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Aptamers incorporating chemically modified bases can achieve superior affinity and specificity compared to natural aptamers, but their characterization remains a labor-intensive, low-throughput task. Here, we describe the “non-natural aptamer array” (N2A2) system, in which a minimally modified Illumina MiSeq instrument is used for the high-throughput generation and characterization of large libraries of base-modified DNA aptamer candidates based on both target binding and specificity. We first demonstrate the capability to screen multiple different base modifications to identify the optimal chemistry for high-affinity target binding. We next use N2A2 to generate aptamers that can maintain excellent specificity even in complex samples, with equally strong target affinity in both buffer and diluted human serum. For both aptamers, affinity was formally calculated with gold-standard binding assays. Given that N2A2 requires only minor mechanical modifications to the MiSeq, we believe that N2A2 offers a broadly accessible tool for generating high-quality affinity reagents for diverse applications.

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Two epimeric metabolites of Larotaxel were synthesized in eight steps from 10-DAB III as a commercial material and their structures were characterized using NMR and MS spectral data. The cytotoxicity of two metabolites was performed on breast cancer cell lines MCF-7, MX-1 and MDA-MB-231. It is remarkable that both of these two desired taxanes showed great potent cytotoxic effect.

Epithelial-mesenchymal transition (EMT) is a developmental process that converts epithelial cells into migratory and invasive cells. This process also plays an important role in cancer progression and metastasis by enabling tumor cells to leave primary sites. EMT is regulated by complex transcription networks and post-transcriptional modulators. MicroRNAs are single-stranded non-coding RNAs that represent a novel class of gene regulators. It has been shown that microRNAs are critical regulators of EMT process. The molecular mechanisms of EMT modulation by microRNAs include the suppression of transcription factors that directly regulate EMT and the down-regulation of cellular genes and pathways that are indirectly involved in EMT process. The expressions of microRNAs that control EMT process are dysregulated in cancer. In this review, we summarize the recent progress of microRNAs in EMT regulation.

The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-junf/f) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, and reduced cellular polarity, migration, and invasiveness. c-Jun increased c-Src mRNA abundance and c-Src promoter activity involving an AP-1 site in the c-Src promoter. Transduction of c-jun–/–cells with either c-Jun or c-Src retroviral expression systems restored the defective cellular migration of c-jun–/–cells. As c-Src is a critical component of pathways regulating proliferation, survival, and metastasis, the induction of c-Src abundance, by c-Jun, provides a novel mechanism of cooperative signaling in cellular invasion.

The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun–induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-junf1/f13T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli and repressed c-jun target genes (cyclin A, β-PAK, and stathmin). DACH1 bound c-Jun and inhibited AP-1 transcriptional activity. c-jun and c-fos were transcriptionally repressed by DACH1, requiring the conserved N-terminal (dac and ski/sno [DS]) domain. c-fos transcriptional repression by DACH1 requires the SRF site of the c-fos promoter. DACH1 inhibited c-Jun transactivation through the δ domain of c-Jun. DACH1 coprecipitated the histone deacetylase proteins (HDAC1, HDAC2, and NCoR), providing a mechanism by which DACH1 represses c-Jun activity through the conserved δ domain. An oncogenic v-Jun deleted of the δ domain was resistant to DACH1 repression. Collectively, these studies demonstrate a novel mechanism by which DACH1 blocks c-Jun-mediated contact-independent growth through repressing the c-Jun δ domain.

To improve the robustness of visual tracking in complex environments such as: cluttered backgrounds, partial occlusions, similar distraction and pose variations, a novel tracking method based on adaptive fusion and particle filter is proposed in this paper. In this method, the image color and shape cues are adaptively fused to represent the target observation; fuzzy logic is applied to dynamically adjust each cue weight according to its associated reliability in the past frame; particle filter is adopted to deal with non-linear and non-Gaussian problems in visual tracking. The method is demonstrated to be robust to illumination changes, pose variations, partial occlusions, cluttered backgrounds and camera motion for a test image sequence.

ABSTRACTArabinomannan (AM) is a polysaccharide of the mycobacterial capsule. The capsular polysaccharides of various microorganisms are diverse, and this diversity is important for classification of organisms into serotypes and vaccine development. In the present study we examined the prevalence and diversity of AM among Mycobacterium tuberculosisstrains using four AM-binding monoclonal antibodies (MAbs). One of these MAbs, MAb 9d8, is known to bind to AM specifically. By whole-cell enzyme-linked immunosorbent assay (ELISA), the AM recognized by MAb 9d8 was detected on the surfaces of 9 of 11 strains, while 2 strains showed no reactivity with MAb 9d8. However, the AM recognized by MAb 9d8 was found in the culture supernatants of all 11 M. tuberculosisstrains tested, as demonstrated by capture ELISA. Other AM-binding MAbs reacted both with the surfaces and with the culture supernatants of all 11 strains. Mice immunized with an experimental AM-recombinant Pseudomonas aeruginosaexoprotein A (rEPA) conjugate vaccine had an increased antibody response to AM and a moderate reduction in the numbers of CFU in their organs 7 days after challenge. Our results indicate that AM was detected in all M. tuberculosisstrains tested, with differences in epitope distributions of certain strains. In addition, our results suggest that an experimental AM-rEPA vaccine has a moderate effect on the numbers of CFU in organs early after infection.

In visual tracking, the object’s appearance may change over time due to illumination changes, pose variations, and partial or full occlusions. This variability makes tracking difficult. This paper proposes an adaptive appearance model for visual tracking. The model can adapt to changes in object appearance over time. The value of each pixel is modeled by a Gaussian mixture distribution. A novel update scheme based on the expectation maximization algorithm is developed to update the appearance model parameters. In designing the tracking algorithm, the observation model is based on the adaptive appearance model, and a particle filter is employed. Outlier pixels and occlusions are handled using a robust-statistics technique. Numerous experimental results demonstrate that the proposed algorithm can track objects well under illumination changes, large pose variations, and partial or full occlusions.

For bipartite tracking consensus of leader-following multi-agent systems (MASs) subject to time-varying disturbances and competitive-cooperative networks, a novel distributed sample-based event-triggered control strategy is proposed in this paper. A class of disturbance observers is analyzed to address the mismatched disturbance in practical systems. In addition, based on the observed disturbance state information, the new dynamic event-triggered control protocols based on periodic sampling data combined with the low-gain feedback technique are proposed. The proposed protocols are designed to resolve the bipartite consensus control problem in general linear MASs containing fixed topologies, using both state and output feedback information. The Lyapunov stability theory demonstrates that a system can achieve leader-following bipartite consensus control under a specified control protocol. The proposed dynamic event-triggered protocol is based on state information obtained through period sampling. This ensures that the interval between two adjacent triggering moments is at least one sampling period and avoids the Zeno phenomenon. Finally, numerical simulations are conducted to prove the feasibility of the theoretical results. • The bipartite consensus control for MASs containing disturbance is investigated • Dynamic event-triggered mechanisms based on periodically sampled data are designed. • The disturbance observer is employed to deal with the mismatched disturbances. • A bipartite consensus control protocol based on output feedback is designed. • Zeno behavior can be directly avoided by using sample-based event-triggered control. [ABSTRACT FROM AUTHOR]

In this paper, the event-triggered guaranteed cost consensus problem is considered for second-order multi-agent systems whose system states are unmeasurable. First, an observer-based distributed event-triggered condition is presented. The triggering time series for each agent is different, and the controller with a time-varying delay is updated only at the triggered times, which can reduce the communication time effectively. Second, using the event-triggered condition and the Lyapunov method, several sufficient conditions are obtained to achieve the guaranteed cost output feedback consensus. Moreover, for each event-triggered interval, a positive lower bound can be calculated, leading to the avoidance of Zeno behaviors. Third, appropriate controller and observer gains can be designed using the linear matrix inequality technique, which is verified through numerical simulations. [ABSTRACT FROM AUTHOR]