170 research outputs found

    PDA: Pooled DNA analyzer

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    BACKGROUND: Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer), to analyze pooled DNA data. RESULTS: We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB(® )language, but it can also be executed on a Windows system without installing the MATLAB(®). PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples. CONCLUSION: PDA is simple to operate and does not require that users have a strong statistical background. The software is available at

    Comparison of secondary signs as shown by unenhanced helical computed tomography in patients with uric acid or calcium ureteral stones

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    AbstractUnenhanced helical computed tomography (UHCT) has evolved into a well-accepted diagnostic method in patients with suspected ureterolithiasis. UHCT not only shows stones within the lumen of the ureter, it also permits evaluation of the secondary signs associated with ureteral obstruction from stones. However, there we could find no data on how secondary signs might differ in relation to different compositions of ureteral stones. In this study, we compared the degree of secondary signs revealed by UHCT in uric acid stone formers and in patients forming calcium stones. We enrolled 117 patients with ureteral stones who underwent UHCT examination and Fourier transform infra-red analysis of stone samples. Clinical data were collected as follows: age, sex, estimated glomerular filtration rate (eGFR), urine pH, and radiological data on secondary signs apparent on UHCT. The uric acid stone formers had significantly lower urine pH and eGFR in comparison to calcium stone formers, and on UHCT they also had a higher percentage of the secondary signs, including rim sign (78.9% vs. 60.2%), hydroureter (94.7% vs. 89.8%), perirenal stranding (84.2% vs. 59.2%) and kidney density difference (73.7% vs. 50.0%). The radiological difference was statistically significant for perirenal stranding (p=0.041). In conclusion, we found that UHCT scanning reveals secondary signs to be more frequent in patients with uric acid ureteral stones than in patients with calcium stones, a tendency that might result from an acidic urine environment

    Potassium {4-[(3S,6S,9S)-3,6-dibenzyl-9-isopropyl-4,7,10-trioxo-11–oxa-2,5,8-triazadodecyl]phenyl}trifluoroborate

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    [[abstract]]The reported compound 4 was synthesized and fully characterized by 1H NMR, 13C NMR, 11B NMR, 19F NMR, and high resolution mass spectrometry.[[booktype]]電子版[[countrycodes]]CH

    TPMD: a database and resources of microsatellite marker genotyped in Taiwanese populations

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    Taiwan Polymorphic Marker Database (TPMD) (http://tpmd.nhri.org.tw/) is a marker database designed to provide experimental details and useful marker information allelotyped in Taiwanese populations accompanied by resources and technical supports. The current version deposited more than 372 000 allelotyping data from 1425 frequently used and fluorescent-labeled microsatellite markers with variation types of dinucleotide, trinucleotide and tetranucleotide. TPMD contains text and map displays with searchable and retrievable options for marker names, chromosomal location in various human genome maps and marker heterozygosity in populations of Taiwanese, Japanese and Caucasian. The integration of marker information in map display is useful for the selection of high heterozygosity and commonly used microsatellite markers to refine mapping of diseases locus followed by identification of disease gene by positional candidate cloning. In addition, our results indicated that the number of markers with heterozygosity over 0.7 in Asian populations is lower than that in Caucasian. To increase accuracy and facilitate genetic studies using microsatellite markers, we also list markers with genotyping difficulty due to ambiguity of allele calling and recommend an optimal set of microsatellite markers for genotyping in Taiwanese, and possible extension of genotyping in other Mongoloid populations

    Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction

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    Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells

    The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

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    Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

    Non-invasive and transdermal measurement of blood uric acid level in human by electroporation and reverse iontophoresis

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    The aim of this study was to find out the optimum combination of electroporation (EP) and reverse iontophoresis (RI) on noninvasive and transdermal determination of blood uric acid level in humans. EP is the use of high-voltage electric pulse to create nano-channels on the stratum corneum, temporarily and reversibly. RI is the use of small current to facilitate both charged and uncharged molecule transportation across the skin. It is believed that the combination of these two techniques has additional benefits on the molecules’ extraction across the human skin. In vitro studies using porcine skin and diffusion cell have indicated that the optimum mode for transdermal uric acid extraction is the combination of RI with symmetrical biphasic direct current (current density = 0.3 mA/cm2; phase duration = 180 s) and EP with 10 pulses per second (voltage = 100 V/cm2; pulse width = 1 ms). This optimum mode was applied to six human subjects. Uric acid was successfully extracted through the subjects’ skin into the collection solution. A good correlation (r2 = 0.88) between the subject’s blood uric acid level and uric acid concentrations in collection solutions was observed. The results suggest that it may be possible to noninvasively and transdermally determine blood uric acid levels

    A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells

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    Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions
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