21 research outputs found

    TAX, TUNNELING ACTIVITIES, CORPORATE GOVERNANCE AND TRANSFER PRICING DECISION

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    Multinational firms consider several factors to decide transfer prices in a-related party transaction. The Purpose of this study was to determine the effect of tax, tunneling activities, and corporate governance on transfer pricing with cash holding as mediating variable. This research used a quantitative approach and panel data analysis by taking data samples from 53 manufacturing companies listed on the IDX in 2013-2019, which met the research criteria as previously set. The result stated that tunneling activities and corporate governance have a significant positive effect on transfer pricing, while the tax has negative effect on transfer pricing. Tax, tunneling activities and corporate governance has no effect on cash holding. Thus, the effect of cash holding cannot intervene the effect of tax, tunneling activities and corporate governance on transfer pricing. In the future, tax authority can narrow the scope of transfer pricing investigation by examinating elements in financial report.  Keywords: cash holding; corporate governance; transfer pricing; tax; tunneling activitie

    Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

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    AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

    Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

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    Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

    Penerapan Metode Story Telling Untuk Melatih Keterampilan Berbicara Mahasiswa Prodi Pendidikan Bahasa Mandarin Angkatan 2016 Universitas Negeri Malang

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    ABSTRAKPurnama, Vara Dina Citra. 2018. Penerapan Metode Story Telling untuk Melatih Keterampilan Berbicara Mahasiswa Prodi Pendidikan Bahasa Mandarin Angkatan 2016 Universitas Negeri Malang. Skripsi, Jurusan Sastra Jerman. Fakultas Sastra, Universitas Negeri Malang. Pembimbing: (I) Dr. Herri Akhmad. B., M. A., M. Hum.Kata Kunci: story telling, keterampilan berbicara, bahasa MandarinPenelitian ini didasarkan pada latar belakang metode pembelajaran bahasa Mandarin di Universitas Negeri Malang masih monoton, yaitu dengan cara menghafalkan kalimat sama persis dengan cerita atau bacaan. Story telling dipilih untuk dijadikan alternatif pembelajaran bahasa di kelas, dengan bercerita mahasiswa tidak harus menghafal. Akan tetapi, mahasiswa dapat bercerita dengan gaya bahasa mereka sendiri. Penelitian ini dilaksanakan dengan tujuan mendeskipsikan beberapa hal, yang mencakup penerapan metode story telling untuk melatih keterampilan berbicara dan respon mahasiswa Prodi Pendidikan Bahasa Mandarin angkatan 2016 terhadap penerapan metode story telling.Metode yang digunakan dalam penelitian ini adalah metode deskriptif kualitatif. Teknik pengumpulan data dilakukan dengan cara observasi, wawancara dan tes lisan. Hasil data yang sudah dikumpulkan kemudian dianalisis dan dipaparkan dalam bentuk kata-kata. Selain itu, didapatkan data lain berbentuk gambar/foto dan rekaman hasil tes lisan mahasiswa. Data berbentuk angka dari tes lisan mahasiswa hanya sebagai data pendukung dalam penelitian.Berdasarkan hasil data tersebut, diperoleh enam simpulan sebagai berikut. Pertama, mahasiswa terlihat aktif dan antusias selama proses penelitian dilaksanakan. Kedua, mahasiswa berebut maju ke depan kelas untuk bercerita. Ketiga, masih ditemukan beberapa mahasiswa yang kurang tepat dalam menyusun kalimat. Keempat, mahasiswa bercerita dengan gaya bahasa mereka sendiri dengan kalimat yang lebih sederhana dan lebih mudah dipahami. Selain itu, mereka juga kreatif dalam menyusun cerita dengan menambahkan simpulan, nasihat atau pepatah diakhir cerita. Kelima, penerapan metode story telling dapat melatih keterampilan berbicara bahasa Mandarin mahasiswa. Tidak hanya itu, story telling juga dapat dijadikan sebagai alternatif pembelajaran bahasa. Keenam, setelah diterapkan metode story telling mahasiswa terlihat lebih percaya diri berbicara bahasa Mandarin di depan kelas

    TAX, TUNNELING ACTIVITIES, CORPORATE GOVERNANCE AND TRANSFER PRICING DECISION

    No full text
    Multinational firms consider several factors to decide transfer prices in a-related party transaction. The Purpose of this study was to determine the effect of tax, tunneling activities, and corporate governance on transfer pricing with cash holding as mediating variable. This research used a quantitative approach and panel data analysis by taking data samples from 53 manufacturing companies listed on the IDX in 2013-2019, which met the research criteria as previously set. The result stated that tunneling activities and corporate governance have a significant positive effect on transfer pricing, while the tax has negative effect on transfer pricing. Tax, tunneling activities and corporate governance has no effect on cash holding. Thus, the effect of cash holding cannot intervene the effect of tax, tunneling activities and corporate governance on transfer pricing. In the future, tax authority can narrow the scope of transfer pricing investigation by examinating elements in financial report.  Keywords: cash holding; corporate governance; transfer pricing; tax; tunneling activitie

    A novel flow cytometry assay using dihydroethidium as redox-sensitive probe reveals NADPH oxidase-dependent generation of superoxide anion in human platelets exposed to amyloid peptide β

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    Reactive oxygen species (ROS) generation is critical in the regulation of platelets, which has important implications in the modulation of hemostasis and thrombosis. Nonetheless, despite several assays have been described and successfully utilized in the past, the analysis of ROS generation in human platelets remains challenging. Here we show that dihydroethidium (DHE) allows the characterization of redox responses upon platelet activation by physiological and pathological stimuli. In particular, the flow cytometry assay that we describe here allowed us to confirm that thrombin, collagen-related peptide (CRP) and arachidonic acid but not adenosine diphosphate (ADP) stimulate superoxide anion formation in a concentration-dependent manner. 0.1unit/ml thrombin, 3 μg/ml CRP and 30 μM arachidonic acid are commonly used to stimulate platelets in vitro and here were shown to stimulate a significant increase in superoxide anion formation. The ROS scavenger N-acetylcysteine (NAC) abolished superoxide anion generation in response to all tested stimuli, but the pan-NADPH oxidase (NOX) inhibitor VAS2870 only inhibited superoxide anion formation in response to thrombin and CRP. The involvement of NOXs in thrombin and CRP-dependent responses was confirmed by the inhibition of platelet aggregation induced by these stimuli by VAS2870, while platelet aggregation in response to arachidonic acid was insensitive to this inhibitor. In addition, the pathological platelet stimulus amyloid β (Aβ) 1–42 peptide induced superoxide anion formation in a concentration-dependent manner. Aβ peptide stimulated superoxide anion formation in a NOX-dependent manner, as proved by the use of VAS2870. Aβ 1–42 peptide displayed only moderate activity as an aggregation stimulus, but was able to significantly potentiate platelet aggregation in response to submaximal agonists concentrations, such as 0.03 unit/ml thrombin and 10 μM arachidonic acid. The inhibition of NOXs by 10 μM VAS2870 abolished Aβ-dependent potentiation of platelet aggregation in response to 10 μM arachidonic acid, suggesting that the pro-thrombotic activity of Aβ peptides depends on NOX activity. Similar experiments could not be performed with thrombin or collagen, as NOXs are required for the signaling induced by these stimuli. These findings shed some new light on the pro-thrombotic activity of Aβ peptides. In summary, here we describe a novel and reliable assay for the detection of superoxide anion in human platelets. This is particularly important for the investigation of the pathophysiological role of redox stress in platelets, a field of research of increasing importance, but hindered by the absence of a reliable and easily accessible ROS detection methodology applicable to platelets

    Pengaruh Edukasi Audiovisual Terhadap Pengetahuan dan Motivasi Antenatal Care Ibu Hamil Risiko Tinggi di Kecamatan Singosari dan Pakis Kabupaten Malang selama pandemi COVID-19

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    Kehamilan risiko tinggi menjadi salah satu faktor penyebab naiknya jumlah Angka Kematian pada Ibu (AKI) di Indonesia. Kunjungan Antenatal Care adalah salah satu faktor yang dapat mencegah permasalahan tersebut. Namun, situasi pandemi COVID-19 menyebabkan berbagai pembatasan pelayanan sehingga terjadi penurunan Antenatal Care sebab kurangnya pengetahuan dan motivasi. Pemberian edukasi dengan media audio visual dalam masa pandemi COVID-19 dirasa sangat untuk efektif untuk menjadi solusi, sebab media audio visual lebih cepat dan mudah untuk dipahami dibandingkan dengan media visual. Tujuan penelitian ini untuk mengetahui pengaruh edukasi audio visual terhadap pengetahuan dan motivasi pada Ibu hamil risiko tinggi di Kecamatan Singosari dan Pakis Kabupaten Malang. Model penelitian ini adalah penelitian kuantitatif dengan quasi eksperimental pre-posttest with control group non-equivalent design, jumlah sampel yang diambil sebanyak 40 Ibu hamil risiko tinggi di Kecamatan Singosari dan Pakis Kabupaten Malang. Hasil penelitian menunjukkan adanya peningkatan yang signifikan pada pengetahuan dan motivasi kelompok intervensi. Analisis data yang digunakan pada pengetahuan juga motivasi adalah menggunakan Uji Wilcoxon (p=0,000; α=0,05) untuk pengetahuan dan (p=0,011; α=0,05) untuk motivasi, dan dengan Uji Mann-Whitney didapatkan perbedaan pengetahuan dan motivasi antara sebelum dan sesudah diberikan edukasi audio visual dengan edukasi visual (p=0,002; α=0,05) untuk pengetahuan dan (p=0,000; α=0,05) untuk motivasi. Kesimpulan terdapat pengaruh edukasi audio visual terhadap pengetahuan dan motivasi kunjungan Antenatal Care pada Ibu hamil risiko tinggi

    Diabetes and thrombosis: a central role for vascular oxidative stress

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    Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes. Diabetes patients display a significant increase in the risk of developing cardiovascular disease compared to the rest of the population. This is associated with increased blood clotting, which results in circulatory complications and vascular damage. Platelets are circulating cells within the vascular system that contribute to hemostasis. Their increased tendency to activate and form thrombi has been observed in diabetes mellitus patients (i.e., platelet hyperactivity). The oxidative damage of platelets and the function of pro-oxidant enzymes such as the NADPH oxidases appear central to diabetes-dependent platelet hyperactivity. In addition to platelet hyperactivity, endothelial cell damage and alterations of the coagulation response also participate in the vascular damage associated with diabetes. Here, we present an updated interpretation of the molecular mechanisms underlying vascular damage in diabetes, including current therapeutic options for its control
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