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Claes Forssell,Niclas Bjarnegård,Fredrik H. Nyström 대한혈관외과학회 2020 Vascular Specialist International Vol.36 No.3
Purpose: Cryoablation, which induces cellular death without extensive tissue damage, has been extensively used to denervate the myocardium. However, periadventitial external circumferential application of cryotherapy to denervate the renal artery sympathetic nerves has, to our knowledge, never been tested in humans. The main aim of this study was to examine the safety and potential effects of cryotherapy on ambulatory blood pressure levels and other outcomes that are indirectly related to sympathetic tone, including pulse-wave velocity, central pulse pressure, and glucose levels. Materials and Methods: Five patients who underwent the denervation of the renal arteries during open surgery of the abdominal aortic aneurysm and four controls who did not undergo denervation during the surgery were enrolled. An argonpowered cryotherapy catheter (Cardioblate; Medtronic Inc., USA) was applied periadventitially to each renal artery in the five patients and then activated by infusion with liquid nitrogen for 1 minute. Results: No cryoablation-related complications occurred in the five consecutive patients. Their ambulatory blood pressures 3 to 5 months after surgery did not demonstrate any general blood pressure-reducing effects, but two patients responded favorably with the reduction of antihypertensive medication and decreased 24-hour blood pressure. The patients’ mean HbA1C levels decreased from 5.9±0.78% to 5.6±0.71% (P=0.042). Conclusion: This pilot study suggests that periadventitial cryoablation during open surgery can be used in the study of renal denervation in humans, as it had no complications in five patients in this study. The effectiveness of cryoablation for treating hypertension should be proven in a phase II clinical trial.
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Elien Claes,Chris Heim,Bart Vanreusel,Hanne Vandermeerschen,Jeroen Scheerder 글로벌지식마케팅경영학회 2020 Journal of Global Sport Management Vol.5 No.3
In this study, local networks surrounding the 11 homeless teams of the Belgian Homeless Football Cup (BHFC), a social football project for socially excluded homeless people, are analyzed from an organizational social capital perspective. Semi-structured interviews with key representatives within the local networks (including social, football, and government-related partners) were conducted. An organizational analysis is performed to explore the composition of the different networks, and to identify significant actors. Facilitating and constraining circumstances in sport for social change projects, like the BHFC, are examined. The features and conditions of the networks revealed in this study are of relevance for field workers and policy-makers and can be key factors for the management of sport for social change projects. This knowledge contributes to the sustainability and stability of the networks, and of the projects for social change in which these networks are embedded.
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Dursun Hakan,Claes Ellen,Agirdag Orhan 한국다문화교육학회 2021 Multicultural Education Review Vol.13 No.4
Previous work on multicultural teaching competence has mainly focused on teachers’ beliefs and attitudes towards ethnocultural diversity. Little attention has been paid to examine the nature of teachers’ ethnocultural diversity knowledge. Drawing upon Shulman’s model of pedagogical content knowledge, this study presents a novel theoretical framework and a performance-based assessment for examining teachers’ ethnocultural diversity knowledge. We collected data from 819 preservice teachers across six teacher education programmes in Belgium, Flanders. Our findings indicate that student teachers in Flanders have limited and low levels of cultural diversity knowledge and there is a significant variation between the mean scores of teacher education programmes. We conclude by arguing that teacher education institutions should make meaningful reforms to develop student teachers’ knowledge base regarding ethnocultural diversity.
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박규상,Andreas Wiederkehr,Claes B. Wollheim 대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.1
Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal β-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus- driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN- Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.
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Park, Kyu-Sang,Wiederkehr, Andreas,Wollheim, Claes B. The Korean Society of Pharmacology 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.1
Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal ${\beta}$-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.
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Practical Aspects of Instantaneous Magnetization Power Functions of Silicon Iron Laminations
Pfützner Helmut,Shilyashki Georgi,Bengtsson Claes,Huber Emanuel 대한전기학회 2023 Journal of Electrical Engineering & Technology Vol.18 No.2
Magnetic energy loss P of SiFe steel represents a key factor for the efficiency of soft magnetic machine cores. Traditionally, they are operated with 50 Hz (or 60 Hz), a frequency value that yields rather balanced portions of hysteresis loss and eddy current loss. In equivalent circuits of transformers, P tends to be represented by a magnetic power resistance RM, as a constant. For the most important case of sinusoidal induction B of 50 Hz, this would correspond to an instantaneous magnetization power function p(t) that is sinusoidal as well, however, with 100 Hz (or 120 Hz). On the other hand, from complex, non-linear mechanisms of hysteresis, it is obvious that p(t) should be strongly non-sinusoidal, even for exactly sinusoidal B(t). So far, almost all corresponding instantaneous investigations were restricted to calculated modelling of loss portions and transient modelling. On the other hand, for the first time, the present study was focussed on functions p(t) as measured at IEC-standardized samples of industrially relevant steel. Practical evaluations are discussed with respect to the revealed “history” of magnetization processes, as well as for product characterization. For these tasks, a novel digitized “Low-mass Single Sheet Tester” was developed that was applied for both non-oriented steel (NO) and grain-oriented steel (GO), for 50 Hz. Interpretations proved to be favoured by relating p(t) to total P, according to an instantaneous power ratio. As a result, both steel types revealed strongly non-sinusoidal power functions, with short durations of negative p. Negative p proved to be most pronounced for NO steel, as a measure for the onset of reversible turns of atomic moments. As a consequence, p(t) comprises strong upper harmonics of 200 Hz and even 300 Hz. Based on theoretical considerations, we split p(t) in a dissipative loss power function pL(t) and in a potential energy power function pP(t). Finally, we used p(t) to determine the corresponding power resistance RM(t) that proves to be a distinctly nonlinear function as well. It resembles a rectified co-sinus, also exhibiting short negative spikes that reflect the crystallographic dis-orientation of the polycrystalline material.
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Integrative epigenomic and genomic analysis of malignant pheochromocytoma
Johanna Sandgren,Robin Andersson,Alvaro Rada-Iglesias,Stefan Enroth,Jan Komorowski,Claes Wadelius,Göran Åkerström,Jan P. Dumanski,Gunnar Westin 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.7
Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology,and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla,indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9,PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1,IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.
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Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes
Luong Dai Ly,Shanhua Xu,최성경,하채명,THOUDAMTHEMIS,차승규,Andreas Wiederkehr,Claes B. Wollheim,이인규,박규상 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca2+ release and thereby deplete ER Ca2+ stores. The resulting ER Ca2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca2+ release, cytosolic and mitochondrial matrix Ca2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca2+ depletion mediate persistent Ca2+ influx, further impairing cytosolic and mitochondrial Ca2+ homeostasis. Mitochondrial Ca2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.
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