bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluasi dan Pengembangan Strategi Bisnis Perusahaan Menggunakan Balanced Scorecard
Authors: Ardianto Ryan , Kurniawati Rina
Published: July 2021

Tujuan dari penelitian ini untuk mengevaluasi, membuat rancangan strategi agar dapat bersaing secara berkelanjutan serta menentukan ukuran keberhasilan kinerja perusahaan. Objek penelitian ialah PD. Anggia yang merupakan sebuah perusahaan yang bergerak di industri makanan yaitu molen kering mini. Teknik dalam penelitian ini adalah dengan mengidentifikasi kekuatan, kelemahan, peluang dan ancaman yang dimiliki oleh perusahaan dengan Matrik Internal Factor Evaluation (IFE) dan Matrik External Factor Evaluation (EFE). Kemudian menentukan posisi perusahaan saat ini untuk mencari alternatif strategi dengan Matrik Boston Consulting Group (BCG), Setelah alternatif strategi diketahui disusunlah strategi perusahaan menggunakan Balanced Scorecard (BSC). Dari salah satu perspektif teknik yang digunakan adalah dengan menyebarkan kuesioner kepada 150 responden dan 14 pernyataan. Berdasarkan hasil penelitian menunjukan bahwa kemampuan perusahaan dalam lingkungan internal external berada pada sel II yang disebut strategi pertahankan dan pelihara, darihasil matrik BCG diketahui bahwa PD. Anggia berada pada kuadran II (Star) yang berarti PD. Anggi berada pada posisi yang sangat kuat sebagai pemimpin dalam bisnis molen kering. Karena peluangnya sangat besar, maka pilihan terbaik bagi perusahaan adalah melaksanakan ekpansi dan meningkatkan kepuasan pelanggan terhadap citra produk serta peningkatan kemampuan kinerja karyawan terhadap perusahaan, sehingga strategi perusahaan dapat dikatakan sangat baik.
Identifikasi Faktor Pendirian Usaha Bata Merah Berdasarkan BOCR
Authors: Darojat M. Zaky , Cahyadi Ujang , Taptajani Dedi Sa’dudin
Published: July 2021

Tujuan penelitian ini yaitu untuk mengetahui dampak – dampak yang berpengaruh terhadap pendekatan total usaha bata merah di Kabupaten Garut. Sering kali muncul kendala didalam usaha bata merah sehingga mengakibatkan kegagalan dalam menjalankan sebuah usaha. Metode yang digunakan adalah ANP ( Analytic Network Process) dan analisis BOCR (Benefit Opportunities Cost Risk). Hasil yang didapat bahwa dampak – dampak yang berpengaruh terhadap total usaha bata merah adalah nilai stabil dengan bobot tertinggi dalam pendekatan BOCR adalah Cost, Risk, Benefit, Opportunites . Dan untuk penentuan strategi menggunakan analisis SWOT. Dan terdapat penentuan strategi Strength-Opportunities, Sterngth-Treats, Weakness-Opportunities, Weakness-Treats untuk menanggulangi dampak – dampak tersebut.
Identifikasi Faktor-Faktor Kunci Keberhasilan Pola Kemitraan Inti Plasma
Authors: Ardiansyah Revy , Aulawi Hilmi
Published: July 2021

Konsep pola kemitraan adalah salah satu konsep upaya untuk mengatasi permasalahan perubahan paradigma bisnis yang telah berubah dari berorientasi pada pasar menjadi berorientasi pada konsumen, Namun masih banyaknya pola kemitraan inti plasma yang belum maksimal dan berkesinambungan maka perlu adanya penelitian mengenai identifikasi faktor-faktor kunci keberhasilan pola kemitran inti plasma. Tujuan penelitian ini adalah merumuskan faktor-faktor kunci keberhasilan seperti apa yang bisa menciptakan kesinambungan proses kemitraan inti plasma. Responden dalam penelitian ini adalah peternak yang bermitra dengan PT. RMB dan Karyawan PT. RMB dengan jumlah total 30 orang. Penelitian ini menggunakan metode pedekatan kualitatif berbasis wawancara, survey dan diskusi kelompok. Hasil penelitian ada 7 CSF yang mewakili 5 Faktor yang menjadi faktor kunci keberhasilan yaitu komunikasi, kerjasama, kepercayaan, komitmen, hubungan nilai.
Penentuan Depot Plastik Menggunakan Metode MDVRP
Authors: Chandrahadinata Dody , Taptajani Dedi Sa’dudin , Wibawa Rian
Published: July 2021

Penelitian ini dilakukan berdasarkan dari masalah distribusi yang dialami perusahaan, dimana lokasi perusahaan yang jauh dengan retailer dan tidak ada rute yang jelas pada saat proses distribusi. Tujuan dari penelitian ini adalah untuk mengetahui lokasi pendistribusian plastik, lokasi sebaran depot plastik, dan rute optimal pendistribusian didaerah Garut. Variabel utama penelitian ini adalah jarak antar retailer plastik. Metode penelitian yang digunakan pada kali ini adalah metode MDVRP. Tahap penelitian terdiri dari Clustering yaitu dengan menggunakan metode nearest neighbor, routing dengan menggunakan Chebishev’s Theorism dan Scheduling menggunakan metode Genetic Algorithm. Hasil yang diperoleh adalah jumlah depot dengan batasan jarak dan lokasi optimal berdasarkan jarak, serta rute distribusi dari tiap depot dan rute distribusi dari wholeseller ke depot. Penelitian ini dapat dikembangkan untuk penelitian selanjutnya mengenai MDVRP yang dapat dilakukan dengan metode yang berbeda pada tiap prosesnya serta dengan perbedaan batasan penelitian yang dilakukan baik dari jumlah retailer, beban angkut, ataupun dengan penambahan waktu.
Strategi Pengembangan Usaha Petani Kentang Berbasis Agroindustri dalam Upaya Meningkatkan Nilai Tambah
Authors: Cahyadi Ujang , Firdaus Fahad Fauzan
Published: July 2021

Penelitian ini bertujuan untuk mengetahui nilai tambah dan strategi pengembangan usaha petani kentang dengan mengolahnya menjadi kerupuk kentang. Penelitian ini dilaksanakan pada bulan Juni-Agustus 2019, sumber data dalam penelitian ini diperoleh dari data primer yang diambil melalui observasi dan wawancara langsung kepada petani kentang di Kecamatan Pasirwangi. Metode analisis data dilakukan dengan menggunakan analisis pendapatan dan nilai tambah, analisis kelayakan bisnis dan analisis SWOT. Hasil penelitian menunjukan dari pengolahan kentang menjadi kerupuk kentang memberikan nilai tambah sebesar Rp. 4.548,09/ Kg, sedangkan dari pengolahan kerupuk kentang dari hasil panen kentang semi/sedang (PL/DN) dan kentang kecil (Ares) pada saat harga kentang naik memberikan nilai tambah sebesar Rp. 7.991,85/ Kg, sedangkan dari pengolahan kerupuk kentang dari hasil panen kentang semi/sedang (PL/DN) dan kentang kecil (Ares) pada saat harga kentang turun memberikan nilai tambah sebesar Rp. 4.200,19/ Kg. Proses pengolahan kerupuk kentang layak dan menguntungkan untuk didirikan. Strategi pengembangan usaha petani kentang ialah melakukan pengolahan kerupuk kentang dengan bahan baku yang dimiliki dengan memasarkannya ke pasar-pasar yang ada disekitar Kabupaten Garut dengan didukung dengan penggunaan media online dan dengan terus meningkatkan inovasi baik itu rasa maupun kemasan agar produk kerupuk kentang ini berbeda dengan produk-produk pesainganya.
ANALISA UJI KUAT TEKAN BETON DENGAN BAHAN TAMBAHAN BATU BATA MERAH
Authors: Syarif Ahmad , Setyawan Chandra , Farida Ida
Published: July 2021

Bata merah merupakan material umum yang dipakai pada bangunan. Bata merah dalam penelitian ini di tujukan untuk pemanfaatan limbah. Limbah batu bata merah dalampenelitian pembuatan beton untuk menghasilkan beton bermutu tinggi.Metode penelitian yang dipakai adalah metode percobaan yang dilakukan di laboratorium STT-Garut, yaitu denganmelakukan pemeriksaan atau percoban secara fisik pada uji beton, yang menggunakan bahan tambahan limbah batu bata merahsebanyak 27 benda uji (10%, 25%, 50%) dankuat tekan beton normal K-200 sebanyak 9 benda uji (200kg/cm 2). Tujuannya untuk mengetahui kuat tekan beton dengan menggunakan bahan tambahan limbah batu bata merah sebanyak 27 benda uji (10%, 25%, 50%) dan kuat tekanbeton normal K-200 sebanyak 9 benda uji (200kg/cm 2 ) sebagai acuan pembanding.Dari hasil penelitian, diketahui beton dengan menggunakan campuran 10%, 25% dan 50% hasil rata-rata sesuai dengan acuan beton pembanding (K-200). Hasil uji kuat tekan limbah batu bata merah 50% campurannya tidak lebih dari 10% dan 25%. Sehingga beton untuk campuran 10% dan 25% menjadi acuan kedepannya sebagai campuran limbah tambahan yang baik untuk pembuatan beton.
ANALISIS ALIRAN AIR MELALUI BANGUNAN TALANG PADA DAERAH IRIGASI WALAHIR KECAMATAN BAYONGBONG KABUPATEN GARUT
Authors: Hakim Indra Lukman Nul , Permana Sulwan , Farida Ida
Published: July 2021

Irigasi adalah kegiatan yang berhubungan dengan usaha mendapatkan air untuk sawah, ladang, perkebunan dan usaha-usaha pertanian lainnya. Oleh sebab itu perlu adanya keseimbangan antara kebutuhan dan ketersediaan air untuk  memenuhi  kebutuhan  air  Irigasi, maka debit  yang  tersedia  harus cukup untuk di salurkan ke setiap saluran sampai kepetakan sawah. Oleh karena itu perlu di lakukan pengukuran debit air, kebutuhan air Irigasi, agar penyaluran air efektif dan efisien. Penelitian ini di lakukan di Daerah Irigasi Walahir, Kecamatan Bayongbong, Kabupaten Garut, penelitian ini di lakukan dengan cara mengambil data sekunder, data tersebut di kompilasikan dengan metode Hamon untuk menentukan evapotranspirasi, penyiapan lahan, penggunaan konsumtif, perlokasi, penggantian lapisan air, dan curah hujan efektif, dan menentukan pola tanamnya. Dengan menggunakan sistem pola tanam Padi-Padi-Palawij, dalam jangka waktu penyiapan lahan satu setengah bulan. Dari hasil analisis di dapatkan  besarnya  nilai  debit  kebutuhan  air  Irigasi maksimum untuk penyaluran air secara keseluruhan untuk Daerah Irigasi Walahir yang di ambil dari Sungai Cipandai melalui bangunan intake sebesar 181,35 lt/dtk, dengan luas area persawahan 60 Ha. Maka dari itu debit air yang mengalir di saat musim penghujan dari Bulan November sampai Bulan Mei sangat mencukupi untuk mengairi sampai ke petakan sawah terakhir, sedangkan hasil analisis terutama pada musim kemarau dari bulan Juni sampai bulan Oktober jumlah kebutuhan air lebih besar dari ketersediaan air. Maka dari itu antisipasinya dengan menggunakan sistem golongan atau sistem gilir pemberian air dengan jangka waktu satu minggu dua kali, supaya debit air yang tersedia di saat musim kemarau bisa mencukupi untuk kebutuhanya. Dengan kebutuhan air Irigasi untuk per hektarnya dari hasil analisis di dapat, kebutuhan air Irigasi 9 Ha dengan debit air 17,682 lt/dtk, kebutuhan air Irigasi 9 Ha dengan debit air 17,682 lt/dtk, kebutuhan air Irigasi 6 Ha dengan debit air 11,788 lt/dtk, kebutuhan air Irigasi 30 Ha dengan debit air 58,939 lt/dtk, dan kebutuhan air Irigasi 6 Ha dengan debit air 11,788l lt/dtk. Dan dari hasil analisis dimensi bangunan talang dengan debit rencana Q = 0,020135m3/dtk, dengan kecepatan standar aliran air V = 0,25 m/dtk, luas penampang basah A = 0,08054 m2, tinggi jagaan fb = 0,30 m, dan tinggi muka air yang baru 0,268 m, maka dimensi bangunan talang baru hasil analisis dengan debit rencana di dapat, lebar dasar saluran B = 0,30 m, dan tinggi total saluran H = 0,60 m.
Penggunaan Limbah Cangkang Telur, Abu Sekam, dan Copper Slag Sebagai Material Tambahan Pengganti Semen
Authors: Siti Fitriani  , Wiki Muhamad Fathul M  , Ida Farida
Published: July 2021

Pembangunan dibidang struktur dewasa ini mengalami kemajuan yang sangat pesat. Baik pada pembangunan perumahan, gedung-gedung, jembatan, bendungan, jalan raya, pelabuhan, bandara dan sebagainya. Beton merupakan salah satu pilihan sebagai bahan struktur dalam konstruksi bangunan selain kayu dan logam. Beton diminati karena banyak memilikin kelebihan-kelebihan dibandingkan dengan bahan lainnya. Beberapa diantaranya adalah harganya relatif murah, mempunyai kekuatan tekan yang besar, tahan lama, tahan terhadap api, bahan baku mudah didapat dan tidak mengalami pembusukan. Hal lain yang mendasari pemilihan dan penggunaan beton sebagai bahan konstruksi adalah faktor efektifitas dan tingkat efisiensinya. Secara umum bahan pengisis (filler) beton terbuat dari bahan-bahan yang mudah diperoleh, mudah diolah (workability) dan mempunyai keawetan (durability) serta kekuatan (strenght) yang sangat diperlukan dalam pembangunan suatu konstruksi. Namun di era sekarang beton ramah lingkungan merupakan hal yang sedang marak diteliti karena beton jenis ini menggunakan bahan yang hampir tidak mempunyai dampak pada lingkungan, begitupun bahan yang kami gunakan pada lomba inovasi beton tahun ini merupakan bahan limbah tak terpakai yaitu cangkang telur, yang dimana cangkang telur ini mempunyai kandungan kalsium karbonat. Dalam cangkang telur dimanfaatkan sebagai bahan aditif dalam campuran beton.
Analisa Efektivitas Waktu dan Biaya Proyek Ditinjau Dari Unsur – Unsur Manajemen Proyek (Studi Kasus Overlay Runway Bandara Innternasional Soekarno - Hatta)
Authors: Ratih Soleha  , Agus Ismail
Published: July 2021

nalisa Efektivitas Waktu dan Biaya Proyek ditinjau dari Unsur – Unsur Manajemen Proyek. Masalah keterlambatan dalam industri konstruksi merupakan fenoemena nasional dan tidak terkecuali pada proyek Overlay Runway Bandara Internasional Soekarno – Hatta. Tujuan dari penelitian ini adalah untuk mengetahui (1)apa saja faktor – fator keterlambatan yang berpengaruh terhadap pelaksanaan proyek Overlay Runway Bandara Internasional Soekarno – Hatta. (2) apa saja yang timbul dari keterlambatan proyek pada pelaksanaan proyek Overlay Runway Bandara Internasional Soekarno – Hatta. (3) Bagaimana pengaruh faktor keterlambatan pelakanaan proyek Overlay Runway Bandara Internasional Soekarno – Hatta.Penelitian ini menggunakan metode deskriptif kaulitatif, penelitian ini tidak diarahkan untuk untuk membuktikan hipotesis, tetapi lebih ditekankan pada pengumpulan data yang bertujuan untuk mendeskripsikan atau menggambarkan keadaan sesungguhnya yang terjadi di lapangan. Teknik analisa data yang digunakan yaitu menggunakan teknik wawancara, observasi dan dokumentasi, faktor keterlambatan dianalisis untukmengetahui pengaruhnya terhadap efektivitas waktu dan biaya proyek.Dari hasil analisis dapat diketahui bahwa: (1) Faktor keterlambatan yang mempengaruhi terhadap keterlambatan proyek adalah faktor NOTAM dan cuaca buruk. (2) Keterlambatan tersebut berdampak terhadap efektivitas waktu dan biaya proyek, dimana efektivitas waktu pada proyek Overlay Runway Bandara Internasional Soekarno – Hatta sebesar 34,88% dan efektivitas biaya proyek sebesar 38,22%. (3) Solusiyang bisa dilakukan berdasarkan faktor keterlambatan yaitu dengan cara mengajukan NOTAM tambahan dan menghindari bulan – bulan musim penghujan.
Evaluasi Pondasi Bored Pile pada Proyek Kolam Ponds dengan Pile Driving Analyze Test
Authors: Permana Sulwan , Gunawan Anggi
Published: July 2021

Dalam merencanakan suatu pondasi tiang, pertama perencana menghitung daya dukung pada pondasi yang menopang beban diatasnya. Pada pengujian pondasi proyek kolam Ponds PT. United Tractors PDA test dipilih untuk mengetahui kondisi pondasi tersebut. Penelitian ini bertujuan menganalisis daya dukung dan penurunan pondasi dibandingkan dengan result PDA serta menganalisis penyebab kerusakan pada tiang yang diuji.  Metode penelitian yang digunakan adalah metode yang bersifat kualitatif lalu secara spesifik lebih diarahkan pada metode pendekatan studi kasus. Hasil dari penelitian ini yaitu perhitungan daya dukung pondasi tiang metode Schertmann & Nottingham Ø30 cm sebesar 39,62 ton, dan Ø40 cm sebesar 71,22 ton, sedangkan dengan metode Mayerhoff pondasi Ø30 cm sebesar 55,84 ton, dan Ø40 cm sebesar 92,49 ton. Hasil result PDA tiang bor titik 2 sebesar 89 ton, titik 10 sebesar 125 ton, titik 7 dan 8 tidak diketahui karena pondasi mengalami kerusakan, selisih daya dukung metode Schertmann & Nottingham dengan result PDA tiang bor titik 2 sebesar 19,97 %, dan tiang bor titik 10 sebesar 43 %, sedangkan metode Mayerhoff dengan result PDA titik 2 sebesar 19,97 %, dan tiang bor titik 10 sebesar -3,92 %, sehingga metode Mayerhoff disarankan untuk menganalisis pondasi tiang bored pile, hasil analisis penurunan pondasi tiang tunggal untuk pondasi Ø40 sebesar 0,055 m, sedangkan  pondasi Ø30 sebesar 0,056 m, hasil penurunan pondasi PDA test untuk pondasi Ø40 masih dalam batas toleransi jika dibandingkan dengan hasil analisa 0,018 m ≤ 0,055 m (titik 2), dan 0,003 m ≤ 0,055 m (titik 10) sedangkan untuk pondasi titik 7 dan 8 tidak dapat dibandingkan karena data yang dibutuhkan tidak tersedia. Beberapa penyebab kerusakan tiang bor titik 7 dan 8 yaitu proses pekerjaan konstruksi, pengaruh air tanah, dan berat hammer, kemudian perbaikan untuk tiang bor yang rusak dengan cara metode chemical anchoor supaya tiang tidak mengalami deformasi.
The relationships of nursing students’ satisfaction and self-confidence after a simulation-based course with their self-confidence while practicing on real patients in Vietnam
Authors: Oanh Tran Thi Hoang , Hoai Nguyen Thi Yen , Thuy Pham Thi
Published: July 2021

Purpose: Simulation teaching refers to the replication of real-life scenarios, enabling students to practice nursing skills and learn actively in a safe environment. It also helps students control their anxiety and fears when caring for real patients. This study investigated the relationships of Vietnamese nursing students’ self-confidence in clinical practice with their satisfaction and self-confidence in simulation-based practice.Methods: This cross-sectional descriptive study included 182 nursing students. The data collection included 2 separate stages with 2 main questionnaires. The Student Satisfaction and Self‐Confidence in Learning Scale was used to measure students’ satisfaction and self‐confidence after learning in the simulation room. The Confidence Scale was used to measure students’ self-confidence when first performing techniques on actual patients. Data were analyzed by descriptive and Pearson correlation statistics.Results: Students’ satisfaction and self-confidence during the simulation course were quite high (mean±standard deviation [SD], 4.06±0.48 and 4.11±0.46 out of 5.0, respectively). In contrast, their confidence when first practicing on a patient was moderate (mean±SD, 3.19±0.62 out of 5.0). Students’ satisfaction showed moderate and weak positive correlations with self-confidence in pre-clinical practice and in clinical practice (r=0.33, P<0.001 and r=0.26, P<0.001, respectively).Conclusion: Simulation has become an effective teaching strategy that can help nursing students be well-prepared for clinical placements in Vietnam. An effective nursing education strategy is needed to enhance the satisfaction and self-confidence of nursing students in simulation and then in clinical practice to help achieve professional engagement and development.
Economic Stimulus Programs Due to Covid-19: Perceptions, Participation and Progress for Black-Owned Small Businesses
Authors: Sledge, Ph.D. Sally
Published: July 2021

The COVID-19 virus has impacted every economic segment and demographic in the world in 2020. Especially hard hit has been small businesses, which often are working day to day to cover costs and remain profitable. In the United States, minority-owned businesses have been more severely impacted than other businesses and in particular, Black-owned businesses have experienced more negative impacts due to the pandemic when compared to their counterparts. This paper will highlight some of the issues and challenges faced by Black small businesses in response to a survey regarding the pandemic. Suggestions and recommendations will be given to assist these firms in recovery and growth.
NONEXISTENCE OF GLOBAL SOLUTIONS FOR A KIRCHHOFF-TYPE VISCOELASTIC EQUATION WITH DISTRIBUTED DELAY
Authors: YÜKSEKKAYA Hazal , PİŞKİN Erhan
Published: July 2021

In this paper, we consider a Kirchhoff-type viscoelastic equation with distributed delay and source terms. We obtain the nonexistence of global solutions under suitable conditions.
In a Dialogue with the Poet
Authors:   Saratov State L.V. Sobinov Conservatory, Korolevskaya Natalia V.
Published: July 2021

The article devoted to questions of musical and poetic synthesis raises the issue of the relationship between the composer and the poet in its special interpretation, defined as spiritual “affinity”. In Elena Gokhman’s song cycle “Insomnia” analyzed from this position, a whole range of points of contact between the artistic worlds of the poet and the composer opens up to the poems of Marina Tsvetaeva. The analysis of the musical-poetic text at the pre-musical and musical levels of its organization, in the unity of syntagmatic and paradigmatic structures, which unfold, on the one hand, as a psychological “drama of the gap”, on the other — as a metaphorical discourse in the space of the title image of the cycle, allowed us to reveal in Elena Gokhman’s “Insomnia” a hidden intertextual plan, also dating back to the work of Marina Tsvetaeva, revealing the closest contact between the creative natures of the poet and the composer. At the same time, spiritual “affinity” as it is considered reveals “flaws” of incompatibility of creative consciousnesses, which, in accordance with the etymology of the Old Slavic “co-kinship”, allows us to see the dialogue between the poet and the composer in the dynamics of rapprochements and divergences — not only moments of striking spiritual unity of artists belonging to different cultural eras,but also differences that determine the exclusive spiritual appearance of the work born in dialogue with the poet.
Metabolomic Analysis of Biosynthesis Mechanism of ε-Polylysine Produced by Streptomyces diastatochromogenes
Authors: Wang Ziyuan , Guo Fengzhu , Dong Tianyu , Tan Zhilei , Abdelraof Mohamed , Wang Zichen , Cui Jiandong , Jia Shiru
Published: July 2021

ε-Polylysine (ε-PL), a natural preservative with broad-spectrum antimicrobial activity, has been widely used as a green food additive, and it is now mainly produced by Streptomyces in industry. In the previous study, strain 6#-7 of high-yield ε-PL was obtained from the original strain TUST by mutagenesis. However, the biosynthesis mechanism of ε-PL in 6#-7 is still unclear. In this study, the metabolomic analyses of the biosynthesis mechanism of ε-PL in both strains are investigated. Results show that the difference in metabolisms between TUST and 6#-7 is significant. Based on the results of both metabolomic and enzymatic activities, a metabolic regulation mechanism of the high-yield strain is revealed. The transport and absorption capacity for glucose of 6#-7 is improved. The enzymatic activity benefits ε-PL synthesis, such as pyruvate kinase and aspartokinase, is strengthened. On the contrary, the activity of homoserine dehydrogenase in the branched-chain pathways is decreased. Meanwhile, the increase of trehalose, glutamic acid, etc. makes 6#-7 more resistant to ε-PL. Thus, the ability of the mutagenized strain 6#-7 to synthesize ε-PL is enhanced, and it can produce more ε-PLs compared with the original strain. For the first time, the metabolomic analysis of the biosynthesis mechanism of ε-PL in the high-yield strain 6#-7 is investigated, and a possible mechanism is then revealed. These findings provide a theoretical basis for further improving the production of ε-PL.
Shedding Light on the Role of Neurotransmitters in the Microenvironment of Pancreatic Cancer
Authors: Liang Yiyi , Li Huimin , Gan Yu , Tu Hong
Published: July 2021

Pancreatic cancer (PC) is a highly lethal malignancy with a 5-year survival rate of less than 8%. The fate of PC is determined not only by the malignant behavior of the cancer cells, but also by the surrounding tumor microenvironment (TME), consisting of various cellular (cancer cells, immune cells, stromal cells, endothelial cells, and neurons) and non-cellular (cytokines, neurotransmitters, and extracellular matrix) components. The pancreatic TME has the unique characteristic of exhibiting increased neural density and altered microenvironmental concentration of neurotransmitters. The neurotransmitters, produced by both neuron and non-neuronal cells, can directly regulate the biological behavior of PC cells via binding to their corresponding receptors on tumor cells and activating the intracellular downstream signals. On the other hand, the neurotransmitters can also communicate with other cellular components such as the immune cells in the TME to promote cancer growth. In this review, we will summarize the pleiotropic effects of neurotransmitters on the initiation and progression of PC, and particularly discuss the emerging mechanisms of how neurotransmitters influence the innate and adaptive immune responses in the TME in an autocrine or paracrine manner. A better understanding of the interplay between neurotransmitters and the immune cells in the TME might facilitate the development of new effective therapies for PC.
NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation in vitro
Authors: Xiang Yuting , Zhou Chuanchuan , Zeng Yanyan , Guo Qi , Huang Jiana , Wu Taibao , Liu Jiawen , Liang Qiqi , Zeng Haitao , Liang Xiaoyan
Published: July 2021

N4-acetylcytidine (ac4C), a newly identified epigenetic modification within mRNA, has been characterized as a crucial regulator of mRNA stability and translation efficiency. However, the role of ac4C during oocyte maturation, the process mainly controlled via post-transcriptional mechanisms, has not been explored. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for ac4C production in mammals and ac4C-binding proteins have not been reported yet. In this study, we have documented decreasing trends of both ac4C and NAT10 expression from immature to mature mouse oocytes. With NAT10 knockdown mediated by small interfering RNA (siRNA) in germinal vesicle (GV)-stage oocytes, ac4C modification was reduced and meiotic maturation in vitro was significantly retarded. Specifically, the rate of first polar body extrusion was significantly decreased with NAT10 knockdown (34.6%) compared to control oocytes without transfection (74.6%) and oocytes transfected with negative control siRNA (72.6%) (p < 0.001), while rates of germinal vesicle breakdown (GVBD) were not significantly different (p = 0.6531). RNA immunoprecipitation and high-throughput sequencing using HEK293T cells revealed that the modulated genes were enriched in biological processes associated with nucleosome assembly, chromatin silencing, chromatin modification and cytoskeletal anchoring. In addition, we identified TBL3 as a potential ac4C-binding protein by a bioinformatics algorithm and RNA pulldown with HEK293T cells, which may mediate downstream cellular activities. Taken together, our results suggest that NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation in vitro and TBL3 is a potential ac4C-binding protein.
Integrated Chromatin Accessibility and Transcriptome Landscapes of Doxorubicin-Resistant Breast Cancer Cells
Authors: Wang Xuelong , Yan Jizhou , Shen Baiyong , Wei Gang
Published: July 2021

Background

Doxorubicin is one of the most effective chemotherapeutic drugs for breast cancer while its common drug resistance leads to poor patient prognosis and survival. Growing evidence indicate dynamically reorganized chromatin allows rapid access of the gene regulatory machinery to open genomic regions facilitating subsequent gene expression through direct transcription factor (TF) activation and regulatory element binding.

Methods

To better understand the regulatory network underlying doxorubicin resistance in breast cancer cells, we explored the systematic alterations of chromatin accessibility and gene expression by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with RNA sequencing, followed by integrative analysis to identify potential regulators and their targets associated with differentially accessible regions (DARs) in doxorubicin-resistant MCF7 (MCF7-DR) cells.

Results

A total of 3,963 differentially expressed genes (DEGs) related to doxorubicin resistance were identified, including dramatically up-regulated MT1E, GSTP1, LDHB, significantly down-regulated TFF1, UBB, DSCAM-AS1, and histone-modifying enzyme coding genes HDAC2, EZH2, PRMT5, etc. By integrating with transcriptomic datasets, we identified 18,228 DARs in MCF7-DR cells compared to control, which were positively correlated with their nearest DEGs (r = 0.6). There were 11,686 increased chromatin-accessible regions, which were enriched in up-regulated genes related to diverse KEGG pathways, such as the cell cycle, regulation of actin cytoskeleton, signaling pathways of MAPK, PI3K/Akt and Hippo, which play essential roles in regulating cell apoptosis, proliferation, metabolism, and inflammatory responses. The 6,542 decreased chromatin-accessible regions were identified for the declined doxorubicin-associated biological processes, for instance, endocrine and insulin resistance, central carbon metabolism, signaling pathways of TGF-beta and P53. Combining data from TCGA, analyses of the DAR sequences associated with the DNA-binding motifs of significantly enriched TF families including AP-1, TEAD and FOX, indicated that the loss-function of FOXA1 might play a critical role in doxorubicin-resistant breast cancer cells (DOX-R BCCs).

Conclusion

These data exhibit the non-genetic landscape of chromatin accessibility and transcript levels in the DOX-R BCCs, and provide clear insights and resources for the detection of critical TFs and potential cis-regulatory elements-based putative therapeutic targets.
SPOP and CUL3 Modulate the Sonic Hedgehog Signal Response Through Controlled Degradation of GLI Family Transcription Factors
Authors: Umberger Patricia A. , Ogden Stacey K.
Published: July 2021

The speckle-type POZ protein (SPOP) functions as a guardian of genome integrity and controls transcriptional regulation by functioning as a substrate adaptor for CUL3/RING-type E3 ubiquitin ligase complexes. SPOP-containing CUL3 complexes target a myriad of DNA-binding proteins involved in DNA repair and gene expression, and as such, are essential modulators of cellular homeostasis. GLI transcription factors are effectors of the Hedgehog (HH) pathway, a key driver of tissue morphogenesis and post-developmental homeostasis that is commonly corrupted in cancer. CUL3-SPOP activity regulates amplitude and duration of HH transcriptional responses by controlling stability of GLI family members. SPOP and GLI co-enrich in phase separated nuclear droplets that are thought to serve as hot spots for CUL3-mediated GLI ubiquitination and degradation. A similar framework exists in Drosophila, in which the Hedgehog-induced MATH (meprin and traf homology) and BTB (bric à brac, tramtrack, broad complex) domain containing protein (HIB) targets the GLI ortholog Cubitus interruptus (Ci) for Cul3-directed proteolysis. Despite this functional conservation, the molecular mechanisms by which HIB and SPOP contribute to Drosophila and vertebrate HH signaling differ. In this mini-review we highlight similarities between the two systems and discuss evolutionary divergence in GLI/Ci targeting that informs our understanding of how the GLI transcriptional code is controlled by SPOP and CUL3 in health and disease.
Isoelectric Point of Proteins at Hydrophobic Interfaces
Authors: Lautenbach Vanessa , Hosseinpour Saman , Peukert Wolfgang
Published: July 2021

Structural and colloidal stability of proteins at different surfaces and interfaces is of great importance in many fields including medical, pharmaceutical, or material science. Due to their flexibility, proteins tend to respond to their environmental conditions and can undergo structural and conformational changes. For instance, alterations in physiological factors such as temperature, ions concentration, or pH as well as the adsorption to an interface can initiate protein aggregation. Therefore, at different surfaces and interfaces the characterization of the structural and colloidal stability of proteins, which is mainly influenced by their electrostatic and hydrophobic interactions, is of fundamental importance. In this study, we utilized sum frequency generation (SFG) spectroscopy to assess the role of solution pH on the polarity and magnitude of the electric field within the hydration shell of selected model proteins adsorbed to a hydrophobic surface. We used polystyrene (PS) as a model hydrophobic surface and determined the isoelectric point (IEP) of four structurally different model proteins. Comparing the measured IEP of proteins at the PS/solution or air/solution interface with that determined in the bulk solution via zeta potential measurement, we found significant similarities between the IEP of surface adsorbed proteins and those in the bulk aqueous phase. The pH dependence behavior of proteins was correlated to their amino acid composition and degree of hydrophobicity.
A U-Shaped Relationship Between Selenium Concentrations and All-Cause or Cardiovascular Mortality in Patients With Hypertension
Authors: Tan Qiu-hong , Huang Yu-qing , Liu Xiao-cong , Liu Lin , Lo Kenneth , Chen Ji-yan , Feng Ying-qing
Published: July 2021

Background: Given the antioxidant activity of selenium, it has been reported benefits for blood pressure control and hypertension prevention, but few studies have investigated the association between serum selenium with mortality in hypertensive population.

Methods: All participants with hypertension aged ≥18 years at baseline were recruited from the National Health and Nutritional Examination Surveys (NHANES) 2003–2004, and followed for mortality through December 31, 2015. Subjects were categorized by quartiles of serum selenium (Q1: ≤124 μg/L, Q2: 125–135 μg/L, Q3: 136–147 μg/L, Q4: ≥148 μg/L). Multivariate Cox regression were implemented to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analysis and two-piecewise linear regression were used to evaluate the relationship of serum selenium with mortality. Survival curves were used to depict cause-specific mortalities.

Results: A total of 929 participants (52.53% were male) were eligible for the current study with the average age of 63.10 ± 12.59 years. There were 307 deaths occurred including 56 cardiovascular death events during the mean follow-up time of 121.05 ± 40.85 months. A U-shaped association was observed between serum selenium and all-cause or cardiovascular mortality. In fully adjusted model, comparisons among quartiles revealed that risks of all-cause [HR (95%CI), 0.57 (0.39–0.81)] and cardiovascular death [HR (95%CI), 0.33 (0.13–0.86)] were lower in Q3. The nadir mortality of all-cause and cardiovascular was occurred at the serum selenium level of 136 μg/L and 130 μg/L, respectively.

Conclusion: Serum selenium concentration showed a U-shaped association with all-cause and cardiovascular mortality.
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure
Authors: Kerp Helena , Hönes Georg Sebastian , Tolstik Elen , Hönes-Wendland Judith , Gassen Janina , Moeller Lars Christian , Lorenz Kristina , Führer Dagmar
Published: July 2021

Purpose: Thyroid hormones (TH) play a central role for cardiac function. TH influence heart rate and cardiac contractility, and altered thyroid function is associated with increased cardiovascular morbidity and mortality. The precise role of TH in onset and progression of heart failure still requires clarification.

Methods: Chronic left ventricular pressure overload was induced in mouse hearts by transverse aortic constriction (TAC). One week after TAC, alteration of TH status was induced and the impact on cardiac disease progression was studied longitudinally over 4 weeks in mice with hypo- or hyperthyroidism and was compared to euthyroid TAC controls. Serial assessment was performed for heart function (2D M-mode echocardiography), heart morphology (weight, fibrosis, and cardiomyocyte cross-sectional area), and molecular changes in heart tissues (TH target gene expression, apoptosis, and mTOR activation) at 2 and 4 weeks.

Results: In diseased heart, subsequent TH restriction stopped progression of maladaptive cardiac hypertrophy and improved cardiac function. In contrast and compared to euthyroid TAC controls, increased TH availability after TAC propelled maladaptive cardiac growth and development of heart failure. This was accompanied by a rise in cardiomyocyte apoptosis and mTOR pathway activation.

Conclusion: This study shows, for the first time, a protective effect of TH deprivation against progression of pathological cardiac hypertrophy and development of congestive heart failure in mice with left ventricular pressure overload. Whether this also applies to the human situation needs to be determined in clinical studies and would infer a critical re-thinking of management of TH status in patients with hypertensive heart disease.
Conditional-GAN Based Data Augmentation for Deep Learning Task Classifier Improvement Using fNIRS Data
Authors: Wickramaratne Sajila D. , Mahmud Md.Shaad
Published: July 2021

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique used for mapping the functioning human cortex. fNIRS can be widely used in population studies due to the technology’s economic, non-invasive, and portable nature. fNIRS can be used for task classification, a crucial part of functioning with Brain-Computer Interfaces (BCIs). fNIRS data are multidimensional and complex, making them ideal for deep learning algorithms for classification. Deep Learning classifiers typically need a large amount of data to be appropriately trained without over-fitting. Generative networks can be used in such cases where a substantial amount of data is required. Still, the collection is complex due to various constraints. Conditional Generative Adversarial Networks (CGAN) can generate artificial samples of a specific category to improve the accuracy of the deep learning classifier when the sample size is insufficient. The proposed system uses a CGAN with a CNN classifier to enhance the accuracy through data augmentation. The system can determine whether the subject’s task is a Left Finger Tap, Right Finger Tap, or Foot Tap based on the fNIRS data patterns. The authors obtained a task classification accuracy of 96.67% for the CGAN-CNN combination.
Relationship Between Dams, Knickpoints and the Longitudinal Profile of the Upper Indus River
Authors: Zhou Liqin , Liu Weiming , Chen Xiaoqing , Wang Hao , Hu Xudong , Li Xuemei , Schwanghart Wolfgang
Published: July 2021

Mass movements in mountainous areas are capable of damming rivers and can have a lasting effect on the river longitudinal profile. The long profile is commonly used to retrieve regional tectonic information, but how much dams may compromise geomorphometry-based tectonic analysis has not been systematically researched. In this study, we investigate the relationship between river dams and the longitudinal profile of the upper Indus River basin, based on interpretation and analysis of remote sensing imagery and digital elevation models (DEMs) and local field work. We identified 178 landslide, glacier and debris flow dams. Using TopoToolbox, we automatically extracted the river longitudinal profile from the 30 m SRTM DEM, determined the location of convex knickpoints and calculated the channel steepness index. One hundred and two knickpoints were detected with heights above 148 m, of which 55 were related to dams. There is good spatial correspondence between dams, convexities in the river longitudinal profile and relatively high steepness index. Different dam types have different impacts on the river profile; on the upper Indus, debris flow dams have a greater impact than landslide and glacier dams and can form knickpoints of up to 900 m. Therefore, dams may have a significant influence on the river longitudinal profile, knickpoints and steepness index, and should be considered when extracting information on regional tectonics using these indices.
The Influence of Previous Biology Lessons on Prospective Teachers’ Beliefs About Learning Biology
Authors: Schumacher Fabian , Basten Melanie , Großschedl Jörg , Klatthaar Moritz , Wilde Matthias
Published: July 2021

Professional teaching competence is significantly influenced by beliefs about learning. Prospective teachers start their teacher training at university with quite persistent beliefs about learning processes. Beliefs about learning can be differentiated into two perspectives: beliefs about student learning and beliefs about one’s own learning. Theoretical considerations suggest that the latter influence beliefs about student learning and both perspectives are influenced by the way in which prospective teachers experienced their own lessons as pupils at school. We investigated how prospective biology teachers remembered their own biology lessons and how these experiences influenced their beliefs about learning regarding both perspectives. The sample consisted of 164 prospective biology teachers (Mage = 21.58 years, SDage = 2.5, 66.02% female) in Germany. Results of a simple mediation model indicate that previous experiences in biology lessons had an impact on both perspectives. Moreover, we found that the influence that previous lessons had on the beliefs about student learning was fully mediated by one’s beliefs about own learning processes. This suggests that experiences from one’s own schooling have an impact on how teachers view learning of their students. As implications for teacher training and future research, our findings suggest that both perspectives of beliefs need to be further taken into account and that an explicit focus on beliefs about teachers’ own learning is needed.
Analysis of IVF/ICSI Outcomes in Endometriosis Patients With Recurrent Implantation Failure: Influence on Cumulative Live Birth Rate
Authors: Zhong Chenyi , Gao Liusijie , Shu Li , Hou Zhen , Cai Lingbo , Huang Jie , Liu Jiayin , Mao Yundong
Published: July 2021

Objective

To study the influence of endometriosis activity on the pregnancy outcomes of patients with recurrent implantation failure (RIF) in in-vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles. The pregnancy outcomes were compared between RIF patients with endometriosis who received treatment at different occasions to explore the appropriate treatment plan for these patients and to optimize the pregnancy-support strategies.

Design

Ambispective cohort study.

Methods

A total of 330 patients with endometriosis were enrolled from 2008 to 2018 and included 1043 IVF/ICSI cycles. All patients were diagnosed with RIF after IVF/ICSI. Patients were assigned to three subtypes according to different control states of endometriosis, including the untreated, early-treatment, and late-treatment groups. The clinical pregnancy rate, live birth rate, and cumulative live birth rate of endometriosis patients with RIF were the main outcomes; additionally, the fertilization rate, available embryonic rate, and high-quality embryonic rate were also compared.

Results

The early-treatment and late-treatment groups showed higher cumulative live birth rate than the untreated group (early-treated 43.6% vs. late-treated 46.3% vs. untreated 27.7%, P<0.001), though patients in the two treatment groups had higher rates of adenomyosis and ovarian surgery. The two treatment group showed a better laboratory result than the untreated and especially, the early-treatment group. The untreated group (46.24%) had a lower IVF fertilization rate than the treated group (early-treated [64.40%] and late-treated [60.27%] (P<0.001). In addition, the rates of available embryos and high-quality embryos in the early-treated group were much higher those that in the untreated group (90.30% vs. 85.20%, 76.50% vs. 64.47%). Kaplan–Meier curve showed that patients in the untreated group needed a mean of 23.126 months to achieve one live birth; whereas those in the treated group needed a comparatively shorter duration (early-treated: 18.479 ± 0.882 months and late-treated: 14.183 ± 1.102 months, respectively).

Conclusion

Endometriosis has a negative influence on IVF/ICSI outcome. The control of endometriosis activity can result in a higher cumulative live birth rate in patients. It is necessary for endometriosis patients to receive medical treatment to achieve a better prognosis especially for those with RIF.
Short-Term Wind Power Forecasting Using Mixed Input Feature-Based Cascade-connected Artificial Neural Networks
Authors: Chen Qin , Folly Komla Agbenyo
Published: July 2021

Accurate short-term wind power forecasting is crucial for the efficient operation of power systems with high wind power penetration. Many forecasting approaches have been developed in the past to forecast short-term wind power. Artificial neural network-based approaches (ANNs) have become one of the most effective and popular short-term wind speed and wind power forecasting approaches in recent years. However, most researchers have used only historical data from a specific station to train the ANNs without considering meteorological variables from many neighboring stations on the forecasting performance. Using additional meteorological variables from neighboring stations can contribute valuable surrounding information to the forecasting model of the target station and improve ANNs performance. In this paper, a mixed input features-based cascade-connected artificial neural network (MIF-CANN) is used to train input features from many neighboring stations without encountering overfitting issues caused by many input features. Multiple ANNs train different combinations of input features in the first layer of the MIF-CANN model to produce preliminary results, then cascading into the second phase of the MIF-CANN model as inputs. The performance of the proposed MIF-CANN model is compared with the ANNs-based spatial correlation models. Simulation results show that the proposed MIF-CANN has better performance than the ANNs-based spatial correlation models.
Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity
Authors: Adhikari Utpal Kumar , Sakiz Elif , Zhou Xian , Habiba Umma , Kumar Sachin , Mikhael Meena , Senesi Matteo , Guang Li Chun , Guillemin Gilles J. , Ooi Lezanne , David Monique Antoinette , Collins Steven , Karl Tim , Tayebi Mourad
Published: July 2021

Background

Previous reports identified proteins associated with ‘apoptosis’ following cross-linking PrPCwith motif-specific anti-PrP antibodiesin vivoandin vitro. The molecular mechanisms underlying this IgG-mediated neurotoxicity and the role of the activated proteins in the apoptotic pathways leading to neuronal death has not been properly defined. Previous reports implicated a number of proteins, including apolipoprotein E, cytoplasmic phospholipase A2, prostaglandin and calpain with anti-PrP antibody-mediated ‘apoptosis’, however, these proteins are also known to play an important role in allergy. In this study, we investigated whether cross-linking PrPCwith anti-PrP antibodies stimulates a neuronal allergenic response.

Methods

Initially, we predicted the allergenicity of the epitope sequences associated with ‘neurotoxic’ anti-PrP antibodies using allergenicity prediction servers. We then investigated whether anti-PrP antibody treatment of mouse primary neurons (MPN), neuroblastoma cells (N2a) and microglia (N11) cell lines lead to a neuronal allergenic response.

Results

In-Silicostudies showed that both tail- and globular-epitopes were allergenic. Specifically, binding regions that contain epitopes for previously reported ‘neurotoxic’ antibodies such as ICSM18 (146-159), ICSM35 (91-110), POM 1 (138-147) and POM 3 (95-100) lead to activation of allergenic related proteins. Following direct application of anti-PrPCantibodies on N2a cells, we identified 4 neuronal allergenic-related proteins when compared with untreated cells. Furthermore, we identified 8 neuronal allergenic-related proteins following treatment of N11 cells with anti-PrPCantibodies prior to co-culture with N2a cells when compared with untreated cells. Antibody treatment of MPN or MPN co-cultured with antibody-treated N11 led to identifying 10 and 7 allergenic-related proteins when compared with untreated cells. However, comparison with 3F4 antibody treatment revealed 5 and 4 allergenic-related proteins respectively. Of importance, we showed that the allergenic effects triggered by the anti-PrP antibodies were more potent when antibody-treated microglia were co-cultured with the neuroblastoma cell line. Finally, co-culture of N2a or MPN with N11-treated with anti-PrP antibodies resulted in significant accumulation of NO and IL6 but not TNF-α in the cell culture media supernatant.

Conclusions

This study showed for the first time that anti-PrP antibody binding to PrPCtriggers a neuronal hypersensitivity response and highlights the important role of microglia in triggering an IgG-mediated neuronal hypersensitivity response. Moreover, this study provides an important impetus for including allergenic assessment of therapeutic antibodies for neurodegenerative disorders to derive safe and targeted biotherapeutics.