bluuebunny/crossref_metadata_2025 huggingface dataset:
Peran Perempuan dalam Mengembangkan Usaha Mikro Kecil dan Menengah dalam rangka menuju Masyarakat Ekonomi ASEAN di Kota Tangerang Selatan
Authors: Harini Setyasih , . Sumarmi , Wicaksono Anggit G
Published: April 2020

Human and nature have bonds that need each other. Conservation of nature and its balance need to be maintained in order to create a more harmonious life. Responsible human behavior is one factor in the occurrence of climate change. The changing climate has a major influence on agricultural management. There are still some Javanese farmers who preserve local wisdom as a way to maintain natural balance. Local wisdom relating to agriculture is the use of calendar as a condition for processing agricultural land. The purpose of this study is to illustrate the importance of preserving calendar for female agricultural laborers to deal with global climate change. The type of data used is primary data. Data was obtained through surveys and interviews with female farmers who were members of six farmer groups in Mojoreno Village, Sidoharjo District, Wonogiri Regency. The results of this study indicate that government, Non Governmental Organization and lecturer to give greater attention to enhance and empower women in agricultural sources.

Key Words: Pranata Mangsa, Local Wisdom, Female Farmer
Peran Perempuan dalam Mengembangkan Usaha Mikro Kecil dan Menengah dalam rangka menuju Masyarakat Ekonomi ASEAN di Kota Tangerang Selatan
Authors: Jovani Audra
Published: April 2020

This article describes the efforts to prevent the practice of women trafficking in Nusa Tenggara Timur (NTT). Data shows that NTT is one of the provinces with a high level of human trafficking practices. This happens because several problems, such as: poverty, low education, weak law enforcement, lack of availability of employment and injustice in the social, political and economic fields. In addition, the strong network of human trafficking mafia actors in the rural areas. This condition is exacerbated by the tradition of the community which places women as second class. Women are often victims of poverty and other social problems. Using case study methods and process tracking analysis, this article argues that with socialization, building cooperation with traditional leaders (tokoh adat), a campaign to eliminate discrimination against women, empower Balai Latihan Kerja and build gender-based products can prevent the practice of trafficking in women in NTT.

Key Words: Prevention, Women Trafficking, Nusa Tenggara Timur
Peran Perempuan dalam Mengembangkan Usaha Mikro Kecil dan Menengah dalam rangka menuju Masyarakat Ekonomi ASEAN di Kota Tangerang Selatan
Authors: Kusumawati Dyah , Agustrijanto Agustrijanto
Published: April 2020

Abstrak: Pengungkapan diri biasa dilakukan dalam komunikasi antar pribadi yangmenandai kedekatan antar orang yang terlibat di dalam komunikasi. Namunpengungkapan diri yang dilakukan oleh pemilik akun @fitrianfuad seorangpenyintas autoimun dilakukan di media sosial instagram. Penelitian ini bertujuanuntuk mendeskripsikan pengungkapan diri perempuan penyintas autoimmune dimedia sosial instagram. Pendekatan yang digunakan adalah kualitatif denganmetode etnografi virtual. Analisis yang digunakan dalam peneleitian ini adalahanalisis media siber dengan level ruang media, level dokumen media, level objekmedia dan pengalaman. Teori yang digunakan dalam penelitian ini adalah teoriself disclosure. Hasil penelitian menunjukkan bahwa pengungkapan diridisampaikan menggunakan foto, video, dan tulisan dalam kolom caption. Setiapteks dan foto yang diproduksi dan dibagikan kepada khalayak penggunainstagram, dengan tujuan untuk melepaskan setiap persoalan yang ada didalamhidupnya sehingga melalui keterbukaan yang diungkapkan ke wilayah publikmembuat dirinya mendapat dukungan moril dalam bentuk support system danorang-orang didekatnya dan orang yang baru dikenalnya melalui instagram.Kata kunci: pengungkapan diri, perempuan, penyintas, autoimun, etnografivirtual, instagram

Abstract: Self-disclosure is usually done in interpersonal communication that marksthe closeness between people involved in communication. Fitri Napiz is a survivor ofautoimmune. This Study aims to discribe the self-disclosure of womanwithautoimmune. The approach used is qualitative with etnography virtual methode.The analysis used in this research is the analysis of cyber media with the level ofmedia space, the level of media documents, the level of media object and theexperience. The Theory used in this reserach is self-disclosure theory. The Resultsshowed that self-disclosure was conveyed using photos, videos, and the text incaption column. Every text and photos produced and distributed to the users ofinstagram, this is a way for Fitria Napiz to release every problem in her life. So thatthrough the oppenness that is revealed to the public domain. She gets moral supportlike support system from people nearby and new people she knows throughinstragam.Key words: self-disclosure, women, autoimmune, etnografi virtual, instagram
ELECTRONINC BANKING AND PERFORMANCE OF DEPOSIT MONEY BANKS IN NIGERIA (2011- 2018)
Authors: MARY ADA, Ph.D. OGENYI , GYANG,  Ph.D. JUGU YOHANNA , TOSIN, M.Sc. BODUNDE D.
Published: April 2020

Electronic banking has become a central concept in the banking industry due to its ability to increase operational efficiency and enhance financial performance. Nevertheless, the challenges of huge capital expenditure on development, and the increased cost of operation on the maintenance of e-banking facilities to achieve operational efficiency subsist in Nigeria. This paper examined the effects of electronic banking on the aggregate financial performance of Deposit Money Banks in Nigeria for eight years. The focus was on selected electronic banking products - Mobile payments, Automated teller machine (ATM), Internet banking (WEB) and Point of sale (POS) transactions. Secondary data were collected and analyzed quantitatively. Four hypotheses were formulated and tested at a ninety-five percent confidence interval using the Ordinary Least Square (OLS) inferential statistical tool. The results indicated that e-banking in the aggregate has a positive but insignificant effect on the overall performance of Deposit Money Banks (DMBs) in Nigeria.
A Rights-based Approach to Oil Spill Investigations: A Case Study of the Bodo Community Oil Spill in Nigeria
Authors: Azubuike Smith I. , Songi Ondotimi
Published: April 2020

Oil-bearing local communities in resource-rich developing countries suffer human rights violations after an oil spill. The violations arise as a result of impacted water sources, destruction of the environment and access to food, affected economic livelihood, etcetera. In the oil spill investigation process, the existing laws do not incorporate an assessment of the human rights impacts of the spill, to forestall subsequent human rights infringement when another oil spill occur. The Bodo community oil spill in Nigeria is a case in point. This article utilises a Human Rights Impact Assessment (HRIA) framework to examine the oil spill investigation regime in Nigeria, regarding the Bodo community oil spill. The essence is to identify the flaws in the investigation process, assist in holding duty-bearers accountable to their human rights obligations and responsibilities while empowering local communities as right-holders in the oil spill investigation process. This article seeks to incorporate the HRIA framework into the oil spill investigation regime to prevent further human rights violations post-oil spill. It notes that the application of the core procedural elements of HRIA – DM-PACT - is fundamental to improving the human rights experience after an oil spill. As a result, the framework could be mainstreamed into policy, legal, regulatory processes and management systems to enhance restorative and energy justice post-spill and to enhance post-spill or accident investigation to improve the human rights experience in the energy sector.
MARKOV ZİNCİRLERİ MODELLEMESİ İLE GENÇLERİN SPOR AYAKKABI MARKA TERCİHLERİNİN BELİRLENMESİ
Authors: ERCAN Özge
Published: April 2020

Stokastik süreçlerin bir çeşidi olan Markov zincirleri önceden tahmin edilemeyen süreçlerde uygulanır. Markov zincirleri matematiksel bir modeldir. Ancak sosyal bilimlerde de pek çok alanda kullanılabilmektedir. Bu çalışmada, genç tüketicilerin spor ayakkabı marka tercihleri belirlenmeye çalışılmıştır. Markov zincirleri analizi için Ankara ilinde yaşayan 14-19 yaş arası genç tüketiciler araştırmaya dahil edilmiştir. Katılımcıların, %47’si (N=102) erkek ve %53’ü (N= 115) kadın olmak üzere toplam 217 katılımcı olarak belirlenmiştir. Araştırma sonucunda, Spor ayakkabısı için marka bağlılığı “0,4483” ile en yüksek Nike markasındadır. Aynı markayı tercih olasılıkları Adidas için %36,11, Reebok için %18,18 Skechers için %33,33, Puma için %14,29, New Balance için %11,11 olarak hesaplanmıştır. Uzun dönemde gençlerin spor ayakkabısı tercihlerinin; %33,02’sinin Nike, %30,47’sinin diğer markalar, %23,32’sinin Adidas, %4,42’sinin Puma, %3,72’sinin New Balance, %1,87’sinin Converse, %1,49’unun Skechers, %0,9’unun Reebok ve %0,8’inin Asics marka spor ayakkabısı olması beklenmektedir.
KEBIJAKAN PENGAWASAN TERHADAP PERBANKAN SYARIAH DALAM SISTEM HUKUM DI INDONESIA
Authors: Shandy Utama Andrew
Published: April 2020

Pada saat terjadinya krisis ekonomi tahun 1998, bank konvensional banyak yang collapse sedangkan bank syariah tidak terkena dampaknya. Setelah krisis, perbankan syariah mengalami perkembangan yang signifikan di Indonesia. Permasalahannya adalah bagaimanakah arah kebijakan mengenai pengawasan terhadap perbankan syariah dalam sistem perbankan nasional di Indonesia? Metode yang digunakan dalam penelitian ini adalah penelitian hukum normatif dengan menggunakan pendekatan peraturan perundang-undangan. Sumber data yang digunakan dalam penelitian ini adalah data sekunder, yaitu data yang diperoleh dari peraturan perundang-undangan, jurnal-jurnal ilmiah, dan literatur hukum. Teknik pengumpulan data yang digunakan dalam penelitian ini adalah studi kepustakaan. Teknik analisis data yang digunakan dalam penelitian ini adalah analisis kualitatif. Hasil dari penelitian ini adalah kebijakan mengenai pengawasan terhadap perbankan syariah dalam sistem perbankan nasional di Indonesia menuju ke arah yang lebih baik. Pada Undang-Undang Nomor 7 Tahun 1992 dan Undang-Undang Nomor 10 Tahun 1998 disebutkan bahwa pengawasan terhadap perbankan syariah dilakukan oleh Bank Indonesia sebagai bank sentral. Akan tetapi, berdasarkan Undang-Undang Nomor 21 Tahun 2008, pengawasan terhadap perbankan syariah tidak hanya dilakukan oleh Bank Indonesia, tetapi juga diawasi secara internal oleh Dewan Pengawas Syariah. Setelah disahkannya Undang-Undang Nomor 21 Tahun 2011, pengawasan terhadap perbankan syariah beralih dari Bank Indonesia ke lembaga independen bernama Otoritas Jasa Keuangan.
EKSISTENSI UPAYA HUKUM BANDING PADA PERADILAN PAJAK DI INDONESIA
Authors: Daria Daria
Published: April 2020

Kedudukan  peradilan  pajak  sesuai  dengan penjelasan Pasal  27  ayat  (1) Undang-Undang  Nomor       48  Tahun  2009  tentang  kekuasaan  kehakiman disebutkan sebagai salah satu pengadilan khusus yang berada di lingkungan peradilan tata usaha  negara.  Dalam hal ini menurut  ketentuan Pasal  ini pengadilan pajak harus sesuai dan tidak boleh bertentangan
dengan prinsip- prinsip            dasar    ketentuan undang-undangn    kekuasaan        kehakiman yang merupakan amanat konstitusi yang semestinya harus ditaati. Dalam Undang-Undang Nomor 14 Tahun 2002 tentang Pengadilan Pajak dikenal empat upaya hukum dalam menyelesaikan sengketa yaitu, keberatan, banding, gugatan dan peninjauan kembali. Yang dimaksud dengan ‘’keberatan’’ dalam pelaksanaan ketentuan peraturan perundang-undangan perpajakan kemungkinan terjadi bahwa wajib pajak merasa kurang atau tidak puas atas suatu ketetapan pajak yang dikenakan kepadanya atau atas pemotongan atau pemungutan oleh pihak ketiga, dalam hal ini WP dapat mengajukan keberatan. Sedangkan upaya hukum banding merupakan kelanjutan dari upaya hukum keberatan. Dalam arti, tidak ada banding sebelum melalui keberatan karena yang diajukan banding adalah surat keputusan keberatan sebagai bentuk penyelesaian sengketa pajak di tingkat Lembaga Keberatan. Banding di Peradilan Pajak dilakukan di Pengadilan Pajak, sedangkan kalau melihat UU Nomor 48 Tahun 2009 Tentang Kekuasaan Kehakiman upaya hukum Banding dalam suatu peradilan seharusnya merupakan kewenangan Pengadilan Tinggi (Pengadilan Tingkat II).
Genomic Scan for Selection Signature Reveals Fat Deposition in Chinese Indigenous Sheep with Extreme Tail Types
Authors: Zhao Fuping , Deng Tianyu , Shi Liangyu , Wang Wenwen , Zhang Qin , Du Lixin , Wang Lixian
Published: April 2020

It is a unique feature that fat can be deposited in sheep tails and rumps. To elucidate the genetic mechanism underlying this trait, we collected 120 individuals from three Chinese indigenous sheep breeds with extreme tail types, namely large fat-tailed sheep (n = 40), Altay sheep (n = 40), and Tibetan sheep (n = 40), and genotyped them using the Ovine Infinium HD SNP BeadChip. Then genomic scan for selection signatures was performed using the hapFLK. In total, we identified 25 genomic regions exhibiting evidence of having been under selection. Bioinformatic analysis of the genomic regions showed that selection signatures related to multiple candidate genes had a demonstrated role in phenotypic variation. Nine genes have documented association with sheep tail types, including WDR92, TBX12, WARS2, BMP2, VEGFA, PDGFD, HOXA10, ALX4, and ETAA1. Moreover, a number of genes were of particular interest, including RXFP2 associated with the presence/absence and morphology of horns; MITF involved in coat color; LIN52 and SYNDIG1L related to the number of teats; MSRB3 gene associated with ear sizes; LTBP2 considered as a positional candidate genes for number of ribs; JAZF1 regulating lipid metabolism; PGRMC2, SPAG17, TSHR, GTF2A1, and LARP1B implicated with reproductive traits. Our findings provide insights into fat tail formation and a reference for carrying out molecular breeding and conservation in sheep.
A Review of the Potential Climate Change Impacts and Adaptation Options for European Viticulture
Authors: Santos João A. , Fraga Helder , Malheiro Aureliano C. , Moutinho-Pereira José , Dinis Lia-Tânia , Correia Carlos , Moriondo Marco , Leolini Luisa , Dibari Camilla , Costafreda-Aumedes Sergi , Kartschall Thomas , Menz Christoph , Molitor Daniel , Junk Jürgen , Beyer Marco , Schultz Hans R.
Published: April 2020

Viticulture and winemaking are important socioeconomic sectors in many European regions. Climate plays a vital role in the terroir of a given wine region, as it strongly controls canopy microclimate, vine growth, vine physiology, yield, and berry composition, which together determine wine attributes and typicity. New challenges are, however, predicted to arise from climate change, as grapevine cultivation is deeply dependent on weather and climate conditions. Changes in viticultural suitability over the last decades, for viticulture in general or the use of specific varieties, have already been reported for many wine regions. Despite spatially heterogeneous impacts, climate change is anticipated to exacerbate these recent trends on suitability for wine production. These shifts may reshape the geographical distribution of wine regions, while wine typicity may also be threatened in most cases. Changing climates will thereby urge for the implementation of timely, suitable, and cost-effective adaptation strategies, which should also be thoroughly planned and tuned to local conditions for an effective risk reduction. Although the potential of the different adaptation options is not yet fully investigated, deserving further research activities, their adoption will be of utmost relevance to maintain the socioeconomic and environmental sustainability of the highly valued viticulture and winemaking sector in Europe.
Evaluation of the Vertical Sky Component without Obstructions for Daylighting in Burgos, Spain
Authors: Granados-López Diego , Díez-Mediavilla Montserrat , Dieste-Velasco M. Isabel , Suárez-García Andrés , Alonso-Tristán Cristina
Published: April 2020

Daylight availability knowledge is the first step for an energetic and visually efficient building and city design. It can be estimated with the Vertical Sky Component (VSC), which is defined as the ratio of the vertical diffuse illuminance over the unobstructed horizontal diffuse illuminance, simultaneously measured at the same point. These illuminance magnitudes are obtained from luxmeter measurements but these data are scarce. Alternatively, VSC can be obtained from prior knowledge of the sky illuminance distribution, which can be measured with a sky scanner device or by reference to the CIE (Commission Internationale de L’Éclairage) Standard classification for homogeneous skies. Both approaches are compared in this study. The coherence of the results obtained for the four cardinal orientations are analyzed by applying classical statistical parameters and luxmeter measurements as references for the results. The measurement campaign was completed between September 2016 and January 2019 in Burgos (Spain), as representative case study and specific contribution of this work. It was observed that the VSC values were higher than 100 in many cases: 21.94% for the south- and 33.6% for the east-facing vertical surfaces. The study highlights the good daylighting conditions in Burgos, mainly due to the predominance of clear skies over much of the year. This fact implies high daylight availability that, with efficient city planning and building design, could potentially lead reduction energy consumption of buildings, improvements in visual comfort, and the well-being of occupants.
Classification of Hydroacoustic Signals Based on Harmonic Wavelets and a Deep Learning Artificial Intelligence System
Authors: Kaplun Dmitry , Voznesensky Alexander , Romanov Sergei , Andreev Valery , Butusov Denis
Published: April 2020

This paper considers two approaches to hydroacoustic signal classification, taking the sounds made by whales as an example: a method based on harmonic wavelets and a technique involving deep learning neural networks. The study deals with the classification of hydroacoustic signals using coefficients of the harmonic wavelet transform (fast computation), short-time Fourier transform (spectrogram) and Fourier transform using a kNN-algorithm. Classification quality metrics (precision, recall and accuracy) are given for different signal-to-noise ratios. ROC curves were also obtained. The use of the deep neural network for classification of whales’ sounds is considered. The effectiveness of using harmonic wavelets for the classification of complex non-stationary signals is proved. A technique to reduce the feature space dimension using a ‘modulo N reduction’ method is proposed. A classification of 26 individual whales from the Whale FM Project dataset is presented. It is shown that the deep-learning-based approach provides the best result for the Whale FM Project dataset both for whale types and individuals.
Performance-Based Analysis of Single-Layer Cylindrical Steel Reticulated Shells in Fire
Authors: Yu Zhiwei , Lu Chen , Zhong Yiqin
Published: April 2020

With the rapid development of architectural technology, long-span structures have been widely used due to their vast interior space and beautiful architectural composition. Due to the characteristics and high costs of coating materials on large steel structures, fire resistance designs for these kinds of structures have become more and more important. This paper presents comprehensive case analyses of the fire performance of single-layer cylindrical reticulated shells. Nonuniform fire temperature fields of single-layer cylindrical reticulated shells in different fire scenarios were generated using a Fire Dynamics Simulator (FDS). The influences of different parameters on the air temperature field during a fire in a reticulated shell structure were analyzed. A Finite Element (FE) model was developed using the FE software ABAQUS to model the structural behavior of single-layer cylindrical reticulated shells in different fire scenarios. The effects of various parameters on the responses of single-layer cylindrical reticulated shells during a fire were investigated. Using the results from the performance-based analysis in this research, we propose some recommendations for fire resistance designs for single-layer cylindrical reticulated shells.
On the Effect of DLC and WCC Coatings on the Efficiency of Manual Transmission Gear Pairs
Authors: Laderou Angela , Mohammadpour Mahdi , Theodossiades Stephanos , Daubney Richard , Meeks Gareth
Published: April 2020

An experimentally validated tribo-dynamic model has been developed to predict the gear teeth frictional losses considering the properties of the diamond-like-carbon (DLC)-coated and tungsten carbide carbon (WCC)-coated surface. The operating conditions used are snapshots of the Real Driving Emissions (RDE) driving cycle. The results demonstrate that the use of these coatings can improve the frictional losses up to 50%. The gear teeth boundary friction model is enriched by experimentally measured coefficients of the surface asperity boundary shear strength using an atomic force microscope (AFM). The computationally efficient model enables the efficiency prediction in a complete transmission. Such an approach, considering the contact mechanics of coated gear and their effect on the viscous and boundary friction, has not been hitherto reported.
Multilayered Balanced Dual-Band Bandpass Filter Based on Magnetically Coupled Open-Loop Resonators with Intrinsic Common-Mode Rejection
Authors: Medran del Rio Jose L. , Lujambio Aintzane , Fernández-Prieto Armando , Martinez-Ros Alejandro Javier , Martel Jesús , Medina Francisco
Published: April 2020

A new dual-band balanced bandpass filter based on magnetically coupled open-loop resonators in multilayer technology is proposed in this paper. The lower differential passband, centered at the Global Positioning System (GPS) L1 frequency, 1.575 GHz, was created by means of two coupled resonators etched in the middle layer of the structure, while the upper differential passband, centered at a Wi-Fi frequency of 2.4 GHz, was generated by coupling two resonators on the top layer. Magnetic coupling was used to design both passbands, leading to an intrinsic common-mode rejection of 39 dB within the lower passband and 33 dB within the upper passband. Simulation and measurement results are provided to verify the usefulness of the proposed dual-band differential bandpass filter.
Improvement of Power Converters Performance by an Efficient Use of Dead Time Compensation Technique
Authors: Iqbal Sheeraz , Xin Ai , Jan Mishkat Ullah , Abdelbaky Mohamed Abdelkarim , Rehman Haseeb Ur , Salman Salman , Aurangzeb Muhammad , Rizvi Syed Asad Abbas , Shah Noor Ahmad
Published: April 2020

The advent of renewable energy resources and distributed energy systems herald a new set of challenges of power quality, efficient distribution, and stability in the power system. Furthermore, the power electronic converters integration has been increased in interfacing alternate energy systems and industries with the transmission and distribution grids. Owing to the intermittency of renewable energy resources and the application of power electronic converters the power distribution faces peculiar challenges. The dead-time effects are among the main challenges, which leads to the distortion of third harmonics, phase angle, torque pulsation, and induction motor current, causing severe quality problems for power delivery. To tackle these problems, this paper proposes a novel dead time compensation technique for improving the power quality parameters and improving the efficiency of power converters. The proposed model is simulated in MATLAB and the parametric equations are plotted against the corresponding parametric values. Furthermore, by implementing the proposed strategy, significant improvements are attained in the torque pulsation, speed, and total harmonic distortion of the induction motor. The comparisons are drawn between with and without dead time compensation technique, the former shows significant improvements in all aspects of the power quality parameters and power converters efficiency.
Self Similar Shocks in Atmospheric Mass Loss Due to Planetary Collisions
Authors: Yalinewich Almog , Remorov Andrey
Published: April 2020

We present a mathematical model for the propagation of the shock waves that occur during planetary collisions. Such collisions are thought to occur during the formation of terrestrial planets, and they have the potential to erode the planet’s atmosphere. We show that, under certain assumptions, this evolution of the shock wave can be determined using the methodologies of Type II self similar solutions. In such solutions, the evolution of the shock wave is determined by boundary conditions at the shock front and a singular point in the shocked region. We show how the evolution can be determined for different equations of state, allowing these results to be readily used to calculate the atmospheric mass loss from planetary cores made of different materials. We demonstrate that, as a planetary shock converges to the self similar solution, it loses information about the collision that created it, including the impact angle for oblique collisions.
Isotopic Results Reveal Possible Links between Diet and Social Status in Late Shang Dynasty (ca. 1250–1046 BC) Tombs at Xiaohucun, China
Authors: Wang Ning , Jia Lianmin , Si Yi , Jia Xin
Published: April 2020

Here, we present evidence of possible links between diet and social status using carbon and nitrogen stable isotope ratios at the site of Xiaohucun in the Central Plains, China. This pilot study from a rescue excavation yielded humans (n = 12) identified to the late Shang Dynasty (ca. 1250–1046 BC), which was a warm climatic period. The population consumed a predominately C4 diet (millets) and no difference was observed between the δ13C results of individuals (n = 7) buried with (−9.1 ± 2.8‰) and without (n = 5) bronze vessels (−8.2 ± 0.7‰). However, individuals buried with bronze vessels (10.3±1.6‰) were found to have significantly higher δ15N values (one-way ANOVA; p = 0.015) compared to individuals buried without bronze vessels (8.0 ± 0.9‰), providing evidence that possible elite members consumed more animal protein (dog, pig, cow, sheep/goat). Isotopic results were also examined for social status in relation to the number of burial coffins that an individual had: double (n = 6), single (n = 3), or no coffin (n = 3). No difference was found in the δ13C values, but variations were observed in the δ15N values: double coffin (10.2 ± 1.7‰) > single coffin (8.8 ± 1.8‰) > no coffin (8.0 ± 1.3‰), again possibly showing increased animal protein consumption linked to social status. Finally, isotopic results and status were studied by looking at the number of coffins and tomb size. Again, no correlation was observed for the δ13C results, but a strong linear correlation (R2 = 0.85) was observed for the δ15N values of the individuals buried in two coffins vs. tomb size.
In Silico Analysis of a Highly Mutated Gene in Cancer Provides Insight into Abnormal mRNA Splicing: Splicing Factor 3B Subunit 1K700E Mutant
Authors: Samy Asmaa , Suzek Baris , Ozdemir Mehmet , Sensoy Ozge
Published: April 2020

Cancer is the second leading cause of death worldwide. The etiology of the disease has remained elusive, but mutations causing aberrant RNA splicing have been considered one of the significant factors in various cancer types. The association of aberrant RNA splicing with drug/therapy resistance further increases the importance of these mutations. In this work, the impact of the splicing factor 3B subunit 1 (SF3B1) K700E mutation, a highly prevalent mutation in various cancer types, is investigated through molecular dynamics simulations. Based on our results, K700E mutation increases flexibility of the mutant SF3B1. Consequently, this mutation leads to i) disruption of interaction of pre-mRNA with SF3B1 and p14, thus preventing proper alignment of mRNA and causing usage of abnormal 3’ splice site, and ii) disruption of communication in critical regions participating in interactions with other proteins in pre-mRNA splicing machinery. We anticipate that this study enhances our understanding of the mechanism of functional abnormalities associated with splicing machinery, thereby, increasing possibility for designing effective therapies to combat cancer at an earlier stage.
Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma
Authors: Fassmannová Dominika , Sedlák František , Sedláček Jindřich , Špička Ivan , Grantz Šašková Klára
Published: April 2020

Proteasome inhibitors are the backbone of multiple myeloma therapy. However, disease progression or early relapse occur due to development of resistance to the therapy. One important cause of resistance to proteasome inhibition is the so-called bounce-back response, a recovery pathway driven by the TCF11/Nrf1 transcription factor, which activates proteasome gene re-synthesis upon impairment of the proteasome function. Thus, inhibiting this recovery pathway potentiates the cytotoxic effect of proteasome inhibitors and could benefit treatment outcomes. DDI2 protease, the 3D structure of which resembles the HIV protease, serves as the key player in TCF11/Nrf1 activation. Previous work found that some HIV protease inhibitors block DDI2 in cell-based experiments. Nelfinavir, an oral anti-HIV drug, inhibits the proteasome and/or pAKT pathway and has shown promise for treatment of relapsed/refractory multiple myeloma. Here, we describe how nelfinavir inhibits the TCF11/Nrf1-driven recovery pathway by a dual mode of action. Nelfinavir decreases the total protein level of TCF11/Nrf1 and inhibits TCF11/Nrf1 proteolytic processing, likely by interfering with the DDI2 protease, and therefore reduces the TCF11/Nrf1 protein level in the nucleus. We propose an overall mechanism that explains nelfinavir’s effectiveness in the treatment of multiple myeloma.
Multimodal Targeted Deep Sequencing of Circulating Tumor Cells and Matched Cell-Free DNA Provides a More Comprehensive Tool to Identify Therapeutic Targets in Metastatic Breast Cancer Patients
Authors: Keup Corinna , Storbeck Markus , Hauch Siegfried , Hahn Peter , Sprenger-Haussels Markus , Hoffmann Oliver , Kimmig Rainer , Kasimir-Bauer Sabine
Published: April 2020

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for therapy management in oncology. We aimed to establish a multimodal liquid biopsy strategy that is usable with minimized blood volume to deconvolute the genomic complexity of metastatic breast cancer. CTCs were isolated from 10ml blood of 18 hormone receptor-positive and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer patients. cfDNA was isolated from plasma generated after CTC depletion and targeted sequencing analyses were conducted. PIK3CA and ESR1 variants were less common in CTC gDNA, while ERBB2 variants were only detected in CTC gDNA. A total of 62% of all cfDNA variants were recovered in the matched CTC gDNA, while 72% of all variants were unique in either cfDNA (14 variants) or CTC gDNA (104 variants). The percentage of patients with no detectable cfDNA variants or CTC gDNA variants was 17%/11%, but a combined analysis identified variants in 94% of all patients. In univariate and multivariate regression models, ESR1 variants in cfDNA and CTC gDNA correlated significantly with survival. We suggest a coordinated analysis of both fractions in order to provide a comprehensive genomic footprint that may contribute to identifying the most suitable therapy for each individual.
MicroRNA Regulation of the Small Rho GTPase Regulators—Complexities and Opportunities in Targeting Cancer Metastasis
Authors: Humphries Brock A. , Wang Zhishan , Yang Chengfeng
Published: April 2020

The small Rho GTPases regulate important cellular processes that affect cancer metastasis, such as cell survival and proliferation, actin dynamics, adhesion, migration, invasion and transcriptional activation. The Rho GTPases function as molecular switches cycling between an active GTP-bound and inactive guanosine diphosphate (GDP)-bound conformation. It is known that Rho GTPase activities are mainly regulated by guanine nucleotide exchange factors (RhoGEFs), GTPase-activating proteins (RhoGAPs), GDP dissociation inhibitors (RhoGDIs) and guanine nucleotide exchange modifiers (GEMs). These Rho GTPase regulators are often dysregulated in cancer; however, the underlying mechanisms are not well understood. MicroRNAs (miRNAs), a large family of small non-coding RNAs that negatively regulate protein-coding gene expression, have been shown to play important roles in cancer metastasis. Recent studies showed that miRNAs are capable of directly targeting RhoGAPs, RhoGEFs, and RhoGDIs, and regulate the activities of Rho GTPases. This not only provides new evidence for the critical role of miRNA dysregulation in cancer metastasis, it also reveals novel mechanisms for Rho GTPase regulation. This review summarizes recent exciting findings showing that miRNAs play important roles in regulating Rho GTPase regulators (RhoGEFs, RhoGAPs, RhoGDIs), thus affecting Rho GTPase activities and cancer metastasis. The potential opportunities and challenges for targeting miRNAs and Rho GTPase regulators in treating cancer metastasis are also discussed. A comprehensive list of the currently validated miRNA-targeting of small Rho GTPase regulators is presented as a reference resource.
Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target
Authors: Yoo Jung , Jeon Yu Hyun , Cho Ha Young , Lee Sang Wu , Kim Go Woon , Lee Dong Hoon , Kwon So Hee
Published: April 2020

Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer.
TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma
Authors: Hsieh Cheng-Han , Chu Cheng-Ying , Lin Sey-En , Yang Yu-Chen S.H. , Chang Hung-Shu , Yen Yun
Published: April 2020

Cholangiocarcinoma is a relatively uncommon but highly lethal malignancy. Improving outcomes in patients depends on earlier diagnosis and appropriate treatment; however, no satisfactory diagnostic biomarkers or targeted therapies are currently available. To address this shortcoming, we analyzed the transcriptomic datasets of cholangiocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and found that TESC is highly expressed in cholangiocarcinoma. Elevated cellular levels of TESC are correlated with larger tumor size and predict a poor survival outcome for patients. Knockdown of TESC via RNA interference suppresses tumor growth. RNA-sequencing analysis showed that silencing of TESC decreases the level of FOXM1, leading to cell cycle arrest. Correlation analysis revealed that the cellular level of TESC is correlated with that of FOXM1 in cholangiocarcinoma patients. We further observed that upon TGF-α induction, TESC is upregulated through the EGFR-STAT3 pathway and mediates TGF-α-induced tumor cell proliferation. In vivo experiments revealed that knockdown of TESC significantly attenuates tumor cell growth. Therefore, our data provide novel insight into TESC-mediated oncogenesis and reveal that TESC is a potential biomarker or serves as a therapeutic target for cholangiocarcinoma.
STAT3: Versatile Functions in Non-Small Cell Lung Cancer
Authors: Mohrherr Julian , Uras Iris Z. , Moll Herwig P. , Casanova Emilio
Published: April 2020

Signal Transducer and Activator of Transcription 3 (STAT3) activation is frequently found in non-small cell lung cancer (NSCLC) patient samples/cell lines and STAT3 inhibition in NSCLC cell lines markedly impairs their survival. STAT3 also plays a pivotal role in driving tumor-promoting inflammation and evasion of anti-tumor immunity. Consequently, targeting STAT3 either directly or by inhibition of upstream regulators such as Interleukin-6 (IL-6) or Janus kinase 1/2 (JAK1/2) is considered as a promising treatment strategy for the management of NSCLC. In contrast, some studies also report STAT3 being a tumor suppressor in a variety of solid malignancies, including lung cancer. Here, we provide a concise overview of STAT3‘s versatile roles in NSCLC and discuss the yins and yangs of STAT3 targeting therapies.
Aberrant Expression of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in Warthin Tumors
Authors: Mandic Robert , Agaimy Abbas , Pinto-Quintero Daniel , Roth Katrin , Teymoortash Afshin , Schwarzbach Hans , Stoehr Christine G. , Rodepeter Fiona R. , Stuck Boris A. , Bette Michael
Published: April 2020

The Warthin tumor represents the second most frequent benign tumor of the parotid gland and is characterized by the presence of oncocytes rich in structurally and functionally altered mitochondria. Next to its role in metabolism, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is also implicated in cellular mitophagy. Immunohistochemistry was carried out on Warthin tumor and normal control (parotid gland with striated ducts) tissues, using anti-GAPDH specific antibodies followed by digital image analysis. Laser capture microdissection was used to isolate the oncocytic tumor cell and normal control striated duct compartments for RNA extraction and qPCR. Warthin tumor oncocytes exhibited a markedly spotted GAPDH staining pattern exhibiting cells with cytoplasmic and nuclear, only nuclear or none GAPDH staining. A significantly lower (p < 0.0001) total GAPDH signal was detected in Warthin tumor oncocytes. Similarly, significantly lower (p < 0.005) GAPDH mRNA levels were seen in oncocytes compared with normal ductal cells. To exclude the possibility of this GAPDH staining pattern being a general feature of oncocytic neoplasms of different organs, we tested a cohort of renal oncocytoma and oncocytic chromophobe carcinoma; none showed this type of staining. The observed progressive GAPDH loss in Warthin tumor oncocytes could be implicated in the pathogenesis of Warthin tumors.
Corticosterone Induces HMGB1 Release in Primary Cultured Rat Cortical Astrocytes: Involvement of Pannexin-1 and P2X7 Receptor-Dependent Mechanisms
Authors: Hisaoka-Nakashima Kazue , Azuma Honami , Ishikawa Fumina , Nakamura Yoki , Wang Dengli , Liu Keyue , Wake Hidenori , Nishibori Masahiro , Nakata Yoshihiro , Morioka Norimitsu
Published: April 2020

A major risk factor for major depressive disorder (MDD) is stress. Stress leads to the release of high-mobility group box-1 (HMGB1), which in turn leads to neuroinflammation, a potential pathophysiological basis of MDD. The mechanism underlying stress-induced HMGB1 release is not known, but stress-associated glucocorticoids could be involved. To test this, rat primary cultured cortical astrocytes, the most abundant cell type in the central nervous system (CNS), were treated with corticosterone and HMGB1 release was assessed by Western blotting and ELISA. Significant HMGB1 was released with treatment with either corticosterone or dexamethasone, a synthetic glucocorticoid. HMGB1 translocated from the nucleus to the cytoplasm following corticosterone treatment. HMGB1 release was significantly attenuated with glucocorticoid receptor blocking. In addition, inhibition of pannexin-1, and P2X7 receptors led to a significant decrease in corticosterone-induced HMGB1 release. Taken together, corticosterone stimulates astrocytic glucocorticoid receptors and triggers cytoplasmic translocation and extracellular release of nuclear HMGB1 through a mechanism involving pannexin-1 and P2X7 receptors. Thus, under conditions of stress, glucocorticoids induce astrocytic HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders such as MDD.
PAI1 is a Marker of Bad Prognosis in Rectal Cancer but Predicts a Better Response to Treatment with PIM Inhibitor AZD1208
Authors: Muñoz-Galván Sandra , Rivero Maria , Peinado-Serrano Javier , Martinez-Pérez Julia , Fernández-Fernández MC , José Ortiz María , García-Heredia José M. , Carnero Amancio
Published: April 2020

Colorectal cancer (CRC) is the third most common cancer worldwide. The standard treatment in locally advanced rectal cancer is preoperative radiation alone or in combination with chemotherapy, followed by adjuvant chemotherapy. Rectal cancer is highly lethal, with only 20% of patients showing a complete remission (by RECIST) after standard treatment, although they commonly show local or systemic relapse likely due to its late detection and high chemotherapy resistance, among other reasons. Here, we explored the role of PAI1 (Serpin E1) in rectal cancer through the analyses of public patient databases, our own cohort of locally advanced rectal cancer patients and a panel of CRC cell lines. We showed that PAI1 expression is upregulated in rectal tumors, which is associated with decreased overall survival and increased metastasis and invasion in advanced rectal tumors. Accordingly, PAI1 expression is correlated with the expression of (Epithelial-to-Mesenchymal Transition) EMT-associated genes and genes encoding drug targets, including the tyrosine kinases PDGFRb, PDGFRa and FYN, the serine/threonine kinase PIM1 and BRAF. In addition, we demonstrate that cells expressing PAI1 protein are more sensitive to the PIM inhibitor AZD1208, suggesting that PAI1 could be used to predict response to treatment with PIM inhibitors and to complement radiotherapy in rectal tumors.
Suppression of CaMKIIβ Inhibits ANO1-Mediated Glioblastoma Progression
Authors: Sim Kyoung Mi , Lee Young-Sun , Kim Hee Jin , Cho Chang-Hoon , Yi Gwan-Su , Park Myung-Jin , Hwang Eun Mi , Park Jae-Yong
Published: April 2020

ANO1, a Ca2+-activated chloride channel, is highly expressed in glioblastoma cells and its surface expression is involved in their migration and invasion. However, the regulation of ANO1 surface expression in glioblastoma cells is largely unknown. In this study, we found that Ca2+/Calmodulin-dependent protein kinase II (CaMKII) β specifically enhances the surface expression and channel activity of ANO1 in U251 glioblastoma cells. When KN-93, a CaMKII inhibitor, was used to treat U251 cells, the surface expression and channel activity of ANO1 were significantly reduced. Only CaMKIIβ, among the four CaMKII isoforms, increased the surface expression and channel activity of ANO1 in a heterologous expression system. Additionally, gene silencing of CaMKIIβ suppressed the surface expression and channel activity of ANO1 in U251 cells. Moreover, gene silencing of CaMKIIβ or ANO1 prominently reduced the migration and invasion of U251 and U87 MG glioblastoma cells. We thus conclude that CaMKIIβ plays a specific role in the surface expression of ANO1 and in the ANO1-mediated tumorigenic properties of glioblastoma cells, such as migration and invasion.
Genome-Wide Association Study of Diabetogenic Adipose Morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort
Authors: Lundbäck Veroniqa , Kulyté Agné , Arner Peter , Strawbridge Rona J. , Dahlman Ingrid
Published: April 2020

An increased adipocyte size relative to the size of fat depots, also denoted hypertrophic adipose morphology, is a strong risk factor for the future development of insulin resistance and type 2 diabetes. The regulation of adipose morphology is poorly understood. We set out to identify genetic loci associated with adipose morphology and functionally evaluate candidate genes for impact on adipocyte development. We performed a genome-wide association study (GWAS) in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort comprising 948 participants who have undergone abdominal subcutaneous adipose biopsy with a determination of average adipose volume and morphology. The GWAS identified 31 genetic loci displaying suggestive association with adipose morphology. Functional evaluation of candidate genes by small interfering RNAs (siRNA)-mediated knockdown in adipose-derived precursor cells identified six genes controlling adipocyte renewal and differentiation, and thus of potential importance for adipose hypertrophy. In conclusion, genetic and functional studies implicate a regulatory role for ATL2, ARHGEF10, CYP1B1, TMEM200A, C17orf51, and L3MBTL3 in adipose morphology by their impact on adipogenesis.
Radiation Potentiates Monocyte Infiltration into Tumors by Ninjurin1 Expression in Endothelial Cells
Authors: Kang Ju-Hee , Woo Jong Kyu , Jang Yeong-Su , Oh Seung Hyun
Published: April 2020

Radiation is a widely used treatment for cancer patients, with over half the cancer patients receiving radiation therapy during their course of treatment. Considerable evidence from both preclinical and clinical studies show that tumor recurrence gets restored following radiotherapy, due to the influx of circulating cells consisting primarily of monocytes. The attachment of monocyte to endothelial cell is the first step of the extravasation process. However, the exact molecules that direct the transmigration of monocyte from the blood vessels to the tumors remain largely unknown. The nerve injury-induced protein 1 (Ninjurin1 or Ninj1) gene, which encodes a homophilic adhesion molecule and cell surface protein, was found to be upregulated in inflammatory lesions, particularly in macrophages/monocytes, neutrophils, and endothelial cells. More recently Ninj1 was reported to be regulated following p53 activation. Considering p53 has been known to be activated by radiation, we wondered whether Ninj1 could be increased in the endothelial cells by radiation and it might contribute to the recruiting of monocytes in the tumor. Here we demonstrate that radiation-mediated up-regulation of Ninj1 in endothelial cell lines such as human umbilical vein endothelial cells (HUVECs), EA.hy926, and immortalized HUVECs. Consistent with this, we found over-expressed Ninj1 in irradiated xenograft tumors, and increased monocyte infiltration into tumors. Radiation-induced Ninj1 was transcriptionally regulated by p53, as confirmed by transfection of p53 siRNA. In addition, Ninj1 over-expression in endothelial cells accelerated monocyte adhesion. Irradiation-induced endothelial cells and monocyte interaction was inhibited by knock-down of Ninj1. Furthermore, over-expressed Ninj1 stimulated MMP-2 and MMP-9 expression in monocyte cell lines, whereas the MMP-2 and MMP-9 expression were attenuated by Ninj1 knock-down in monocytes. Taken together, we provide evidence that Ninj1 is a key molecule that generates an interaction between endothelial cells and monocytes. This result suggests that radiation-mediated Ninj1 expression in endothelial cells could be involved in the post-radiotherapy recurrence mechanism.