The Cauchy problem for a class of two-dimensional nonlocal nonlinear wave equations governing anti-plane shear motions in elastic materials

This paper is concerned with the analysis of the Cauchy problem of a general class of two-dimensional nonlinear nonlocal wave equations governing anti-plane shear motions in nonlocal elasticity. The nonlocal nature of the problem is reflected by a convolution integral in the space variables. The Fourier transform of the convolution kernel is nonnegative and satisfies a certain growth condition at infinity. For initial data in $L^{2}$ Sobolev spaces, conditions for global existence or finite time blow-up of the solutions of the Cauchy problem are established.Comment: 15 pages. "Section 6 The Anisotropic Case" added and minor changes. Accepted for publication in Nonlinearit

Tanggung Jawab Keperdataan Media Cetak terhadap Kesalahan Pemberitaan yang Mencemarkan Nama Baik Seseorang Atau Kelompok di Masyarakat

Dalam penulisan ini membahas mengenai tanggung jawab keperdataan media cetak terhadap kesalahan pemberitaan yang mencemarkan nama baik seseorang atau kelompok di masyarakat.Penulisan ini di latar belakangi oleh perkara mengenai pemberitaan dalam media cetak dimana seseorang atau kelompok di masyarakat merasa dirugikan atas pemberitaan yang dimuat oleh media cetak terkait dengan cara menggugat secara materiil dan immateriil, baik secara perdata maupun pidana sehingga menimbulkan kesalahpahaman antara penggugat dengan pihak tergugat yang merasa diri mereka yang benar. Adapun tujuan penulis mengangkat topik permasalahan ini untuk mengetahui bentuk-bentuk kesalahan pemberitaan dan pertanggung jawabnya dalam media cetak yang mencemaran nama baik seseorang atau kelompok di masyarakat.Penelitian ini merupakan jenis penelitian Yuridis Normatif dengan menggunakan beberapa pendekatan, yaitu pendekatan Perundang-undangan dengan menelaah beberapa Undang-Undang dan regulasi yang bersangkut paut dengan isu hukum yang sedang ditangani dan pendekatan kenseptual (conceptual approach). Pendekatan kasus dalam penelitian ini digunakan untuk meneliti dan membahas permasalahan berdasarkan peraturan Perundang-undangan yang berlaku yaitu pasal 1376 KUHPerdata dan Pasal 6 UU Tentang Pers No. 40 Tahun 1999 khususnya dan pasal 1365, 1367, 1372, 1380 pada umumnya.Berdasarkan hasil pembahasan, penulis memperoleh jawaban atas permasalahan yang ada yaitu mengetahui bentuk-bentuk kesalahan pemberitaan yang ditinjau dari KUHPerdata yang tidak disebutkan secara eksplisit, namun jika penulis menyimak ketentuan dan bunyi pasal 1365 KUHPerdata, maka kesalahan pemberitaan merupakan perbuatan melawan hukum. Seperti kesalahan yang dapat merugikan orang lain yaitu berita yang bersifat pencemaran nama baik, fitnah, dan dusta tersebut dapat dikategorikan sebagai bentuk-bentuk kesalahan pemberitaan.Berkaitan dengan masalah pencemaran nama baik tersebut tidak dapat diselesaikan melalui jalur jurnalistik maupun dengan UU pers, melainkan dapat diselesaikan melalui jalur pengadilan, segala kerugian dan ganti rugi baik materiil maupun immateriil dibebankan pada Perusahaan pers terdapat pada Pasal 1376KUHPdt yaitu: sebagai akibat hukum tuntutan perdata dalam hal penghinaan adalah bertujuan untuk mendapat penggantian kerugian serta pemulihan nama baik. Sedangkan di dalam UU Pers No. 40 tahun 1999 bentuk dari tanggung jawab keperdataan dalam hal terjadinya pemberitaan adalah dengan melalui Hak Jawab seperti pada Pasal 5 ayat (2) UU No. 40 tahun 1999 tentang pers, Hak jawab dapat disampaikan dengan cara tertulis maupun secara lisan.Perlunya pengaturan mengenai permasalahan pemberitaan di media cetak yang berkaitan dengan tanggung jawab keperdataannya khususnya untuk pihak media yang bersangkutan sebelum melakukan penerbitan maka terlebih dahulu melakukan wawancara dengan subyek berita disamping sumber berita, karena informasi yang diberikan secara sepihak oleh nara dumber berita kebenarannya masih diragukan dan berita tersebut bisa disebut sebagai penghinaan atau fitnah, agar visi dan misinya terpenuhi sehingga media yang menyebarkan informasi mencerdaskan masyarakat dan tidak membodohi masyarakat. Dan sebagai pembuat kebijakan pemerintah diharuskan untuk memperhatikan pelaksanaan UU Pers dengan KUHPdt, penerapannya tidak rancu dalam memutuskan suatu perkara pers di pengadilan.Kata kunci: Tanggung jawab keperdataan, Media cetak, Penghinaan (defamation) dan pencemaran nama baik

Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages [RAW264.7 makrofajlarında lipotoksik endoplazmik retikulum stres s�recinde ifadesi değişen mikroRNAların tanımlanması]

Objective: Increased fatty acids in the circulation and their accumulation in non-adipose tissues play a significant role in the development of obesity related metabolic and inflammatory disorders such as insulin resistance, diabetes and atherosclerosis. While fat tissue has the ability to store excess fatty acids, uptake of excess fatty acids to other tissues burdens intracellular metabolic organelles such as mitochondria and endoplasmic reticulum (ER), leading to stress response and lipotoxic cell death. Unfolded protein response (UPR) is a key adaptation of the ER to stress. It is still not completely clear how lipids engage the UPR and how UPR manages both the adaptive and destructive consequences under its control. Increasing evidence point to the importance of miRNA regulation of the UPR as well as UPR’s role in miRNA biogenesis. In order to understand how lipids engage the UPR, we set forth to identify microRNAs regulated by lipotoxic ER stress in macrophages. Methods: We stressed the mouse macrophage cell line (RAW 264.7) with a saturated fatty acid, 500μM palmitate, reflecting the levels found in the circulation of obese patients. We analyzed the microRNAome profiles of this cell line using QRT-PCR based miScript miRNA PCR array which contained all known mouse microRNAs in miRBase release16 and performed pathway analysis for potential targets. Results: 227 microRNAs showed altered expression levels; 43 microRNAs above 2 fold difference and 13 microRNAs 3-24 fold difference. Pathway analysis enriched the target mRNAs of these lipotoxic ER stress associated miRNAs. Conclusion: When exposed to high concentrations of saturated fatty acids that can induce ER stress, macrophages display a dynamic range of changes in their microRNAome profiles. Our findings reflect the consequences of lipotoxic stress on circulating monocytes and tissue-associated macrophages in obesity. Further studies are needed to deliniate which UPR arm is reponsible for the microRNA changes reported here. � 2016, Turkish Biochemistry Society. All rights reserved

Macrophage mal1 deficiency suppresses atherosclerosis in low-density lipoprotein receptor-null mice by activating peroxisome proliferator-activated receptor-γ-regulated genes

Objective- The adipocyte/macrophage fatty acid-binding proteins aP2 (FABP4) and Mal1 (FABP5) are intracellular lipid chaperones that modulate systemic glucose metabolism, insulin sensitivity, and atherosclerosis. Combined deficiency of aP2 and Mal1 has been shown to reduce the development of atherosclerosis, but the independent role of macrophage Mal1 expression in atherogenesis remains unclear. Methods and Results- We transplanted wild-type (WT), Mal1, or aP2 bone marrow into low-density lipoprotein receptor-null (LDLR) mice and fed them a Western diet for 8 weeks. Mal1→LDLR mice had significantly reduced (36%) atherosclerosis in the proximal aorta compared with control WT→LDLR mice. Interestingly, peritoneal macrophages isolated from Mal1-deficient mice displayed increased peroxisome proliferator-activated receptor-γ (PPARγ) activity and upregulation of a PPARγ-related cholesterol trafficking gene, CD36. Mal1 macrophages showed suppression of inflammatory genes, such as COX2 and interleukin 6. Mal1→LDLR mice had significantly decreased macrophage numbers in the aortic atherosclerotic lesions compared with WT→LDLR mice, suggesting that monocyte recruitment may be impaired. Indeed, blood monocytes isolated from Mal1→LDLR mice on a high-fat diet had decreased CC chemokine receptor 2 gene and protein expression levels compared with WT monocytes. Conclusion- Taken together, our results demonstrate that Mal1 plays a proatherogenic role by suppressing PPARγ activity, which increases expression of CC chemokine receptor 2 by monocytes, promoting their recruitment to atherosclerotic lesions. © 2011 American Heart Association, Inc

Feasibility and diagnostic reliability of quantitative flow ratio in the assessment of non-culprit lesions in acute coronary syndrome

Several studies have demonstrated the feasibility and safety of hemodynamic assessment of non-culprit coronary arteries in setting of acute coronary syndromes (ACS) using fractional flow reserve (FFR) measurements. Quantitative flow ratio (QFR), recently introduced as angiography-based fast FFR computation, has been validated with good agreement and diagnostic performance with FFR in chronic coronary syndromes. The aim of this study was to assess the feasibility and diagnostic reliability of QFR assessment during primary PCI. A total of 321 patients with ACS and multivessel disease, who underwent primary PCI and were planned for staged PCI of at least one non-culprit lesion were enrolled in the analysis. Within this patient cohort, serial post-hoc QFR analyses of 513 non-culprit vessels were performed. The median time interval between primary and staged PCI was 49 [42-58] days. QFR in non-culprit coronary arteries did not change between acute and staged measurements (0.86 vs 0.87, p = 0.114), with strong correlation (r = 0.94, p ≤ 0.001) and good agreement (mean difference -0.008, 95%CI -0.013-0.003) between measurements. Importantly, QFR as assessed at index procedure had sensitivity of 95.02%, specificity of 93.59% and diagnostic accuracy of 94.15% in prediction of QFR ≤ 0.80 at the time of staged PCI. The present study for the first time confirmed the feasibility and diagnostic accuracy of non-culprit coronary artery QFR during index procedure for ACS. These results support QFR as valuable tool in patients with ACS to detect further hemodynamic relevant lesions with excellent diagnostic performance and therefore to guide further revascularisation therapy

Macrophage Mal1 Deficiency Suppresses Atherosclerosis in Low-Density Lipoprotein Receptor -Null Mice by Activating Peroxisome Proliferator-Activated Receptor-g-Regulated Genes

Cataloged from PDF version of article.Objective-The adipocyte/macrophage fatty acid-binding proteins aP2 (FABP4) and Mal1 (FABP5) are intracellular lipid chaperones that modulate systemic glucose metabolism, insulin sensitivity, and atherosclerosis. Combined deficiency of aP2 and Mal1 has been shown to reduce the development of atherosclerosis, but the independent role of macrophage Mal1 expression in atherogenesis remains unclear. Methods and Results-We transplanted wild-type (WT), Mal1(-/-), or aP2(-/-) bone marrow into low-density lipoprotein receptor-null (LDLR(-/-)) mice and fed them a Western diet for 8 weeks. Mal1(-/-)-> LDLR(-/-) mice had significantly reduced (36%) atherosclerosis in the proximal aorta compared with control WT -> LDLR(-/-) mice. Interestingly, peritoneal macrophages isolated from Mal1-deficient mice displayed increased peroxisome proliferator-activated receptor-gamma (PPAR gamma) activity and upregulation of a PPAR gamma-related cholesterol trafficking gene, CD36. Mal1(-/-) macrophages showed suppression of inflammatory genes, such as COX2 and interleukin 6. Mal1(-/-)-> LDLR(-/-) mice had significantly decreased macrophage numbers in the aortic atherosclerotic lesions compared with WT -> LDLR(-/-) mice, suggesting that monocyte recruitment may be impaired. Indeed, blood monocytes isolated from Mal1(-/-)-> LDLR(-/-) mice on a high-fat diet had decreased CC chemokine receptor 2 gene and protein expression levels compared with WT monocytes. Conclusion-Taken together, our results demonstrate that Mal1 plays a proatherogenic role by suppressing PPAR gamma activity, which increases expression of CC chemokine receptor 2 by monocytes, promoting their recruitment to atherosclerotic lesions. (Arterioscler Thromb Vasc Biol. 2011;31:1283-1290.

Jnk1 deficiency in hematopoietic cells suppresses macrophage apoptosis and increases atherosclerosis in low-density lipoprotein receptor null mice

Objective - The c-Jun NH 2 -terminal kinases (JNK) are regulated by a wide variety of cellular stresses and have been implicated in apoptotic signaling. Macrophages express 2 JNK isoforms, JNK1 and JNK2, which may have different effects on cell survival and atherosclerosis. Approach and Results - To dissect the effect of macrophage JNK1 and JNK2 on early atherosclerosis, Ldlr-/- mice were reconstituted with wild-type, Jnk1-/-, and Jnk2-/- hematopoietic cells and fed a high cholesterol diet. Jnk1-/- →Ldlr-/- mice have larger atherosclerotic lesions with more macrophages and fewer apoptotic cells than mice transplanted with wild-type or Jnk2-/- cells. Moreover, genetic ablation of JNK to a single allele (Jnk1+/- /Jnk2-/- or Jnk1-/- /Jnk2+/-) in marrow of Ldlr-/- recipients further increased atherosclerosis compared with Jnk1-/- →Ldlr-/- and wild-type→Ldlr-/- mice. In mouse macrophages, anisomycin-mediated JNK signaling antagonized Akt activity, and loss of Jnk1 gene obliterated this effect. Similarly, pharmacological inhibition of JNK1, but not JNK2, markedly reduced the antagonizing effect of JNK on Akt activity. Prolonged JNK signaling in the setting of endoplasmic reticulum stress gradually extinguished Akt and Bad activity in wild-type cells with markedly less effects in Jnk1-/- macrophages, which were also more resistant to apoptosis. Consequently, anisomycin increased and JNK1 inhibitors suppressed endoplasmic reticulum stress-mediated apoptosis in macrophages. We also found that genetic and pharmacological inhibition of phosphatase and tensin homolog abolished the JNK-mediated effects on Akt activity, indicating that phosphatase and tensin homolog mediates crosstalk between these pathways. Conclusions - Loss of Jnk1, but not Jnk2, in macrophages protects them from apoptosis, increasing cell survival, and this accelerates early atherosclerosis. © 2016 American Heart Association, Inc

Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon

The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d(-1) at days 2 and 3 of the culture, increasing to 66% d(-1) at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells (IGFBP5.1 and 5.2, IGFBP-6, IGFBP-rP1, IGFBP-2.2 and IGF-II), the initial proliferation phase (IGF-I, IGFBP-4, FGF2 and IGF-IRb) and terminal differentiation and myotube production (IGF2R, IGF-IRa). In cells starved of amino acids and serum for 72 h, IGF-I mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in IGF-I mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism. IGF-II, IGFBP-5.1 and IGFBP-5.2 expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of IGFBP5.2 and IGFBP-4, but not IGFBP5.1 were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated IGFBP-6 expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.Publisher PDFPeer reviewe

Targeting IRE1 with small molecules counteracts progression of atherosclerosis

Metaflammation, an atypical, metabolically induced, chronic lowgrade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ERresident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1β and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis