bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategi Pengembangan Wisata Kesehatan melalui Pemberdayaan Kelompok Sadar Wisata pada Masyarakat Kepulauan (Studi Kasus: Pulau Giliyang Kecamatan Dungkek Kabupaten Sumenep)
Authors: Zainuri Ach. Muhib , Patma Tundung Subali , Purwanti Elly
Published: June 2020

The objective of this community services is to design strategy of health tourism which combines economic, social, and ecological values in tourism development at Giliyang Island - subdistrict Dungkek, Sumenep regency. The problem that faced to achieve the objective are the weakness of institutions and human resources. The methodology used in this activity are focus group discussion (FGD) and stakeholder need analysis (SNA) and system approach that develop from questioners and deep interviews with all stakeholders. The result of community services are (1) empowerment tourism  awarness  group of Sora Laksana, (2) practice and training of a appropriate technology, and (3) conservation of mangrove and coast forest. Impact of the activities show that such as preservation, conservation, and tourist satisfaction indicate positive value. Meanwhile impact on local economy and community empowerment have not been shown positive value. These phenomenous happen because the tourism zone still under development. Therefore there is need a strategic strategy to achieve sustainable development of health tourism. ABSTRAKTujuan yang hendak dicapai dari kegiatan pengabdian masyarakat ini adalah untuk merancang strategi pengembangan wisata kesehatan yang mengombinasikan aspek ekonomi, sosial, dan ekologi dalam pengembangan kepariwisataan di Pulau Giliyang, Kecamatan Dungkek, Kabupaten Sumenep. Untuk mencapai tujuan ini, masalah yang nampak adalah lemahnya institusi pariwisata dan sumberdaya manusia. Metodologi yang digunakan dalam kegiatan ini adalah melalui diskusi kelompok fokus, analisis kebutuhan seluruh pemangku kepentingan, dan mengembangkan pendekatan sistem melalui wawancara mendalam dengan semua pemangku kepentingan. Hasil  kegiatan pengabdian kepada masyarakat ini adalah (1) pemberdayaan kelompok sadar wisata - Pokdarwis Sora Laksana, (2) penerapan dan pelatihan teknologi tepat guna, dan (3) konservasi hutan mangrove dan hutan pantai. Dampak kegiatan seperti konservasi, pemeliharaan, dan kenyamanan pengunjung menunjukkan nilai positif. Sedangkan pengaruh terhadap perekonomian lokal dan pemberdayaan masyarakat belum menunjukkan nilai positif. Hal ini terjadi karena zonasi wisata masih baru. Sehingga masih dibutuhkan cara yang strategis untuk mencapai pengembangan pariwisata kesehatan yang berkelanjutan.Kata kunci : wisata kesehatan, daya dukung, tata ruang, wisata berkelanjutan,
Pembuatan Virgin Coconut Oil (VCO) Menggunakan Enzim Bromelin di Kampung Kekupu, Depok
Authors: Putri Elfia Siska Yasa
Published: June 2020

Virgin Coconut Oil (VCO) merupakan produk olahan dari buah kelapa (Cocos nucifera L). Pada kegiatan pengabdian ini tim pengabdian mengajarkan pembuatan VCO melalui cara enzimatis dengan memanfaatkan buah nanas (Ananas comosus) yang banyak tumbuh di  Kampung Kekupu, Depok. Kegiatan ini dilakukan untuk (1) meningkakan pengetahuan mitra tentang VCO (2) mengajarkan cara pembuatan dan pengemasan VCO sehingga mitra bisa secara mandiri untuk memproduksi VCO. Dengan demikian, mitra dapat membantu penghasilan keluarga. Pada tahap pembuatan VCO ini, enzim bromelin dari buah nanas yang dicampur dengan krim kelapa. Setelah itu VCO yang terbentuk diambil menggunakan sendok sayur dan dikemas dalam wadah yang aman. Untuk menunjang kegiatan ini maka mitra diberikan buku saku panduan pembuatan VCO menggunakan enzim bromelin. Penyuluhan  tentang kandungan zat-zat kimia yang  yang terdapat pada buah kelapa , buah nenas, dan VCO serta  manfaat dan keunggulan VCO diberikan oleh narasumber. Setelah kegiatan ini, 86,7 % peserta berpendapat bahwa materi pelatihan mudah dipahami. Sebanyak 93,3 % peserta memperoleh banyak manfaat dari acara ini.
Program Kemitraan Masyarakat Universitas Widyagama Malang Pada Usaha Peningkatan Industri Rumah Tangga Keripik Tempe Pemula
Authors: Priyandoko Gigih , Rofii Faqih , Sujianto Agus Tugas
Published: June 2020

Tempe merupakan salah satu makanan khas Indonesia yang sudah lama dikenal. Di berbagai daerah di Indonesia, banyak sekali jenis olahan makanan berbahan dasar kedelai. Walau bagaimanapun terdapat berbagai kendala dalam melaksanakan bisnis kripik tempe bagi pemula. Kendala yang akan diatasi dalam program kali ini adalah perlu mencari pisau yang sesuai untuk memotong tempe yang lebih tipis, sehingga dapat menghasilkan jumlah irisan kripik yang lebih banyak dan lebih renyah, perlunya mendesain ulang kemasan bungkus kripik tempe yang lebih menarik, pemberian merk yang lebih spesifik sebagai tanda mudah untuk mengingat dan perlunya menghasilkan kripik tempe dengan berbagai varian rasa untuk menjangkau pembeli yang lebih luas. Penilaian keberhasilan pelaksanaan program pengabdian masyarakat ini dilakukan dengan pembuatan kuisioner kepada pembeli untuk mengetahui seberapa besar efek perubahan sebelum dan setelah dilakukan beberapa perubahan oleh mitra produsen kripik tempe.
On Dual $k-$ Pell Bicomplex Numbers and Some Identities Including Them
Authors: HALICI Serpil , ÇÜRÜK Şule
Published: June 2020

In the paper, we have considered the real and dual bicomplex numbers separately. Firstly, we examine the dual numbers and investigate the characteristic properties of them. Then, we give the definition, feature and related concepts about bicomplex numbers. And we define the number of dual $k-$ Pell bicomplex numbers that are not found for the first time in the literature and we examine the norm and conjugate properties of these numbers. We give equations about conjugates and give also some important characteristic of these newly defined numbers, and we write the recursive correlations of these numbers. Using these relations we give some important identities such as Vajda's, Honsberger's and d'Ocagne identities.
Numerical Investigation on the Effect of Piston Bowl Geometry on Combustion Characteristics of a Heavy-Duty Diesel Engine
Authors: Adeniyi Oladapo
Published: June 2020

Today, due to increased efficiency of heavy-duty diesel engines in the global industry, discussion of the performance of these motors, including higher efficiency and lower emissions, is very important. Several methods exist to meet these demands by the diesel engine. Piston bowl geometry deformation strategy is a reliable method for achieving pollutants of lower nitrogen oxides (Nox) and soot and higher yield. This paper has used Converge software to model the CFD for the performance of a Caterpillar 3401 engine with three different piston bowl geometries and various depths and chamfers for one of the geometries. The compression, inlet temperature, and pressure ratio are assumed to be constant. The results of efficiency and pollution of the engine are presented at all stages for analysis, comparisons, and conclusions. The results show that the cylindrical piston bowl geometry has a proper performance in terms of efficiency and the pollutions produced.
POTENSI DAN KENDALA YANG DIHADAPI PETANI MANGGA DALAM MENGAKSES LEMBAGA PEMASARAN (STUDI KASUS DI KECAMATAN GREGED KABUPATEN CIREBON)
Authors: Rasmikayati Elly , Azizah Mentari Nur , Saefudin Bobby Rachmat
Published: June 2020

Kabupaten Cirebon memiliki potensi besar dalam mengembangkan dan meningkatkan produksi mangganya namun trennya berfluktuatif dari tahun ke tahun. Salah satu penyebabnya adalah masalah sulitnya petani mengakses lembaga pemasaran mangga yang lebih bersaing dalam harga jual mangganya seperti pasar induk, pasar modern atau pasar ekspor. Kecamatan Greged yang merupakan pemekaran dari Kecamatan Beber dan Kecamatan Astanajapura merupakan kecamatan yang paling berpotensi dalam pengembangan agribisnis mangga. Penelitian ini bertujuan untuk mengidentifikasi potensi dan kendala petani dalam mengakses lembaga pemasaran di Kecamatan Greged. Metode yang digunakan dalam penelitian ini adalah metode survei dengan alat analisis data yaitu analisis statistika deskriptif dan analisis crosstabulation. Hasil penelitian menunjukkan bahwa potensi petani manga di Kec. Greged dalam mengakses lembaga pemasaran diantaranya mudahnya akses mendapatkan Informasi Pemasaran, system pembayaran tunai, pengetahuan mengenai informasi harga jual manga di pasar, kendali penentuan harga yang sudah banyak ditentukan oleh pihak petani dari pada pembeli, kemudahan syarat mengakses pasar dan sudah tersedianya sarana transportasi. Sedangkan kendala yang dihadapi petani mangga dalam mengakses lembaga pemasaran diantaranya cara penjual manga yang masih banyak dilakukan petani melalui perantara dan pembeli mangga yang sebagian besar masih ke pedagang pengepul atau bandar. Lebih lanjut, kebijakan revitalisasi kelembagaan mangga terutama lembaga kelompok tani harus dilakukan agar lembaga ini lebih berperan dalam memasarkan hasil mangga dari para petani. Selain itu petani harus lebih didorong untuk mampu menjual hasil panennya ke pasar secara langsung baik pasar tradisional, pasar induk, pasar modern maupun pasar ekspor. Kata Kunci: Akses Petani, Lembaga Pemasaran, Petani Mangga, Kelompok Tani.
ANALISIS KELAYAKAN USAHA INDUSTRI KECIL TAHU (Kasus di Desa Danawinangun Kecamatan Klangenan Kabupaten Cirebon)
Authors: Faqih Achmad , Kurniati Eli , Suciati Tety
Published: June 2020

Penelitian ini dilakukan di Desa Danawinangun, Kecamatan Klangenan, Kabupaten Cirebon, Provinsi Jawa Barat, Pada bulan Mei 2013. Penelitian ini bertujuan untuk mengetahui : (1) Return Cost Ratio (R/C Ratio), (2) Break Even Point (BEP), (3) Return of Investment (ROI) usaha industri kecil tahu. Metode yang digunakan dalam penelitian ini adalah metode sensus. Satuan analisis penelitian adalah industri kecil yang melaksanakan usaha tahu. Pengumpulan data primer diperoleh melalui wawancara dengan responden menggunakan daftar pertanyaan, dan data sekunder diperoleh dari instansi yang ada kaitannya dengan penelitian ini. Data yang dihasilkan dianalisis secara deskrptif. Hasil penelitian menunjukan bahwa usaha industri kecil tahu di Desa Danawinangun, Kecamatan Klangenan, Kabupaten Cirebon, layak untuk diusahakan dilihat dari: (1) Nilai R/C 1,46 berarti pengusaha industri kecil tahu layak untuk diusahakan, (2) Nilai BEP Produksi 26 kg/produksi, sedangkan tahu yang dihasilkan 27,5 kg/produksi berarti pengusaha industri kecil tahu layak untuk diusahakan, (3) Nilai BEP Harga Rp 11.251 per papan-, sedangkan harga jual Rp.24.000 per papan berarti pengusaha industri kecil tahu layak untuk diusahakan, (4) Nilai ROI sebesar 49% sedangkan bunga bank yang berlaku 1% per bulan berarti pengusaha industri kecil tahu layak untuk diusahakan.Kata Kunci : Analisis, Kelayakan usaha, Industri tahu.
Türk Siyasal Düşüncesinde Modernleşme ve Bergsonculuk: Anti mi Alternatif mi?
Authors: LİVAN H. Furkan
Published: June 2020

Bergson felsefesi, modernizm/modernleşme bağlamında oldukça etkilidir. Çünkü bu felsefe, modernizmin hâkim paradigması olan pozitivizme, ilerleme fikrine ve aklın yüceltildiği Aydınlanma’ya itirazlar getirmektedir. Hâkim paradigma yerine metafiziğin dışlanmadığı, yaşamın varlık yerine oluş vasfına vurgu yapan ve yaşam atılımına (élan vital’e) dayalı evrimsel dönüşümü savunan bir felsefe sunmaktadır. Determinizme, mekanizme ve entelektüelizme karşı çıkan Bergsonculuk, toplumları ve etik-politik sistemleri de bu bağlamda değerlendirmektedir. Bergsonculuk, Türk siyasal düşüncesinde de bu argümanlarıyla oldukça önemli etkiler yapmıştır. Osmanlı-Türk modernleşmesinin hâkim paradigması pozitivist, ilerlemeci ve Aydınlanmacı özelliklere sahipken; Bergsoncu çevreler, modernleşme sürecini farklı bir perspektifle ele
almıştır. Bu sayede, Millî Mücadele’nin ve Cumhuriyet’in yaşam atılımı (élan vital) ve yaratıcı tekâmül kavramlarına dayalı, farklı bir yorumu mümkün hâle gelebilmiştir. Ancak, tartışmalı olan husus Bergsonculuk düşüncesinin modernleşmenin neresinde yer aldığı hususudur. Şimdiye kadar Bergsonculuk muhafazakârlık çerçevesinde değerlendirilmiş olsa da, bir felsefeyi yalnızca bir ideolojinin tahakkümünde ele almak hatalı olacaktır. Bu bağlamda çalışma, Bergsonculuk düşüncesinin Osmanlı-Türk modernleşmesinde anti mi yoksa alternatif mi olduğu tartışmasını yürütmektedir.
The Media and Modernity: Film and New Media in the Highlands and Islands 1946–1971: Introduction
Authors: Goode Ian , Neely Sarah , Brown Callum G. , Munro Ealasaid
Published: June 2020

The Highlands and Islands Film Guild is briefly surveyed in this article that introduces the Special Issue on Media and Modernity. The foundations, principles and manner of operation are outlined, as well as the interdisciplinary research project. The article starts with a review of literature on the nature of society in the Highlands and Islands, and the way that researchers regard it as ‘the other’ in historical and ethnographic research within the United Kingdom. We note the work undertaken in cultural history that has tended to treat the Highland zone as disjoined in governance and everyday life. The researchers’ different approaches and methods are then discussed, moving through specialists in film and television, creative arts, religious and cultural history, and social geography. Finally, the article introduces the articles that follow in the Special Issue.
The Individual, the Community and the Impact of Touring Film: Interviews with Jim Hunter and Others
Authors: Brown Callum G. , Munro Ealasaid
Published: June 2020

The impact of the Highlands and Islands Film Guild is here explored through narrators interviewed in the 2010s about their experiences of touring film shows between the late 1940s and early 1970s. Centrally featured is the testimony of Jim Hunter, journalist, historian, erstwhile director of the Scottish Crofters’ Union and chairman of the Highlands and Islands Enterprise, whose testimony is analysed for six major narrative features – cultural and religious transformation, cinema as enchantment, sense of community, the sense of ‘the other’, social rescue for the Highland zone, and religion as social danger or social lifeboat for the Highlands. Other narrators, including Dr Finlay Macleod, are cited as foils in some of these narrative strands. The reception of the Guild in English and Gaelic-speaking areas is noted, as its place in the arrival of new broadcasting technologies.
The Unsatisfactory Medium: the Transition from Mobile Cinema to Television in the Post-war Highlands and Islands
Authors: Goode Ian
Published: June 2020

Becky Conekin et al. identify the Queen's Coronation and its mediation by television in 1953 as the defining moment in post-war British modernity (Conekin, Mort, Waters 1999). The population of the Highlands and Islands mostly watched this event on 16mm film, via the mobile cinema shows provided by the Highlands and Islands Film Guild. Film assumed the audio-visual functions of television because the geography of the Highlands and Islands did not readily accommodate television broadcasting. Television arrived slowly and unevenly. This paper traces arrival of television into the Highlands and Islands and the uncertainty over accessibility and quality of reception. It argues that whilst the Scottish Education Department assumed that the mobile cinema service had been succeeded by television; the inherent problems of delivering television enabled the more communal, educative, legitimate and reliable cinema to prevail. This asynchronous relationship compels us to recognise the geography of British modernity. Drawing on archival sources, oral history interviews and media histories, this paper presents an account of the Highland experience of a transition typically aligned with an urban perspective.
Displaying information on remuneration in budget institution reporting
Authors: Olga Bunda , Yuriy Kozachuk
Published: June 2020

The purpose of the article is to investigate remuneration information in varioustypes of budget institution reporting. the methodology of the study is to use aset of methods: dialectical, structural-analytical, induction and deduction, statistical,observation, generalization. The scientific novelty of the results obtained is thecomprehensive coverage of the presentation of information on remuneration invarious types of reporting budgetary institution. conclusions. In order to providedetailed and efficient of remuneration information on remuneration, an institutionmay, on the basis of existing reporting forms, develop analytical remunerationdocuments. The use of such analytical documents will increase the efficiency andpromptness of employees to formulate the required forms of reporting to abudgetary institution.
Audit of cash-less calculations of sport enterprises
Authors: Olga Bunda , Alona Olianina
Published: June 2020

The purpose of the article is to summarize and improve the organizational andmethodological aspects of the audit of cash-less payments of enterprises in thefield of sports. research methodology is to use the following methods: analysis,synthesis, induction, deduction, analogy, modeling, formalization. the scientificnovelty of the article is to substantiate the information concept of non-cashpayments audit and the system of modeling cash-less payments audit of enterprisesin the field of sports. conclusions. The application of the information concept ofcash-less payments audit and the system of modeling cash-less payments at a sportsenterprise will significantly increase the efficiency of audits, which will directlyaffect the financial and economic activity of the enterprise. The proposed plan andprogram for the audit of cash-less payments will allow qualitative and detailedaudit of the enterprise in the field of sports.
Peculiarities of management of preparation of call-centeroperators in the banking area
Authors: Olesia Totska , Myroslava Bleianiuk
Published: June 2020

The purpose of the article is to study the peculiarities of management trainingof call-center operators in the banking sector. the methodology of the study is touse the method of analysis. the scientific novelty of the obtained results is thatthe article describes the theoretical aspects of training of call-center operators inone of the leading banks in Ukraine. In particular, the process of training traineesand newcomers is described in detail. conclusions. The results of the study madeit possible to outline certain aspects of training of call-center operators in thebanking sector at different stages.
Planning a project of the creation of an electric vehicle technical assistance point
Authors: Olesia Totska , Anastasia Glovatsky
Published: June 2020

The purpose of the article is to plan a project of an electric vehicle technicalassistance point. the methodology of the study is to use the critical path method.the scientific novelty of the obtained results is that the article describes the practicalaspects of project planning of the creation of an electric vehicle technical assistancepoint. In particular, the tasks of the project are described, labor, material and financialresources necessary for its realization are specified. conclusions. The implementationof the developed project will effectively manage the content, time and resources ofthe project of the creation of an electric vehicle technical assistance point.
Assessment of external factors in the formation of the innovation space
Authors: Inna Stenicheva
Published: June 2020

The purpose of the article is to analyze and evaluate external factors of influence on the formation of a new profile of the innovation space of the regions ofUkraine.research methodology. During the study, the works of foreign and domestic scientists involved in the diagnosis of the socio-economic development ofterritories were used, methods of scientific comparative analysis, general scientific methods of theoretical, empirical research and methods of expert assessmentswere used. scientific novelty lies in a clear, streamlined approach to the determination and diagnosis of external factors influencing the formation and developmentof the innovation space of the regions of Ukraine. conclusions and offers. Theproposed approaches to developing a system and assessing the factors of influenceon the formation of the innovation space, as well as analyzing the nature of thesechanges, can serve as a scientific basis for further diagnostics of spatial development, identifying the strengths and weaknesses of regions, their opportunities andthreats in the field of developing an innovative space and creating this basis ofthe modern innovative profile of the regions.
Social politics and problems of providing of financial safety of man are in the system of national economic security
Authors: Irina Tkachenko
Published: June 2020

The article of research is totality of organizationally-economic relations thatarise up in the process of forming of social politics and providing of financialsafety of man in the system of national economic security. the aim of the articleconsists in the analysis of basic problems, contradictions that arise up in the processof realization of complex of events in relation to forming of effective social politicsin the system of strengthening of financial safety of Ukraine. research methodologyconsists in the use of totality of methods : dialectical, analytical, comparative. Themarked methodological approach allowed to analyse theoretical and methodological,and practical aspects forming of social politics, that is represented in works ofhome and foreign scientists and to define their connection and influence on thesystem of financial safety of man in Ukraine. the scientific novelty of the got results consists in complex illumination of the generalized going near determinationof priorities of social politics in the system of strengthening of financial safety ofman in Ukraine. Done scientific conclusions in relation to character, features ofthe state of realization of social politics and ground of necessity and expediencyof further study of her influence on strengthening of financial safety of man inUkraine. conclusions. In the article there are the lighted up questions of necessityof scientific comprehension and practical decision of the problems related to theimprovement of social politics, determinations of their priorities in the system ofstrengthening of financial safety of man in Ukraine. Taking into account thatpresently there is determination of list of national economic interests importantscientific and practical tasks, providing of realization of that straight depends onthe state of safety of different constituents of the financial system of Ukraine, tothe improvement of social politics the center of that are a man and his necessities,it is necessary to spare the special attention.
Features of interaction of the state and transnational companies
Authors: Оlena Poradenko
Published: June 2020

The purpose of the article is to assess the global experience of TNCs in stateinvestment processes. The instruments of state influence on the activities of TNCsare characterized. It is shown that the legal regulation of the activities of TNCsis impossible without resorting to international legal sources of regulation offoreign direct investment. the research methodology consists in using a combinationof methods: expert assessments, comparative and system analysis. The indicatedmethodological approach made it possible to analyze the strengths and weaknessesof the interaction between the state and TNCs and, through them, justify the useof a specific strategy. the scientific novelty of the results obtained is to determinethe role of TNCs in the world economy and countries’ politics, given in particularthe positive and negative consequences of their activities and the fact that theemergence of such international corporations is a logical step in the developmentof the international economy and is a necessary stage in the modern reorganizationand development of the country’s economy. conclusion. In the current stage ofeconomic development, government influence is necessary to maintain andredistribute investment flows to high-tech sectors related to the development ofindustries, which will increase the long-term international competitiveness of TNCsin the markets of global economy sectors.
INTERIM HOME CARE FOR DENTAL PAIN DURING COVID19 PANDEMIC-a mini review
Authors: Shabir Shayan
Published: June 2020

Since the whole world is in the grip of covid-19 pandemic and all the routine dental procedures are suspended, there is a high viral load in the nasal cavity of infected patients, which especially puts dental specialty at risk for a SARS-CoV-2 infection as transmission is mainly by respiratory droplets. So it’s of paramount importance that the dental professionals reach out to people through technology and instruct them regarding various home remedies to relieve their dental problems. It’s true that not all dental problems can be treated at home but the pain due to many of these can be relieved at home temporarily (though permanent treatment is needed later on). This is the need of the hour and the public must know about it. So this article will be highlighting dental care from home with brief information on the causes of dental pain.

Key Words: covid19, dental pain, cloves, home care
Contactless Liquid Height and Property Estimation Using Surface Acoustic Waves
Authors: Alhazmi Hani , Guldiken Rasim
Published: June 2020

The propagation of surface acoustic waves over a solid plate is highly influenced by the presence of liquid media on the surface. At the solid–liquid interface, a leaky Rayleigh wave radiates energy into the liquid, causing a signification attenuation of the surface acoustic wave amplitude. In this study, we take advantage of this spurious wave mode to predict the characteristics of the media, including the volume or height. In this study, the surface acoustic waves were generated on a thick 1018 steel surface via a 5 MHz transducer coupled through an angle beam wedge. A 3D-printed container was inserted on the propagation path. The pulse-echo time-domain responses of the signal were recorded at five different volumes (0, 400, 600, 1000, and 1800 µL). With the aid of parametric CAD analysis, both the position and distance of the entire traveling wave in the liquid layer were modeled and verified with experimental studies. The results indicated that the average drop in the reflected wave amplitude due to liquid loading is −62.5% compared to the empty container, with a percentage of error within 10% for all cases. The localized-time frequency components of the reflected wave were obtained via a Short-Time Fourier Transform technique. Up to 10% reduction (500 KHz) in the central frequency was observed due to the liquid volume increasing. The method discussed herein could be useful for many applications, where some of the liquid’s parameters or the ultrasonic wave behavior in the liquid need to be assessed.
Impact of Cover Crops on Insect Community Dynamics in Organic Farming
Authors: Martinez Lili , Soti Pushpa , Kaur Jasleen , Racelis Alexis , Kariyat Rupesh R.
Published: June 2020

Manipulating cover crops as an integrated pest management strategy has recently gained popularity in both traditional and organic agroecosystems. However, little information is available for producers to make informed decisions about cover crop selection, management, and their potential use as a pest management tool. To address this, we conducted a two-year, four-season field experiment on the potential of various cover crops during the summer seasons of both years, followed by monocultures of cash crops during winters. We hypothesized that the cover crop treatments would attract beneficial insects and repel damaging herbivores in a species-specific manner, and the insect community dynamics would be bridged to the cash crops in the subsequent season. In addition, we hypothesized that cash crops would suffer lower herbivory damage following specific cover crop treatments. Our design comprised of three cover crops. Our results indicate that cover crops support beneficial insects during the early summer season, while the time of growing season doesnot affect herbivore abundance. Crop-specific effects were found for herbivore abundance with possible cascading effects on insect community as well as damage levels on the subsequent cash crop, but without any impact on the growth traits of the cash crop. Together, our data suggest that cover crops, when carefully selected, can be an integral part of a pest management strategy for sustainable agriculture.
The Genetic Diversity and Population Genetic Structure of the Red Panda, Ailurus fulgens, in Zoos in China
Authors: Xiu Yun-fang , Liu Cheng-Chi , Xu Su-hui , Lin Chen-Si , Chou Chin-Cheng
Published: June 2020

In China, red pandas (Ailurus fulgens) have been raised in zoos for 60 years. It is very important to understand the genetic diversity and population genetic structure of the captive red pandas. Based on 19 microsatellite loci, we investigated genetic diversity and population genetic structure of 116 captive red pandas, with samples taken from 11 captive populations in China. Our results revealed a high genetic diversity among the populations, with mean allelic richness varying from 3.505 (Beijing) to 4.026 (Mianning), and expected heterozygosities varying from 0.631 (Huangshan) to 0.782 (Wenling). In particular, significant deviation from Hardy–Weinberg equilibrium was found in populations of Fuzhou and Jiangsu. The genetic differentiation index across all populations was 0.055, indicating a significant genetic differentiation among the 11 populations. These populations could be divided into three genetic clusters using a microsatellite-based Bayesian clustering analysis, which were consistent with the clustering results of wild populations. We conclude that the genetic diversity among captive red pandas is as high as that of the wild population. More attention should be paid to develop a proper and scientifically-based management program to avoid inbreeding and maintain a high genetic diversity in captive red pandas.
Risk Associated with the LEPR rs8179183 GG Genotype in a Female Korean Population with Obesity
Authors: Jang Kyunghye , Shin Gurum , Yoo Hye Jin , Lee Jong Ho , Kim Minjoo
Published: June 2020

The difference between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) phenotypes might be partly attributable to genetic traits modulating body fat distribution and other obesity-related metabolic traits, specifically with regard to LEPR rs8179183 in Korean women with obesity. A total of 177 females with obesity participated in the study and were grouped by genotype (GC or GG) and metabolic health status (MHO and MUO). Between the MHO and MUO groups, significant differences were found in waist circumference, waist-to-hip ratio, lipid profiles, glucose-related markers, biomarkers of liver health, adiponectin, oxidative stress markers, whole fat area (WFA), and subcutaneous fat area (SFA) at the level of the L1 vertebra, and WFA and visceral fat area (VFA) at the level of the L4 vertebra. Lipid profiles, glucose-related markers, adipokines, oxidative stress markers, and WFA and VFA at the L4 level were significantly different between the GC and GG genotypes. Notably, the individuals with the MUO phenotype and the GG genotype had the least favorable values of glucose-related markers, lipid profiles, adipokines, oxidative stress markers, and regional fat distribution. These observations suggest that the development of obesity-related metabolic traits is highly associated not only with the rs8179183 genotype but also with metabolic status in Korean females with obesity.
Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1
Authors: Grimm Clemens , Pelz Jann-Patrick , Schneider Cornelius , Schäffler Katrin , Fischer Utz
Published: June 2020

Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails. They serve as multifunctional scaffolds, allowing the recruitment of diverse factors containing a poly(A)-interacting motif (PAM) into mRNPs. We present the crystal structure of the variant PAM motif (termed PAM2w) in the N-terminal part of the positive translation factor LARP4B, which binds to the MLLE domain of the poly(A) binding protein C1 cytoplasmic 1 (PABPC1). The structural analysis, along with mutational studies in vitro and in vivo, uncovered a new mode of interaction between PAM2 motifs and MLLE domains.
Targeting the CBP/β-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells
Authors: Che Mingtian , Kweon Soo-Mi , Teo Jia-Ling , Yuan Yate-Ching , Melstrom Laleh G. , Waldron Richard T. , Lugea Aurelia , Urrutia Raul A. , Pandol Stephen J. , Lai Keane K. Y.
Published: June 2020

Background: Although cyclic AMP-response element binding protein-binding protein (CBP)/β-catenin signaling is known to promote proliferation and fibrosis in various organ systems, its role in the activation of pancreatic stellate cells (PSCs), the key effector cells of desmoplasia in pancreatic cancer and fibrosis in chronic pancreatitis, is largely unknown. Methods: To investigate the role of the CBP/β-catenin signaling pathway in the activation of PSCs, we have treated mouse and human PSCs with the small molecule specific CBP/β-catenin antagonist ICG-001 and examined the effects of treatment on parameters of activation. Results: We report for the first time that CBP/β-catenin antagonism suppresses activation of PSCs as evidenced by their decreased proliferation, down-regulation of “activation” markers, e.g., α-smooth muscle actin (α-SMA/Acta2), collagen type I alpha 1 (Col1a1), Prolyl 4-hydroxylase, and Survivin, up-regulation of peroxisome proliferator activated receptor gamma (Ppar-γ) which is associated with quiescence, and reduced migration; additionally, CBP/β-catenin antagonism also suppresses PSC-induced migration of cancer cells. Conclusion: CBP/β-catenin antagonism represents a novel therapeutic strategy for suppressing PSC activation and may be effective at countering PSC promotion of pancreatic cancer.
Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma
Authors: Zhang Huiyuan , Qi Lin , Du Yuchen , Huang L. Frank , Braun Frank K. , Kogiso Mari , Zhao Yanling , Li Can , Lindsay Holly , Zhao Sibo , Injac Sarah G. , Baxter Patricia A. , Su Jack M. , Stephan Clifford , Keller Charles , Heck Kent A. , Harmanci Akdes , Harmanci Arif O. , Yang Jianhua , Klisch Tiemo J. , Li Xiao-Nan , Patel Akash J.
Published: June 2020

Background. Meningiomas constitute one-third of all primary brain tumors. Although typically benign, about 20% of these tumors recur despite surgery and radiation, and may ultimately prove fatal. There are currently no effective chemotherapies for meningioma. We, therefore, set out to develop patient-derived orthotopic xenograft (PDOX) mouse models of human meningioma using tumor. Method. Of nine patients, four had World Health Organization (WHO) grade I tumors, five had WHO grade II tumors, and in this second group two patients also had recurrent (WHO grade III) meningioma. We also classified the tumors according to our recently developed molecular classification system (Types A, B, and C, with C being the most aggressive). We transplanted all 11 surgical samples into the skull base of immunodeficient (SCID) mice. Only the primary and recurrent tumor cells from one patient—both molecular Type C, despite being WHO grades II and III, respectively—led to the formation of meningioma in the resulting mouse models. We characterized the xenografts by histopathology and RNA-seq and compared them with the original tumors. We performed an in vitro drug screen using 60 anti-cancer drugs followed by in vivo validation. Results. The PDOX models established from the primary and recurrent tumors from patient K29 (K29P-PDOX and K29R-PDOX, respectively) replicated the histopathology and key gene expression profiles of the original samples. Although these xenografts could not be subtransplanted, the cryopreserved primary tumor cells were able to reliably generate PDOX tumors. Drug screening in K29P and K29R tumor cell lines revealed eight compounds that were active on both tumors, including three histone deacetylase (HDAC) inhibitors. We tested the HDAC inhibitor Panobinostat in K29R-PDOX mice, and it significantly prolonged mouse survival (p < 0.05) by inducing histone H3 acetylation and apoptosis. Conclusion. Meningiomas are not very amenable to PDOX modeling, for reasons that remain unclear. Yet at least some of the most malignant tumors can be modeled, and cryopreserved primary tumor cells can create large panels of tumors that can be used for preclinical drug testing.
TGFα Promotes Chemoresistance of Malignant Pleural Mesothelioma
Authors: Staumont Bernard , Jamakhani Majeed , Costa Chrisostome , Vandermeers Fabian , Sriramareddy Sathya Neelature , Redouté Gaëlle , Mascaux Céline , Delvenne Philippe , Hubert Pascale , Safari Roghaiyeh , Willems Luc
Published: June 2020

Background: There is no standard chemotherapy for refractory or relapsing malignant pleural mesothelioma (MPM). Our previous reports nevertheless indicated that a combination of an anthracycline (doxorubicin) and a lysine deacetylase inhibitor (valproic acid, VPA) synergize to induce the apoptosis of MPM cells and reduce tumor growth in mouse models. A Phase I/II clinical trial indicated that this regimen is a promising therapeutic option for a proportion of MPM patients. Methods: The transcriptomes of mesothelioma cells were compared after Illumina HiSeq 4000 sequencing. The expression of differentially expressed genes was inhibited by RNA interference. Apoptosis was determined by cell cycle analysis and Annexin V/7-AAD labeling. Protein expression was assessed by immunoblotting. Preclinical efficacy was evaluated in BALB/c and NOD-SCID mice. Results: To understand the mechanisms involved in chemoresistance, the transcriptomes of two MPM cell lines displaying different responses to VPA-doxorubicin were compared. Among the differentially expressed genes, transforming growth factor alpha (TGFα) was associated with resistance to this regimen. The silencing of TGFα by RNA interference correlated with a significant increase in apoptosis, whereas the overexpression of TGFα desensitized MPM cells to the apoptosis induced by VPA and doxorubicin. The multi-targeted inhibition of histone deacetylase (HDAC), HER2 and TGFα receptor (epidermal growth factor receptor/EGFR) improved treatment efficacy in vitro and reduced tumor growth in two MPM mouse models. Finally, TGFα expression but not EGFR correlated with patient survival. Conclusions: Our data show that TGFα but not its receptor EGFR is a key factor in resistance to MPM chemotherapy. This observation may contribute to casting light on the promising but still controversial role of EGFR signaling in MPM therapy.
Liver Tumor Burden in Pancreatic Neuroendocrine Tumors: CT Features and Texture Analysis in the Prediction of Tumor Grade and 18F-FDG Uptake
Authors: Beleù Alessandro , Rizzo Giulio , De Robertis Riccardo , Drudi Alessandro , Aluffi Gregorio , Longo Chiara , Sarno Alessandro , Cingarlini Sara , Capelli Paola , Landoni Luca , Scarpa Aldo , Bassi Claudio , D’Onofrio Mirko
Published: June 2020

Pancreatic neuroendocrine tumors (p-NETs) are a rare group of neoplasms that often present with liver metastases. Histological characteristics, metabolic behavior, and liver tumor burden (LTB) are important prognostic factors. In this study, the usefulness of texture analysis of liver metastases in evaluating the biological aggressiveness of p-NETs was assessed. Fifty-six patients with liver metastases from p-NET were retrospectively enrolled. Qualitative and quantitative CT features of LTB were evaluated. Histogram-derived parameters of liver metastases were calculated and correlated with the tumor grade (G) and 18F-fluorodeoxyglucose (18F-FDG) standardized uptake value (SUV). Arterial relative enhancement was inversely related with G (−0.37, p = 0.006). Different metastatic spread patterns of LTB were not associated with histological grade. Arterialentropy was significantly correlated to G (−0.368, p = 0.038) and to Ki67 percentage (−0.421, p = 0.018). The ROC curve for the Arterialentropy reported an area under the curve (AUC) of 0.736 (95% confidence interval 0.545–0.928, p = 0.035) in the identification of G1–2 tumors. Arterialuniformity values were correlated to G (0.346, p = 0.005) and Ki67 levels (0.383, p = 0.033). Arterialentropy values were directly correlated with the SUV (0.449, p = 0.047) which was inversely correlated with Arterialuniformity (−0.499, p = 0.025). Skewness and kurtosis reported no significant correlations. In conclusion, histogram-derived parameters may predict adverse histological features and metabolic behavior of p-NET liver metastases.
Hepatocellular Carcinoma Emergence in Diabetic Mice with Non-Alcoholic Steatohepatitis Depends on Diet and Is Delayed in Liver Exhibiting an Active Immune Response
Authors: Simoes Eugénio Mélanie , Farooq Muhammad , Dion Sarah , Devisme Christelle , Raguenes-Nicol Céline , Piquet-Pellorce Claire , Samson Michel , Dimanche-Boitrel Marie-Thérèse , Le Seyec Jacques
Published: June 2020

The increase of the sedentary lifestyle and high-calorie diet have modified the etiological landscape of hepatocellular carcinoma (HCC), with a recrudescence of non-alcoholic fatty liver disease (NAFLD), especially in Western countries. The purpose of our study was to evaluate the impact of high-fat diet feeding on non-alcoholic steatohepatitis (NASH) establishment and HCC development. Streptozotocin-induced diabetic male mice were fed with high-fat-high-cholesterol diet (HFHCD) or high-fat-high-sugar diet (HFHSD) from 1 to 16 weeks. Even if liver tumors appear regardless of the high-fat diet, two distinct physiopathological patterns were evidenced, with much more severe NASH hallmarks (liver injury, inflammation and fibrosis) in diabetic mice fed with HFHCD. The mild hepatic injury, weak inflammation and fibrosis observed in HFHSD were interestingly associated with earlier emergence of more numerous liver tumors. When activated helper and cytotoxic T cells, detected by flow cytometry, infiltrated the liver of HFHCD-fed diabetic mice, a delay in the appearance of tumor nodules and a limitation of their numbers were observed, suggesting that the immune activities partly controlled tumor emergence. These data highlighted two different mouse models of HCC progression in diabetic mice depending on diet, which could be useful to evaluate new therapeutic approaches for HCC by targeting the immune response.
Inhibition of Patched Drug Efflux Increases Vemurafenib Effectiveness against Resistant BrafV600E Melanoma
Authors: Signetti Laurie , Elizarov Nelli , Simsir Méliné , Paquet Agnès , Douguet Dominique , Labbal Fabien , Debayle Delphine , Di Giorgio Audrey , Biou Valérie , Girard Christophe , Duca Maria , Bretillon Lionel , Bertolotto Corine , Verrier Bernard , Azoulay Stéphane , Mus-Veteau Isabelle
Published: June 2020

Melanoma patients harboring the BRAFV600E mutation are treated with vemurafenib. Almost all of them ultimately acquire resistance, leading to disease progression. Here, we find that a small molecule from a marine sponge, panicein A hydroquinone (PAH), overcomes resistance of BRAFV600E melanoma cells to vemurafenib, leading to tumor elimination in corresponding human xenograft models in mice. We report the synthesis of PAH and demonstrate that this compound inhibits the drug efflux activity of the Hedgehog receptor, Patched. Our SAR study allowed identifying a key pharmacophore responsible for this activity. We showed that Patched is strongly expressed in metastatic samples from a cohort of melanoma patients and is correlated with decreased overall survival. Patched is a multidrug transporter that uses the proton motive force to efflux drugs. This makes its function specific to cancer cells, thereby avoiding toxicity issues that are commonly observed with inhibitors of ABC multidrug transporters. Our data provide strong evidence that PAH is a highly promising lead for the treatment of vemurafenib resistant BRAFV600E melanoma.
Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity
Authors: Hajeri Praveensingh B. , Sharma Nikita S. , Yamamoto Masato
Published: June 2020

Cancer is a major health problem. Most of the treatments exhibit systemic toxicity, as they are not targeted or specific to cancerous cells and tumors. Adenoviruses are very promising gene delivery vectors and have immense potential to deliver targeted therapy. Here, we review a wide range of strategies that have been tried, tested, and demonstrated to enhance the specificity of oncolytic viruses towards specific cancer cells. A combination of these strategies and other conventional therapies may be more effective than any of those strategies alone.
Dementia, Depression, and Associated Brain Inflammatory Mechanisms after Spinal Cord Injury
Authors: Li Yun , Cao Tuoxin , Ritzel Rodney M. , He Junyun , Faden Alan I. , Wu Junfang
Published: June 2020

Evaluation of the chronic effects of spinal cord injury (SCI) has long focused on sensorimotor deficits, neuropathic pain, bladder/bowel dysfunction, loss of sexual function, and emotional distress. Although not well appreciated clinically, SCI can cause cognitive impairment including deficits in learning and memory, executive function, attention, and processing speed; it also commonly leads to depression. Recent large-scale longitudinal population-based studies indicate that patients with isolated SCI (without concurrent brain injury) are at a high risk of dementia associated with substantial cognitive impairments. Yet, little basic research has addressed potential mechanisms for cognitive impairment and depression after injury. In addition to contributing to disability in their own right, these changes can adversely affect rehabilitation and recovery and reduce quality of life. Here, we review clinical and experimental work on the complex and varied responses in the brain following SCI. We also discuss potential mechanisms responsible for these less well-examined, important SCI consequences. In addition, we outline the existing and developing therapeutic options aimed at reducing SCI-induced brain neuroinflammation and post-injury cognitive and emotional impairments.
Neurological Complications and Associated Risk Factors in Children Affected with Chronic Kidney Disease
Authors: Safdar Osama , Sindi Sulafa , Nazer Njood , Milyani Asmaa , Makki Abdulrahman
Published: June 2020

To investigate the correlation between chronic kidney disease (CKD) and the development of neurological disease among pediatric patients in Saudi Arabia. The present retrospective study recruited patients admitted to King Abdulaziz University Hospital during 2018. We reviewed electronic records to collect data on essential demographics including age, gender, and nationality; history of prior CNS disease or related symptoms; results of neurological physical examination; and findings of radiological investigations such as abdominal ultrasound, dimercaptosuccinic acid scan, micturating cystourethrogram, diethylene triamine pentaacetic acid scan, brain computed tomography, and magnetic resonance imaging. The most commonly diagnosed renal pathologies were neurogenic bladder and cystic kidney disease. The most common neurological manifestation was seizure disorder. Males were more frequently affected with neurological sequelae than females. The prevalence of neurological disorders was higher in patients over two years old. The most frequently observed stage of chronic kidney disease was stage 5. Most children who were affected with a neurological disorder required hemodialysis as part of their management plan. Patients with chronic kidney disease are at a high risk of neurocognitive defects. The type of management and renal diagnosis are significant factors that should be considered when anticipating central nervous system involvement in the case of chronic kidney disease.