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1.
Nat Commun ; 15(1): 3990, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734685

ABSTRACT

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

2.
Phys Rev Lett ; 126(12): 125001, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33834790

ABSTRACT

Predictive 3D optimization reveals a novel approach to modify a nonaxisymmetric magnetic perturbation to be entirely harmless for tokamaks, by essentially restoring quasisymmetry in perturbed particle orbits as much as possible. Such a quasisymmetric magnetic perturbation (QSMP) has been designed and successfully tested in the KSTAR and DIII-D tokamaks, demonstrating no performance degradation despite the large overall amplitudes of nonaxisymmetric fields and strong response otherwise expected in the tested plasmas. The results indicate that a quasisymmetric optimization is a robust path of error field correction across the resonant and nonresonant field spectrum in a tokamak, leveraging the prevailing concept of quasisymmetry for general 3D plasma confinement systems such as stellarators. The optimization becomes, in fact, a simple eigenvalue problem to the so-called torque response matrices if a perturbed equilibrium is calculated consistent with nonaxisymmetric neoclassical transport.

3.
Phys Rev Lett ; 119(20): 205001, 2017 Nov 17.
Article in English | MEDLINE | ID: mdl-29219375

ABSTRACT

The propagation dynamics of resonant magnetic perturbation fields in KSTAR H-mode plasmas with injection of small edge perturbations produced by a supersonic molecular beam injection is reported for the first time. The results show that the perturbation field first excites a plasma response on the q=3 magnetic surface and then propagates inward to the q=2 surface with a radially averaged propagation velocity of resonant magnetic perturbations field equal to 32.5 m/ s. As a result, the perturbation field brakes the toroidal rotation on the q=3 surface first causing a momentum transport perturbation that propagates both inward and outward. A higher density fluctuation level is observed. The propagation velocity of the resonant magnetic perturbations field is larger than the radial propagation velocity of the perturbation in the toroidal rotation.

4.
Eur Rev Med Pharmacol Sci ; 21(4): 890-899, 2017 02.
Article in English | MEDLINE | ID: mdl-28272690

ABSTRACT

OBJECTIVE: Nephrotoxicity is one of the major side effects that limit the use of cisplatin in cancer therapy. Cisplatin-induced apoptosis in renal cells is associated with reactive oxygen species (ROS)-mediated p53 activation. Licorice (Glycyrrhiza uralensis Fischer) is one of the most widely used medicinal herbs in Korea, China and Japan. The aim of the study was to evaluate the protective effects of licorice extract (LE) and its active compound glycyrrhizic acid (GA) against cisplatin-induced nephrotoxicity in human renal proximal tubular epithelial (HK-2) cells. MATERIALS AND METHODS: HK-2 cells were pretreated with LE or GA for 1 h and then treated with 40 µM of cisplatin for indicated times under the serum-free condition. Cell viability was evaluated by MTT assay. Apoptosis was evaluated by flow cytometric analysis and caspase-3 activity. The intracellular ROS levels were determined by DCFH-DA assay. The expression and phosphorylation levels of protein were evaluated by Western blot and densitometry analysis. RESULTS: When treating HK-2 cells with LE or GA, both of them alleviated cisplatin-induced cytotoxicity and apoptosis. LE and GA inhibited caspase-3 activity and polymerase (PARP) cleavage in cisplatin-treated cells. LE and GA also inhibited p53 expression and its phosphorylation as well as ROS production in cells exposed to cisplatin. Meanwhile, LE and GA enhanced cisplatin-induced p21 expression, which then led to S-phase arrest in cell cycle and limited cell growth. Presumably, increased p21 expression may contribute to cellular prevention from cisplatin-induced apoptosis, because p21 is the key molecule to cytoprotection during cisplatin-induced nephrotoxicity. CONCLUSIONS: These results suggest that LE and GA ameliorate cisplatin-induced apoptosis through reduction of ROS-mediating p53 activation and promotion of p21 expression in HK-2 cells.


Subject(s)
Cisplatin/adverse effects , Epithelial Cells/drug effects , Glycyrrhizic Acid/pharmacology , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Antineoplastic Agents/adverse effects , Apoptosis/drug effects , Cell Line , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Epithelial Cells/metabolism , Glycyrrhiza/chemistry , Humans , Kidney Tubules, Proximal/cytology , Tumor Suppressor Protein p53/metabolism
5.
Rev Sci Instrum ; 85(11): 11D407, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25430170

ABSTRACT

In the KSTAR Tokamak, a "Tangential Thomson Scattering" (TTS) diagnostic system has been designed and installed to measure electron density and temperature profiles. In the edge system, TTS has 12 optical fiber bundles to measure the edge profiles with 10-15 mm spatial resolution. These 12 optical fibers and their spatial resolution are not enough to measure the pedestal width with a high accuracy but allow observations of L-H transition or H-L transitions at the edge. For these measurements, the prototype ITER edge Thomson Nd:YAG laser system manufactured by JAEA in Japan is installed. In this paper, the KSTAR TTS system is briefly described and some TTS edge profiles are presented and compared against the KSTAR Charge Exchange Spectroscopy and other diagnostics. The future upgrade plan of the system is also discussed in this paper.

6.
Rev Sci Instrum ; 85(11): 11E413, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25430320

ABSTRACT

Measuring rotation profiles with a reliable spatial resolution is one of the critical diagnostics in understanding the plasma behavior especially for the edge transport. In the KSTAR experiments, it has been consistently observed from the charge exchange spectroscopy measurements that the magnetic perturbations not only suppresses edge localized modes (ELMs) but also reduces toroidal rotations. In this paper, toroidal velocities of the carbon impurity and their profile evolutions during ELMy and ELM-suppressed phases are presented. The rotation profiles are shown to collapse immediately after an ELM burst and continue to build up until the next burst that accompanies another collapse. Toroidal rotations following the resonant magnetic perturbations applications are observed to be reduced along with the ELMs suppressed.

7.
Phys Rev Lett ; 111(9): 095002, 2013 Aug 30.
Article in English | MEDLINE | ID: mdl-24033042

ABSTRACT

One of the important rotational resonances in nonaxisymmetric neoclassical transport has been experimentally validated in the KSTAR tokamak by applying highly nonresonant n=1 magnetic perturbations to rapidly rotating plasmas. These so-called bounce-harmonic resonances are expected to occur in the presence of magnetic braking perturbations when the toroidal rotation is fast enough to resonate with periodic parallel motions of trapped particles. The predicted and observed resonant peak along with the toroidal rotation implies that the toroidal rotation in tokamaks can be controlled naturally in favorable conditions to stability, using nonaxisymmetric magnetic perturbations.

8.
Phys Rev Lett ; 109(14): 145003, 2012 Oct 05.
Article in English | MEDLINE | ID: mdl-23083252

ABSTRACT

Dual (or sometimes multiple) flux tubes (DFTs) have been observed in the core of sawtoothing KSTAR tokamak plasmas with electron cyclotron resonance heating. The time evolution of the flux tubes visualized by a 2D electron cyclotron emission imaging diagnostic typically consists of four distinctive phases: (1) growth of one flux tube out of multiple small flux tubes during the initial buildup period following a sawtooth crash, resulting in a single dominant flux tube along the m/n=1/1 helical magnetic field lines, (2) sudden rapid growth of another flux tube via a fast heat transfer from the first one, resulting in approximately identical DFTs, (3) coalescence of the two flux tubes into a single m/n=1/1 flux tube resembling the internal kink mode in the normal sawteeth, which is explained by a model of two current-carrying wires confined on a flux surface, and (4) fast localized crash of the merged flux tube similar to the standard sawtooth crash. The dynamics of the DFTs implies that the internal kink mode is not a unique prerequisite to the sawtooth crash, providing a new insight on the control of the sawtooth.

9.
Eur Phys J E Soft Matter ; 35(9): 86, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22972228

ABSTRACT

Using self-consistent field theory (SCFT), morphology development in symmetric linear ABC triblock copolymer films on neutral and selective substrates has been studied, and it is compared with the triblock copolymer morphologies in bulk. In particular, the effects of the substrate preferable to B (interior) block on nanopattern formation of the copolymer films are of our central interest. Here, we report various nanopatterns with tunable square morphologies. The domain patterns are much more diverse than those parallel to the substrate with substrate selectivity for end-block or those vertical to the substrate without substrate selectivity. Furthermore, in order to figure out an economical and efficient way to fabricate useful passive pattern transfer layers, which have potential applications in microelectronic processes and ultrahigh density storage media, we propose a two-step strategy and scrutinize the conditions for generating square symmetries using cylinder-forming or lamella-forming AB diblock copolymers deposited on substrates created from ABC triblock copolymer films. It is found that a thinner film with weak incompatibility can produce square patterns.

10.
Phys Rev Lett ; 109(3): 035004, 2012 Jul 20.
Article in English | MEDLINE | ID: mdl-22861864

ABSTRACT

Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.

11.
Transplant Proc ; 44(3): 755-6, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22483487

ABSTRACT

Thrombocytopenia (platelet < 60,000/mm(3)) and uncontrolled massive ascites (ascitic fluid > 1000 mL/d over 10 days) after liver transplantation (OLT), although uncommon, usually represent serious complications. Splenectomy is a useful treatment despite its many side effects. Recently, partial splenic artery embolization (PSAE) is considered to be a nonsurgical, less invasive treatment. In this study, we retrospectively reviewed the results of PSAE after OLT. Between October 2008 and February 2010, 11 patients underwent PSAE after OLT due to thrombocytopenia (n = 6) or refractory ascites (RA; n = 5). Six patients (54.5%) were males and 3 (27.3%) were children. The primary liver disease was virus-related liver cirrhosis (n = 6), biliary atresia (n = 3), fulminant hepatitis (n = 1), or alcoholic liver cirrhosis (n = 1). Seven grafts were from living and four from deceased donors. The major axial size of spleen was 12.1 to 23.4 cm and its average embolized volume, 76.4% (range = 70%-80%). As the result, the platelet count significantly increased after PSAE in all patients maintaining values greater than 100,000/mm(3) in four thrombocytopenic patients (66.7%). Cases of RA showed marked decreases after PSAE (100%). The follow-up was 6 to 28 months. After PSAE, patients experienced abdominal pain (n = 9, 81.8%), fever (n = 2, 18.2%), and abdominal distension (n = 2, 18.2%). However, there was no serious complication after PSAE such as splenic abscess, rupture, pancreatic infarction, sepsis, or death. In conclusion, PSAE was effective and safe and can be the choice for thrombocytopenia or RA related to hypersplenism after OLT.


Subject(s)
Ascites/therapy , Embolization, Therapeutic , Liver Transplantation/adverse effects , Splenic Artery , Thrombocytopenia/therapy , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
12.
J Nanosci Nanotechnol ; 11(7): 6262-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-22121698

ABSTRACT

Morphology, crystallinity and electrochemical properties of Si powders fabricated by a mechanical milling process with milling time of 6-40 h were investigated by means of FESEM, XRD, Raman, TEM and cell test. Average size of Si powders was reduced to sub-micrometer scale after 10 h-milling and 40 nm-Si powders could be obtained at 48 h-milling. With increasing milling time, Si powders mostly changes from crystalline Si to amorphous one and the content of amorphous Si was increased. TEM result showed that a negligiable amount of crystalline Si remained even after 48 h-milling. Si electrode with 48 h-milled Si powders exhibited the best electrochemical properties in terms of capacity, efficiency and cycle performance: initial capacity of 3025 mAh g(-1), coulrombic efficiency of 79.4% and the capacity retention of 1000 mAh g(-1) (at 130 cycles). The good electrochemical properties of nano- and amorphous-Si are due to the high resistance against volume change and good reversibility of Li ion.

13.
Rev Sci Instrum ; 81(10): 10D934, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21033962

ABSTRACT

A scheme to obtain relatively scaled profiles of electron cyclotron emission (ECE) temperature directly from uncalibrated raw radiometer data is proposed and has been tested for the 2009 campaign KSTAR plasmas. The proposed method utilizes a position controlled system to move the plasma adiabatically and compares ECE radiometer channels at the same relative radial positions assuming the profile consistency during the adiabatic change. This scaling method is an alternative solution when an absolute calibration is unreliable or too time consuming. The application to the two dimensional ECE imaging data, wherein calibration is extremely difficult, may also prove to be useful.

14.
Rev Sci Instrum ; 81(9): 093505, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20886980

ABSTRACT

Images of plasma from a fast-framing camera are the most intuitive and reliable data to understand the status of tokamak plasmas. Generation, movement, size variation, and disruptions of plasmas can be clearly observed from these images. However, it is not a simple task to obtain the exact positions and sizes of plasmas using these images because measured two-dimensional images inevitably lose the three-dimensional position information of their targets. In this paper, the exact positions and sizes of plasmas have been calculated from tangentially viewed images using the toroidal symmetry of the plasma in the Korea Superconducting Tokamak Advanced Research (KSTAR) device. The positions and sizes of the plasmas have been manually determined with displayed cursors on images and automatically determined using a correlation factor with calculated virtual plasma images as well. These two results correspond well with each other. The estimated positions have also been compared with those obtained from magnetic diagnostics analysis.

15.
Int J Oral Maxillofac Surg ; 38(4): 316-20, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19231136

ABSTRACT

Botulinum toxin type A (BTX-A) injection into the masseter muscles is used to treat masseteric hypertrophy. No serious side effects of BTX-A have been reported, but patients sometimes complain of xerostomia. The aim of this study was to evaluate the effect of injecting BTX-A into the masseter for the treatment of masseteric hypertrophy on the flow of saliva from the parotid gland. 34 volunteers enrolled in this study. A total of 25 units of BTX-A was injected into each side bilaterally at two points at the center of the lower third of the masseter muscle. Saliva was collected from the parotid gland over a period of 10 min to determine the flow rate for 18 weeks after injection. The flow rate was calculated by dividing the amount in milliliters by the collection time in minutes. There were no significant changes in the stimulated parotid saliva flow at 4, 8, 12 or 18 weeks compared with the baseline. Within this limited study, it can be concluded that BTX-A injection into the masseter does not cause any significant decrease in the production of saliva from the parotid gland.


Subject(s)
Botulinum Toxins, Type A/adverse effects , Masseter Muscle/pathology , Neuromuscular Agents/adverse effects , Parotid Gland/metabolism , Salivation/drug effects , Xerostomia/chemically induced , Adult , Botulinum Toxins, Type A/administration & dosage , Electromyography , Female , Follow-Up Studies , Humans , Hypertrophy/drug therapy , Hypertrophy/physiopathology , Injections, Intramuscular , Male , Masseter Muscle/drug effects , Masseter Muscle/physiopathology , Neuromuscular Agents/administration & dosage , Saliva/metabolism , Secretory Rate , Young Adult
16.
J Periodontal Res ; 44(3): 402-10, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18842115

ABSTRACT

BACKGROUND AND OBJECTIVE: The cellular response of human gingival fibroblasts to a mechanical force is considered to be primarily anti-osteoclastic because they produce relatively high levels of osteoprotegerin. However, there is little information available on the effects of compression force on the production of osteoprotegerin and osteoclastic differentiation by these cells. In this study, we examined how mechanical force affects the nature of human gingival fibroblasts to produce osteoprotegerin and inhibit osteoclastogenesis. MATERIAL AND METHODS: Human gingival fibroblasts were exposed to mechanical force by centrifugation for 90 min at a magnitude of approximately 50 g/cm(2). The levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-1beta and tumor necrosis factor-alpha were measured at various time-points after applying the force. The effect of the centrifugal force on the formation of osteoclast-like cells was also determined using a co-culture system of human gingival fibroblasts and bone marrow cells. RESULTS: Centrifugal force stimulated the expression of osteoprotegerin, RANKL, interleukin-1beta and tumor necrosis factor-alpha by the cells, and produced a relatively high osteoprotegerin to RANKL ratio at the protein level. Both interleukin-1beta and tumor necrosis factor-alpha accelerated the force-induced production of osteoprotegerin, which was inhibited significantly by the addition of anti-(interleukin-1beta) immunoglobulin Ig isotype; IgG (rabbit polyclonal). However, the addition of anti-(tumor necrosis factor-alpha) immunoglobulin Ig isotype; IgG1 (mouse monoclonal) had no effect. Centrifugal force also had an inhibitory effect on osteoclast formation. CONCLUSION: Application of centrifugal force to human gingival fibroblasts accelerates osteoprotegerin production by these cells, which stimulates the potential of human gingival fibroblasts to suppress osteoclastogenesis. Overall, human gingival fibroblasts might have natural defensive mechanisms to inhibit bone resorption induced by a mechanical stress.


Subject(s)
Dental Stress Analysis , Gingiva/physiology , Osteoclasts/physiology , Osteoprotegerin/biosynthesis , RANK Ligand/biosynthesis , Adult , Alveolar Bone Loss/prevention & control , Animals , Bone Marrow Cells , Cell Differentiation , Cells, Cultured , Centrifugation , Coculture Techniques , Fibroblasts/physiology , Gingiva/cytology , Humans , Interleukin-1beta/pharmacology , Interleukin-1beta/physiology , Male , Mice , Mice, Inbred BALB C , Osteoclasts/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Stress, Mechanical , Tooth Movement Techniques , Tumor Necrosis Factor-alpha/pharmacology , Tumor Necrosis Factor-alpha/physiology , Young Adult
17.
Cancer Genet Cytogenet ; 117(2): 97-103, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10704677

ABSTRACT

Genetic changes leading to the development of gastric cancers are still in dispute. In the following study, we used comparative genomic hybridization (CGH) to screen for DNA copy number changes along all chromosomes in 37 gastric carcinomas, and fluorescence in situ hybridization (FISH) with the C-MYC and TP53 probes in 14 cases for comparison. The aim of this study was to identify those chromosome regions that contain genes important for the development of gastric carcinomas and to identify genetic markers associated with tumor progression. The most often involved gains were 2q, 7pq, 8pq, 13q, 17q, 18q, and 20pq. The most commonly deleted regions were 17p. The pattern of genetic changes was different depending on the existence of nodal metastasis and histologic types. Gains in 8q and losses in 17p were the most common features of the CGH changes. However, only 3 among the available 10 cases (30%) showed an amplification of the C-MYC gene by FISH. Allelic loss of TP53 was found in 2 of 4 cases (50%). This difference might be due to another rearrangement of these 2 genes which cannot be detected by FISH, or other possible genes in that area may be involved in the tumorigenesis and nodal metastasis of gastric carcinomas.


Subject(s)
Chromosome Aberrations , Stomach Neoplasms/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , DNA/analysis , Female , Gene Amplification , Genes, myc , Genes, p53 , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Neoplasm Staging , Nucleic Acid Hybridization , Stomach Neoplasms/pathology
18.
J Neurosurg Anesthesiol ; 11(4): 231-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10527141

ABSTRACT

A decrease of 1-2 degrees C core temperature provides protection against cerebral ischemia. However, shivering usually prevents reduction in core temperature in unanesthetized patients. Therefore, it was tested whether facial and airway heating increases the shivering threshold and enables core cooling in unanesthetized patients. Nine trials were performed on seven healthy male volunteers. Each subject was positioned supine on a circulating-water mattress (8-15 degrees C) with a convective-air coverlet (15-18 degrees C) extending from the neck to the feet. A dynamic study protocol governed by individualized physiological responses was used. Focal facial (and airway) warming was employed to suppress involuntary motor activity (muscle tensing, shivering) and, thereby, enabling noninvasive cooling to lower the core temperature. The following parameters were monitored: 1) heart rate, 2) blood pressure, 3) core temperature (tympanic, axilla, and rectal), 4) cutaneous temperatures, and 5) a subjective shiver index (scale 1-10). In three, electromyograms and infrared thermographs were also obtained. Upon cooling without facial and airway warming, involuntary motor activity increased until it was widespread. This vigorous motor activity prevented any significant lowering of core temperature or caused it to slightly increase. Subsequently, in all subjects, within seconds after the application of facial focal warming, motor activity was suppressed almost completely, and within minutes core temperatures significantly decreased. Preliminary studies described here indicate that focal facial warming applied during active whole body cooling to initiate mild hypothermia might minimize the need to pharmacologically suppress involuntary motor activity. Such a procedure might be useful for initiating as soon as possible (such as during emergency transport), cerebral mild hypothermia in order to maximize protection and thus improve outcome in neurologically injured patients (head trauma, stroke).


Subject(s)
Body Temperature , Face , Shivering/physiology , Skin Temperature/physiology , Adult , Analysis of Variance , Hot Temperature , Humans , Humidity , Male , Thermography/methods
19.
Cancer Genet Cytogenet ; 110(2): 87-93, 1999 Apr 15.
Article in English | MEDLINE | ID: mdl-10214355

ABSTRACT

Comparative genomic hybridization (CGH) and conventional cytogenetic karyotyping were used to screen for losses and gains of DNA sequences along all chromosome arms in 16 bladder tumors. Cytogenetic results were highly complex. The most frequently affected chromosomes were 5, 8, 9, 21, and Y as determined by karyotyping. There was close correlation between the CGH data and cytogenetic results in near-diploid tumors with simple karyotypes. However, some unexpected results were observed by CGH in tumors with several composite clones. Common amplification of copy numbers of DNA sequences by CGH were seen at 1q, 3q, 4q, 5p, 6p/q, 7p, 8q, 11q, 12q, 13q, 17q, 18q, and 20p/q (more than 20% of cases). High level amplification was noted at 1p32, 3p21, 3q24, 4q26, 8q21-qter, 11q14-22, 12q15-21, 12q21-24, 13q21-31, 17q22, and 18q22. Deletions were noted at 2q21-qter. 4q13-23, 5q, 8p12-22, 9p/q, and 11p13-15 (more than 20% of cases). Although most amplifications and deletions have been previously described in the literature, our study showed some intriguing and uncommon regions, different from those found in past studies. These were the amplification of 7p, 8q, 11q14-qter 12q24-24, 13q21-31, and 18q22, and deletion on 4q13-23, even though loss of heterozygosity was not detected at this locus. In spite of the very complex pattern of genetic changes in bladder tumors, most of these uncommon aberrations have to be implicated in bladder tumors, and further molecular genetic methods are necessary to establish whether the chromosomal regions contain candidate genes which contributed to the initiation and progression of bladder tumors.


Subject(s)
Chromosome Aberrations , In Situ Hybridization/methods , Urinary Bladder Neoplasms/genetics , Aged , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Cytogenetics/methods , Female , Gene Dosage , Humans , Loss of Heterozygosity , Male , Middle Aged , Urinary Bladder Neoplasms/pathology
20.
FEBS Lett ; 443(3): 297-302, 1999 Jan 29.
Article in English | MEDLINE | ID: mdl-10025951

ABSTRACT

Receptor activator of NF-kappaB (RANK) is a recently cloned member of the tumor necrosis factor receptor (TNFR) superfamily, and its function has been implicated in osteoclast differentiation and dendritic cell survival. Many of the TNFR family receptors recruit various members of the TNF receptor-associated factor (TRAF) family for transduction of their signals to NF-kappaB and c-Jun N-terminal kinase. In this study, the involvement of TRAF family members and the activation of the JNK pathway in signal transduction by RANK were investigated. TRAF1, 2, 3, 5, and 6 were found to bind RANK in vitro. Association of RANK with each of these TRAF proteins was also detected in vivo. Expression of RANK in cultured cells also induced the activation of JNK, which was blocked by a dominant-negative form of JNK. Furthermore, by employing various C-terminal deletion mutants of RANK, the regions responsible for TRAF interaction and JNK activation were identified. TRAF5 was determined to bind to the C-terminal 11 amino acids and the other TRAF members to a region N-terminal to the TRAF5 binding site. The domain responsible for JNK activation was localized to the same region where TRAF1, 2, 3, and 6 bound, which suggests that these TRAF molecules might mediate the RANK-induced JNK activation.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Carrier Proteins , Membrane Glycoproteins , Mitogen-Activated Protein Kinases , Proteins/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Amino Acid Sequence , Binding Sites , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Cell Line , Enzyme Activation , HeLa Cells , Humans , JNK Mitogen-Activated Protein Kinases , Precipitin Tests , Protein Binding , Proteins/genetics , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Receptors, Tumor Necrosis Factor/chemistry , Receptors, Tumor Necrosis Factor/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Deletion , Signal Transduction , TNF Receptor-Associated Factor 1 , TNF Receptor-Associated Factor 2 , TNF Receptor-Associated Factor 3 , TNF Receptor-Associated Factor 5 , TNF Receptor-Associated Factor 6 , Transfection
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