HSP90 inhibitors stimulate DNAJB4 protein expression through a mechanism involving N6-methyladenosine.

Small-molecule inhibitors for the 90-kDa heat shock protein (HSP90) have been extensively exploited in preclinical studies for the therapeutic interventions of human diseases accompanied with proteotoxic stress. By using an unbiased quantitative proteomic method, we uncover that treatment with three HSP90 inhibitors results in elevated expression of a large number of heat shock proteins. We also demonstrate that the HSP90 inhibitor-mediated increase in expression of DNAJB4 protein occurs partly through an epitranscriptomic mechanism, and is substantially modulated by the writer, eraser, and reader proteins of N6-methyladenosine (m6A). Furthermore, exposure to ganetespib leads to elevated modification levels at m6A motif sites in the 5'-UTR of DNAJB4 mRNA, and the methylation at adenosine 114 site in the 5'-UTR promotes the translation of the reporter gene mRNA. This m6A-mediated mechanism is also at play upon heat shock treatment. Cumulatively, we unveil that HSP90 inhibitors stimulate the translation of DNAJB4 through an epitranscriptomic mechanism

Design of Automatic Extraction Algorithm of Knowledge Points for MOOCs

In recent years, Massive Open Online Courses (MOOCs) are very popular among college students and have a powerful impact on academic institutions. In the MOOCs environment, knowledge discovery and knowledge sharing are very important, which currently are often achieved by ontology techniques. In building ontology, automatic extraction technology is crucial. Because the general methods of text mining algorithm do not have obvious effect on online course, we designed automatic extracting course knowledge points (AECKP) algorithm for online course. It includes document classification, Chinese word segmentation, and POS tagging for each document. Vector Space Model (VSM) is used to calculate similarity and design the weight to optimize the TF-IDF algorithm output values, and the higher scores will be selected as knowledge points. Course documents of “C programming language” are selected for the experiment in this study. The results show that the proposed approach can achieve satisfactory accuracy rate and recall rate

Emotion Analysis of Telephone Complaints from Customer Based on Affective Computing

Customer complaint has been the important feedback for modern enterprises to improve their product and service quality as well as the customer’s loyalty. As one of the commonly used manners in customer complaint, telephone communication carries rich emotional information of speeches, which provides valuable resources for perceiving the customer’s satisfaction and studying the complaint handling skills. This paper studies the characteristics of telephone complaint speeches and proposes an analysis method based on affective computing technology, which can recognize the dynamic changes of customer emotions from the conversations between the service staff and the customer. The recognition process includes speaker recognition, emotional feature parameter extraction, and dynamic emotion recognition. Experimental results show that this method is effective and can reach high recognition rates of happy and angry states. It has been successfully applied to the operation quality and service administration in telecom and Internet service company

Research progress of E3 ubiquitin ligase regulating biological behavior of human placental trophoblast cells

E3 ubiquitin ligases are important components of the ubiquitin protease system. This family includes many proteins, which can catalyze the ubiquitination of a variety of protein substrates and promote the degradation of them by the proteasome system. Recent studies have shown that E3 ubiquitin ligase plays a key role in the process of fetal development and placental formation. It affects the biological behavior of placental trophoblast cells, leading to a series of pregnancy complications that threaten mothers and babies greatly. This review focuses on the regulation, target and mechanism of E3 ubiquitin ligase on the biological behavior of human placental trophoblast cells

A novel epigenetic AML1-ETO/THAP10/miR-383 mini-circuitry contributes to t(8;21) leukaemogenesis

DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML. Our findings also show that THAP10 is a bona fide target of miR-383 that can be epigenetically activated by the AML1-ETO recruiting co-activator p300. In this study, we demonstrated that epigenetic suppression of THAP10 is the mechanistic link between AML1-ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein that inhibits myeloid proliferation and promotes differentiation both in vitro and in vivo Altogether, our results revealed an unexpected and important epigenetic mini-circuit of AML1-ETO/THAP10/miR-383 in t(8;21) AML, in which epigenetic suppression of THAP10 predicts a poor clinical outcome and represents a novel therapeutic target

An aphid-transmitted polerovirus is mutualistic with its insect vector by accelerating population growth in both winged and wingless individuals

The occurrence and increased dispersion of plant viruses and insect vectors are serious global threat to the production of agricultural crops. Facing novel pathogenic plant viruses, the ability to accurately identify plant virus species, and understand the interaction between plant viruses, host plants and their insect vectors would provide an important basis for formulating effective plant virus control measures. In this study, we explored the transmission mechanism, pathogenic symptoms, host range and the interactions between virus and aphid vectors of a novel polero virus from Nicotianatabacum, named Tobacco yellow virus (TYV). The results indicate that TYV can be transmitted by Myzus persicae in a persistent manner, and cause yellowing and shrinking of tobacco leaves. TYV can successfully infect a total of 9 plant species belonging to 3 families. The effect of TYV-infected tobacco plants on M. persicae behavior and life characteristics was found to be stage-dependent. TYV can directly and indirectly manipulate the performance and life history traits of M. persicae vectors to promote their own transmission. These results provide a certain theoretical basis for the possibility of control strategies of the virus, and the in-depth exploration of the interaction among plant virus, vector aphid and host plants

Experimental comparison of Yb/Al/Ce and Yb/Al/P co-doped fibers on the suppression of transverse mode instability

We presented an experimental comparison of the core-composition difference on the suppression of the photodarkening and transverse mode instability effects. Two core-composition fibers, entailing Yb/Al/Ce and Yb/Al/P co-doped fibers, were fabricated by MCVD process combined with solution doping technique. The parameters of two fibers were almost the same. The PD-induced loss at equilibrium was 3.94 dB/m at 702 nm in Yb/Al/Ce fiber, while it was 0.99 dB/m in Yb/Al/P fiber. To obtain a deeper understanding of the impact of PD on laser performance, a bidirectional pumping fiber amplifier was constructed. Compared with Yb/Al/Ce co-doped fiber, the TMI thresholds of Yb/Al/P co-doped fiber were enhanced in co-pumped and counter-pumped schemes. Meanwhile, the slope efficiency in bidirectional scheme was promoted by 4%. Moreover, the transmittance at 638 nm confirmed the superior PD resistance of Yb/Al/P co-doped fiber. These experimental results pave the way for the further development of high-power fiber lasers

Combined Scaling for Open-Vocabulary Image Classification

We present a combined scaling method - named BASIC - that achieves 85.7% top-1 accuracy on the ImageNet ILSVRC-2012 validation set without learning from any labeled ImageNet example. This accuracy surpasses best published similar models - CLIP and ALIGN - by 9.3%. Our BASIC model also shows significant improvements in robustness benchmarks. For instance, on 5 test sets with natural distribution shifts such as ImageNet-{A,R,V2,Sketch} and ObjectNet, our model achieves 84.3% top-1 average accuracy, only a small drop from its original ImageNet accuracy. To achieve these results, we scale up the contrastive learning framework of CLIP and ALIGN in three dimensions: data size, model size, and batch size. Our dataset has 6.6B noisy image-text pairs, which is 4x larger than ALIGN, and 16x larger than CLIP. Our largest model has 3B weights, which is 3.75x larger in parameters and 8x larger in FLOPs than ALIGN and CLIP. Finally, our batch size is 65536 which is 2x more than CLIP and 4x more than ALIGN. We encountered two main challenges with the scaling rules of BASIC. First, the main challenge with implementing the combined scaling rules of BASIC is the limited memory of accelerators, such as GPUs and TPUs. To overcome the memory limit, we propose two simple methods which make use of gradient checkpointing and model parallelism. Second, while increasing the dataset size and the model size has been the defacto method to improve the performance of deep learning models like BASIC, the effect of a large contrastive batch size on such contrastive-trained image-text models is not well-understood. To shed light on the benefits of large contrastive batch sizes, we develop a theoretical framework which shows that larger contrastive batch sizes lead to smaller generalization gaps for image-text models such as BASIC