Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression.

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of Pharbitis nil, also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether Pharbitis nil seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Seeds of Pharbitis nil (Pharbitis semen) were separated by chromatography and the active compound of Pharbitis semen (PN) was purified by HPLC. The compound PN efficiently suppressed the proliferation of mutated KRAS-driven CRC cells and their clonogenic potentials in a concentration-dependent manner. It also induced apoptosis of SW480 human colon cancer cells and cell cycle arrest at the G2/M phase. The CRC related pathways, including RAS/ERK and AKT/mTOR, were assessed and PN reduced the phosphorylation of AKT and mTOR. Furthermore, PN preserved muscle cell proliferation and myotube formation in cancer conditioned media. In summary, PN significantly suppressed mutated KRAS-driven cell growth and reserved muscle cell function. Based on the current study, PN could be considered as a promising starting point for the development of a nature-derived drug against KRAS-mutated CRC progression

Accurate quantification of transcriptome from RNA-Seq data by effective length normalization

We propose a novel, efficient and intuitive approach of estimating mRNA abundances from the whole transcriptome shotgun sequencing (RNA-Seq) data. Our method, NEUMA (Normalization by Expected Uniquely Mappable Area), is based on effective length normalization using uniquely mappable areas of gene and mRNA isoform models. Using the known transcriptome sequence model such as RefSeq, NEUMA pre-computes the numbers of all possible gene-wise and isoform-wise informative reads: the former being sequences mapped to all mRNA isoforms of a single gene exclusively and the latter uniquely mapped to a single mRNA isoform. The results are used to estimate the effective length of genes and transcripts, taking experimental distributions of fragment size into consideration. Quantitative RT–PCR based on 27 randomly selected genes in two human cell lines and computer simulation experiments demonstrated superior accuracy of NEUMA over other recently developed methods. NEUMA covers a large proportion of genes and mRNA isoforms and offers a measure of consistency (‘consistency coefficient’) for each gene between an independently measured gene-wise level and the sum of the isoform levels. NEUMA is applicable to both paired-end and single-end RNA-Seq data. We propose that NEUMA could make a standard method in quantifying gene transcript levels from RNA-Seq data

Relative Codon Adaptation Index, a Sensitive Measure of Codon Usage Bias

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Broadband Virtual-Stub Doherty Power Amplifier Using Asymmetric Structure

The load networks of advanced Doherty power amplifiers (DPAs) have traditionally been designed according to the ABCD parameters. In this paper, design conditions as an impedance transformation condition and an effective electrical length were used to design the output matching networks (OMNs) for the carrier and peaking amplifiers of the virtual-stub DPAs (VS-DPAs). An optimization method for the effective electrical length was proposed that was specifically constructed for the load impedances of the carrier amplifier at the low power level to have broadband characteristics through the load-pull simulation. Using the optimized design conditions for broadband design, compact OMNs for the carrier and peaking amplifiers were designed using quasi-lumped components. Moreover, an asymmetric structure with an increased power capacity of the peaking amplifier for the VS-DPA was proposed to compensate for a relatively low peak fundamental current of the peaking amplifier due to its deep class-C operation as well as the extended output back-off (OBO) range of the VS-DPA. To verify the proposed load network, a broadband asymmetric VS-DPA for the 3.3 - 4.2 GHz band was designed and implemented using GaN HEMTs with power capacities of 6 and 10 W. Using a 5G new radio (5G NR) signal with a signal bandwidth of 100 MHz and a peak-to-average power ratio (PAPR) of 7.8 dB, power gain of 8.2 - 9.1 dB, DE of 46.0 - 57.0%, ACLR of better than −45 dBc after DPD linearization at an average power of 35.0 dBm were achieved at the broad frequency range of 3.3 - 4.2 GHz