bluuebunny/crossref_metadata_2025 huggingface dataset:
Встановлення базового стандарту визначення розміру штрафів в адміністративному та кримінальному законодавстві: аналіз міжнародно-правових актів та матеріалів судової практики
Authors: Nadoiev  A. A. , Pavlenko  T. A.
Published: November 2020

Стаття присвячена питанню встановлення базових стандартів обчислення розміру штрафів у Кримінальному кодексі України та Кодексі України про адміністративні правопорушення, аналізу положень зарубіжного кримінального та адміністративного законодавства, матеріалів судової практики та теоретичних позиції з цього питання, формулюванню висновків та пропозицій, спрямованих на вдосконалення відповідних кримінально-правових та адміністративно-правових норм.
З огляду на те, що представники міжнародної спільноти активно досліджують можливість застосування альтернативної форми покарань, пов’язаних з мінімальним обмеженнями прав людини, в межах зазначеного наукового дослідження вивчено зарубіжний досвід встановлення належних та справедливих розмірів штрафу.
Метою статті є визначення актуальних розмірів штрафів, відповідних завданій шкоді вчиненням адміністративного правопорушення або кримінального злочину, як альтернативних видів адміністративного чи кримінального покарання.
Наукову новизну становлять розроблені на основі зарубіжного досвіду пропозиції щодо реструктуризації механізму обчислення розміру штрафу, що дозволить забезпечити однаковий ступінь репресивності штрафних санкцій для осіб, що мають різний рівень доходів.
Висновки. Реструктуризація механізму обчислення розміру штрафу є актуальною потребою адміністративного та кримінального законодавства України. Найбільш ефективним способом його вдосконалення виступає впровадження в якості базового стандарту розміру штрафних санкцій розміру середнього доходу винного.
Проте впровадження такого способу визначення розміру штрафу потребує чіткого нормативно-правового закріплення ефективного механізму обчислення доходу винної особи та врахування його майнового стану.
У зв’язку з відсутністю такого механізму видається, що на сьогоднішній день найбільш доцільним способом реформування порядку обчислення штрафу є встановлення його розміру кратно розміру податкової соціальної пільги. Це дає можливість забезпечити економічну обґрунтованість та високий рівень репресивності зазначеної форми покарання та її взаємозв’язок з динамікою доходів населення. Використання єдиного базового стандарту для розрахунку ступеня тяжкості правопорушення та розміру штрафу дозволить забезпечити пропорційність між рівнем соціальної небезпечності злочину та його караністю в умовах динамічної економічної ситуації в Україні.
Державне регулювання розвитку сільського зеленого туризму в Україні в умовах пандемії COVID-19
Authors: Nikoliuk  O. V. , Khaustova  V. Ye. , Petriv  I. M.
Published: November 2020

Метою статті є обґрунтування особливостей та перспектив організаційно-інституційного забезпечення державної політики розвитку сільського зеленого туризму в Україні в умовах пандемії COVID-19.
Наукова новизна. Запропоновано концептуальний підхід до визначення стратегічних напрямків підтримки розвитку сільського зеленого туризму в Україні у контексті формування дієвих інструментів та засобів організаційно-інституційного забезпечення в умовах пандемії COVID-19.
Висновки. Досліджено особливості державного регулювання розвитку сільського зеленого туризму в Україні в умовах пандемії COVID-19. Через виникнення на глобальному рівні безпрецедентної надзвичайної ситуації, спровокованої спалахом пандемії COVID-19, яка має масштабний вплив на всі сфери соціально-економічного розвитку країн світу, туристична індустрія потрапила до числа найбільш постраждалих секторів світових економік, а тому вимагає термінового впровадження відповідних заходів із відновлення та підтримки. Саме тому рівень державного стимулювання та підтримки розвитку сільського зеленого туризму визначає масштаби туристичних потоків у відповідних регіонах України і на глобальному рівні. Результати досліджень показують, що в кризових умовах розвиток сільського зеленого туризму супроводжується постійними динамічними інституційними змінами, а саме зміною правил, неофіційних обмежень, особливостей характеру та дотримання таких правил учасниками соціально-економічного процесу щодо обміну людськими, фінансовими, інформаційними й іншими ресурсами. Сформульовані основні положення організаційно-інституційної моделі розвитку сільського зеленого туризму в Україні в умовах пандемії COVID-19, яка орієнтована на досягнення консенсусу ключових груп суб’єктів економічних інтересів досліджуваної галузі, а саме: 1) інституційні форми (сільський зелений туристичний бізнес, держава, громадськість); 2) складові системи державного регулювання розвитку сільського зеленого туризму (фінансово-економічна, функціональна, споживацька, інтелектуальна-інноваційна).
Student cruise: Observing techniques for Physical Oceanographers Cruise No. AL529
Authors: Karstensen Johannes , Andrae Alexandra , Bitzan Ludwig , Deutloff Jakob , Lösel Christiane , Witting Paul J. , Niebaum Nils O. , Hänsch Martje , Lederer Jana , Staubert Tim , Menzel Daniel , Freund Marlene , Witt Rene , Strehl Anna-Marie , Großlindemann Hendrik , Posern Conny
Published: November 2020

Oct. 07 2019 – Oct. 10, 2019 Kiel (Germany) – Kiel (Germany) MNF-Pher-110The main purpose of the ALKOR cruise AL529 was the training of students in observational techniques applied by physical oceanographers. The students who participated in the trip attend the module "Measurement Methods of Oceanography" which is offered in the Bachelor program "Physics of the Earth System" at CAU Kiel. During the AL529 the students were instructed in instrument calibration and in the interpretation of measurement data at sea. In addition, the students had the opportunity to learn about working and living at sea and to explore and study the impact of physical processes in the western Baltic Sea, the sea at their doorstep. The observations show a quasi-synoptic picture of the hydrography and currents in the western Baltic Sea. Twice-repeated hydrographic and current sections across the Fehmarn Belt show well the short time scales where significant changes occur. A zonal section along the deepest topography, from about 10°40'E to 014°21'E, shows very nicely the two-layer system of outflowing low salinity and inflowing North Sea water. A bottom shield anchorage shows the currents in the water column and the near-bottom temperature and salinity variations in the Fehmarnbelt area.
Bridging Information Worlds
Authors: Kutner Laurie
Published: November 2020

The topic of global inequities in scholarly communication is complex and may be viewed from different perspectives depending upon multiple variables, including where you live in the world. This “Report from the Field” presents the author’s experiences and reflections on facilitating formal discussions of this topic at the Monteverde Institute (MVI) in Costa Rica. The Monteverde Institute (MVI) is a Costa Rican non-profit organization that provides infrastructure and support for education abroad programs focused on community engaged scholarship, as well as support for both international and locally based researchers who focus their study in the area. Its middle vantage point provides unique advantages for engaging multiple constituencies in conversations about the inherent inequalities of our current scholarly information universe from both Global North and Global South perspectives. This report focuses on the author’s experiences and reflections on discussions about equity issues in scholarly access and production, with North American students as well as local researchers and community members in Latin America that took place between 2017-2019. The richness of engagement with this topic was facilitated by the opportunities afforded by the ability to hear multiple perspectives, backgrounds, and lived realities in this single space.
Diversity, Inclusivity, Social Responsibility Aspects, and Outcomes of a Mobile Digital Library and Information Service Model for a Developing Country
Authors: Moshoeshoe-Chadzingwa Matseliso 'Mamahlape
Published: November 2020

The provision of library services through rigid compartmentalisation of academic, public, school, and special libraries operating in one country can be cost-effective if a country has strong socio-economic, cultural, educational, and political structures. This arrangement is apparently a fallacy for countries that lack such structures, as is the case with Lesotho. This study examined the outcomes and the impact of the UNESCO-funded project titled Distance and Rural Learner-Teacher Support through a Mobile Digital Library (DRULETSMODIL) in Lesotho. The National University of Lesotho (NUL) Library proposed DRULETSMODIL whose objective was to reach out to NUL’s de jure distant teachers and learners. Additionally, the project expanded its scope to include library services to rural and poor communities. This paper outlines how use of the descriptive method, called the corporate social responsibility (CSR) principle, utilised the case study approach to interrogate DRULETSMODIL’s performance. The findings reveal that the project embodied various levels of diversity, inclusivity, and (mainly) social responsibility aspects of providing information for free, to the marginalized communities. From DRULETSMODIL’s three phases covering all the ten districts of Lesotho, positive outcomes were recorded. Through Information, Communication, and Technology apparatuses, DRULETSMODIL’s offerings, and the support of Participatory Initiative for Social Accountability (PISA), diverse information was easily and cost-effectively accessible. The project attracted various partners; beneficiaries included academic library users, secondary schools, and male and female youth and adults in the villages. The study recommends advocacy on CSR for all types of businesses and consideration of this model for developing countries.
Endogenous and combination retinoids are active in myelomonocytic leukemias
Authors: Di Martino Orsola , Niu Haixia , Hadwiger Gayla , Kuusanmaki Heikki , Ferris Margaret A. , Vu Anh , Beales Jeremy , Wagner Carl , Menéndez-Gutiérrez María P. , Ricote Mercedes , Heckman Caroline , Welch John S.
Published: November 2020

Retinoid therapy transformed response and survival outcomes in acute promyelocytic leukemia (APL), but has demonstrated only modest activity in non-APL forms of acute myeloid leukemia (AML). The presence of natural retinoids in vivo could influence the efficacy of pharmacologic agonists and antagonists. We found that natural RXRA ligands, but not RARA ligands, were present in murine MLL-AF9-derived myelomonocytic leukemias in vivo and that the concurrent presence of receptors and ligands acted as tumor suppressors. Pharmacologic retinoid responses could be optimized by concurrent targeting RXR ligands (e.g. bexarotene) and RARA ligands (e.g. all-trans retinoic acid, ATRA), which induced either leukemic maturation or apoptosis depending on cell culture conditions. Co-repressor release from the RARA:RXRA heterodimer occurred with RARA activation, but not RXRA activation, providing an explanation for the combination synergy. Combination synergy could be replicated in additional, but not all, AML cell lines and primary samples, and was associated with improved survival in vivo, although tolerability of bexarotene administration in mice remained an issue. These data provide insight into the basal presence of natural retinoids in leukemias in vivo and a potential strategy for clinical retinoid combination regimens in leukemias beyond acute promyelocytic leukemia.
Real and gitopetical risks of the future accumulative level of pension insurance in Ukraine
Authors:   Polissia National University, Zaburanna L. , Shubenko I. ,   Polissia National University, Godniuk I. ,   Podilsky Special Education and Rehabilitation Socio-Economic College
Published: November 2020

No decisive steps have been taken in Ukraine to introduce a cumulative level of pension provision. The significant number of risks is one of the reasons for this. The purpose of the article is to study the theoretical foundations of hypothetical and real risks of the cumulative level of the pension system in Ukraine, which is expected to be introduced. A number of methods were used in the study, including abstract-logical, methods of analysis and synthesis and comparative analysis. It is argued that the cumulative level of pension provision will be characterized by a number of real risks: organizational and managerial risk, risk of high administrative costs, risk of depreciation of pension savings, selective risk, and risk of insufficient contributions. Hypothetical risks include market volatility risk and criminal risk. The cumulative level of pension provision is significantly affected by the risk of depreciation of pension savings, because given the high inflation rate and devaluation of the national currency, one should not expect a decent level of pensions in the long term, even taking into account the investment component of the cumulative level. It has been established that the domestic legal framework does not specify a mechanism for protection against such a risk, which undermines credibility to the functioning of the entire cumulative component of the pension system. Selective risk and the risk of financial market volatility are closely related to financial market trends and, under adverse conditions, may manifest themselves in the investment component of pension savings. It has been determined that the mechanism for overcoming such risks has not been defined in regulatory legal acts yet. Jointly, these risks determine the lack of principal steps in the process of reforming the modern pension system. In the case of the introduction of the cumulative level of pension provision, a system should be provided to prevent the risks of depreciation of pension savings and selective risks. Further studies will address the mechanisms that can prevent or reduce selective risks and risks of depreciation of pension savings.
Cost-effective methods for evaluation of pig breeding value in breeding farms in Khmelnytskyi region
Authors:   Khmelnytskyi State Agricultural Research Station Institute of Feed and Agriculture of Podillya NAAS, Verbuch I. , Bratkovska H. ,   Khmelnytskyi State Agricultural Research Station Institute of Feed and Agriculture of Podillya NAAS
Published: November 2020

The results of estimation of breeding value for Large White and Poltava meat pig breeds in breeding farms of the region by cost-effective methods are presented, namely: combined assessment of repair young stock on person’s productivity, estimation indices of fattening and meat qualities and new method BLUP. The best indicators for assessing the breeding value of animals were found on the basis of using the modern, most promising method BLUP, as it is considered the most accurate. The average value of the BLUP index (parent lines) for boars of Large White breed is 101.71±1.681, pigs – 96.94±0.724 points and Poltava meat breed, respectively, 106.23±2.167 and 93.65±0.719 points. The most positive correlation between live weight of piglets at weaning with their body length (r=0.16), average daily gain (r=0.19) and fat thickness (r=0.24), average correlation between the indices of fattening and meat qualities according to Berezovskyi M.D. and Tailer B. (r=0.56) P>0.99 and a weak correlation between live weight of piglets at weaning and the BLUR index (r=0.21) P>0.99.
Dynamics of Ukrainian insurance market development through the prism of top-rating indicators of insurance companies
Authors:   Polissia  National University, Demyanyuk I.
Published: November 2020

Insurance is a powerful catalyst for development of economy around the world. The domestic market of insurance services promotes to the redistribution of risks in the economy and forms the social protection of the population. Constant changes in economic processes and improvement of the provisions of state regulation form the relevance of the study of changes in insurance market indicators. The purpose of the study is to establish the dynamics of development of the insurance market in Ukraine through the prism of the top rating of insurance companies, including analysis of indicators of Zhytomyr region and to identify major gaps in the insurance sector and ways to remove it. The key tasks include: analysis of insurance payments and payouts of the top rating of insurance companies of Ukraine; assessment of the insurance market of Zhytomyr region in terms of insurance types; analysis of risks and prospects of the insurance market in the conditions of COVID-19. General scientific and statistical methods became research methods, namely: system analysis and generalization; methods of scientific abstraction, observation and comparison. The level of insurance payments and insurance payouts according to the top rating of insurance companies in Zhytomyr region and in Ukraine in general is assessed. A tendency to reduce the number of insurance companies due to changes in government regulation is detected. The specific weight of insurance payments and insurance payouts of Zhytomyr region within Ukraine is determined. A need to restore public confidence in the insurance market in order to increase the percentage of life insurance is detected. Leading companies in risky types of insurance in Zhytomyr region are identified. The risks and prospects of the insurance market in a pandemic are studied. The types of insurance that will suffer mostly from COVID-19 are identified. Ways to solve the problems of the modern insurance market in Ukraine are offered. Prospects for further research in this area are to improve regulations and to evaluate the actual indicators of the insurance market in a pandemic.
Implementation Evaluation Based Learning Curriculum 2013 Implementation of Activity Based on Learning Tematik in Elementary Schools in Labuhanbatu District
Authors: Putri Saadah Wan Sri , Husein Rahmad , Julaeha Siti
Published: November 2020

This research is a descriptive qualitative research which aims to describe the implementation of the 2013 Curriculum in the learning process in terms of learning planning, learning implementation, and learning evaluation. The population and sample in this study were teachers and students of Public Elementary Schools throughout Labuhanbatu Regency who have implemented the 2013 Curriculum since its inception in 2013, namely SD Negeri 28 Bilah Barat, SD Negeri 01 Bilah Barat, SD Negeri 08 Rantau Selatan, SD Negeri 11 Rantau Selatan, SD Negeri 15 Rantau Utara, and SD Negeri 06 Rantau Utara. The samples in this study were 46 for teacher respondents and 182 for student respondents at SD Negeri Labuhanbatu Regency. The instrument in this study was a semi-open questionnaire containing statement items, and the variable questionnaire was measured using a Likert scale. The results showed that the teacher's understanding of 2013 Curriculum-based learning planning was in the quite good category, with an average percentage of 74.72%. This is evidenced by the teacher's ability to compile a syllabus and lesson plans. The teacher's understanding of the implementation of curriculum-based learning in 2013 is in the good category, with an average percentage value of 76.13%. This can be seen from the teacher's ability in terms of class mastery. The teacher's understanding of the 2013 Curriculum-based learning evaluation is in the quite good category, with an average percentage of 73.5%. This can be proven by the teacher's ability to take an authentic approach. Meanwhile, the students' responses about the implementation of 2013 Curriculum-based learning carried out by the teacher showed a fairly good category, with an average percentage of 72.75%. For students' perceptions about the evaluation or assessment of learning based on the 2013 Curriculum conducted by the teacher, it is in the quite good category, with an average percentage of 73%.
İŞBİRLİKLİ ÖĞRENME İLE BİRLİKTE KULLANILAN MODELLERİN, ANİMASYONLARIN VE YEDİ İLKE’NİN KİMYA BAŞARISINA ETKİSİ
Authors: ALYAR Mustafa , DOMUŞ Kemal
Published: November 2020

Kimya, içerisinde birçok soyut kavramın yer aldığı bir disiplindir. Kimyanın öğrenilmesi için soyut yapıların anlaşılmasının önemli olduğu düşünülmektedir. Bu yüzden bu araştırma, soyut kavramların anlaşılması da göz önünde bulundurularak, işbirlikli öğrenme ile animasyonların, modellerin (oyun hamuru ve çubuk-top) ve yedi ilkenin (lisans eğitiminde niteliği arttırmak amacıyla ileri sürülen iyi bir eğitim için yedi ilke) birlikte uygulanmasının kimya başarısına etkisini incelemektedir. Araştırma ön test-son test karşılaştırmalı grup yarı deneysel desene göre yürütülmüştür. Araştırmaya 91 fen bilgisi öğretmenliği birinci sınıf öğrencisi katılmıştır. Öğrenciler dört farklı gruba ayrılmış ve birinci grupta işbirlikli öğrenme, ikinci grupta işbirlikli öğrenme ve yedi ilke, üçüncü grupta işbirlikli öğrenme ve animasyon, dördüncü grupta ise işbirlikli öğrenme ve modellerle uygulamalar gerçekleştirilmiştir. Katılımcılardan veriler iki ölçekle toplanmıştır. Deney gruplarının homojen olma durumlarını belirlemek için Ön Bilgi Testi, uygulanan yöntem ve tekniklerin kimya başarısına etkisini belirlemek için Akademik Başarı Testi kullanılmıştır. Araştırmadan elde edilen bulgular incelendiğinde işbirlikli öğrenmenin yedi ilke ile birlikte uygulanmasının kimya başarısı üzerinde ciddi bir etkisi (p
SOSYAL BİLGİLER ÖĞRETİMİNDE GÜNCEL OLAYLAR
Authors: SÖMEN Tuğba
Published: November 2020

Sosyal bilgiler dersi çevresinde olup biten olaylara duyarlı, yaşanan problemlerin farkında olan ve onlara bir çözüm yolu üretebilen, sorumluluklarının bilincinde, iyi vatandaşlar yetiştirmeyi amaçlayan bir derstir. Bu amacı gerçekleştirebilmek için öğrencilerin farkındalıklarını geliştirecek kaynaklara yer verilmesi önemlidir. Bunlardan biri de güncel olaylardır. Sosyal bilgiler öğretiminde güncel olaylara yer verilmesi ile öğrenciler, çeşitli kaynaklardan edindikleri güncel olaylarla ilgili bilgileri arkadaşlarıyla tartışabilir, analiz edebilir ve değerlendirebilirler. Güncel olayların öğretimi sırasında yapılabilecek etkinlikler ve kullanılacak materyallerin hazırlanmasında öğrencilerin aktif olarak rol alması gerekmektedir. Bilindiği üzere aktif katılım öğrenilenlerin kalıcılığını artırmada kilit rol üstlenmiştir. Öğrencilerin yaparak yaşayarak öğrenecekleri bir öğretim ortamı, sosyal bilgiler dersinin amaçlarını gerçekleştirmesine yardımcı olacaktır. Bu çalışmada öğrencilerin aktif katılımıyla gerçekleştirilen, güncel olayların sosyal bilgiler dersinde kullanımı konusu ele alınmıştır. Çalışmada güncel olaylarla ilgili temel bilgilere, güncel olayların öğretim sürecinde kullanılmasının faydalarına, güncel olayların öğretiminde benimsenen yaklaşımlara, güncel olayların sosyal bilgilerde kullanımı esnasında uygulanabilecek etkinliklere ve kullanılabilecek materyallere ve son olarak da sosyal bilgilerde güncel olayların öğretimine yönelik geliştirilen etkinlik örneklerine yer verilmiştir.
Motivos do abandono ou interrupção do tratamento de pacientes hansenianos atendidos em uma unidade de saúde da família da Cidade de São Luís, Estado do Maranhão, Brasil
Authors: Silva Carlene de Jesus Alves da , Moura Márcia Raquel Lima Amaral , Oliveira Jhessyca Silva de , Silva Raissa Sousa da , Ramos Nayra Regina Mendonça , Belfort Ilka Kassandra Pereira
Published: November 2020

No Brasil a hanseníase é um grave problema de saúde pública. Objetivo: Identificar os motivos associados ao abandono ou interrupção do tratamento de hanseníase em uma Unidade de Saúde da Família.  Metodologia: Trata-se de uma pesquisa de campo, de caráter exploratório, descritivo e documental com abordagem mista, realizada em uma Unidade de Saúde da Família no município de São Luís, com 4 pacientes, utilizando questionários e roteiro de entrevista semiestruturada, que foram gravadas e transcritas na íntegra. Resultados: Indicaram que acomete indivíduos homens e mulheres na mesma proporção, com faixas etárias diversificadas, com predominância na cor/raça parda e com baixo nível de escolaridade e ocupações, com renda total de até 1 salário mínimo, tornando-se fatores que favorecem à irregularidade ou abandono da poliquimioterapia. Conclusão: O estudo mostrou que os motivos expostos pelos respondentes destacaram-se: a indisponibilidade da medicação, subestimar a importância do tratamento e encaminhamento para outras unidades.
Cemaat izinde bir görme biçimi arayışı: “İhsan Hala” belgeseli
Authors: EKŞİ Sabri , BULUT Meryem
Published: November 2020

Bu çalışma, gündelik hayatın her alanında kendisini farklı tanımlamalar ekseninde döndüren aidiyet diye adlandırdığımız anlam setlerine dair bir temas alanıdır. Bireylerin bu aidiyet setleri özelinde güvenli alan uğruna fedakârlığa hazır olmaları ve diğer bir anlamda güvensiz olan alanların nasıl ötekileştirildikleri ile ilgili bakış açısının yazıya dönüştürülme çabalarından bir tanesidir. Cemaat sınırları diye atfedilen alanların nasıl korunduğunu keşfetme yöntemi, bu çalışmada görsel antropolojinin sunduğu veriler ile anlamlandırılmaya çalışılmıştır. Tabii bu kutsal olan gizemli sınırlarla temas etmek, büyük bir direniş ile karşılanmaktadır. Görsel antropolojinin bu direniş üzerinde sunduğu veriler teması en azamiye indirmektedir. Çalışmanın araştırma nesnesi Veysel Akşahin’in yönettiği “Hala” belgeselidir. Belgesel kurgusallıktan uzak olması nedeniyle tercih edilmiştir. İhsan Hala özelinde ele alınan bu belgeselin bölümlendirilerek başlıklar altında incelenmesinin akabinde, büyük bir ifade biçimine dönüşen hala etiketinin, İhsan Çolak üzerinde performatif olarak gelişen imajın nasıl anlamlandırıldığı ifade edilmeye çalışılmıştır.
Psychodrama Techniques in Adult Education
Authors: Schaefer Barbara
Published: November 2020

Where previous generations in the occurrence of apocalyptic fears may have been able to ward them off by either referring to old paradigms as safeguards or by having new authority figures introduced, we may have to face the 'Runaway World' , come to terms with it, and shape it without either of those patterns. We move into the unknown... (Written 2002) My professional experience using the technique and research in applied epistemology on related issues, form the basis of my hypothesis, that Psychodrama techniques developed by J.L. Moreno and his followers since the 1920s, can be applied and prove useful in Education in the above context.
Effective Biophysical Modeling of Cell Free Transcription and Translation Processes
Authors: Adhikari Abhinav , Vilkhovoy Michael , Vadhin Sandra , Lim Ha Eun , Varner Jeffrey D.
Published: November 2020

Transcription and translation are at the heart of metabolism and signal transduction. In this study, we developed an effective biophysical modeling approach to simulate transcription and translation processes. The model, composed of coupled ordinary differential equations, was tested by comparing simulations of two cell free synthetic circuits with experimental measurements generated in this study. First, we considered a simple circuit in which sigma factor 70 induced the expression of green fluorescent protein. This relatively simple case was then followed by a more complex negative feedback circuit in which two control genes were coupled to the expression of a third reporter gene, green fluorescent protein. Many of the model parameters were estimated from previous biophysical studies in the literature, while the remaining unknown model parameters for each circuit were estimated by minimizing the difference between model simulations and messenger RNA (mRNA) and protein measurements generated in this study. In particular, either parameter estimates from published studies were used directly, or characteristic values found in the literature were used to establish feasible ranges for the parameter estimation problem. In order to perform a detailed analysis of the influence of individual model parameters on the expression dynamics of each circuit, global sensitivity analysis was used. Taken together, the effective biophysical modeling approach captured the expression dynamics, including the transcription dynamics, for the two synthetic cell free circuits. While, we considered only two circuits here, this approach could potentially be extended to simulate other genetic circuits in both cell free and whole cell biomolecular applications as the equations governing the regulatory control functions are modular and easily modifiable. The model code, parameters, and analysis scripts are available for download under an MIT software license from the Varnerlab GitHub repository.
Exofucosylation of Adipose Mesenchymal Stromal Cells Alters Their Secretome Profile
Authors: García-Bernal David , García-Arranz Mariano , García-Guillén Ana I. , García-Hernández Ana M. , Blanquer Miguel , García-Olmo Damián , Sackstein Robert , Moraleda Jose M. , Zapata Agustín G.
Published: November 2020

Mesenchymal stromal cells (MSCs) constitute the cell type more frequently used in many regenerative medicine approaches due to their exclusive immunomodulatory properties, and they have been reported to mediate profound immunomodulatory effectsin vivo. Nevertheless, MSCs do not express essential adhesion molecules actively involved in cell migration, a phenotypic feature that hampers their ability to home inflamed tissues following intravenous administration. In this study, we investigated whether modification by fucosylation of murine AdMSCs (mAdMSCs) creates Hematopoietic Cell E-/L-selectin Ligand, the E-selectin-binding CD44 glycoform. This cell surface glycan modification of CD44 has previously shown in preclinical studies to favor trafficking of mAdMSCs to inflamed or injured peripheral tissues. We analyzed the impact that exofucosylation could have in other innate phenotypic and functional properties of MSCs. Compared to unmodified counterparts, fucosylated mAdMSCs demonstrated higherin vitromigration, an altered secretome pattern, including increased expression and secretion of anti-inflammatory molecules, and a higher capacity to inhibit mitogen-stimulated splenocyte proliferation under standard culture conditions. Together, these findings indicate that exofucosylation could represent a suitable cell engineering strategy, not only to facilitate thein vivoMSC colonization of damaged tissues after systemic administration, but also to convert MSCs in a more potent immunomodulatory/anti-inflammatory cell therapy-based product for the treatment of a variety of autoimmune, inflammatory, and degenerative diseases.
Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers
Authors: Muraca Giuliana , Berti Ignacio Rivero , Sbaraglini María L. , Fávaro Wagner J. , Durán Nelson , Castro Guillermo R. , Talevi Alan
Published: November 2020

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy–safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy–safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.
Porous Fe2O3 Nanorods on Hierarchical Porous Biomass Carbon as Advanced Anode for High-Energy-Density Asymmetric Supercapacitors
Authors: Yu Pingping , Duan Wei , Jiang Yanfeng
Published: November 2020

In this study, a novel negative electrode material was prepared by aligning α-Fe2O3 nanorods on a hierarchical porous carbon (HPC) skeleton. The skeleton was derived from wheat flour by a facile hydrothermal route to enhance conductivity, improve surface properties, and achieve substantially good electrochemical performances. The α-Fe2O3/HPC electrode exhibits enhanced specific capacitance of 706 F g−1, which is twice higher than that of α-Fe2O3. The advanced α-Fe2O3/HPC//PANI/HPC asymmetrical supercapacitor was built with an expanded voltage of 2.0 V in 1 M Li2SO4, possessing a specific capacitance of 212 F g−1 at 1 A g−1 and a maximum energy density of 117 Wh kg−1 at 1.0 kW kg−1, along with an excellent stability of 5.8% decay in capacitance after 5,000 cycles. This study affords a simple process to develop asymmetric supercapacitors, which exhibit high electrochemical performances and are applicable in next-generation energy storage devices, based on α-Fe2O3 hybrid materials.
Provocation to Dialog in a Third Space: Helping Teachers Walk Toward Equity Pedagogy
Authors: Ratnam Tara
Published: November 2020

This study examines the conceptual basis of how teachers learn, including, importantly, how they learn to relate to social concerns of equity in their teaching, and makes this understanding experientially accessible using a live case of the “practical” (Schwab, 1969). The conceptual understanding emerges from questioning the assumptions behind the valorization in teacher education of “theory” over “practice” that has led to the “theory into practice”/“input–output” model of teacher education. An examination of the constraints posed by this monolithic model of teacher education to teacher learning, development, and change has provided the impetus to work toward a more pluralistic view of knowledge and the new understanding of the nature of teacher learning which ensues. This alternative formation, which is informed by insights from the sociocultural perspectives of Lev Vygotsky and Mikhail Bakhtin among others, has helped in constructing a view of teacher learning as taking shape in authentic social interaction in a “third space” through hybridization of diverse voices. Most importantly, the paper considers its implications for teacher education by abstracting from experience the nature of mediation that facilitates hybridization.
Changing Relationship Between Tibetan Plateau Temperature and South China Sea Summer Monsoon Precipitation
Authors: Liang Mei , Xu Jianjun , Chan Johnny C. L. , Wu Liguang , Xu Xiangde
Published: November 2020

The present study documents the changes in the relationship between the Tibetan Plateau summer surface temperature (TPST) and the South China Sea summer monsoon precipitation (SCSSMP). A stepwise regression model is used to exclude the signals of global warming, El Niño–Southern Oscillation (ENSO), western North Pacific Subtropical High (WNPSH), Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO). The results indicate that the relationship between TPST–SCSSMP changes with time, going from a negative correlation during the period of 1980–1994 to an obvious positive correlation during 1998–2016 in the South China Sea. Meanwhile, the negative correlation between TPST and the East Asia subtropical front (Meiyu) is enhanced during 1998–2016. This change in the TPST–SCSSMP relationship is associated with the change of the atmospheric circulation, which is mainly due to TPST interdecadal variation. A wave–like structure at the low latitude moves eastward along the low–level monsoon flow, and a strong cyclonic circulation is apparent in the southwestern part of the Plateau, including the Indochina Peninsula, South China Sea, and the ocean to the east of the Philippines, which is consistent with the negative correlation between TPST and Outgoing Longwave Radiation (OLR). The increase in water–vapor convergence and more favorable convection conditions lead to more precipitation in the region after the late 1990s. The present results suggest that, in a changing climate, we should be cautious when using predictor with interdecadal variations.
Novel Method to Image and Quantify Cogwheel Structures in Foraminiferal Shells
Authors: van Dijk Inge , Raitzsch Markus , Brummer Geert-Jan A. , Bijma Jelle
Published: November 2020

Most studies designed to better understand biomineralization by foraminifera focus mainly on their shell chemistry in order to retrace processes responsible for element uptake and shell formation. Still, shell formation is a combination of not only chemical and biological processes, but is also limited by structural features. Since the processes involved in the formation of the foraminifera shell remains elusive, new focus has been put on potential structural constraints during shell formation. Revealing structural details of shells of foraminifera might increase our mechanistic understanding of foraminifera calcification, and even explain species-specific differences in element incorporation. Recently, shell structures have been studied in increasingly higher resolution and detail. This paper aims to provide new insights on the structural features on foraminifera shells, so-called cogwheels, which can be observed in the shell wall and at its surface. Here, we present a novel method to image and quantify these cogwheel structures, using field specimens from different environments and ecological groups, including benthic and planktonic species. Application of this method allows for comparing shell structures at specimen and species level, to unravel potential drivers of shell formation.
Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1
Authors: Tseng Jui-Cheng , Wei James Cheng-Chung , Deodhar Atul , Martin Ruvie , Porter Brian , McCreddin Suzanne , Talloczy Zsolt
Published: November 2020

Objectives

To present the long-term (4-year) efficacy and safety of secukinumab in Taiwanese patients with active AS in the MEASURE 1 extension study.

Methods

This post hoc analysis reports data from Taiwanese patients originally randomized to subcutaneous secukinumab 150 or 75mg or placebo every 4 weeks (following intravenous loading dose) who were invited to enter the 3-year extension study. Assessments at Week 208 included ASAS20/40 responses and other clinically relevant endpoints. Efficacy data are presented as observed. Safety analyses included all patients who received ≥1 dose of secukinumab.

Results

Of the 57 Taiwanese patients in the core trial, 48 entered the extension study and 87.5% patients (42/48) completed 4 years of treatment. Thirteen Taiwanese patients (including placebo-switchers) were escalated from 75 to 150mg (approved dose) at some point starting from Week 172. ASAS20/40 responses were sustained through 4 years in the Taiwanese patients who were originally randomized to secukinumab 150mg. Clinical responses were improved in those patients who received dose-escalation from 75 to 150mg during the study. No unexpected safety signals were reported.

Conclusion

Secukinumab 150mg demonstrated sustained efficacy over 4 years in Taiwanese patients with active ankylosing spondylitis. The safety profile of secukinumab was consistent with previous reports.

ClinicalTrials.gov identifier

NCT01863732.
Accurate and Efficient KIR Gene and Haplotype Inference From Genome Sequencing Reads With Novel K-mer Signatures
Authors: Roe David , Kuang Rui
Published: November 2020

The killer-cell immunoglobulin-like receptor (KIR) proteins evolve to fight viruses and mediate the body’s reaction to pregnancy. These roles provide selection pressure for variation at both the structural/haplotype and base/allele levels. At the same time, the genes have evolved relatively recently by tandem duplication and therefore exhibit very high sequence similarity over thousands of bases. These variation-homology patterns make it impossible to interpret KIR haplotypes from abundant short-read genome sequencing data at population scale using existing methods. Here, we developed an efficient computational approach for in silico KIR probe interpretation (KPI) to accurately interpret individual’s KIR genes and haplotype-pairs from KIR sequencing reads. We designed synthetic 25-base sequence probes by analyzing previously reported haplotype sequences, and we developed a bioinformatics pipeline to interpret the probes in the context of 16 KIR genes and 16 haplotype structures. We demonstrated its accuracy on a synthetic data set as well as a real whole genome sequences from 748 individuals from The Genome of the Netherlands (GoNL). The GoNL predictions were compared with predictions from SNP-based predictions. Our results show 100% accuracy rate for the synthetic tests and a 99.6% family-consistency rate in the GoNL tests. Agreement with the SNP-based calls on KIR genes ranges from 72%–100% with a mean of 92%; most differences occur in genes KIR2DS2, KIR2DL2, KIR2DS3, and KIR2DL5 where KPI predicts presence and the SNP-based interpretation predicts absence. Overall, the evidence suggests that KPI’s accuracy is 97% or greater for both KIR gene and haplotype-pair predictions, and the presence/absence genotyping leads to ambiguous haplotype-pair predictions with 16 reference KIR haplotype structures. KPI is free, open, and easily executable as a Nextflow workflow supported by a Docker environment at https://github.com/droeatumn/kpi.
Managing Granulomatous–Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders: e-GLILDnet International Clinicians Survey
Authors: van de Ven Annick A. J. M. , Alfaro Tiago M. , Robinson Alexandra , Baumann Ulrich , Bergeron Anne , Burns Siobhan O. , Condliffe Alison M. , Fevang Børre , Gennery Andrew R. , Haerynck Filomeen , Jacob Joseph , Jolles Stephen , Malphettes Marion , Meignin Véronique , Milota Tomas , van Montfrans Joris , Prasse Antje , Quinti Isabella , Renzoni Elisabetta , Stolz Daiana , Warnatz Klaus , Hurst John R.
Published: November 2020

Background

Granulomatous–lymphocytic interstitial lung disease (GLILD) is a rare, potentially severe pulmonary complication of common variable immunodeficiency disorders (CVID). Informative clinical trials and consensus on management are lacking.

Aims

The European GLILD network (e-GLILDnet) aims to describe how GLILD is currently managed in clinical practice and to determine the main uncertainties and unmet needs regarding diagnosis, treatment and follow-up.

Methods

The e-GLILDnet collaborators developed and conducted an online survey facilitated by the European Society for Immunodeficiencies (ESID) and the European Respiratory Society (ERS) between February–April 2020. Results were analyzed using SPSS.

Results

One hundred and sixty-one responses from adult and pediatric pulmonologists and immunologists from 47 countries were analyzed. Respondents treated a median of 27 (interquartile range, IQR 82–maximum 500) CVID patients, of which a median of 5 (IQR 8–max 200) had GLILD. Most respondents experienced difficulties in establishing the diagnosis of GLILD and only 31 (19%) had access to a standardized protocol. There was little uniformity in diagnostic or therapeutic interventions. Fewer than 40% of respondents saw a definite need for biopsy in all cases or performed bronchoalveolar lavage for diagnostics. Sixty-six percent used glucocorticosteroids for remission-induction and 47% for maintenance therapy; azathioprine, rituximab and mycophenolate mofetil were the most frequently prescribed steroid-sparing agents. Pulmonary function tests were the preferred modality for monitoring patients during follow-up.

Conclusions

These data demonstrate an urgent need for clinical studies to provide more evidence for an international consensus regarding management of GLILD. These studies will need to address optimal procedures for definite diagnosis and a better understanding of the pathogenesis of GLILD in order to provide individualized treatment options. Non-availability of well-established standardized protocols risks endangering patients.
Phytoplankton Diversity Effect on Ecosystem Functioning in a Coastal Upwelling System
Authors: Otero Jaime , Álvarez-Salgado Xosé Antón , Bode Antonio
Published: November 2020

Species composition plays a key role in ecosystem functioning. Theoretical, experimental and field studies show positive effects of biodiversity on ecosystem processes. However, this link can differ between taxonomic and functional diversity components and also across trophic levels. These relationships have been hardly studied in planktonic communities of coastal upwelling systems. Using a 28-year time series of phytoplankton and zooplankton assemblages, we examined the effects of phytoplankton diversity on resource use efficiency (RUE, ratio of biomass to limiting resource) at the two trophic levels in the Galician upwelling system (NW Iberian peninsula). By fitting generalized least square models, we show that phytoplankton diversity was the best predictor for RUE across planktonic trophic levels. This link varied depending on the biodiversity component considered: while the effect of phytoplankton richness on RUE was positive for phytoplankton RUE and negative for zooplankton RUE, phytoplankton evenness effect was negative for phytoplankton RUE and positive for zooplankton RUE. Overall, taxonomic diversity had higher explanatory power than functional diversity, and variability in phytoplankton and zooplankton RUE decreased with increasing phytoplankton taxonomic diversity. Phytoplankton used resources more efficiently in warmer waters and at greater upwelling intensity, although these effects were not as strong as those for biodiversity. These results suggest that phytoplankton species numbers in highly dynamic upwelling systems are important for maintaining the planktonic biomass production leading us to hypothesize the relevance of complementarity effects. However, we further postulate that a selection effect may operate also because assemblages with low evenness were dominated by diatoms with specific functional traits increasing their ability to exploit resources more efficiently.
Mitochondria: Potential Targets for Osteoarthritis
Authors: Mao Xingjia , Fu Panfeng , Wang Linlin , Xiang Chuan
Published: November 2020

Osteoarthritis (OA) is a common and disabling joint disorder that is mainly characterized by cartilage degeneration and narrow joint spaces. The role of mitochondrial dysfunction in promoting the development of OA has gained much attention. Targeting endogenous molecules to improve mitochondrial function is a potential treatment for OA. Moreover, research on exogenous drugs to improve mitochondrial function in OA based on endogenous molecular targets has been accomplished. In addition, stem cells and exosomes have been deeply researched in the context of cartilage regeneration, and these factors both reverse mitochondrial dysfunctions. Thus, we hypothesize that biomedical approaches will be applied to the treatment of OA. Furthermore, we have summarized the global status of mitochondria and osteoarthritis research in the past two decades, which will contribute to the research field and the development of novel treatment strategies for OA.