MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.
During the 100 years since the initial discovery of meiotic phenomenon many brilliant aspects have been elucidated, but further researches based on light microscopy alone as an experimental tool have been found to have some limits and shortcomings. By the use of electron microscopy and armed with the advanced knowledges on modern genetics and biochemistry it has been possible to applu molecular technology in gaining information on the detailed aspects of meiosis. As synapsis takes place, a three-layered proteinous structure called the synatonemal complex starts to form in the space between the homologous chromosomes. To be more precise, it begins to form along the paired chromosomes early in the prophase I of meiotic division. The mechanism that leads to precise point-by-point pairing between homologous chromocomes division. The mechamism that leads to precise point-by-point pairing between homologous chromosomes remains to be ascertained. Several items of information, however, suggest that chromsome alignment leading to synapsis may be mediated somehow by the nuclear membrane. Pachytene bivalents in eukaryotes are firmly attached to the inner niclear membrane at both termini. This attached begins with unpaired leptotene chromosomes that already have developed a lateral element. Once attached, the loptotene chromosomes begin to synapse. A number of different models have been proposed to account for genetic recombination via exchange between DNA strands following their breakage and subsequent reunion in new arrangement. One of the models accounting for molecular recombination leading to chromatid exchange and chiasma formation was first proposed in 1964 by Holliday, and 30 years later still a modified version of his model is favored. Nicks are made by endomuclease at corresponding sites on one strant of each DNA duplex in nonsister chromatid of a bivalent during prophase 1 of meiosis. The nicked strands loop-out and two strands reassociate into an exchanged arrangement, which is sealed by ligase. The remaining intact strand of each duplex is nicked at a site opposite the cross-over, and the exposed ends are digested by exonuclease action. Considerable progress has been made in recent years in the effort to define the molecular and organization features of the centromere region in the yeast chromosome. Centromere core region of the DNA duplex is flanked by 15 densely packed nucleosomes on ons side and by 3 packed nucleosomes on the other side, that is, 2000 bp on one side and 400 400 bp in the other side. All the telomeres of a given species share a common DNA sequence. Two ends of each chromosome are virtually identical. At the end of each chromosome there exist two kinds of DNA sequence" simple telpmeric sequences and telpmere-associated sequencies. Various studies of telomere replication, function, and behabior are now in progress, all greatly aided by molecular methods. During nuclear division in mitosis as well as in meiosis, the nucleili disappear by the time of metaphase and reappear during nuclear reorganizations in telophase. When telophase begins, small nucleoli form at the NOR of each nucleolar-organizing chromosome, enlarge, and fuse to form one or more large nucleoli. Nucleolus is a special structure attached top a specific nucleolar-organizing region located at a specific site of a particular chromosome. The nucleolus is a vertical factory for the synthesis of rRNAs and the assenbly of ribosome subunit precursors.sors.
Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.
Lee Hyun-Ryong;Moon Sung-Tae;Kim Jong-Won;Shin Dong-Yun
The Journal of Korean Institute of Communications and Information Sciences
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v.31
no.5B
/
pp.430-441
/
2006
As the various A/V devices and home networks are delivered to users, home networks are changing to an entertainment network. It is expected that the required network bandwidth and the amount of usage of media content in home entertainment networks will be increased. Although the access networks and home networks becoming a high speed network, there remains the problems for QoS-guaranteed media content transfer in home networks. Also, in the home network, there can be network traffic caused by applications like video conferencing, video telephone, and VoIP(voice over IP) as well as inner network traffic of home network. Since media content transfer requires the real-time delivery, it is very important and basic requirement that is to transfer media content to A/V device user wants while keeping the media quality. Even though there are many middleware protocol for home networking, they provide basic device discovery and control or simple functions for QoS-guaranteed media content transfer that are not enough to provide QoS-guaranteed media transfer service that user wants. Thus, in this paper, we propose the technique based on UPnP(universal plug and play) protocol for QoS-guaranteed media content transfer in the home network. The proposed technique is compatible with UPnP and can be used with UPnP as additional functions. In this paper, we utilize VideoLAN application to verify the proposed technique. We add the additional modules that support the proposed technique's function to VideoLAN and we verify the its functions through various test scenarios.
A gallery provides the function to make opportunities for artist to meet the customers who would buy the products from them. And there was performed the place where artist who production provider, planner, managers and private collectors met to distribute artworks and to educate fine art for public and provide a chance sending leisure time. We investigated this galleries at old urban center in daegeon region by the deep interview and Delphi method. A galleries was operated by a sense of duty and pride. Though its environment is poor, it grows up the young artist and art trends. By delphi results, the role of gallery is recognized as the discovery of an unknown young artist and provider of art trend and paradigm. Also they was recognized as the space for social and cultural responsibility operation culture. Galleries was recognized as key factors as literary value, marketability and harmony between gallery and artworks. Artist was known as a key factors as gallery's expertise, gallery awareness and capacity for artworks selling. Gallery will be considered the functions as the various cultural experience space and culture service space. Although galleries are passive and one dimensional functions.
The dispute between China and Japan regarding $Di\grave{a}oy\acute{u}t\acute{a}i$ is believed to be quite similar to the controversy surrounding Dokdo in terms of historical and post-war processes except for the point that the phenomena of occupation is different with regard to Dokdo. China's claim to $Di\grave{a}oy\acute{u}t\acute{a}i$ is based on historical title and continuous use while the basis of Japan's claim is summarized as preoccupancy of ownerless land. Even though Japan acknowledges that China discovered $Di\grave{a}oy\acute{u}t\acute{a}i$, Japan claims that the act to establish sovereignty over the island from the standpoint of International Law was not taken by China. However, at that time, effective occupation was not an essential prerequisite for the acquisition of a territory. That is to say, from a legal perspective, the legal right for an area could be established based on the discovery of the land, and so it is thought that Japan is applying the current criteria of International Law in a manner that is inappropriate. When we review the post-war process, the San Francisco Peace Treaty does not directly mention $Di\grave{a}oy\acute{u}t\acute{a}i$. But based on the said treaty, we can note that Japan gave up all rights for the southern area that is north of the boundary line that equates to latitude $29^{\circ}$ and that includes the Ryuku Islands and $Di\grave{a}oy\acute{u}t\acute{a}i$. Of course, the provisions for the territory in the San Francisco Peace Treaty and its disposal are not the final factor for the judgment regarding dominium of $Di\grave{a}oy\acute{u}t\acute{a}i$. However, it seems clear that Japan's attitude and interpretation regarding the issues of $Di\grave{a}oy\acute{u}t\acute{a}i$, the Kuril Islands and Dokdo is problematic.
Proceedings of the Korean Society of Toxicology Conference
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2006.11a
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pp.65-74
/
2006
Modem drug discovery requires rapid pharmacokinetic evaluation of chemically diverse compounds for early candidate selection. This demands the development of analytical methods that offer high-throughput of samples. Naturally, liquid chromatography / tandem mass spectrometry (LC-MS/MS) is choice of the analytical method because of its superior sensitivity and selectivity. As a result of the short analysis time(typically 3-5min) by LC-MS/MS, sample preparation has become the rate- determining step in the whole analytical cycle. Consequently tremendous efforts are being made to speed up and automate this step. In a typical automated 96-well SPE(solid-phase extraction) procedure, plasma samples are transferred to the 96-well SPE plate, internal standard and aqueous buffer solutions are added and then vacuum is applied using the robotic liquid handling system. It takes only 20-90 min to process 96 samples by automated SPE and the analyst is physically occupied for only approximately 10 min. Recently, the ultra-high flow rate liquid chromatography (turbulent-flow chromatography)has sparked a huge interest for rapid and direct quantitation of drugs in plasma. There is no sample preparation except for sample aliquotting, internal standard addition and centrifugation. This type of analysis is achieved by using a small diameter column with a large particle size(30-5O ${\mu}$m) and a high flow rate, typically between 3-5 ml/min. Silica-based monolithic HPLC columns contain a novel chromatographic support in which the traditional particulate packing has been replaced with a single, continuous network (monolith) of pcrous silica. The main advantage of such a network is decreased backpressure due to macropores (2 ${\mu}$m) throughout the network. This allows high flow rates, and hence fast analyses that are unattainable with traditional particulate columns. The reduction of particle diameter in HPLC results in increased column efficiency. use of small particles (<2 urn), however, requires p.essu.es beyond the traditional 6,000 psi of conventional pumping devices. Instrumental development in recent years has resulted in pumping devices capable of handling the requirements of columns packed with small particles. The staggered parallel HPLC system consists of four fully independent binary HPLC pumps, a modified auto sampler, and a series of switching and selector valves all controlled by a single computer program. The system improves sample throughput without sacrificing chromatographic separation or data quality. Sample throughput can be increased nearly four-fold without requiring significant changes in current analytical procedures. The process of Bioanalytical Method Validation is required by the FDA to assess and verify the performance of a chronlatographic method prior to its application in sample analysis. The validation should address the selectivity, linearity, accuracy, precision and stability of the method. This presentation will provide all overview of the work required to accomplish a full validation and show how a chromatographic method is suitable for toxirokinetic sample analysis. A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method developed to quantitate drug levels in dog plasma will be used as an example of tile process.
Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their interassay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
The new rocks of the oceanic crust, like basalt, are created in the mid-oceanic ridge, and the magnetic polarities of the rocks are supposed to be oriented as following the Earth's magnetic field. An extensive magnetic survey of total field at sea level reveals mainly unusual north-south magnetic stripes parallel to the axis of the mid-oceanic ridge, especially in the Atlantic Ocean. From this stripes the Earth's magnetic field is considered as repeatedly 'flipped'(the N pole becoming the S pole, and vice versa) and many times over geological time. The discovery of stripes of alternately normal and reversed-magnetized rocks forming the ocean floor has been a key evidence for the sea-floor spreading, continental drift, and plate tectonics. This study introduces a simple apparatus to explain a possible mechanism of the magnetic reversal in the new oceanic crust, which makes a magnetic stripe adjacent to the mid-oceanic ridge. The apparatus shows a bar magnet effect of adjoined stripes to have a special magnetic polarity on the rocks in the center of the mid-oceanic ridge. The new magnetic stripe seems to be generated not only by Earth's magnetic field, but also by neighbored stripes in the mid-oceanic ridge, acting as a bar magnet.
We empirically examine the price discovery dynamics among the VKOSPI, the KOSPI200 spot, and the KOSPI200 futures markets. The analysis employs the vector-autoregression, Granger causality, impulse response function, and variance decomposition using both daily data from 2009. 04. 13 to 2011. 12. 30 and 1 minute data from the bull market, bear market, and the flat period. The main results are as follows; First, the lead lag relationships between KOSPI200 spot(futures) yield VKOSPI returns could not be found from the daily data analysis. But KOSPI200 spot(futures) have a predictive power for VKOSPI from 1 minute data. Especially KOSPI200 spot(futures) and VKOSPI show the bi-directional effects to each other during the return rising period Second, We chose the VAR(1) the model in daily data but adopt the VAR(3) model in the one minute data to determine the lead lag time. We know that there is predictability during the very short period Third, Spot returns and futures returns makes no difference in daily data results. According to the one minite data results, VKOSPI returns have a predictive power for KOSPI200 spot return, but have no predictive power for KOSPI200 futures return.
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