Wei-Chih Huang

miRTarBase: a database curates experimentally validated microRNA–target interactions

MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (∼22 nt), can bind to one or more target sites on a gene transcript to negatively regulate protein expression, subsequently controlling many cellular mechanisms. A current and curated collection of miRNA–target interactions (MTIs) with experimental support is essential to thoroughly elucidating miRNA functions under different conditions and in different species. As a database, miRTarBase has accumulated more than 3500 MTIs by manually surveying pertinent literature after data mining of the text systematically to filter research articles related to functional studies of miRNAs. Generally, the collected MTIs are validated experimentally by reporter assays, western blot, or microarray experiments with overexpression or knockdown of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657 miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest amount of validated MTIs by comparing with other similar, previously developed databases. The MTIs collected in the miRTarBase can also provide a large amount of positive samples to develop computational methods capable of identifying miRNA–target interactions. miRTarBase is now available on http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously surveying research articles.

High-power, diode-end-pumped, multigigahertz self-mode-locked Nd:YVO 4 laser at 1342 nm

We report on a high-power, diode-pumped, self-mode-locked laser at 1342 nm with the Kerr effect arising from large third-order nonlinearity of Nd:YVO(4) crystal. At the pump power of 10.2 W, the average output power of 1.2 W was generated with a repetition rate in the range of 2-6 GHz. The mode-locked pulse width can be smoothly varied from 11.5 to 37 ps by controlling the amount of spatial hole burning.

miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions

Abstract MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.

Passively Q-switched photonic crystal fiber laser and intracavity optical parametric oscillator

We report on a passively Q-switched photonic crystal fiber (PCF) laser with Cr(4+):YAG as a saturable absorber. Under a pump power of 14.2 W, the maximum pulse energy is up to 630 microJ with a pulse width of 36 ns at a repetition rate of 5.6 kHz. With an intracavity optical parametric oscillator, the passively Q-switched PCF laser is used to generate the signal wave at 1515 nm. The output pulse energy of the signal wave is found to be 140 microJ with a pulse width as short as 1.0 ns at a repetition rate of 3.3 kHz. The very short pulse width leads to the peak power up to 140 kW.

Comparative studies for Cr(4+):YAG crystal and AlGaInAs semiconductor used as a saturable absorber in Q-switched Yb-doped fiber lasers

We demonstrate comparative studies for Cr(4+):YAG crystal and AlGaInAs quantum-well (QW) used as a saturable absorbers in passively Q-switched Yb-doped fiber lasers. Both saturable absorbers were designed to be possessed of nearly the same initial transmission. Under a pump power of 24 W, the average output powers were up to 14.4 W and 13.8 W obtained with the AlGaInAs QWs and with the Cr(4+):YAG crystal, respectively. The maximum pulse energies obtained with the Cr(4+):YAG crystal and with the AlGaInAs QWs were found to be 0.35 mJ and 0.45 mJ, respectively.

Hybrid Q-switched Yb-doped fiber laser

We investigate the performance of a hybrid Q-switched (HQS) fiber laser that is constructed with a low RF-power driven acousto-optic (AO) Q-switch and an AlGaInAs semiconductor saturable absorber. Compared to a pure passively Q-switched (PQS) fiber laser, the ratio of timing jitter to pulse period can be significantly reduced from 2% to 0.3% in the regime of far above threshold. On the other hand, the prelasing effect in a pure actively Q-switched fiber laser can be considerably improved. More importantly, the maximum pulse energy of the HQS fiber laser can be increased approximately 25% in comparison with the result of the PQS fiber laser. At a pump power of 24 W, the highest pulse energy is up to 0.56 mJ with the pulse duration of 50 ns at the repetition rate of 23 kHz.

Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma

Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.

The aquatic animals’ transcriptome resource for comparative functional analysis

BackgroundAquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome.ResultsTo improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis.ConclusionIn conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/.

Development of a computational promoter with highly efficient expression in tumors

BackgroundGene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients’ health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy.MethodsBioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs.ResultsWe analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1α (HIF-1α), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size.ConclusionsOur results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.

>100-kW linearly polarized pulse fiber amplifier seeded by a compact efficient passively Q-switched Nd:YVO4 Laser

We thoroughly develop compact high-peak-power Nd:YVO4/Cr4+:YAG passively Q-switched lasers (PQS) as the seed source of the fiber amplifier. We exploit a nearly hemispherical cavity to reach the second threshold criterion and systematically consider the thermal lensing effect and the mode-size matching in the overall optimization. Employing a Cr4+:YAG absorber with 70% initial transmission, we obtain a 50-kHz seed pulse train with the pulse duration of 4.8 ns and the pulse energy of 22 μJ at a pump power of 5.4 W. Injecting this seed laser into a polarization maintained Yb-doped fiber, the pulse energy and peak power at a pump power of 16 W are enhanced up to 178 μJ and 37 kW, respectively. We also use an absorber with 40% initial transmission to generate a 25 kHz pulse train with the pulse duration of 1.6 ns and the pulse energy of 36 μJ at a pump power of 5.4 W. With this seed laser, we find that the surface damage of the fiber limits the maximum pulse energy and peak power to be 192 μJ and 120 kW, respectively.