bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelatihan Pemasaran dan Labeling pada Usaha Jajan Laklak di Denpasar
Authors: Suardika I Gede , Untari Made Dewi Ayu , Dewi Nyoman Ayu Nila
Published: February 2021

Bali merupakan salah satu kota yang memiliki beraneka macam masakan dan makanan khas Bali. Jajanan tradisional di Bali mulai dari jajan sangait, klepon, laklak, pisang rai, dan masih banyak lagi jajan tradisional lainnya. Saat ini jajanan tradional di Bali mulai digemari dan menjadi makanan yang sangat digemari oleh masyarakat. Seperti halnya kini banyak ditemui jajan tradisional laklak Bali yang memiliki bahan dasar tepung terigu, santan dan kepala parut. Industri rumah tangga jajan laklak bali yang menjadi mitra dalam kegiatan ini adalah Ibu Sri yang memiliki aktivitas untuk memproduksi jajan tradisional yang telah di produksi dari tahun 1990an. Mitra dalam kegiatan pengabdian ini memiliki kendala untuk memasarkan dan mengenalkan hasil karya jajan yang di produksi, dimana jajan tradisional yang ada saat ini hanya di produksi dan dijual di sekitaran rumah. Terkadang beberapa pembeli datang langsung ke tempat produksi yakni di rumah mitra. Melihat hal tersebut dalam kegiatan pengabdian masyarakat ini akan diberikan suatu pelatihan media pemasaran untuk dapat memasarkan jajanan yang telah diproduksi. Kegiatan pengabdian masyarakat ini memberikan pelatihan media pemsaran dimana pemasaran yang dilakukan yaitu dengan memberikan pelatihan media sosial seperti instagram, dan media sosial lainnya.
Peningkatan Kualitas Pelayanan Aparatur Pemerintah Kelurahan Limo Depok
Authors: Pangestuti Dewi Cahyani , Husniaty Renny
Published: February 2021

Peningkatan dan tuntutan masyarakat1akan pelayanan public yang efektif dan efisien menuntut aparatur pemerintah memiliki kinerja yang lebih baik sehingga dapat memberikan pelayanan pada masyarakat.  Tujuan pengabdian pada masyarakat ini adalah meningkatkan kualitas pelayanan aparat Kelurahan Limo Depok dengan meningkatkan kemampuan menguasai ilmu pengetahuan dan teknologi. Pengabdian masyarakat ini dilaksanakan dua kali yaitu pada bulan November 2019 dan Januari 2020 di kantor Kelurahan Limo dengan memberikan pelatihan peningkatan kualitas pelayanan. Hasil dari pengabdian masyarakat ini, diharapkan ada peningkatan pelayanan yang meliputi 6 indikator kualitas pelayanan, yaitu :      ketepatan waktu pelayanan, akurasi pelayanan, kesopanan dan keramahan dalam memberikan pelayanan, kemudahan dalam mendapatkan pelayanan, kenyamanan dalam peroleh       pelayanan dan   atribut pendukung lainnya seperti sarana prasarana. Sesuai dengan hasil pengabdian di lapangan dari ke enam indikator yang menentukan kualitas       pelayanan yang dijadikan tolok ukur untuk mengevaluasi kualitas pelayanan publik agar1memenuhi kepuasan masyarakat, maka masih banyak hal yang harus dibenahi dalam rangka peningkatan kualitas pelayanan kepada masyarakat. Saran yang dapat disampaikan yaitu perlu peningkatan disiplin pegawai, perlu adanya bimbingan dan pelatihan yang terus-menerus serta perlu pembenahan dan penambahan beberapa fasilitas kantor untuk menunjang kelancaran aktivitas pelayanan.
Peculiarities of acid-releasing renal function of rats in the dynamics of experimental diabetes mellitus with underlying pharmacological blockade of renin-angiotensin-aldosterone system
Authors: Olenovych О.А.
Published: February 2021

Annotation. The aim of the study was to explore the peculiarities of acid-releasing renal function of rats in the dynamics of alloxan-induced experimental diabetes mellitus (EDM) with underlying pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS). The experiments were carried out on 78 white non-linear mature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlying pharmacological blockade of RAAS by administration of captopril. The study of acid-releasing renal function was provided under the condition of water 2-hour diuresis by changes in urine pH, excretion of titrated acids (TA), ammonia and active hydrogen ions with calculations of their excretion and ratio indices, standardization per 100 μl of glomerular filtrate (GF) volume. It was found that after administration of captopril to rats with 11-day long EDM urine pH, excretion of active hydrogen ions, ammonia excretion increased, TA excretion reduced, including it standardized by the volume of GF, as well as standardized excretion of ammonium compounds. After captopril administration to the animals with a 26-day long EDM, urine pH and TA excretion raised, and the excretion of ammonium and hydrogen ions decreased, still exceeding the control values. Standardized by GF, these indices changed similarly. After pharmacological blockade of RAAS on the 46th day of EDM urine pH, TA excretion, including it standardized by GF, excretion of hydrogen ions enhanced. Excretion of ammonium compounds, including it standardized by GF, and standardized excretion of hydrogen ions declined as compared with control parameters. Thus, the intensification of acid-release at the early stages of EDM is systemic by character and develops due to glomerular hyperfiltration, overload of the nephron with acidic products of metabolism and accompanied by structural intactness of the tubular apparatus of the kidneys. Prolonged glomerular hyperfiltration, probably, is the initiating damaging factor for the tubular apparatus of the diabetic kidney, which in 26-day long EDM is accompanied by the inability of enzyme systems of tubular epithelial cells of proximal tubules, mostly, to provide adequate ammoniogenesis, despite the high efficacy of renal transport mechanisms of acid-release. Proximal tubulopathy on the background of augmented aciduria in animals with 46-day long EDM causes relative functional insufficiency of the distal tubular apparatus.
Clinical and organizational aspects of providing medical care to victims with combined closed thoraco-cranial trauma
Authors: Guriev S. O. , Tanasienko P. V. , Khmel V. V.
Published: February 2021

Annotation. In the general structure of injuries, the frequency of combined injuries is 40-60%. There is an increase in the dynamics of combined injuries in terms of both the number and severity of injuries, with mortality reaching 35–80%. It is necessary to develop adequate and optimal tactics for providing medical care to victims, which would take into account the features of closed thoraco-cranial trauma as a separate clinical and nosological form of polysystemic injury that requires clinical and organizational protocol schemes and routes. The aim of the study was to improve the results of treatment of patients with combined thoraco-cranial trauma by implementing a risk-oriented protocol scheme of clinical organization of medical care for victims with combined closed thoraco-cranial trauma. Two randomized controlled groups were formed with guaranteed homogeneity according to clinical-epidemiological and clinical-nosological features from patients who were in the department of polytrauma of KMKL SHMD during 2012–2013. Using a correlation method of risk assessment with the standard of medical care for victims with polytrauma at an early hospital stage, we formed a risk-oriented routing scheme for victims with cancer and cranial trauma. This scheme was formed on the basis of risk analysis and definition of tasks for the provision of medical care to victims with closed thoraco-cranial trauma. Clinical routes of the patient with catastrophic, critical, essential and minimum risk of lethal outcome are developed and their high efficiency is revealed. The developed risk-based protocol scheme for providing medical care to victims with closed combined thoraco-cranial trauma in the early hospital stage using the concept of clinical routing of patients has proven its effectiveness based on the results of implementation and can be recommended for widespread implementation.
SOFTWARE SELECTION ON BASE OF FUZZY AHP METHOD
Authors: Salimov Vagif Hasan Oglu  , Damirova Javida Rizvan Qizi
Published: February 2021

The article is devoted to the problem of multi-criteria decision making. As application problem is used the software selection problem. The analysis of existing methods for solving this problem is given. As a method for solving this problem, the most popular fuzzy AHP method (Analytic Hierarchy Process) is proposed. This method use original algorithm for pairwise comparison of criteria and alternatives. The issues of practical implementation of this method are discussed in details. The results of the solution test problem at all stages are presented.
Estudos experimentais com bilíngues bimodais: aspectos metodológicos
Authors: Müller de Quadros Ronice , Lillo-Martin Diane , Mafra Klamt Marilyn , Tasso Pires Karina
Published: February 2021

A proposta deste artigo é apresentar aspectos metodológicos envolvidos em pesquisas com participantes bilíngues bimodais, ou seja, aqueles que utilizam duas línguas em diferentes modalidades (uma língua de sinais, visual-espacial e uma língua falada, oral-auditiva). O artigo vai abordar o uso de estudos experimentais considerando-se a elaboração das tarefas, a coleta em si, o registro dos resultados e aspectos a serem levados em consideração na análise dos resultados. Este artigo resulta de pesquisas que foram conduzidas com bilíngues bimodais, em especial, os estudos que temos desenvolvido ao longo dos últimos dez anos (tais como LILLO-MARTIN et al. 2010; 2016; 2020; QUADROS et al. 2015; 2016; QUADROS, 2017). O objetivo do artigo é divulgar o desenvolvimento de ferramentas metodológicas que foram sendo aprimoradas com base nas pesquisas realizadas para servirem de referências nos estudos com bilíngues bimodais. Consideramos isso importante, uma vez que vários estudos precisam ser feitos nesta área, tanto do ponto de vista teórico, como aplicado. Sendo assim, envolve contribuições para as teorias sobre o bilinguismo trazendo novos elementos com base nesta forma peculiar de uso de duas línguas com modalidades diferentes. Este estudo também contribui para o campo da formação de profissionais bilíngues bimodais para atuarem tanto no ensino de Libras, como na educação bilíngue e na tradução e interpretação de língua de sinais.
Entrevista com Diane Brentari em Língua Brasileira de Sinais (Libras)
Authors: Costa Marília Uchôa Cavalcanti Lott de Moraes , Azevedo Loise Soares de , Silva Anderson Almeida da
Published: February 2021

Entrevista traduzida para Libras.https://www.youtube.com/watch?v=NKQT2Abfklw
ASEAN Defence Ministers’ Meeting Plus (ADMM+) as a New Element in the Emerging Security Architecture of the Southeast Asia
Authors:   MGIMO University, Vershinina Valeria V.
Published: February 2021

In the recent decades despite the existing broad network of the multilateral security formats in the Asia-Pacific region a high level of conflicts and old disputes remain, while non-military security challenges and threats are becoming more complicated. Among the most well-known are the ASEAN Regional Forum (ARF) and the East Asian Summit (EAS). Nevertheless, given the increasing destabilization in the region, one can state that the above-mentioned formats proved ineffective and as a result, new solutions need to be found. One of such possible solutions is an initiative proposed by Vietnam to create a new format known as ASEAN Defence Ministers’ Meeting Plus (ADMM+).
HYPOTACTIC STRUCTURE IN ENGLISH
Authors: Kurniasy Dessy
Published: February 2021

This present study focuses on the study of a hypotactic structure in English. It is concerned with clause complex which is comprised of two or more clauses logically connected. The relation between clauses can be interpreted in terms of ‘logical’ semantic relations and system of interdependency relation – parataxis and hypotaxis. The method used in this study was qualitative approach in which the data were taken from some linguistic books. The finding shows that the concept of hypotactic structure in English is divided into two types: expansion and projection. There are three kinds of expanding a clause i.e. elaboration (=), extension (+) and enhancement (x), and two kinds of projection i.e. locution (”) and idea (’). Elaboration shows that the meaning of the secondary clause is equal to the primary one, but the secondary clause does not introduce a new element into the picture but rather provides a further characterization of one that is already there. Extension is a clause that extends the meaning of another by adding something new to it. Meanwhile, enhancement shows the meaning of another clause by qualifying it with adverbial clause in traditional grammar. Furthermore, the three clauses can be finite or non-finite. Locution, on the other hand, is a projection with verbal process, in which the clause containing the sayer and the reporting verb is thedominant clause and the reported element is the dependent clause. Thus, idea is a projection with mental process that is used to report ideas, beliefs, fears and speculations. The combination of mental process with a dependent ‘reporting’ clause is the nominal ways of representing what people say, think and believe.
ATTITUDES OF INDIGENOUS ACEHNESE PEOPLE TOWARDS THEIR VERNACULAR MAINTENANCE IN LANGSA.
Authors: Fakhrurrazi Fakhrurrazi
Published: February 2021

This research is a study on native people’s attitudes towards Acehnese language in Langsa Aceh. The research design used a qualitative research method that examines the attitudes of native speakers of the language of Aceh in Langsa in prewserving the language. The subject of research is the native speakers of Acehnese who live in the city of Langsa from eighteen years to twenty years old. This study used observation, questionnaire and interview. The data obtained from this study were analyzed based on the cooperative model intrcidued by Miles and Hubermann. The study shows that 55% of respondents indicates a very positive attitude towards in preserving the Acehnese by using the language in everyday communication. While 45% of respondents indicates a negative attitude where they seldom use Acehnese in their daily interaction and very often switch the language to Indonesian in their communication. The study also reveals that the use of Acehnese at home, the pride of using Acehnese and the Acehnese as identity are the factors that contribute to the preservation of Acehnese.
Vitaminas Antioxidantes na Prevenção do Câncer do Colo Uterino
Authors: Sampaio Lúcia da Cunha , Almeida Cristiane Fonseca de
Published: February 2021

O câncer do colo uterino é a terceira neoplasia maligna mais comum nas mulheres, entretanto apresenta um dos mais altos potenciais de prevenção e cura se descoberto no início e tratado adequadamente. O principal fator etiológico para esse câncer é o Papilomavírus Humano (HPV) que induz a lesões no epitélio cervical, podendo evoluir para lesões precursoras e neoplasia invasiva. Os fatores dietéticos apresentam papel importante como cofatores no desenvolvimento da neoplasia intraepitelial cervical (NIC) e consequentemente do câncer cervical. Este trabalho de revisão bibliográfica tem como objetivo analisar a associação das vitaminas antioxidantes com a prevenção do câncer do colo uterino, identificando suas ações na prevenção das lesões displásicas. A oferta de vitaminas antioxidantes como A, C e E apresenta benefícios para prevenção do câncer do colo uterino, principalmente nos estágios iniciais da carcinogênese cervical. A vitamina A, através dos carotenoides, tem capacidade de inibir a formação dos radicais livres, sendo também potentes moduladores da diferenciação celular, o que confere proteção para inibir o desenvolvimento do HPV. As vitaminas C e E podem evitar a formação de carcinógenos, além de aumentar a imunidade. Dessa forma, a terapêutica nutricional, baseada na utilização de nutrientes antioxidantes, pode ser uma estratégia preventiva para o câncer do colo uterino, podendo assim ampliar os conceitos da terapia oncológica atual, o que permitirá melhores resultados quanto ao controle dessa doença.
Tumores primários cardíacos em pacientes pediátricos
Authors: Fernandes Adriany Melissa Pinto , Cardoso Ana Luiza Caires , Oliveira Igor de Sousa , Brandão Lara Bianca Soares , Lima Mara Georgia de Sousa , Souza Maria Paula Costa de , Oliveira Rayssa Maria Furtado , Silva Rhane Pereira da , Almeida Suélen da Silva , Moura Viviane Silva de , Portella Gabriel Mendes
Published: February 2021

Contexto: Os tumores cardíacos primários são entidades raras correspondentes ao crescimento e proliferação anormais de células do miocárdio, endocárdio ou pericárdio. Esses tumores podem ser benignos ou malignos, além de serem capazes de apresentar quadros clínicos variáveis e abranger todas as faixas etárias. Na população pediátrica, essa patologia possui baixa incidência e a notável maioria dos casos são benignos com alta taxa de sobrevivência, os quais contém predomínio histológico do tipo rabdomioma, frequentemente associado à esclerose tuberosa, seguido de fibroma e teratoma. Por outro lado, os tumores malignos equivalem a cerca de 10% dos casos e geralmente possuem natureza sarcomatosa, a qual é associada a prognósticos ruins e alta mortalidade. Objetivo: Compreender os meios diagnósticos, mapeamento, fisiopatologia, clínica e tratamentos dos tumores primários cardíacos em pacientes pediátricos. Metodologia: Trata-se de uma revisão bibliográfica com abordagem quanti-qualitativa. Tal ocorreu por meio das bases virtuais da Biblioteca Virtual em Saúde (BVS), PubMed e Google Scholar, recorrendo aos termos disponíveis nos Descritores em Ciências da Saúde (DeCS) para a formatação da fórmula de busca, entre os quais foram selecionados: “neoplasias cardíacas”, “crianças” e “mixoma”, nos idiomas português, inglês e espanhol. Após isso, foram utilizados como critérios o recorte temporal de dez anos e os idiomas espanhol, inglês e português. De acordo com isso, selecionaram-se 13 artigos que estavam de acordo com o objeto da pesquisa e contemplavam os critérios de inclusão. Principais resultados: O estudo elucidou as principais causas e consequências relacionadas à presença de tumor primário no período da infância, analisando, para isso, desde sinais e sintomas, apresentação clínica e fisiopatológica, bem como os exames auxiliares dessa patologia. A leitura da bibliografia disponível permitiu classificar os tipos mais comuns de tumores cardíacos pediátricos, a exemplo do rabdomioma e fibroma, como também elucidar os processos de repercussão nas partes adjacentes do coração do indivíduo e, consequentemente, suas repercussões gerais no bem estar geral do indivíduo. Conclusões: Finalmente, os pesquisadores constataram a escassez de estudos dessa temática, caracterizando uma alerta para a comunidade acadêmica, uma vez que, apesar de raro, as aparições clínicas devem ser analisadas e conduzidas corretamente pelos profissionais.
A adesão do uso de máscaras contra a pandemia da Covid-19 na cidade do Gama/DF
Authors: Noleto Guilherme de Oliveira
Published: February 2021

Desde 31 de dezembro de 2019, o mundo enfrenta o SARS-CoV-2, um vírus que provocou uma doença que progrediu a um patamar problemático de pandemia, fazendo com que fosse necessário adotar medidas rígidas e agressivas para a tentativa de contenção da doença, como, por exemplo, o uso de máscaras de proteção. O presente artigo tem como objetivo observar o uso dessas máscaras na população do Gama/DF a fim de responder ao seguinte problema, qual o nível de adesão do uso de máscaras nesta cidade? Para se alcançar tal objetivo, bem como a pergunta problema estabelecida, a modalidade de pesquisa descritiva com abordagem quantitativa foi adotada, e a observação em ambiente público da população do Gama foi efetuada em consonância com um aplicativo desenvolvido pelo autor para o auxílio da contagem, de modo a se observar: a) o uso adequado da máscara, b) o uso inadequado da máscara e c) o desuso da mesma. Os principais resultados foram que 58,5% da amostra da população gamense fazia o uso correto da máscara, 15,5% fazia o uso incorreto e 26% não utilizava máscara; implicando em um comportamento insatisfatório frente a crise sanitária promovida pela Covid-19.
Progressivism of Judges in Deciding Applications for Marriage Dispensation
Authors: Pardede Josua Navirio , Asih Wigati Taberi , Siregar Thogu Ahmad
Published: February 2021

Regulation on the age limit for a marriage through Act No. 16 of 2019 is based on the spirit of anti-discrimination and protection of children's rights from the adverse effects of child marriage. However, the efforts to complicate and prevent child marriage has yet to have a significant impact on reducing the rate of child marriage in Indonesia. This condition is occurred by the high level of applications for marriage dispensation that are granted by the court. Hence, the construction of the judge's reasoning in observe the relationship between the substance of the law and the reasons for proposing marriage dispensation is one of the most vital and influential elements. The positivism-legism legal reasoning used in understanding of Act No.16 of 2019 is considered to be the cause of the malfunction of the regulation in protecting and guaranteeing children's human rights. By using doctrinal legal research methods, this research produces a conceptual analysis in the form of a meta-juridical critique on positivist legal reasoning which tends to lead to the legism when trying to understand the objectives of Act No. 16 of 2019 and proposes a progressive legal notion as an ideal reasoning framework in producing decisions on applications for dispensation of marriage that have a perspective on the protection and guarantee of children's rights.
The Effect of Career Development on Employee Performance at Aswin Hotel and Spa Makassar
Authors: Firman Ahmad
Published: February 2021

This study aims to determine the effect of career development toward employee performance at Aswin Hotels and Spa Makassar. The model used in this study is a questionnaire using a Likert scale. And the method of determining the sample used is a saturated sample with the total sample represented the total population of 53 people. The analytical method used is a simple regression analysis method. The results of this study indicate that career development had a positive and significant effect toward employee performance at the Aswin Hotel and Spa Makassar. Career development affected the performance of Aswin Hotel and Spa Makassar employees by 54.4%, while 45.6% of employee performance variables were affected by other variables who did not observe by researchers.
Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
Authors: Choi Eun-Ji , Cho Young-Uk , Hur Eun-Hye , Jang Seongsoo , Kim Nayoung , Park Han-Seung , Lee Jung-Hee , Lee Kyoo-Hyung , Kim Si-Hwan , Hwang Sang-Hyun , Seo Eul-Ju , Park Chan-Jeoung , Lee Je-Hwan
Published: February 2021

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.
USE OF THE SURFACE TRANSVERSE WAVES (STW) – ONE OF EFFICIENT METHODS FOR ENHANCEMENT OF THE SAW DEVICES OPERATING FREQUENCIES
Authors: Bagdasaryan A. S. , Gulyaev Yu. V. , Dobershtein S. A. , Sinitsina T. V.
Published: February 2021

This paper presents an efficient method for enhancement of the operating frequen-cies of the SAW devices - use of surface transverse waves (STW) with high propa-gation velocity V = 5000 m/s on a standard piezomaterial quartz. The approaches for a realization of the STW resonators with the high quality factor and STW filters with the low insertion loss were considered. The quantitative and qualitative char-acteristics of above 1 GHz STW devices for each approach were given.
IDENTIFICATION OF NON-UNIFORM DISTRIBUTION OF ELECTRICAL CHARACTERISTICS AND PHASE COMPOSITION IN TIN OXIDE THIN FILMS BY CONDUCTIVE ATOMIC FORCE MICROSCOPY
Authors: Davletkildeev N. A. , Mosur E. Yu. , Sokolov D. V. , Lobov I. A.
Published: February 2021

Using conductive atomic force microscopy, current images and I – V characteristics of tin oxide thin films deposited at various substrate temperatures were obtained. When analyzing current images and I – V characteristics, it was found that tin oxide films formed at a higher substrate temperature consist of the SnO2 phase, however, they include local areas with increased resistance that contain the SnO phase.
INFLUENCE ESTIMATION OF A THERMAL SHIELD
IN A QUARTZ RESONATOR-THERMOSTAT
ON THE GENERATED FREQUENCY INSTABILITY
Authors: Karagusov V. I. , Rozanova A. V.
Published: February 2021

The results of a study of the effect of using a heat shield in a quartz resonator-thermostat on the temperature instability of the frequency of a thermostated quartz generator on a three-dimensional temperature-dynamic model of a resonator-thermostat are presented. The model takes into account a complex design and physical factors that affect the generation frequency. Examples of calculating the temperature field in the elements of the resonator-thermostat and the results of calculating the generated frequency under normal conditions and at the extreme values of the range of operating ambient temperatures are given. Conclusions about the effectiveness of the use of the heat shield are made.
The Effect of Solvents and Drying Temperature on the Physicochemical Properties of Darunavir and Darunavir Ethanolate Substances
Authors: Zolotov S. A. , Dain I. A. , Demina N. B. , Zolotova A. S. , Ponomarev E. S.
Published: February 2021

Introduction. Usage of aggressive conditions (solvents, high temperature, etc.) in a dosage form manufacturing can lead to a change in the properties of a pharmaceutical substance. Darunavir (D) amorphous and darunavir ethanolate (DE) crystalline both have poor solubility, ability to pseudopolymorphism and are sensitive to high temperatures.

Aim. Study the effect of solvents and drying temperature on the physicochemical properties of D and DE substances

Materials and methods. D (Mylan Laboratories Limited), DE (Mylan Laboratories Limited), D (reference standard) 99,9 % (MSN Pharmachem Private Limited). D and DE weighed quantity was suspended in one of the solvents via magnetic stirrer and was dried via universal oven. Powder X-ray diffraction of dried samples was carried out via automatic powder diffractometer. Using DSC thermal properties of the samples were studied. Crystalline samples were examined using IR spectroscopy. Identification of D and DE was performed by HPLC method.

Results and discussion. This article summarizes study results of the investigation of various solvents and drying temperature influence on the physicochemical properties of D and DE are presented. The impact of solvent type and drying temperatures in physicochemical properties of the APIs was studied by X-ray powder diffraction, differential scanning calorimetry, IR spectroscopy and HPLC methods. It was shown, that solvent type and drying temperatures can result in the presence of crystalline D solvates or amorphous D.

Conclusion. To obtain the final drug containing as an API amorphous D, which perform better dissolution, one of the enlisted solvents can be used: dichloromethane, chloroform and heptane. In such case the intermediate product drying should be performed at not exceeding the solvent boiling point temperatures. In case of ethanol, methanol, acetone and tetrahydrofuran drying phase can be performed at temperatures, that are higher than melting points of obtained pseudopolymorphs. For the utilization of DE as an API only ethanol usage is efficient and drying temperature should not exceed 73.4 °C.
Características físico-químicas e composição centesimal de queijos de coalho comercializados em cidades do Ceará
Authors: Silva Edilene Ferreira da , Silva Priscila Luana da , Barcelos Samuel Carneiro de , Nascimento Vera Lúcia Viana do , Ramos Lidiana de Siqueira Nunes , Cavalcante Antônio Belfort Dantas
Published: February 2021

Queijo de coalho é um produto popular da cultura nordestina, sendo comum o processo de elaboração com uso de leite cru, o conhecimento prévio da composição físico-química e centesimal do alimento é relevante, tanto por influenciar na escolha saudável, como para obter dados a respeito do que está sendo consumido com qualidade. Objetivou avaliar as características físico-químicas e a composição centesimal do queijo de coalho comercializado em cidades do Ceará. Foram coletadas cinco diferentes marcas de queijos de coalho (A, B, C, D e E) em três repetições, encaminhadas para a Planta Piloto de Leite e Derivados do IFCE – Campus Limoeiro do Norte (CE). As amostras foram homogeneizadas em ralador doméstico, e acondicionadas sob refrigeração (4 ± 2 ºC) até o momento das análises. Análises realizadas: físico-químicas (pH, atividade de água (Aw), acidez titulável e cor), composição centesimal (umidade, proteínas, cinzas, lipídios, carboidratos totais, e valor calórico total). Os dados estatísticos por delineamento inteiramente casualizados, foram submetidos à análise de variância (ANOVA) e teste de Tukey, através do programa R Core Team, 2018, versão 3.5.0, nível de 5% de significância.  As análises físico-químicas dos queijos de coalho demonstraram variabilidade entre as amostras, associadas às condições da produção, variação da temperatura de armazenamento e comercialização dos queijos. A composição centesimal e o valor calórico expresso em Kcal variaram entre as amostras estudadas, estando os teores de umidades de acordo com o que a legislação preconiza para queijo de coalho e os valores lipídicos abaixo do mínimo exigido pela legislação.
Práticas de Gestão do Conhecimento e Capacidade Absortiva Aplicadas à Melhoria de Desempenho e Qualidade na Manutenção Industrial
Authors: Zyrianoff Wladmir , Kuniyoshi Marcio Shoiti , Gaspar Marcos Antonio , Nascimento Hugo do
Published: February 2021

Esta pesquisa tem como objetivo identificar e descrever como as práticas de gestão do conhecimento e a capacidade absortiva têm sido utilizadas para a melhoria do desempenho e qualidade na área de manutenção de uma indústria automobilística do ABC paulista. Para tanto, executou-se pesquisa descritiva de cunho qualitativo mediante a utilização do método de estudo de caso. Foram aplicados como instrumentos de investigação roteiro de entrevista semiestruturada, observação direta não participativa e pesquisa documental em registros de arquivos e artefatos físicos da empresa analisada. Foram entrevistados gestores e funcionários técnicos de elevada hierarquia da área de manutenção industrial da empresa prospectada. Por meio da análise e triangulação dos dados auferidos na pesquisa de campo executada, identificou-se que os profissionais da área de manutenção percebem a necessidade da gestão do conhecimento em seus processos de trabalho e que as práticas de gestão do conhecimento têm influência na capacidade absortiva da área. Ficou ainda evidente que a capacidade absortiva influencia no desempenho e qualidade das ações desempenhadas pelos funcionários da manutenção. Como conclusão, os resultados da pesquisa permitem inferir que se as organizações derem maior atenção às práticas de gestão do conhecimento e à capacidade absortiva por elas proporcionada, poderão ser capazes de criar e sustentar vantagens competitivas sobre seus concorrentes.
Qualidade da água de abastecimento de um abatedouro-frigorífico no município de Castanhal, Pará
Authors: Barboza Andressa Souza , Damasceno Neto Manoel Soares , Silva Welligton Conceição da , Auriema Bruna Emygdio
Published: February 2021

A água de abastecimento é um recurso fundamental em abatedouros frigoríficos que fazem uso da água em diversas operações, seja de contato direto ou indireto com os produtos. Este estudo teve como objetivo avaliar os parâmetros de qualidade da água de abastecimento de um abatedouro frigorífico de bovinos, localizado no município de Castanhal, no estado do Pará. Para isto, as amostras de água foram coletadas em três diferentes pontos, sendo obtido amostras no setor de abate, miúdos e triparia. Realizou-se avaliação das características físico-químicas (cloro residual livre, cor aparente, pH e turbidez) e microbiológicos (coliformes totais e coliformes a 45 °C), durante o período de janeiro a dezembro de 2019. Os resultados mostraram que todos os parâmetros físico-químicos e microbiológicos das amostras analisadas mantiveram-se dentro dos padrões exigidos pelo Ministério da Saúde. Estes resultados podem ser reflexo do tratamento da água que o abatedouro emprega, que consiste nas etapas de correção do pH, floculação, coagulação, filtração e cloração.
Comparison of methods used for evaluation of mutagenicity/genotoxicity of model chemicals - parabens
Authors: Chrz J , Hošíková B , Svobodová L , Očadlíková D , Kolářová H , Dvořáková M , Kejlová K , Malina L , Jírová G , Vlková A , Mannerström M
Published: February 2021

Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.
Rapamycin-Loaded Lipid Nanocapsules Induce Selective Inhibition of the mTORC1-Signaling Pathway in Glioblastoma Cells
Authors: Séhédic Delphine , Roncali Loris , Djoudi Amel , Buchtova Nela , Avril Sylvie , Chérel Michel , Boury Frank , Lacoeuille Franck , Hindré François , Garcion Emmanuel
Published: February 2021

Inhibition of the PI3K/Akt/mTOR signaling pathway represents a potential issue for the treatment of cancer, including glioblastoma. As such, rapamycin that inhibits the mechanistic target of rapamycin (mTOR), the downstream effector of this signaling pathway, is of great interest. However, clinical development of rapamycin has floundered due to the lack of a suitable formulation of delivery systems. In the present study, a novel method for the formulation of safe rapamycin nanocarriers is investigated. A phase inversion process was adapted to prepare lipid nanocapsules (LNCs) loaded with the lipophilic and temperature sensitive rapamycin. Rapamycin-loaded LNCs (LNC-rapa) are ~110 nm in diameter with a low polydispersity index (<0.05) and the zeta potential of about −5 mV. The encapsulation efficiency, determined by spectrophotometry conjugated with filtration/exclusion, was found to be about 69%, which represents 0.6 wt% of loading capacity. Western blot analysis showed that LNC-rapa do not act synergistically with X-ray beam radiation in U87MG glioblastoma model in vitro. Nevertheless, it demonstrated the selective inhibition of the phosphorylation of mTORC1 signaling pathway on Ser2448 at a concentration of 1 μM rapamycin in serum-free medium. Interestingly, cells cultivated in normoxia (21% O2) seem to be more sensitive to mTOR inhibition by rapamycin than those cultivated in hypoxia (0.4% O2). Finally, we also established that mTOR phosphorylation inhibition by LNC-rapa induced a negative feedback through the activation of Akt phosphorylation. This phenomenon was more noticeable after stabilization of HIF-1α in hypoxia.
Prediction of lncRNA–Protein Interactions via the Multiple Information Integration
Authors: Chen Yifan , Fu Xiangzheng , Li Zejun , Peng Li , Zhuo Linlin
Published: February 2021

The long non-coding RNA (lncRNA)–protein interaction plays an important role in the post-transcriptional gene regulation, such as RNA splicing, translation, signaling, and the development of complex diseases. The related research on the prediction of lncRNA–protein interaction relationship is beneficial in the excavation and the discovery of the mechanism of lncRNA function and action occurrence, which are important. Traditional experimental methods for detecting lncRNA–protein interactions are expensive and time-consuming. Therefore, computational methods provide many effective strategies to deal with this problem. In recent years, most computational methods only use the information of the lncRNA–lncRNA or the protein–protein similarity and cannot fully capture all features to identify their interactions. In this paper, we propose a novel computational model for the lncRNA–protein prediction on the basis of machine learning methods. First, a feature method is proposed for representing the information of the network topological properties of lncRNA and protein interactions. The basic composition feature information and evolutionary information based on protein, the lncRNA sequence feature information, and the lncRNA expression profile information are extracted. Finally, the above feature information is fused, and the optimized feature vector is used with the recursive feature elimination algorithm. The optimized feature vectors are input to the support vector machine (SVM) model. Experimental results show that the proposed method has good effectiveness and accuracy in the lncRNA–protein interaction prediction.
Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage
Authors: Eremichev Roman , Kulebyakina Maria , Alexandrushkina Nataliya , Nimiritsky Peter , Basalova Nataliya , Grigorieva Olga , Egiazaryan Mane , Dyikanov Daniyar , Tkachuk Vsevolod , Makarevich Pavel
Published: February 2021

Besides certain exceptions, healing of most tissues in the human body occurs via formation of scar tissue, rather than restoration of lost structures. After extensive acute injuries, this phenomenon substantially limits the possibility of lost function recovery and, in case of chronic injury, it leads to pathological remodeling of organs affected. Managing outcomes of damaged tissue repair is one of the main objectives of regenerative medicine. The first priority for reaching it is comparative investigation of mechanisms responsible for complete restoration of damaged tissues and mechanisms of scarring. However, human body tissues that undergo complete scar-free healing are scarce. The endometrium is a unique mucous membrane in the human body that heals without scarring after various injuries, as well as during each menstrual cycle (i.e., up to 400 times during a woman’s life). We hypothesized that absence of scarring during endometrial healing may be associated with tissue-specific features of its stromal cells (SCs) or their microenvironment, since SCs transform into myofibroblasts—the main effector link of scarring. We found that during healing of the endometrium, soluble factors are formed that inhibit the transition of SCs into myofibroblasts. Without influence of these factors, the SCs of the endometrium undergo transformation into myofibroblasts after transforming growth factor β1 (TGF-β1) treatment as well as the SCs from tissues that heal by scarring—skin or fat. However, unlike the latter, endometrial SCs organize extracellular matrix (ECM) in a specific way and are not prone to formation of bulky connective tissue structures. Thus, we may suggest that tissue-specific features of endometrial SCs along with effects of soluble factors secreted in utero during menstruation ensure scar-free healing of human endometrium.
Deactivation of the JNK Pathway by GSTP1 Is Essential to Maintain Sperm Functionality
Authors: Llavanera Marc , Mateo-Otero Yentel , Delgado-Bermúdez Ariadna , Recuero Sandra , Olives Samuel , Barranco Isabel , Yeste Marc
Published: February 2021

Fifty percent of male subfertility diagnosis is idiopathic and is usually associated with genetic abnormalities or protein dysfunction, which are not detectable through the conventional spermiogram. Glutathione S-transferases (GSTs) are antioxidant enzymes essential for preserving sperm function and maintaining fertilizing ability. However, while the role of GSTP1 in cell signaling regulation via the inhibition of c-Jun N-terminal kinases (JNK) has been enlightened in somatic cells, it has never been investigated in mammalian spermatozoa. In this regard, a comprehensive approach through immunoblotting, immunofluorescence, computer-assisted sperm assessment (CASA), and flow cytometry analysis was used to characterize the molecular role of the GSTP1–JNK heterocomplex in sperm physiology, using the pig as a model. Immunological assessments confirmed the presence and localization of GSTP1 in sperm cells. The pharmacological dissociation of the GSTP1–JNK heterocomplex resulted in the activation of JNK, which led to a significant decrease in sperm viability, motility, mitochondrial activity, and plasma membrane stability, as well as to an increase of intracellular superoxides. No effects in intracellular calcium levels and acrosome membrane integrity were observed. In conclusion, the present work has demonstrated, for the first time, the essential role of GSTP1 in deactivating JNK, which is crucial to maintain sperm function and has also set the grounds to understand the relevance of the GSTP1–JNK heterocomplex for the regulation of mammalian sperm physiology.
TFEB Gene Promoter Variants Effect on Gene Expression in Acute Myocardial Infarction
Authors: Zhang Jie , Zhang Yexin , He Xiaohui , Wang Shuai , Pang Shuchao , Yan Bo
Published: February 2021

Autophagy is involved in many physiological processes. Transcription factor EB (TFEB) is a master regulator of autophagy and coordinates the expression of autophagic proteins, lysosomal hydrolases, and lysosomal membrane proteins. Though autophagy has been implicated in several human diseases, little is known regarding TFEB gene expression and regulation in the process. Since dysfunctional autophagy plays critical roles in acute myocardial infarction (AMI), dysregulated TFEB gene expression may be associated with AMI by regulating autophagy. In this study, the TFEB gene promoter was genetically and functionally analyzed in AMI patients (n= 352) and ethnic-matched controls (n= 337). A total of fifteen regulatory variants of the TFEB gene, including eight single-nucleotide polymorphisms (SNPs), were identified in this population. Among these, six regulatory variants [g.41737274T>C (rs533895008), g.41737144A>G, g.41736987C > T (rs760293138), g.41736806C > T (rs748537297), g.41736635T > C (rs975050638), and g.41736544C > T] were only identified in AMI patients. These regulatory variants significantly altered the transcriptional activity of the TFEB gene promoter. Further electrophoretic mobility shift assay revealed that three of the variants evidently affected the binding of transcription factors. Therefore, this study identified novel TFEB gene regulatory variants which affect the gene expression. These TFEB gene regulatory variants may contribute to AMI development as a rare risk factor.
Targeting the NLRP3 Inflammasome via BTK
Authors: Weber Alexander N. R.
Published: February 2021

The NLRP3 inflammasome represents a critical inflammatory machinery driving pathology in many acute (e. g., myocardial infarction or stroke) and chronic (Alzheimer's disease, atherosclerosis) human disorders linked to the activity of IL-1 cytokines. Although the therapeutic potential of NLRP3 is undisputed, currently no clinically approved therapies exist to target the NLRP3 inflammasome directly. The recent discovery of BTK as a direct and positive regulator of the NLRP3 inflammasome has, however, raised the intriguing possibility of targeting the NLRP3 inflammasome via existing or future BTK inhibitors. Here, I review the mechanistic basis for this notion and discuss the molecular and cellular role of BTK in the inflammasome process. Specific attention will be given to cell-type dependent characteristics and differences that may be relevant for targeting approaches. Furthermore, I review recent (pre-)clinical evidence for effects of BTK inhibitors on NLRP3 activity and highlight and discuss open questions and future research directions. Collectively, the concept of targeting BTK to target NLRP3-dependent inflammation will be explored comprehensively at the molecular, cellular and therapeutic levels.