bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Inhibition of Polysialyltranseferase ST8SiaIV Through Heparin Binding to Polysialyltransferase Domain (PSTD)
Authors: Peng Li-Xin , Liu Xue-Hui , Lu Bo , Liao Si-Ming , Zhou Feng , Huang Ji-Min , Chen Dong , Troy II Frederic A. , Zhou Guo-Ping , Huang Ri-Bo 
Published: December 2018

Background:The polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface Of Neuronal Cell Adhesion Molecule (NCAM) in a number of cancer cells, and strongly correlates with the migration and invasion of tumor cells and with aggressive, metastatic disease and poor clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX). Selective inhibition of polySTs, therefore, presents a therapeutic opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. Heparin has been found to be effective in inhibiting the ST8Sia IV activity, but no clear molecular rationale. It has been found that polysialyltransferase domain (PSTD) in polyST plays a significant role in influencing polyST activity, and thus it is critical for NCAM polysialylation based on the previous studies.Objective:To determine whether the three different types of heparin (unfractionated hepain (UFH), low molecular heparin (LMWH) and heparin tetrasaccharide (DP4)) is bound to the PSTD; and if so, what are the critical residues of the PSTD for these binding complexes?Methods:Fluorescence quenching analysis, the Circular Dichroism (CD) spectroscopy, and NMR spectroscopy were used to determine and analyze interactions of PSTD-UFH, PSTD-LMWH, and PSTD-DP4.Results:The fluorescence quenching analysis indicates that the PSTD-UFH binding is the strongest and the PSTD-DP4 binding is the weakest among these three types of the binding; the CD spectra showed that mainly the PSTD-heparin interactions caused a reduction in signal intensity but not marked decrease in α-helix content; the NMR data of the PSTD-DP4 and the PSTDLMWH interactions showed that the different types of heparin shared 12 common binding sites at N247, V251, R252, T253, S257, R265, Y267, W268, L269, V273, I275, and K276, which were mainly distributed in the long α-helix of the PSTD and the short 3-residue loop of the C-terminal PSTD. In addition, three residues K246, K250 and A254 were bound to the LMWH, but not to DP4. This suggests that the PSTD-LMWH binding is stronger than the PSTD-DP4 binding, and the LMWH is a more effective inhibitor than DP4.Conclusion:The findings in the present study demonstrate that PSTD domain is a potential target of heparin and may provide new insights into the molecular rationale of heparin-inhibiting NCAM polysialylation.
Synthesis, Molecular Modelling and Biological Studies of 3-hydroxypyrane- 4-one and 3-hydroxy-pyridine-4-one Derivatives as HIV-1 Integrase Inhibitors
Authors: Sirous Hajar , Fassihi Afshin , Brogi Simone , Campiani Giuseppe , Christ Frauke , Debyser Zeger , Gemma Sandra , Butini Stefania , Chemi Giulia , Grillo Alessandro , Zabihollahi Rezvan , Aghasadeghi Mohammad R. , Saghaie Lotfollah , Memarian Hamid R. 
Published: December 2018

Background:Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against HIV, for avoiding the drug resistance issue.Objective:To develop novel HIV-1 IN inhibitors, a series of 3-hydroxy-pyrane-4-one (HP) and 3- hydroxy-pyridine-4-one (HPO) derivatives have been rationally designed and synthesized.Methods:To provide a significant characterization of the novel compounds, in-depth computational analysis was performed using a novel HIV-1 IN/DNA binary 3D-model for investigating the binding mode of the newly conceived molecules in complex with IN. The 3D-model was generated using the proto-type foamy virus (PFV) DNA as a structural template, positioning the viral polydesoxyribonucleic chain into the HIV-1 IN homology model. Moreover, a series of in vitro tests were performed including HIV-1 activity inhibition, HIV-1 IN activity inhibition, HIV-1 IN strand transfer activity inhibition and cellular toxicity.Results:Bioassay results indicated that most of HP analogues including HPa, HPb, HPc, HPd, HPe and HPg, showed favorable inhibitory activities against HIV-1-IN in the low micromolar range. Particularly halogenated derivatives (HPb and HPd) offered the best biological activities in terms of reduced toxicity and optimum inhibitory activities against HIV-1 IN and HIV-1 in cell culture.Conclusion:Halogenated derivatives, HPb and HPd, displayed the most promising anti-HIV profile, paving the way to the optimization of the presented scaffolds for developing new effective antiviral agents.
Ligand-based Pharmacophore Model for Generation of Active Antidepressant- like Agents from Substituted 1,3,5 Triazine Class
Authors: Gahtori Archana , Singh Abhishek 
Published: December 2018

Introduction:
Although the transition of a lead candidate into a drug is currently structured by
well-defined milestone, it is still most challenging and offers no guarantee in success to the end. In fact,
ligand-based pharmacophore modeling has become a key motive force for retrieving potential leads across
several therapeutic areas.

Methods:
An urgent need towards the development of novel antidepressant agents led us to generate a
pharmacophore model from an existing 44 compounds dataset. The best model with one hydrophobic, two
ring aromatic, and one positive ionization features was chosen on behalf of the correlation coefficient, sensitivity,
specificity, yield of actives and accuracy measures using HypoGen module of Discovery Studio. In
house library consisting of 10,000 substituted 1,3,5 triazine derivatives were shortlisted to select four insilico
hits. All shortlisted compounds were synthesized and characterized by FTIR, 1H-& 13C-NMR spectroscopy
and finally tested for antidepressant-like activity using behavioral models on rats viz. Forced Swim Test (FST)
and Elevated Plus Maze (EPM).

Results:
Two shortlisted compounds with optimal fit values showed a significant decrease in the duration
of immobility as compared to standard drug Imipramine in FST while time spent in open arm in enhanced
in case of EPM.
Evaluation of Angiogenesis Process after Metformin and LY294002 Treatment in Mammary Tumor
Authors: Moschetta Marina G. , Leonel Camila , Maschio-Signorini Larissa B. , Borin Thaiz F. , Gelaleti Gabriela B. , Jardim-Perassi Bruna V. , Ferreira Lívia C. , Sonehara Nathália M. , Carvalho Livia G.S. , Hellmén Eva , de Campos Zuccari Debora A.P. 
Published: December 2018

Background:The angiogenesis process is regulated by many factors, such as Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF). Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties.Methods:Canine mammary tumor cell lines CMT-U229 and CF41 were treated with metformin and LY294002. Cell viability, protein and gene expression of VEGF and HIF-1 were determined in vitro. For the in vivo study, CF41 cells were inoculated in female athymic nude mice treated with either metformin or LY294002. The microvessel density by immunohistochemistry for CD31 as well as the gene and protein expression of HIF-1 and VEGF were evaluated.Results:The treatment with metformin and LY294002 was able to reduce the cellular viability after 24 hours. The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002. In the in vivo study, there was a decrease in tumor size, protein and gene expression of HIF-1 and VEGFA, in addition to the decreasing of CD31 expression after all treatments.Conclusion:Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.
Поведение кобальтовой и редкоземельной подсистем в фрустрированных кобальтитах DyBaCo-=SUB=-4-=/SUB=-O-=SUB=-7+x-=/SUB=-
Authors: Казей З.А. , Снегирев В.В. , Столяренко М.С. , Пигальский К.С. , Козеева Л.П. , Каменева М.Ю. , Лавров А.Н. 
Published: December 2018

AbstractStructural, elastic, and magnetic properties of cobaltites DyBaCo_4O_7 + _ x produced by various technologies and distinguished by oxygen excess x are experimentally studied. It was found that rhombic distortion of the crystal structure of annealed stoichiometric samples with x = 0 results in frustration removal and elastic property anomalies in the T _ N region, caused by cobalt subsystem ordering. At an insignificant oxygen nonstoichiometry, no structural distortions occur in quenched samples, and anomalies in elastic characteristics in the T _ N region smooth and disappear. The studies of DyBaCo_4O_7 + _ x magnetic properties show that the rare-earth (RE) subsystem remains paramagnetic and its contribution exceeds the contribution of the Co-subsystem with strong antiferromagnetic couplings by an order of magnitude. The magnetic susceptibility of the stoichiometric sample does not exhibit an appreciable anomaly at T _ N , since cobalt subsystem ordering is not accompanied by the formation of a noticeable effective field on RE ions.
Adaptive Antiretroviral Therapy Adherence Interventions for Youth Living With HIV Through Text Message and Cell Phone Support With and Without Incentives: Protocol for a Sequential Multiple Assignment Randomized Trial (SMART) (Preprint)
Authors: Belzer Marvin E , MacDonell Karen Kolmodin , Ghosh Samiran , Naar Sylvie , McAvoy-Banerjea Julie , Gurung Sitaji , Cain Demetria , Fan Carolyn A , Parsons Jeffrey T 
Published: December 2018

BACKGROUND

Youth living with HIV (YLH) aged 13 to 24 years made up over a fifth (21%) of new HIV diagnoses in 2016, yet only 27% of YLH are virally suppressed. YLH have been shown to be poorly adherent to antiretroviral therapy (ART); however, there has been limited research investigating how to increase adherence in YLH. Mobile health (mHealth) interventions may be one promising way to do this.

OBJECTIVE

This study (ATN [Adolescent Trials Network] 144 SMART) aimed to compare adaptive interventions that could increase ART adherence in YLH aged 15 to 24 years. This includes mHealth initiatives, the tapering of interventions, and the use of incentives. Cost-effectiveness of sequencing the interventions without incentives before providing incentives and the savings on societal costs due to suppressed viral loads will be determined. This protocol is part of the ATN Scale It Up program described in this issue by Naar et al.

METHODS

This study uses a Sequential Multiple Assignment Randomized Trial design. Approximately 190 participants are being recruited, enrolled, and randomized to either cell phone support or text message support. Both intervention groups receive 3 months of intervention, followed by a second randomization based on response to the intervention. Responders test tapering their intervention, and nonresponders test receiving incentives.

RESULTS

Data collection for this study is projected to begin in August 2018 and last until June 2020.

CONCLUSIONS

This is an innovative study, particularly in terms of population, intervention types, focus on cost-effectiveness, and recruitment. This study could be particularly effective in improving adherence in YLH while reducing long-term individual and societal costs.

CLINICALTRIAL

ClinicalTrials.gov NCT03535337; https://clinicaltrials.gov/ct2/show/NCT03535337 (Archived by WebCite at http://www.webcitation.org/74alXb92z)

INTERNATIONAL REGISTERED REPOR

PRR1-10.2196/11183
Kontribusi Pemuda dalam Menjawab Permasalahan Sosial Ekonomi Pascabencana
Authors: Istriyani Ratna 
Published: December 2018

Bencana merupakan masalah serius sebab tidak hanya berdampak pada kerusakan fisik melainkan juga aset produktif atau sumber daya alam yang kemudian mempengaruhi aspek sosial ekonomi masyarakat. Krisis tersebut tidak cukup hanya diatasi dengan upaya pragmatis yaitu distribusi bantuan. Namun, butuh upaya solutif untuk mengatasi kevakuman aktivitas produktif masyarakat korban bencana. Salah satunya adalah mekanisme kewirausahaan sosial dengan didorong oleh aktor yang inovatif dalam meramu ide sesuai dengan masalah yang terjadi dan kapasitas lokal yang dapat diberdayakan. Pemuda dalam hal ini merupakan aktor potensial dan kreatif yang mampu menjawab kompleksitas masalah tersebut melalui social entrepreneurship. Hal itu tercermin dalam pengelolaan daerah terdampak bencana menjadi destinasi wisata di Umbulharjo Cangkringan yang kemudian dinamakan dengan wisata Volcano Tour. Tim Volcano Tour adalah organisasi yang bergerak pada pengelolaan daerah terdampak bencana menjadi wisata. Tim tersebut diinisiasi dan dirintis oleh tokoh muda lokal, dengan melibatkan masyarakat lokal (korban bencana) agar dapat merasakan manfaat sosial maupun ekonomi. Dengan demikian, tokoh muda dalam hal ini berposisi sebagai social entrepreneur. Secara ekonomi, pengelolaan wisata erupsi menjadi sumber pendapatan bagi masyarakat lokal. Secara sosial, pengelolaan wisata erupsi melalui Tim Volcano Tour mampu menjamin pemerataan akses ekonomi, mereduksi gesekan sosial yang sempat muncul, menciptakan kohesi sosial, dan perubahan mindset.
Abnormal Fees and Timely Loss Recognition—A Long-Term Perspective
Authors: Amir Eli , Guan Yanling , Livne Gilad 
Published: December 2018

SUMMARY
We examine the relation between timely loss recognition and abnormal audit, non-audit, and total fees over a period of thirteen years. We use positive abnormal audit (non-audit) fees as a measure of abnormal audit effort (economic bond). We report some evidence suggesting audit effort is associated with slower loss recognition in accruals before the Sarbanes-Oxley Act (SOX) became effective. We find stronger evidence that audit effort is associated with slower loss recognition post-SOX when clients raise substantial external funds or when the auditor is not an industry specialist. Using C_Score, we find a negative association between changes in abnormal audit fees and total fees, and changes in C_Score only post-SOX. We do not find abnormal non-audit fees are associated with the speed of loss recognition. Collectively, the results suggest post-SOX auditors exert more effort when losses are delayed and that non-audit services do not compromise auditor independence.
Antologia na gaveta: considerações sobre a poética do grupo modernista de Belo Horizonte
Authors: Pasini Leandro 
Published: December 2018

Entre 1927 e 1928 seria lançada uma Antologia dos quatro poetas mineiros − Drummond, Emílio Moura, João Alphonsus e Pedro Nava −, com prefácio de Martins de Almeida. Essa obra não foi publicada na época nem posteriormente, embora Drummond tenha revelado estar de posse dos materiais. Diante disso, este texto procura recompor o contexto dessa antologia, analisar alguns poemas contemporâneos à sua concepção e, a partir daí, propor que havia um tipo de poética compartilhada pelo grupo modernista mineiro de A Revista (1925-1926). A hipótese que se persegue é a de que essa poética não só unificava as pesquisas e a produção do grupo mas também dava contornos mais fortes e precisos à originalidade individual de cada poeta.
Important Role of Civic Education in Multi-Ethnic Countries Malaysia and Singapore
Authors: Sari Serli Retno 
Published: December 2018

This article discusses about the role of citizenship education in multi-ethnic countries, namely in Malaysia and Singapore. Malaysia and Singapore are two former British colonies, and in the population, there are three main ethnic groups namely China, Malay and India. This article is study of literature by using the comparative method by analyzing 14 national and international journals related to citizenship and diversity education in Malaysia and Singapore. Based on the results of this research, there is a difference in the management of ethnic diversity in Malaysia and Singapore. However, both in Malaysia and Singapore, citizenship education equally play an important role in creating a harmonious society even in the diversity of cultures, languages, religions and customs.
Keywords: citizenship education, multi-ethnic, multicultural, Malaysia, Singapura
Abstrak
Artikel ini membahas tentang peran pendidikan kewarganegaraan dalam menciptakan masyarakat yang harmonis di negara multietnik, yaitu di Malaysia dan Singapura. Malaysia dan Singapura adalah dua negara yang sama-sama bekas jajahan Inggris, dan dalam populasinya terdapat tiga etnis utama yaitu China, Melayu dan India. Tulisan ini merupakan studi literatur dengan menggunakan metode komparasi dengan menganalisis 14 jurnal nasional dan internasional terkait pendidikan kewarganegaraan dan keberagaman di Malaysia dan Singapura. Dari hasil penelitian dapat diketahui bahwa terdapat perbedaan dalam pengelolaan keberagaman etnis di Malaysia dan Singapura. Namun demikian baik di Malaysia maupun di Singapura, Pendidikan Kewarganegaraan sama-sama memegang peranan penting dalam menciptakan masyarakat yang harmonis walau dalam keberagaman budaya, bahasa, agama dan adat istiadat.
Kata Kunci: Pendidikan Kewarganegaraan, multietnik, multikultural, Malaysia, Singapura
El posicionamiento argentino frente al terrorismo internacional en la Asamblea General de la ONU (1992-2017)
Authors: Ciccone Carlos Sebastian , Clemente Aldana , Pretti Carlos Javier 
Published: December 2018

El terrorismo internacional ha sido un tema central en la agenda en cuestiones de seguridad externa de la República Argentina de las últimas décadas. Los atentados ocurridos en los años 1992 y 1994: el primero la voladura de la Embajada de Israel y, el segundo, la voladura de la Asociación Mutual Israelita Argentina (AMIA) actuaron como un disparador que obligó, a partir del gobierno de Carlos Menem, a que sus sucesores, más allá de su pertenencia ideológica, se posicionen al respecto.
Este artículo tiene como objetivo identificar y analizar los posicionamientos de la República Argentina frente al terrorismo internacional en el ámbito de la Asamblea General de la ONU, identificando cambios y continuidades.
Qualitative study of owner perceptions of chronic pain in their dogs
Authors: Davis Kelly N. , Hellyer Peter W. , Carr Eloise C. J. , Wallace Jean E. , Kogan Lori R. 
Published: December 2018

Abstract
OBJECTIVE To understand the experiences of owners of dogs with chronic pain and explore owner perceptions of their pets' pain.
DESIGN Observational study.
SAMPLE 10 owners of dogs with chronic pain.
PROCEDURES Owners were interviewed by means of a semistructured and conversational technique. Interviews were then transcribed and analyzed with standard qualitative methodology to code for major themes.
RESULTS Major themes that were identified included changes in owner schedule, effects on owner relationships, and necessary resources when owning a pet with chronic pain. Owners discussed their perceptions of their pets' pain, and several participants referred to empathizing with their pet owing to their own experiences with pain. Owners also suggested ways that veterinarians can support them during the experience of owning a dog with chronic pain.
CONCLUSIONS AND CLINICAL RELEVANCE By understanding the impact of chronic pain on dog owners and appreciating how owners perceive pain in their pets, veterinarians may be able to provide better care for patients and clients.
Rhabdomyolisys as a Cause of Acute Renal Injury
Authors: Nikolova M. , Guerguinova N. , Tsocheva T. , Vasilieou D. , Hristova M. , Hubanov N. , Papazov V. , Kirilov Al. , Mushekov V. , Manov E. , Vlahov Y. , Bogdanova V. , Petkov K. , Davidov K. , Yosifov D. , Ivanova D. , Krasteva R. , Bogov B. 
Published: December 2018

Abstract
Rhabdomyolysis (RM) is defined as striate muscle-cell damage with disintegration of skeletal muscles and release of intracellular constituents to the circulation, with or without subsequent kidney injury. RM is one of the leading causes of acute kidney injury and is associated with substantial morbidity. The major signs of acute kidney injury in rhabdomyolysis are: pain, weakness and swelling of the injured muscle or muscle groups and myoglobinuria with reddish discoloration of the urine and decrease in urine output to anuria. The authors describe three cases of rhabdomyolysis with acute renal injury and discuss the current knowledge on the etiopathogenesis, clinical manifestations, diagnosis and treatment of this condition.
An attempt to reconstruct selected elements of the original site topography of the Teutonic castles at Unisław and Starogród (Chełmno Land, Northern Poland) based on archaeological and cartographic data
Authors: Molewski Paweł , Wasik Bogusz , Wiewióra Marcin 
Published: December 2018

Abstract
The article presents an attempt to reconstruct the original site topographies of 13th-century Teutonic castles at Unisław and Starogród, which have not been preserved in the surface terrain. The archaeological remains of both castles are located in the west of Chełmno Land, on the edge of a moraine plateau 30 to 50 metres above the floor of the Vistula valley. The reconstruction used a research approach known as Historical GIS (HGIS), which, besides archaeological data, employs digitised historical cartographic sources. The research showed that changes in the original site topography are associated with anthropogenic transformations in the plateau surface, mainly due to agricultural use, and with retreat of the plateau edge resulting from natural and man-made landslide processes. The authors believe that the reconstruction of the castles’ original site topographies could be used to verify detailed hypotheses related to the conditions of their construction and operation.
Hydromorphological and physicochemical conditions of the Parsęta River
Authors: Szpikowski Józef , Szpikowska Grażyna 
Published: December 2018

Abstract
Rivers are hydromorphologically assessed in line with the Water Framework Directive. In order to assess the quality of the Parsęta River environment, the River Habitat Survey method was applied. The research studies, conducted in June 2016, provided an overview of hydromorphological issues, and also covered measurements and laboratory analyses on the quality of its waters. There were 24 measuring sections selected along the whole river. The selection of these sections took into account the representativeness of genetically various types of river valley, its size and discharge, and the variability of anthropogenic pressure. The assessment showed that the Parsęta River varies in natural quality (its HQA index ranged from 17 to 61) and that the modification of its valley is variable but generally low (its HMS index ranged from 0 to 33). Seventy-nine percent of the analysed sections were classified to the second (II) and third (III) hydromorphological classes, 8% to the first (I), and 13% to the fourth (IV). The central section of the Parsęta River has the highest degree of naturalness and the lowest degree of transformation. The river valley sections of kettle-hole origin are more transformed than those of fluvial origin. The quality of the Parsęta River waters assessed on the grounds of their physicochemical parameters indicates that the river is in good condition. The individual river water parameters are most often within the first (I) and second (II) classes. Any instances of the quality of waters being below the “good” level are due to phosphate concentrations exceeding the second (II) class and are contained within a 15-km stretch of the river below Białogard. A river section with a high degree of hydromorphological naturalness has the worst quality of waters.