PKCα-induced drug resistance in pancreatic cancer cells is associated with transforming growth factor-β1

<p>Abstract</p> <p>Background</p> <p>Drug resistance remains a great challenge in the treatment of pancreatic cancer. The goal of this study was to determine whether TGF-β1 is associated with drug resistance in pancreatic cancer.</p> <p>Methods</p> <p>Pancreatic cancer BxPC3 cells were stably transfected with TGF-β1 cDNA. Cellular morphology and cell cycle were determined and the suppressive subtracted hybridization (SSH) assay was performed to identify differentially expressed genes induced by TGF-β1. Western blotting and immunohistochemistry were used to detect expression of TGF-β1-related genes in the cells and tissue samples. After that, the cells were further treated with an anti-cancer drug (e.g., cisplatin) after pre-incubated with the recombinant TGF-β1 plus PKCα inhibitor Gö6976. TGF-β1 type II receptor, TβRII was also knocked down using TβRII siRNA to assess the effects of these drugs in the cells. Cell viability was assessed by MTT assay.</p> <p>Results</p> <p>Overexpression of TGF-β1 leads to a markedly increased invasion potential but a reduced growth rate in BxPC3 cells. Recombinant TGF-β1 protein increases expression of PKCα in BxPC3 cells, a result that we confirmed by SSH. Moreover, TGF-β1 reduced the sensitivity of BxPC3 cells to cisplatin treatment, and this was mediated by upregulation of PKCα. However, blockage of PKCα with Gö6976 and TβRII with siRNA reversed the resistance of BxPC3 cells to gemcitabine, even in the presence of TGF-β1. Immunohistochemical data show that pancreatic cancers overexpress TGF-β1 and P-gp relative to normal tissues. In addition, TGF-β1 expression is associated with P-gp and membranous PKCα expression in pancreatic cancer.</p> <p>Conclusions</p> <p>TGF-β1-induced drug resistance in pancreatic cancer cells was associated with PKCα expression. The PKCα inhibitor Gö6976 could be a promising agent to sensitize pancreatic cancer cells to chemotherapy.</p

Monolithic integration of GaN-based NMOS digital logic gate circuits with E-mode power GaN MOSHEMTs

In this work, we demonstrate high-performance NMOS GaN-based logic gates including NOT, NAND, and NOR by integration of E/D-mode GaN MOSHEMTs on silicon substrates. The load-to-driver resistance ratio was optimized in these logic gates by using a multi-finger gate design of E-mode GaN MOSHEMT to increase the logic swing voltage and noise margins, and reduce the transition periods. State-of-the-art NMOS inverter was achieved with logic swing voltage of 4.93 V at a supply voltage of 5 V, low-input noise margin of 2.13 V and high-input noise margin of 2.2 V at room temperature. Excellent high temperature performance, at 300 C, was observed with a logic swing of 4.85 V, low-input noise margin of 1.85 V and high output noise margin of 2.2V. In addition, GaN-based NAND and NOR NMOS logic gates are reported for the first time with very good performance. Finally, the logic gates were monolithically integrated with high-voltage E-mode power transistors, which reveals a significant step forward towards monolithic integration of GaN power transistors with gate drivers

Missing Modality meets Meta Sampling (M3S): An Efficient Universal Approach for Multimodal Sentiment Analysis with Missing Modality

Multimodal sentiment analysis (MSA) is an important way of observing mental activities with the help of data captured from multiple modalities. However, due to the recording or transmission error, some modalities may include incomplete data. Most existing works that address missing modalities usually assume a particular modality is completely missing and seldom consider a mixture of missing across multiple modalities. In this paper, we propose a simple yet effective meta-sampling approach for multimodal sentiment analysis with missing modalities, namely Missing Modality-based Meta Sampling (M3S). To be specific, M3S formulates a missing modality sampling strategy into the modal agnostic meta-learning (MAML) framework. M3S can be treated as an efficient add-on training component on existing models and significantly improve their performances on multimodal data with a mixture of missing modalities. We conduct experiments on IEMOCAP, SIMS and CMU-MOSI datasets, and superior performance is achieved compared with recent state-of-the-art methods

Positive and Negative Regulation of FcɛRI-Mediated Signaling by the Adaptor Protein LAB/NTAL

Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcɛRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcɛRI-mediated signaling than LAT−/− mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcɛRI-mediated signaling

Searching for bidirectional promoters in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>A "bidirectional gene pair" is defined as two adjacent genes which are located on opposite strands of DNA with transcription start sites (TSSs) not more than 1000 base pairs apart and the intergenic region between two TSSs is commonly designated as a putative "bidirectional promoter". Individual examples of bidirectional gene pairs have been reported for years, as well as a few genome-wide analyses have been studied in mammalian and human genomes. However, no genome-wide analysis of bidirectional genes for plants has been done. Furthermore, the exact mechanism of this gene organization is still less understood.</p> <p>Results</p> <p>We conducted comprehensive analysis of bidirectional gene pairs through the whole <it>Arabidopsis thaliana </it>genome and identified 2471 bidirectional gene pairs. The analysis shows that bidirectional genes are often coexpressed and tend to be involved in the same biological function. Furthermore, bidirectional gene pairs associated with similar functions seem to have stronger expression correlation. We pay more attention to the regulatory analysis on the intergenic regions between bidirectional genes. Using a hierarchical stochastic language model (HSL) (which is developed by ourselves), we can identify intergenic regions enriched of regulatory elements which are essential for the initiation of transcription. Finally, we picked 27 functionally associated bidirectional gene pairs with their intergenic regions enriched of regulatory elements and hypothesized them to be regulated by bidirectional promoters, some of which have the same orthologs in ancient organisms. More than half of these bidirectional gene pairs are further supported by sharing similar functional categories as these of handful experimental verified bidirectional genes.</p> <p>Conclusion</p> <p>Bidirectional gene pairs are concluded also prevalent in plant genome. Promoter analyses of the intergenic regions between bidirectional genes could be a new way to study the bidirectional gene structure, which may provide a important clue for further analysis. Such a method could be applied to other genomes.</p

900 V Reverse-Blocking GaN-on-Si MOSHEMTs With a Hybrid Tri-Anode Schottky Drain

In this letter, we present high-performance GaN-on-Si metal-oxide-semiconductor high electron mobility transistors with record reverse-blocking (RB) capability. By replacing the conventional ohmic drain with a hybrid tri-anode Schottky drain, a high reverse breakdown voltage (V-B(R)) of -900 V was achieved (at 1 mu A/mm with grounded substrate), along with a small reverse leakage current (I-R) of similar to 20 nA/mm at -750 V. The devices also presented a small turn-ON voltage (V-ON) of 0.58 +/- 0.02 V, a small increase in forward voltage (Delta V-F) of similar to 0.8 V, a high ON/OFF ratio over 1010, and a high forward breakdown voltage (V-B(F)) of 800 V at 20 nA/mm with grounded substrate. These results demonstrate a new milestone for RB GaN transistors, and open enormous opportunities for integrated GaN power devices