bluuebunny/crossref_metadata_2025 huggingface dataset:
KEADILAN DI JALAN RAYA
Authors: Zamzami Abid
Published: June 2019

AbstractAccessing public road is the right of every citizen since they have to pay taxes for motor vehicle which is principally allocated for road maintenance. Even though all citizens have right to use public road facilities, there are some particular groups of people that are prioritized and always guarded by police guards or using voorijder. The regulation about road users that have primary right to be prioritized in using public road is regulated in Traffic and Commodity Transportation Act No.22/2009 Article 134. However, voorijder is often misused by elites or public figures within social service reasoning so that justice in using public road is not well implemented. Keywords: voorijder, law objectives. AbstrakMenggunakan jalan raya merupakan hak semua warga negara karena semua warga negara pasti sudah membayar pajak kendaraan bermotor, yang mana pajak tersebut digunakan untuk perawatan jalan raya. Meskipun semua warga berhak menggunakan fasiltas jalan raya ada golongan-golongan tertentu yang harus diprioritaskan dan harus menggunakan pengawalan dari kepolisian menggunakan voorijder. Pengguna jalan yang memperoleh hak utama untuk didahulukan diatur dalam pasal 134 UU No 22 Tahun 2009 tentang Lalu Lintas dan Angkutan Jalan. Namun pada kenyataannya penggunaan voorijder banyak disalahgunakan oleh orang-orang kaya dengan alih-alih mengadakan bakti sosial sehingga keadilan dalam menggunakan jalan raya tidak terlaksana dengan baik.Kata Kunci: voorijder, tujuan hukum
KESELAMATAN TENAGA KERJA DALAM PERSPEKTIF HAK ASASI MANUSIA (Perspektif Islam, UDHR, dan Hukum Positif)
Authors: Misranto Misranto , Taufik M
Published: June 2019

Salah satu hak yang dimiliki oleh tenaga kerja adalah hak atas keselamatan. Hak atas keselamatan ini menjadi kewajiban yang harus dilaksanakan atau diimplementasikan oleh  perusahaan. Perusahaan mempunyai kewajiban yang bersifat asasi untuk menegakkan kepentingan yang bersifat asasi pula. Sayangnya, kepentingan yang bersifar asasi ini kurang menjadi perhatian serius di kalangan pengusahaa atau perusahaan. Tidak sedikit ditemukan kasus-kasus pelanggaran terhadap hak tenaga kerja ini. Banyak tenaga kerja yang tidak mendapatkan perlindungan keselamatannya saat menjalankan kerjanya. Perusahaan yang demikian ini dapat dikategorikan melakukan pelanggaran terhadap hak asasi manusia.Kata Kunci:  tenaga kerja,  perusahaan, hak atas keselamatan
PERLINDUNGAN HUKUM TERHADAP KONSUMEN DARI PRAKTIK KLINIK KECANTIKAN ILEGAL DI KARAWANG
Authors: Apriani Rani
Published: June 2019

Kebutuhan akan kecantikan sudah menjadi kebutuhan primer yang harus dipenuhi khususnya oleh kaum wanita. Hal ini menyebabkan industry kecantikan seperti klinik kecantikan bertumbuh pesat dan melakukan berbagai cara untuk menarik perhatian konsumen di Indonesia. Saat ini banyak klinik kecantikan illegal yang bermunculan di Kabupaten Karawang, klinik ini menggunakan dan/atau mengedarkan sediaan farmasi berupa kosmetika dan alat kesehatan tanpa izin edar dari lembaga yang berwenang. Hal ini tentu tidak sesuai dengan peraturan perundang-undangan yang ada di Indonesia yang telah mengatur bahwa kosmetika dan alat kesehatan dapat diedarkan hanya setelah mendapatkan izin edar dari BPOM dan Kementerian Kesehatan.  Perlindungan hukum terhadap konsumen yang dirugikan akibat praktik klinik kecantikan ilegal yang menggunakan dan/atau mengedarkan sediaan farmasi berupa kosmetika dan alat kesehatan tanpa izin edar belum optimal karena lemahnya pengawasan dari BPOM dan Kementerian Kesehatan terkait dengan peredaran kosmetika dan alat kesehatan tersebut. Selain itu, UU Kesehatan dan UU Perlindungan Konsumen telah mengatur mengenai bentuk pertanggung jawaban pelaku usaha terhadap konsumen yang dirugikan akibat penggunaan dan/atau peredaran kosmetika dan alat kesehatan tanpa izin edar secara perdata, administrative maupun pidana.Kata Kunci: Klinik Kecantikan, Ilegal, Perlindungan Konsumen, Izin Edar
INFORMATION TECHNOLOGY-BASED LEARNING (Media Development Applications Quizlet on students in MI DDI Seppange Bone)
Authors: Zakiah Wardana,
Published: June 2019

pplication quizlet is one of media-based learning android application that can be
used to a limited extent to the students, that is, their use by teachers who provided the material
is in the form of questions relating to the learning and grating exam questions that will be
dihadapai by the students of classes VI MI DDI Seppange Bone. Granting of quizlet is done
gradually so that absorption to the students can be more rapid and structured. Use of the
media learning is very beneficial to students because it can be developed by entering (input)
the subject matter in the form of questions that melingupi an important part of the sub a lesson.
Quizlet apps is also a means of contracting the message and information learned. As well as
the power tTarik learning using information technology is well designed to help learners in the
digest and understand the subject matter. On dasarya this research uses Quasi Experimental
Research method, by using the subject of research in the form of a group (class). Class VI MI
DDI Seppange taken as the population because, this class was considered qualified and
already have knowledge about android-based learning, this can be seen from the quizlet
diajuan at the time of pre-test. Variables that are revealed in this research is a study of the
response against the application of learning to the students ' quizlet klas VI students taught
using quizlet and response application of their learning. Next design research is applied in this
study isThe pre-test – post-test control group design.
THE EXISTENCE OF MEDIA EDUCATION IN IMPROVING THE QUALITY OF HUMAN RESOURCES
Authors: Musyarif Ahdar,
Published: June 2019

Abstract: a contemporary phenomenon describes the life competitive competition. In this regard, which can be advanced is are people who have qualified human resources. Demands
and urging mankind to be independent and do not depend on institutions that can recruit later after plunging into the world of work. Because given the employment is getting narrower and
more and more unemployment. Therefore, in answering this question in the competent institutions must cultivate human resources. In the world of education has several important elements, one of which is the media. Media merupakan alat komunikasi dan informasi yang
dapat mengakses ilmu pengetahuan kepada anak didik. Whether a successful learning process in the world of education is strongly influenced by the role of the media.
POTENSI PANGSA PASAR PERGURUAN TINGGI SWASTA DI INDONESIA [Studi Pada Universitas Islam Syekh-Yusuf Tangerang]
Authors: Handayani Femi
Published: June 2019

Tujuan dari penelitian ini berkaitan dengan melakukan analisis potensi pangsa pasar perguruan tinggi swasta di Indonesia, studi pada Universitas Islam Syekh-Yusuf Tangerang. Dengan melakukan wawancara mendalam, observasi dan data yang berkaitan dengan potensi pangsa pasar. Hasil penelitian menunjukkan pangsa pasar pada Universitas Islam Syekh-Yusuf Tangerang adalah cukup potensial berkaitan dengan calon mahasiswa baru yang masuk. Penelitian ini memberikan saran bahwa pangsa pasar di perguruan tinggi swasta khususnya di Universitas Islam Syekh-Yusuf Tangerang perlu dijaga sehingga animo mahasiswa baru tetap tinggi.
KOMPETENSI SUMBER DAYA MANUSIA DALAM ERA TEKNOLOGI: ANALISIS TERHADAP PEGAWAI DI LINGKUNGAN PEMERINTAHAN
Authors: . Suhaya , Dahlan Jarnawi Afgani , . Afriani , Sohibah Siti
Published: June 2019

Tujuan dalam penelitian ini adalah mengkaji perbedaan kompetensi dalam kognitif, afektif, dan psikomotor sumber daya manusia dalam teknologi informasi, mengkaji hubungan antara kompetensi dalam teknologi informasi dengan pengelolaan informasi; kebutuhan akan informasi, mengakses informasi, memilih informasi, serta mengevaluasi informasi yang diperoleh melalui internet. Sleain itu dikaji juga secara komprehensif hubungan-hubungan antar peubah yang memberikan pengaruh terhadap tinggi rendahnya kinerja karyawan dikaitkan dengan manajemen mutu yang dikaitan dengan tingginya apikasi teknologi. Metode survei cross sectional terhadap pegawai di pemerintahan Kota Tangerang diperoleh hasil bahwa Kompetensi kognitif, afektif dan psikomotor literasi informasi pegawai di lingkungan pemerintahan dapat dikatakan baik. Ada perbedaan yang berarti antara literasi kognitif, afektif dan psikomotor. Kebutuhan infromasi melalui internet sangat dipengaruhi oleh aspek kognitif, afektif dan psikomotor. Akses informasi melalui internet yang dimiliki dikatakan cukup baik dan dipengaruhi oleh tinggi redahnya kompetensi dalam literasi pengetahuan akan teknologi informasi, sikap terhadap informasi melalui internet, serta ketrampilan dalam penggunaan teknologi informasi. Pemilihan informasi yang diperoleh dari internet dilakukan dengan baik oleh pegawai. Pemilihan informasi ini sangat dipengaruhi oleh dua aspek yakni afektif dan psikomotor. Evaluasi terhadap informasi yang diperoleh dalam internet secara umum dianggap penting agar data yang diperoleh valid. Factor evaluasi ini hanya dipengatuhi secara berarti oleh ketrampilan responden dalam menggunakan teknologi infromasi.
Estrategias del marketing viral y el posicionamiento de marca en los restaurantes turísticos de la Región de Puno
Authors: Carpio Maraza Amira , Hancco Gomez Miriam Serezade , Cutipa Limache Alberto Magno , Flores Mamani Emilio
Published: June 2019

La investigación tiene como objetivos analizar las estrategias del marketing viral y del posicionamiento de marca que utilizan los restaurantes turísticos de la región de Puno e identificar el posicionamiento de marca en internet de los restaurantes turísticos de la región de Puno, a partir del uso del marketing viral, periodo 2016. Para dar a conocer la problemática existente y los esfuerzos para incrementar el posicionamiento de la marca a través del marketing viral, los métodos aplicados fueron: enfoque cuantitativo, método deductivo, tipo descriptivo - explicativo y diseño no experimental, usando técnicas de recolección como el análisis de contenido y observación estructurada. El resultado revela que la conectividad es la estrategia principal del marketing viral que contribuye al posicionamiento de marca por internet, sin embargo 43.75% difunden temas relevantes, 18.75% incentivos y 12.50% canje de cupones anunciados, lo cual contribuye a un moderado posicionamiento de marca de los restaurantes turísticos en un 50.0%, gracias a su presencia en el motor de búsqueda Tripadvisor y en la red social Foursquare. Concluyéndose que la conectividad en redes sociales genera un posicionamiento de marca moderado.
Mathematical communication profile of female student who is mathematics teacher candidate in implementing teaching practice program
Authors: Ansori Hidayah , Budayasa I Ketut , Suwarsono St
Published: June 2019

Students who are mathematics teacher candidates have different mathematical communication skills. They carry out mathematics learning when doing teaching practice. Their mathematical communication skills greatly influence the communication that is implemented into mathematics learning in the classroom. This study aims to describe the mathematical communication profile of female students who are mathematics teacher candidates. The participant of this study was a female teacher candidate who was carrying out teaching practice (PPL) at the training school. Data collection was done by recording the implementation of learning, which was presented through learning video transcripts and analyzed by data reduction, data displaying, and interpretation-verification. The results of this study are prospective female teachers always ask students to repeat their answers, to ensure the answers mentioned. This has resulted in the fact that female mathematics teacher candidates are not strict in making decisions, seem rambling in making decisions. The nonverbal communication of female teacher candidates is a clear voice heard throughout the class; ways/gestures, movements of appearance and facial expressions show calmness and smile to students, so learning flows smoothly.
The Influence of Perceived Risk and Fatalism on Job Security Perception in Underground Mining
Authors: YAVAN Öznur
Published: June 2019

Occupational health and safety issues, which have very important consequences from economic, psychological and sociological aspects, are as old as working life. Occupational health and safety perceptions of employees operating in hazardous and risky industries are among the most powerful elements affecting the sustainability of organizations within the context of safety performance. The aim of this study is to reveal the effects of the risk perception that result from accidents and injuries and fatalism on the perception of occupational health and safety in underground mining. As a result of the factor analyzes, the risk perception is divided into two dimensions as internal and external risk. Internal risk perception and fatalism have a statistically significant positive effect on the job security perception and the external risk perception does not have a statistically significant effect on the job security perception. Relations were performed by correlations and regression analyzes with SPSS 19 packet program.
Developing Rail Safety Competencies Based on Accident and Incident Investigations: Using Root Cause Taxonomies to Learn from Accidents
Authors: BAŞARAN İbrahim , YILMAZ Sinan
Published: June 2019

Bilgi çağında; bilginin örgütsel başarının temel belirleyici faktörlerinden biri haline gelmesi ile birlikte, "Örgütsel Emniyet" kavramı da giderek bilgi yönetim sistemlerine daha bağımlı hale gelmektedir. Bir yönetim süreci olarak Bilgi Yönetimi, örgütsel bilginin elde edilmesi, geliştirilmesi, paylaşılması ve etkin biçimde kullanılması ile ilgili faaliyetleri kapsar. Örgütsel etkinliğin sağlanabilmesi için bilgi yönetimi yaklaşımları, örgütsel hafıza ve örgütsel öğrenme sistemleri birbiriyle etkileşim halindedir. Bu çalışmada kaza ve olay araştırma yaklaşımlarını ve "Emniyet Yönetimi" kavramını "Örgütsel Emniyet Stratejileri", "Örgütsel Emniyet Yetkinlikleri" ve "Bilgi Yönetim Sistemleri" açısından yazında mevcut araştırmalar ışığında inceledik.
A decuplet of periapical cysts: A pilot study of case series.
Authors: Farha Syeda , Sodhi Sonia , Shaikh Firdous
Published: June 2019

The radicular cyst has been classified as inflammatory cyst, as a consequence of pulpal necrosis following caries, with an associated periapical inflammatory response. A case series of 10 periapical cysts have been described in this article. We have also derived basic data from these cases to check for relevance of incidence of radicular cyst with age, its gender predilection, the common aetiological factor, and to rule out the common site and region of occurrence.

Key words: Radicular cyst, periapical cyst, Non vital tooth
Model Based Study of Crop Evapotranspiration under Canopy Shading
Authors: Yu Qiang , Shah Krishna , Wang Dong , Ma Yanbao , Wang Zhifeng
Published: June 2019

California has some of the key agricultural regions in the United States. One of these key regions, San Joaquin Valley, frequently experiences severe droughts leading to shortage of irrigation water. This has a significant impact on the agricultural based economy of the region. It is imperative to develop new strategies to reduce overall water consumption in agriculture without affecting crop yield. A large fraction of irrigation water is lost due to the evapotranspiration (ET) process in the crops and the soil. The classical Penman-Monteith model has been used in the present work to analyze the effect of different environmental variables and water saving strategies on the ET. Some of the scenarios considered show potential for significant water savings without much reduction in the amount of sunlight available to facilitate crop growth. The central idea considered in this study is the use of canopy shading to cover the crop field resulting in reduction in the ET. Among the strategies considered, the most promising strategy is to partially cover the crop field for a certain part of the day by employing a partially covering retractable canopy. Based on numerical calculations, total reduction in ET is calculated to be 37% from June to August for the partially covering retractable canopy.
The Use of Infrared Thermography for the Monitoring of Udder Teat Stress Caused by Milking Machines
Authors: Tangorra Francesco Maria , Redaelli Veronica , Luzi Fabio , Zaninelli Mauro
Published: June 2019

The aim of this study was to test infrared thermography (IRT) as a possible tool for scoring teat color changes after cluster removal; thus, indirectly, to classify the short-term stress of teats caused by milking machines. Thermographic images (n = 137) from three farms were collected and evaluated to calculate the average and maximum skin surface temperatures (SSTs) at the base, center, and tip of each teat (Tavg,B, Tavg,C, Tavg,T, Tmax,B, Tmax,C, and Tmax,T). Obtained results confirmed a significant relationship between the indicators Tavg, Tmax and the levels of teat color change (level one: pink-colored teat; level two: red-colored teat; level three: blue or purple-colored teat). Nevertheless, when a teat was considered to be stressed because its scoring fell in level 3 of the color-change scale used, sensitivity and specificity in the classification of the teat status ranged respectively between 45.6% and 54.3%, and 54.4% and 59.2%, for the indicators Tavg; and 56.5% and 60.9%, and 59.7% and 61.8%, for the indicators Tmax. When a teat was considered stressed because its scoring fell between the levels 2 and 3 of the scale adopted, sensitivity and specificity were between 49.0% and 55.8%, and 58.3% and 61.8%, for the indicators Tavg; and 55.8% and 59.9%, and 60.6% and 61.4%, for the indicators Tmax. As a consequence, the low values of sensitivity and specificity do not seem to justify the development of an ad hoc infrared device for the monitoring of udder teat stress. Nonetheless, this technology can be a viable solution for a preliminary evaluation of the mechanical stress of teats if a milking system would be equipped with an infrared sensor already in place for other purposes (e.g., the monitoring of udder health status).
Antioxidant-Rich Extracts of Terminalia ferdinandiana Interfere with Estimation of Cell Viability
Authors: Akter Saleha , Addepalli Rama , Netzel Michael E. , Tinggi Ujang , Fletcher Mary T. , Sultanbawa Yasmina , Osborne Simone A.
Published: June 2019

The impact of plant extracts and phytochemicals on in vitro cell viability is usually assessed by employing cell viability assays dependent upon the activity of dehydrogenase enzymes. The CellTiter 96® AQueous One Solution Cell Proliferation Assay (CellTiter) was used to measure cell viability in response to antioxidant-rich extracts of Terminalia ferdinandiana fruits. Conflicting results were obtained from this assay whereby higher concentrations of extracts significantly increased cell viability compared to lower concentrations. Intrinsic reductive potential was observed in a cell-free system when extracts were added directly to the CellTiter assay reagent. To confirm this effect in a similar cell proliferation assay, we employed the CellTiter-Blue® Cell Viability Assay and again observed increased viability with increased concentrations of the extracts and direct reduction of the assay reagent by the extracts in cell-free systems. In the search for a cell proliferation assay that would not be directly affected by the plant extracts, we identified the CyQUANT® NF Cell Proliferation Assay that is based on the estimation of DNA content in viable cells. Cell viability decreased with increasing concentrations of the extracts. Accordingly, the results of the present study indicated that cell viability assays reliant upon dehydrogenase activity may lead to false positive results when testing antioxidant-rich plant extracts with intrinsic reductive potential, and alternative cell viability assays should be used to measure the cell viability.
Paraoxonase 1, HDL Subclasses and Post Surgery Acute Inflammation: A Pilot Study
Authors: Bains Yasmin , Caccavello Russell , Kotani Kazuhiko , Gugliucci Alejandro
Published: June 2019

High density lipoproteins (HDL) structure and function studies are needed to better understand the heterogeneous nature of the HDL particle, and its interaction with associated proteins such as apolipoprotein A-1 (ApoA-1), paraoxonase 1 (PON1) and the environment. Our study assesses the effects of acute inflammation on PON1 and HDL subclasses in post-surgical colorectal cancer patients. PON1 was measured kinetically through its arylesterase and lactonase activity and HDL sub-classes were measured using Quantimetrix Lipoprint® System. White blood cells (WBC) counts, c-reactive protein (CRP) and serum amyloid A (SAA) levels were also analyzed using standard techniques. Our findings show that baseline PON1 activity is lower in colorectal cancer patients and significant reductions are observed in the acute inflammatory state post-surgery. PON1 changes are also inversely related to inflammatory markers such as SAA and CRP. In addition, our preliminary findings show that small and intermediate HDL decreases post-op Day 1. In conclusion, our study demonstrates the effects of chronic and acute inflammation on PON1. Specifically, PON1 arylesterase and lactonase activity is lower in states of chronic inflammation and further decreased in the acute inflammatory state. Additionally, in our limited sample size, while changes in PON1 and HDL subclasses may be variable in the acute inflammatory period, small HDL decreased with a loss of PON1 activity in the subacute phase.
OntoIMM: An Ontology for Product Intelligent Master Model
Authors: Yu Cong , Zhang Fa-ping , Butt Shahid I. , Yan Yan , Lv Wu
Published: June 2019

Information organizing principle is one of the key issues of intelligent master model (IMM), which is an enhancement of the master model (MM) based on KBE (knowledge-based engineering). Despite the fact that the core product model (CPM) has been confirmed to be an organizing mechanism for product master model, the key issue of supporting the information organizing for IMM is not yet well addressed, mainly due to the following two reasons; (1) lack of representation of complete information and knowledge with regard to product and process, including the know-why, know-how, and know-what information and knowledge, and (2) lack of semantic richness. Therefore, a multiaspect extension to CPM was first defined, and then an ontology was constructed to represent the information and design knowledge. The extension refers to adding a design process model, context model, product control structure model, and design rationale model to CPM concerning the enhancement of master model, which is to comprehensively represent the reason, process, and result information and knowledge of the product. The ontology construction refers to representing the concepts, relationships among these concepts and consistency rules of IMM information structure. Finally, an example of barrel design and analysis process is illustrated to verify the effectiveness of proposed method.
Spatiotemporal Variability of Actual Evapotranspiration and the Dominant Climatic Factors in the Pearl River Basin, China
Authors: Gao Weizhi , Wang Zhaoli , Huang Guoru
Published: June 2019

Evapotranspiration is a vital component of the land surface process, thus, a more accurate estimate of evapotranspiration is of great significance to agricultural production, research on climate change, and other activities. In order to explore the spatiotemporal variation of evapotranspiration under global climate change in the Pearl River Basin (PRB), in China, this study conducted a simulation of actual evapotranspiration (ETa) during 1960–2014 based on the variable infiltration capacity (VIC) model with a high spatial resolution of 0.05°. The nonparametric Mann–Kendall (M–K) test and partial correlation analysis were used to examine the trends of ETa. The dominant climatic factors impacting on ETa were also examined. The results reveal that the annual ETa across the whole basin exhibited a slight but not significant increasing trend during the 1960–2014 period, whereas a significant decreasing trend was found during the 1960–1992 period. At the seasonal scale, the ETa showed a significant upward trend in summer and a significant downward trend in autumn. At the spatial scale, the ETa generally showed a decreasing, but not significant, trend in the middle and upper stream of the PRB, while in the downstream areas, especially in the Pearl River Delta and Dongjiang River Basin, it exhibited a significant increasing trend. The variation of the ETa was mainly associated with sunshine hours and average air pressure. The negative trend of the ETa in the PRB before 1992 may be due to the significant decrease in sunshine hours, while the increasing trend of the ETa after 1992 may be due to the recovery of sunshine hours and the significant decrease of air pressure. Additionally, we found that the “paradox” phenomenon detected by ETa mainly existed in the middle-upper area of the PRB during the period of 1960–1992.
Riemann–Liouville Operator in Weighted Lp Spaces via the Jacobi Series Expansion
Authors: Kukushkin Maksim V.
Published: June 2019

In this paper, we use the orthogonal system of the Jacobi polynomials as a tool to study the Riemann–Liouville fractional integral and derivative operators on a compact of the real axis. This approach has some advantages and allows us to complete the previously known results of the fractional calculus theory by means of reformulating them in a new quality. The proved theorem on the fractional integral operator action is formulated in terms of the Jacobi series coefficients and is of particular interest. We obtain a sufficient condition for a representation of a function by the fractional integral in terms of the Jacobi series coefficients. We consider several modifications of the Jacobi polynomials, which gives us the opportunity to study the invariant property of the Riemann–Liouville operator. In this direction, we have shown that the fractional integral operator acting in the weighted spaces of Lebesgue square integrable functions has a sequence of the included invariant subspaces.
Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer
Authors: Zhao Jiangang , Schlößer Hans A. , Wang Zhefang , Qin Jie , Li Jiahui , Popp Felix , Popp Marie Christine , Alakus Hakan , Chon Seung-Hun , Hansen Hinrich P. , Neiss Wolfram F. , Jauch Karl-Walter , Bruns Christiane J. , Zhao Yue
Published: June 2019

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Tumor-derived extracellular vesicles (EVs) induce pre-metastatic niche formation to promote metastasis. We isolated EVs from a highly-metastatic pancreatic cancer cell line and patient-derived primary cancer cells by ultracentrifugation. The protein content of EVs was analyzed by mass spectrometry. The effects of PDAC-derived EVs on natural kill (NK) cells were investigated by flow cytometry. The serum EVs’ TGF-β1 levels were quantified by ELISA. We found that integrins were enriched in PDAC-derived EVs. The expression of NKG2D, CD107a, TNF-α, and INF-γ in NK cells was significantly downregulated after co-culture with EVs. NK cells also exhibited decreased levels of CD71 and CD98, as well as impaired glucose uptake ability. In addition, NK cell cytotoxicity against pancreatic cancer stem cells was attenuated. Moreover, PDAC-derived EVs induced the phosphorylation of Smad2/3 in NK cells. Serum EVs’ TGF-β1 was significantly increased in PDAC patients. Our findings emphasize the immunosuppressive role of PDAC-derived EVs and provide new insights into our understanding of NK cell dysfunction regarding pre-metastatic niche formation in PDAC.
Can Dendritic Cell Vaccination Prevent Leukemia Relapse?
Authors: O’Brien Liam J. , Guillerey Camille , Radford Kristen J.
Published: June 2019

Leukemias are clonal proliferative disorders arising from immature leukocytes in the bone marrow. While the advent of targeted therapies has improved survival in certain subtypes, relapse after initial therapy is a major problem. Dendritic cell (DC) vaccination has the potential to induce tumor-specific T cells providing long-lasting, anti-tumor immunity. This approach has demonstrated safety but limited clinical success until recently, as DC vaccination faces several barriers in both solid and hematological malignancies. Importantly, vaccine-mediated stimulation of protective immune responses is hindered by the aberrant production of immunosuppressive factors by cancer cells which impede both DC and T cell function. Leukemias present the additional challenge of severely disrupted hematopoiesis owing to both cytogenic defects in hematopoietic progenitors and an abnormal hematopoietic stem cell niche in the bone marrow; these factors accentuate systemic immunosuppression and DC malfunction. Despite these obstacles, several recent clinical trials have caused great excitement by extending survival in Acute Myeloid Leukemia (AML) patients through DC vaccination. Here, we review the phenotype and functional capacity of DCs in leukemia and approaches to harness DCs in leukemia patients. We describe the recent clinical successes in AML and detail the multiple new strategies that might enhance prognosis in AML and other leukemias.
Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study
Authors: Incoronato Mariarosaria , Grimaldi Anna Maria , Mirabelli Peppino , Cavaliere Carlo , Parente Chiara Anna , Franzese Monica , Staibano Stefania , Ilardi Gennaro , Russo Daniela , Soricelli Andrea , Catalano Onofrio Antonio , Salvatore Marco
Published: June 2019

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies.
DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy
Authors: Sanchez-Correa Beatriz , Valhondo Isabel , Hassouneh Fakhri , Lopez-Sejas Nelson , Pera Alejandra , Bergua Juan M. , Arcos Maria Jose , Bañas Helena , Casas-Avilés Ignacio , Durán Esther , Alonso Corona , Solana Rafael , Tarazona Raquel
Published: June 2019

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.
Targeting of Histone Demethylases KDM5A and KDM6B Inhibits the Proliferation of Temozolomide-Resistant Glioblastoma Cells
Authors: Romani Massimo , Daga Antonio , Forlani Alessandra , Pistillo Maria Pia , Banelli Barbara
Published: June 2019

Lysine histone demethylases (KDMs) are considered potential therapeutic targets in several tumors, including glioblastoma (GB). In particular, KDM5A is involved in the acquisition of temozolomide (TMZ) resistance in adult GB cells and UDX/KDM6B regulates H3K27 methylation, which is involved in the pediatric diffuse intrinsic pontine glioma (DIPG). Synthetic inhibitors of KDM5A (JIB 04 and CPI-455) efficiently block the proliferation of native and TMZ-resistant cells and the KDM6B inhibitor GSK J4 improves survival in a model of DIPG. The aim of our work was to determine if GSK J4 could be effective against GB cells that have acquired TMZ resistance and if it could synergize with TMZ or JIB 04 to increase the clinical utility of these molecules. Standard functional and pharmacological analytical procedures were utilized to determine the efficacy of the molecules under study when used alone or in combination against native GB cells and in a model of drug resistance. The results of this study indicated that although GSK J4 is active against native and TMZ-resistant cells, it does so at a lower efficacy than JIB 04. Drug combination studies revealed that GSK J4, differently from JIB 04, does not synergize with TMZ. Interestingly, GSK J4 and JIB 04 strongly synergize and are a potent combination against TMZ-resistant cells. Further studies in animal models will be necessary to determine if this combination of molecules might foster the development of novel therapeutic approaches for glioblastoma.
Prognostic Role of Albumin, Bilirubin, and ALBI Scores: Analysis of 1000 Patients with Hepatocellular Carcinoma Undergoing Radioembolization
Authors: Antkowiak Mark , Gabr Ahmed , Das Arighno , Ali Rehan , Kulik Laura , Ganger Daniel , Moore Christopher , Abecassis Michael , Katariya Nitin , Mouli Samdeep , Mahalingam Devalingam , Lewandowski Robert J. , Salem Riad , Riaz Ahsun
Published: June 2019

Introduction: We compared the efficacy of the ALBI (albumin–bilirubin) score to the established Child–Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75–6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89–14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71–2.43); CP C vs. CP A was 3.27 (2.08–5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81–3.41); albumin 3 vs. 1 was 4.74 (3.44–6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82–1.44); bilirubin 3 vs. 1 was 2.37 (1.66–3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.
(Pro)renin Receptor Expression Increases throughout the Colorectal Adenoma—Adenocarcinoma Sequence and It Is Associated with Worse Colorectal Cancer Prognosis
Authors: Beitia Maider , Solano-Iturri Jon Danel , Errarte Peio , Calvete-Candenas Julio , Loizate Alberto , Etxezarraga Mari Carmen , Sanz Begoña , Larrinaga Gorka
Published: June 2019

(Pro)renin receptor (PRR) is a protein that takes part in several signaling pathways such as Renin Angiotensin System and Wnt signalling. Its biological role has recently been related to cancer progression and in this study, we investigated its relevance in colorectal cancer (CRC). To that end, we analysed the immunohistochemical expression of PRR in adenomatous polyps and CRCs from the same patients (n = 42), and in primary tumours and nodal and liver metastases from advanced CRC patients (n = 294). In addition, the soluble fraction of PRR was measured by ELISA in plasma samples from 161 CRC patients. The results showed that PRR expression was gradually augmented along the uninvolved mucosa–adenoma–adenocarcinoma sequence. Besides, the stronger expression of PRR in primary tumours was markedly associated with local tumour extent and the onset of metastases. Moreover, PRR expression in both primary and distant metastases was associated with worse 5- and 10-year survival of CRC patients. Plasmatic PRR levels did not change with respect to controls and were not associated with CRC aggressiveness. These results suggest a key role of PRR in the development and progression of CRC and a potential use of this protein as a new prognostic biomarker and/or therapeutic target for this disease.
Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
Authors: Amirnasr Azadeh , Gits Caroline M.M. , van Kuijk Patricia F. , Smid Marcel , Vriends Anne L.M. , Rutkowski Piotr , Sciot Raf , Schöffski Patrick , Debiec-Rychter Maria , Sleijfer Stefan , Wiemer Erik A. C.
Published: June 2019

Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n = 11/exon 11; n = 41/exon 17; n = 1) and comprising imatinib-naïve (IM-n) (n = 33) and imatinib-resistant (IM-r) (n = 20) tumors, were analyzed. The microRNA expression profiles were determined and from a subset (IM-n, n = 14; IM-r, n = 15) the mRNA expression profile was established. Ingenuity pathway analyses were used to unravel biochemical pathways and gene networks in IM-r GIST. Thirty-five differentially expressed miRNAs between IM-n and IM-r GIST samples were identified. Additionally, miRNAs distinguished IM-r samples with and without secondary KIT mutations. Furthermore 352 aberrantly expressed genes were found in IM-r samples. Pathway and network analyses revealed an association of differentially expressed genes with cell cycle progression and cellular proliferation, thereby implicating genes and pathways involved in imatinib resistance in GIST. Differentially expressed miRNAs and mRNAs between IM-n and IM-r GIST were identified. Bioinformatic analyses provided insight into the genes and biochemical pathways involved in imatinib-resistance and highlighted key genes that may be putative treatment targets.
Custom-Made Chemically Modified Graphene Oxide to Improve the Anti-Scratch Resistance of Urethane-Acrylate Transparent Coatings
Authors: Domene-López Daniel , Sarabia-Riquelme Rubén , García-Quesada Juan C. , Martin-Gullon Ignacio
Published: June 2019

In this work, a thermoset ultraviolet (UV)-cured polyurethane-acrylate resin was doped with different chemically-modified graphene obtained from a commercial graphene oxide (GO): as-received GO, chemically reduced GO (rGO), GO functionalized with vinyltriethoxysilane (VTES) (GOvtes), and GO functionalized with VTES and subsequently reduced with a chemical agent (rGOvtes). Modified graphene was introduced in the oligomer component via solvent-assisted process using acetone, which was recovered after completion of the process. Results indicate that the GO-doped oligomers produce cured coatings with improved anti-scratch resistance (above the resistance of conventional coatings), without surface defects and high transparency. The anti-scratch resistance was measured with atomic force microscopy (AFM). Additionally, results are presented in terms of Wolf–Wilburn scale, a straightforward method widely accepted and employed in the coating industry.
The Composition and Assembly of Bacterial Communities across the Rhizosphere and Phyllosphere Compartments of Phragmites Australis
Authors: Zhou Qi , Zhang Xiaomin , He Rujia , Wang Shuren , Jiao Congcong , Huang Rui , He Xiaowei , Zeng Jin , Zhao Dayong
Published: June 2019

The rhizosphere and the phyllosphere represent two different epiphytic compartments of host plant, which are closely related to plant growth, health, and productivity. However, the understanding of the diversity, composition, and assembly of the bacterial communities in different epiphytic microenvironments of large emerged macrophytes has remained elusive, especially the abundant and rare taxa across rhizosphere and phyllosphere communities. In this study, we collected samples of two different epiphytic compartments (rhizosphere and phyllosphere) of Phragmites australis. Both 16S rRNA gene-based high-throughput sequencing and null-model analysis were employed to determine the difference in the composition and assembly of above-mentioned epiphytic bacterial communities. Our results indicated that bacterial communities of rhizosphere exhibited higher diversity and richness than those of phyllosphere. Deterministic processes dominated the assembly of bacterial community in both compartments, and stochastic processes contributed a certain proportion (30.30%) in the assembly of phyllosphere bacterial community. We also found that rare taxa contributed more significantly to the alpha- and beta-diversity of bacterial community than those of abundant taxa. The obtained data are useful for better understanding the bacterial community of different epiphytic compartments of P. australis.
User-Oriented Summaries Using a PSO Based Scoring Optimization Method
Authors: Villa-Monte Augusto , Lanzarini Laura , Bariviera Aurelio F. , Olivas José A.
Published: June 2019

Automatic text summarization tools have a great impact on many fields, such as medicine, law, and scientific research in general. As information overload increases, automatic summaries allow handling the growing volume of documents, usually by assigning weights to the extracted phrases based on their significance in the expected summary. Obtaining the main contents of any given document in less time than it would take to do that manually is still an issue of interest. In this article, a new method is presented that allows automatically generating extractive summaries from documents by adequately weighting sentence scoring features using Particle Swarm Optimization. The key feature of the proposed method is the identification of those features that are closest to the criterion used by the individual when summarizing. The proposed method combines a binary representation and a continuous one, using an original variation of the technique developed by the authors of this paper. Our paper shows that using user labeled information in the training set helps to find better metrics and weights. The empirical results yield an improved accuracy compared to previous methods used in this field.
Experimental Investigation of a 300 kW Organic Rankine Cycle Unit with Radial Turbine for Low-Grade Waste Heat Recovery
Authors: Wang Ruijie , Kuang Guohua , Zhu Lei , Wang Shucheng , Zhao Jingquan
Published: June 2019

The performance of a 300 kW organic Rankine cycle (ORC) prototype was experimentally investigated for low-grade waste heat recovery in industry. The prototype employed a specially developed single-stage radial turbine that was integrated with a semi-hermetic three-phase asynchronous generator. R245fa was selected as the working fluid and hot water was adopted to imitate the low-grade waste heat source. Under approximately constant cooling source operating conditions, variations of the ORC performance with diverse operating parameters of the heat source (including temperature and volume flow rate) were evaluated. Results revealed that the gross generating efficiency and electric power output could be improved by using a higher heat source temperature and volume flow rate. In the present experimental research, the maximum electric power output of 301 kW was achieved when the heat source temperature was 121 °C. The corresponding turbine isentropic efficiency and gross generating efficiency were up to 88.6% and 9.4%, respectively. Furthermore, the gross generating efficiency accounted for 40% of the ideal Carnot efficiency. The maximum electric power output yielded the optimum gross generating efficiency.