strain No. 1 induced the accumulation of fluid in the loop, and the volume of fluid was reduced by simultaneous administration of anti-CT antiserum into the loop. The volume of fluid in the loop caused by strains No. 2 and 3 was small and undetectable, respectively. Then, we cultured these three strains in liquid medium in vitro at two temperatures, 25°C and 37°C, and examined the amount of CT accumulated in the culture supernatant. CT was accumulated in the culture supernatant of strain No.1 when the strain was cultured at 25°C, but that was low when cultured at 37°C. The CT amount accumulated in the culture supernatants of the No. 2 and No. 3 strains was extremely low at both temperature under culture conditions examined. In order to clarify the virulence properties of these strains, genome sequences of the three strains were analyzed. The analysis showed that there was no noticeable difference among three isolates both in the genes for virulence factors and regulatory genes of ctx. However, vibrio seventh pandemic island-II (VSP-II) was retained in strain No. 1, but not in strains No. 2 or 3. Furthermore, it was revealed that the genotype of the B subunit of CT in strain No. 1 was type 1 and those of strains No. 2 and 3 were type 8. Histopathological examination showed the disappearance of villi in intestinal tissue exposed to strain No. 1. In addition, fluid accumulated in the loop due to the action of strain No. 1 had hemolytic activity. This indicated that strain No. 1 may possesses virulence factors to induce severe syndrome when the strain infects humans, and that some strains of NAG vibrio inhabiting pond water in Kolkata have already acquired virulence, which can cause illness in humans. There is a possibility that these virulent NAG vibrios, which have acquired genes encoding factors involved in virulence of V. cholerae O1, may emerge in various parts of the world and cause epidemics in the future.
Molecular Dynamics Simulations Reveal the Interaction Fingerprint of Remdesivir Triphosphate Pivotal in Allosteric Regulation of SARS-CoV-2 RdRp
Authors: Srivastava Mitul , Mittal Lovika , Kumari Anita , Asthana Shailendra
Published: August 2021

The COVID-19 pandemic has now strengthened its hold on human health and coronavirus’ lethal existence does not seem to be going away soon. In this regard, the optimization of reported information for understanding the mechanistic insights that facilitate the discovery towards new therapeutics is an unmet need. Remdesivir (RDV) is established to inhibit RNA-dependent RNA polymerase (RdRp) in distinct viral families including Ebola and SARS-CoV-2. Therefore, its derivatives have the potential to become a broad-spectrum antiviral agent effective against many other RNA viruses. In this study, we performed comparative analysis of RDV, RMP (RDV monophosphate), and RTP (RDV triphosphate) to undermine the inhibition mechanism caused by RTP as it is a metabolically active form of RDV. The MD results indicated that RTP rearranges itself from its initial RMP-pose at the catalytic site towards NTP entry site, however, RMP stays at the catalytic site. The thermodynamic profiling and free-energy analysis revealed that a stable pose of RTP at NTP entrance site seems critical to modulate the inhibition as its binding strength improved more than its initial RMP-pose obtained from docking at the catalytic site. We found that RTP not only occupies the residues K545, R553, and R555, essential to escorting NTP towards the catalytic site, but also interacts with other residues D618, P620, K621, R624, K798, and R836 that contribute significantly to its stability. From the interaction fingerprinting it is revealed that the RTP interact with basic and conserved residues that are detrimental for the RdRp activity, therefore it possibly perturbed the catalytic site and blocked the NTP entrance site considerably. Overall, we are highlighting the RTP binding pose and key residues that render the SARS-CoV-2 RdRp inactive, paving crucial insights towards the discovery of potent inhibitors.
Dose-Dependent Variation of Synchronous Metabolites and Modules in a Yin/Yang Transformation Model of Appointed Ischemia Metabolic Networks
Authors: Qi Yifei , Zhou Niwen , Jiang Qing , Wang Zhi , Zhang Yingying , Li Bing , Xu Wenjuan , Liu Jun , Wang Zhong , Zhu Lixing
Published: August 2021

Aim

Chinese medicine Danhong injection (DHI) is an effective pharmaceutical preparation for treating cerebral infarction. Our previous study shows that DHI can remarkably reduce the ischemic stroke-induced infarct volume in a dose-dependent manner, but the pharmacological mechanism of the DHI dose-dependent relationship is not clear. Therefore, the dose-dependent efficacy of DHI on cerebral ischemia and the underlying mechanisms were further investigated in this study.

Methods

A middle cerebral artery occlusion (MCAO) model was established and the rats were randomly divided into six groups: sham, vehicle, DHI dose-1, DHI dose-2, DHI dose-3, and DHI dose-4. Forty-one metabolites in serum were selected as candidate biomarkers of efficacy phenotypes by the Agilent 1290 rapid-resolution liquid chromatography system coupled with the Agilent 6550 Q-TOF MS system. Then, the metabolic networks in each group were constructed using the Weighted Correlation Network analysis (WGCNA). Moreover, the Yang and Yin transformation of six patterns (which are defined by up- and downregulation of metabolites) and synchronous modules divided from a synchronous network were used to dynamically analyze the mechanism of the drug’s effectiveness.

Results

The neuroprotective effect of DHI has shown a dose-dependent manner, and the high-dose group (DH3 and DH4) effect is better. The entropy of the metabolic network and the Yin/Yang index both showed a consistent dose–response relationship. Seven dose-sensitive metabolites maintained constant inverse upregulation or downregulation in the four dose groups. Three synchronous modules for the DH1–DH4 full-course network were identified. Glycine, N-acetyl-L-glutamate, and tetrahydrofolate as a new emerging module appeared in DH2/DH3 and enriched in glutamine and glutamate metabolism-related pathways.

Conclusion

This study takes the DHI metabolic network as an example to provide a new method for the discovery of multiple targets related to pharmacological effects. Our results show that the three conservative allosteric module nodes, taurine, L-tyrosine, and L-leucine, may be one of the basic mechanisms of DHI in the treatment of cerebral infarction, and the other three new emerging module nodes glyoxylate, L-glutamate, and L-valine may participate in the glutamine and glutamate metabolism pathway to improve the efficacy of DHI.
The Evaluation of UPro as a New Nutrient on High-Quality Egg Production From the Perspective of Egg Properties, Intestinal Histomorphology, and Oviduct Function of Laying Hens
Authors: Chang Xinyu , Qiu Kai , Wang Jing , Zhang Haijun , You Shizhou , Mi Shuichao , Qi Guanghai , Wu Shugeng
Published: August 2021

This study was to investigate the effects of UPro as a new nutritive fortifier on high-quality egg production from the perspective of egg properties, intestinal histomorphology, and oviduct function of laying hens. Four hundred thirty-two Hy-Line Brown laying hens aged 56 weeks were allocated to four groups. Layers were given a basal diet or supplemented with different levels of small peptides (0.2, 0.4, and 0.8%) to replace soybean meal. After 1-week adaptation period, the feeding trial was conducted for 12 weeks. The results showed that UPro addition significantly decreased (P < 0.05) the hardness, stickiness, and chewiness of albumen of layers on weeks 12. A linear elevation (P < 0.05) in the albumen height, Haugh unit (HU), and crude protein content of albumen of layers were noted on week 12 along with dietary UPro addition increasing, and the villus height (VH) and villus height-to-crypt depth radio (VCR) of jejunum also linearly increasing (P < 0.05). In addition, there were linear elevations (P < 0.05) in the relative mRNA expression of Sec23 homolog A (Sec23A) and protein-O-mannosyltransferase1 (POMT1) in layers as dietary UPro addition increased. In conclusion, dietary UPro addition could improve intestinal health, increase the absorption of nutrients, and improve egg quality of laying hens. The possible mechanism underlying UPro improving the quality and processing characteristics of albumen is up-regulating Sec23A and POMT1 expression of magnum. These findings will promote the application of UPro as a new nutritional additive in the production of high-quality eggs.
Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications
Authors: Steverink Jasper G. , Piluso Susanna , Malda Jos , Verlaan Jorrit-Jan
Published: August 2021

The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painful overall. Current literature showed that bupivacaine induced dose-dependent myo-, chondro-, and neurotoxicity, as well as delayed osteogenesis and disturbed wound healing in vitro. These observations did not translate to animal and clinical research, where toxic phenomena were seldom reported. An exception was bupivacaine-induced chondrotoxicity, which can mainly occur during continuous joint infusion. To decrease opioid consumption and provide sustained pain relief following musculoskeletal surgery, new strategies incorporating high concentrations of bupivacaine in drug delivery carriers are currently being developed. Local toxicity of these high concentrations is an area of further research. This review appraises relevant in vitro, animal and clinical studies on musculoskeletal local toxicity of bupivacaine.
Fiberized Diamond-Based Vector Magnetometers
Authors: Chatzidrosos Georgios , Rebeirro Joseph Shaji , Zheng Huijie , Omar Muhib , Brenneis Andreas , Stürner Felix M. , Fuchs Tino , Buck Thomas , Rölver Robert , Schneemann Tim , Blümler Peter , Budker Dmitry , Wickenbrock Arne
Published: August 2021

We present two fiberized vector magnetic-field sensors, based on nitrogen-vacancy (NV) centers in diamond. The sensors feature sub-nT/Hz magnetic sensitivity. We use commercially available components to construct sensors with a small sensor size, high photon collection, and minimal sensor-sample distance. Both sensors are located at the end of optical fibres with the sensor-head freely accessible and robust under movement. These features make them ideal for mapping magnetic fields with high sensitivity and spatial resolution (≤ mm). As a demonstration we use one of the sensors to map the vector magnetic field inside the bore of a ≥100 mT Halbach array. The vector field sensing protocol translates microwave spectroscopy data addressing all diamonds axes and including double quantum transitions to a 3D magnetic field vector.
Lattice Boltzmann Simulation of Multicomponent Porous Media Flows With Chemical Reaction
Authors: Lei Timan , Luo Kai H.
Published: August 2021

Flows with chemical reactions in porous media are fundamental phenomena encountered in many natural, industrial, and scientific areas. For such flows, most existing studies use continuum assumptions and focus on volume-averaged properties on macroscopic scales. Considering the complex porous structures and fluid–solid interactions in realistic situations, this study develops a sophisticated lattice Boltzmann (LB) model for simulating reactive flows in porous media on the pore scale. In the present model, separate LB equations are built for multicomponent flows and chemical species evolutions, source terms are derived for heat and mass transfer, boundary schemes are formulated for surface reaction, and correction terms are introduced for temperature-dependent density. Thus, the present LB model offers a capability to capture pore-scale information of compressible/incompressible fluid motions, homogeneous reaction between miscible fluids, and heterogeneous reaction at the fluid–solid interface in porous media. Different scenarios of density fingering with homogeneous reaction are investigated, with effects of viscosity contrast being clarified. Furthermore, by introducing thermal flows, the solid coke combustion is modeled in porous media. During coke combustion, fluid viscosity is affected by heat and mass transfer, which results in unstable combustion fronts.
A Complete and Low-Cost Cardiac Optical Mapping System in Translational Animal Models
Authors: Marina-Breysse Manuel , García-Escolano Alba , Vila-García Joaquín , Reale-Nosei Gabriel , Alfonso-Almazán José M. , Yan Ping , Quintanilla Jorge G. , Loew Leslie M. , Lee Peter , Filgueiras-Rama David
Published: August 2021

Clinicians, biologists, physicists, engineers, and computer scientists are coming together to better understand heart disease, which is currently the leading cause of death globally. Optical mapping, a high-speed fluorescence imaging technique that visualizes and measures key cardiac parameters such as action potentials, cytosolic calcium transients, and fibrillation dynamics, is a core research tool that has arisen from such interdisciplinary collaborations. In an effort to broaden its use, especially among clinical scientists and students, we developed a complete and low-cost optical mapping system, including a constant-flow Langendorff perfusion system, which minimizes the economic threshold to widespread use of this powerful tool in cardiac electrophysiology research. The system described here provides high spatiotemporal resolution data about action potentials, intracellular calcium transients and fibrillation wave dynamics in isolated Langendorff-perfused hearts (pigs and rabbits), relevant for translational research. All system components and software elements are fully disclosed with the aim of increasing the use of this affordable and highly versatile tool among clinicians, basic scientists and students wishing to tackle their own research questions with their own customizable systems.