IFIT1 and IFIT3 are abundant products of interferon-stimulating genes. While the importance of IFIT1 and IFIT3 in the prognosis of cancer has been reported, the molecular basis of IFIT1 and IFIT3 in ...cancer progression remains unexplored. In the present study, we investigated the modes of action and the clinical significance of IFIT1 and IFIT3 in oral squamous cell carcinoma (OSCC). Ectopic expression of IFIT1 or IFIT3 induced OSCC cell invasion by promoting the epithelial-mesenchymal transition, whereas IFIT1 or IFIT3 knockdown exhibited opposite effects. Overexpression of IFIT1 or IFIT3 promoted tumor growth, regional and distant metastasis in xenograft and orthotopic nude mice models. Most importantly, IFIT1 or IFIT3 overexpression increased the levels of p-EGFR
and p-AKT
in OSCC cells and also enhanced tumor inhibitory effect of gefitinib. By immunoprecipitation and LC-MS/MS analysis, we found that IFIT1 and IFIT3 interacted with ANXA2 that enhanced p-EGFR
endosomal recycling. Depletion of ANXA2 using siRNA therefore abolished p-EGFR
and p-AKT
expression in IFIT1- or IFIT3-overexpressed cells. Furthermore, a significant positive association of increased IFIT1 and IFIT3 expression with advanced T-stage, lymph node metastasis, perineural invasion, lymphovascular invasion, extranodal extension, and poor overall survival rate was confirmed in OSCC patients. We also found a statistically positive correlation of p-EGFR
expression with IFIT1 and IFIT3 in OSCC tumors and poor clinical outcome in patients. Collectively, we demonstrated a novel role of IFIT1 and IFIT3 in driving OSCC progression and metastasis by interacting with ANXA2 and hence enhancing p-EGFR recycling and its downstream signaling.
A heterogeneous sensing multiunmanned aerial vehicle (UAV) system is developed to track a moving target undergoing unknown motion. Using heterogeneous sensors for tracking can increase robustness and ...reduce costs. However, the formation configuration of the multi-UAV system needs to be designed to ensure the best estimation performance. A metric based on the Fisher information matrix is used to determine the best formation configuration since the state covariance matrix was proven to be lower bounded by the Cramer-Rao lower bound. In other words, the determinant value of the Fisher information matrix is designed to be the cost function, and limitation of the field of view (FOV), limitation of the tracking distance, and avoiding inter-UAV collisions are considered as constraints. Finally, the generated optimal formation configuration is converted to the relative position for the distributed controller of the UAVs to achieve tracking. Controllers for UAVs are designed to ensure that tracking of the target is achieved in the optimal configuration with the constraints satisfied. In addition to performing the theoretical analysis, experiments and simulations were conducted to verify the efficacy of the developed heterogeneous sensing system.
To track moving targets undergoing unknown translational and rotational motions, a tracking controller is developed for unmanned aerial vehicles (UAVs). The main challenges are to control both the ...relative position and orientation between the target and the UAV to within desired values, and to guarantee that the generated control input to the UAV is feasible (i.e., below its motion capability). Moreover, the UAV is controlled to ensure that the target always remains within the field of view of the onboard camera. These control objectives were achieved by developing a nonlinear-model predictive controller, in which the future motion of the target is predicted by quadratic programming (QP). Since constraints of the feature vector and the control input are considered when solving the optimal control problem, the control inputs can be bounded and the target can remain inside the image. Three simulations were performed to compare the efficacy and performance of the developed controller with a traditional image-based visual servoing controller.
A tracking controller for unmanned aerial vehicles (UAVs) is developed to track moving targets undergoing unknown translational and rotational motions. The main challenges are to control both the ...relative positions and angles between the target and the UAVs to within desired values, and to guarantee that the generated control inputs to the UAVs are feasible (i.e., within their motion capabilities). Moreover, the UAVs are controlled to ensure that the target always remains within the fields of view of their onboard cameras. To the best of our knowledge, this is the first work to apply multiple UAVs to cooperatively track a dynamic target while ensuring that the UAVs remain connected and that both occlusion and collisions are avoided. To achieve these control objectives, a designed controller solved based on the aforementioned tracking controller using quadratic programming can generate minimally invasive control actions to achieve occlusion avoidance and collision avoidance. Furthermore, control barrier functions (CBFs) with a distributed design are developed in order to reduce the amount of inter-UAV communication. Simulations were performed to assess the efficacy and performance of the developed CBF-based controller for the multi-UAV system in tracking a target.
Water permeability of the kidney collecting ducts is regulated by the peptide hormone vasopressin. Between minutes and hours (short-term), vasopressin induces trafficking of the water channel protein ...aquaporin-2 to the apical plasma membrane of the collecting duct principal cells to increase water permeability. Between hours and days (long-term), vasopressin induces aquaporin-2 gene expression. Here, we investigated the mechanisms that bridge the short-term and long-term vasopressin-mediated aquaporin-2 regulation by α-actinin 4, an F-actin crosslinking protein and a transcription co-activator of the glucocorticoid receptor. Vasopressin induced F-actin depolymerization and α-actinin 4 nuclear translocation in the mpkCCD collecting duct cell model. Co-immunoprecipitation followed by immunoblotting showed increased interaction between α-actinin 4 and glucocorticoid receptor in response to vasopressin. ChIP-PCR showed results consistent with α-actinin 4 and glucocorticoid receptor binding to the aquaporin-2 promoter. α-actinin 4 knockdown reduced vasopressin-induced increases in aquaporin-2 mRNA and protein expression. α-actinin 4 knockdown did not affect vasopressin-induced glucocorticoid receptor nuclear translocation, suggesting independent mechanisms of vasopressin-induced nuclear translocation of α-actinin 4 and glucocorticoid receptor. Glucocorticoid receptor knockdown profoundly reduced vasopressin-induced increases in aquaporin-2 mRNA and protein expression. In the absence of glucocorticoid analog dexamethasone, vasopressin-induced increases in glucocorticoid receptor nuclear translocation and aquaporin-2 mRNA were greatly reduced. α-actinin 4 knockdown further reduced vasopressin-induced increase in aquaporin-2 mRNA in the absence of dexamethasone. We conclude that glucocorticoid receptor plays a major role in vasopressin-induced aquaporin-2 gene expression that can be enhanced by α-actinin 4. In the absence of vasopressin, α-actinin 4 crosslinks F-actin underneath the apical plasma membrane, impeding aquaporin-2 membrane insertion. Vasopressin-induced F-actin depolymerization in one hand facilitates aquaporin-2 apical membrane insertion and in the other hand frees α-actinin 4 to enter the nucleus where it binds glucocorticoid receptor to enhance aquaporin-2 gene expression.
Water permeability of the kidney collecting ducts is regulated in part by the amount of the molecular water channel protein aquaporin-2 (AQP2), whose expression, in turn, is regulated by the ...pituitary peptide hormone vasopressin. We previously showed that stable glucocorticoid receptor knockdown diminished the vasopressin-induced
gene expression in the collecting duct cell model mpkCCD. Here, we investigated the pathways regulated by the glucocorticoid receptor by comparing transcriptomes of the mpkCCD cells with or without stable glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown downregulated 5,394 transcripts associated with 55 KEGG pathways including "vasopressin-regulated water reabsorption," indicative of positive regulatory roles of these pathways in the vasopressin-induced
gene expression. Quantitative RT-PCR confirmed the downregulation of the vasopressin V2 receptor transcript upon glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown upregulated 3,785 transcripts associated with 42 KEGG pathways including the "TNF signaling pathway" and "TGFβ signaling pathway," suggesting the negative regulatory roles of these pathways in the vasopressin-induced
gene expression. Quantitative RT-PCR confirmed the upregulation of TNF and TGFβ receptor transcripts upon glucocorticoid receptor knockdown. TNF or TGFβ inhibitor alone, in the absence of vasopressin, did not induce
gene transcription. However, TNF or TGFβ blunted the vasopressin-induced
gene expression. In particular, TGFβ reduced vasopressin-induced increases in Akt phosphorylation without inducing epithelial-to-mesenchymal transition or interfering with vasopressin-induced apical AQP2 trafficking. In summary, our RNA-seq transcriptomic comparison revealed positive and negative regulatory pathways maintained by the glucocorticoid receptor for the vasopressin-induced
gene expression.
Polyacrylonitrile (PAN) nanofibrous membrane was prepared by an electrospinning technique. After heat treatment and alkaline hydrolysis, the weak ion exchange membrane was grafted with chitosan ...molecule and then covalently immobilized with a Cibacron Blue F3GA (CB). Fibre diameter, porosity and pore size of the membrane and immobilized dye density were characterized. Furthermore, the membrane was applied to evaluate the binding performance of lysozyme under various operating parameters (pH, chitosan mass per volume ratio, dye concentration, ionic strength and temperature) in batch mode. The experimental results were directly applied to purify lysozyme from chicken egg white by membrane chromatography. The results showed that the capture efficiency, recovery yield and purification factor were 90 and 87%, and 47-fold, respectively, in a single step. The binding capacity remained consistent after five repeated cycles of adsorption-desorption operations. This work demonstrates that the dye-affinity nanofibrous membrane holds great potential for purification of lysozyme from real feedstock.
This study analyzes Chinese tag questions in contrast to English tag questions. Whereas English tags are syntax-based, Chinese tags are more discourse-based and the choice of tag verbs is decided ...mainly according to the speaker's discourse intentions, such as asking for an agreement of the host proposition, seeking consent of an invitation, making a refutation, etc. The Chinese tag question comprises a tag verb in the interrogative form, namely V-not-V, V-particle, or Neg-V-particle, and a null pro of CP, which is identical with the host sentence. The various interrogative forms of the tag verb display varied degrees of presupposition from the speaker. Tag verbs include mostly the declarative tags of dui, shi, you, etc. and imperative tags of hao, xing, keyi. Some epistemic modals such as yinggai, keneng and some discourse commentary verbs such as guai, zan, ku, sheng, etc. can also be tag verbs, though in relatively low frequency. From the cross-linguistic comparison, it is concluded that English tags might be harder for Chinese EFL learners to acquire than Chinese tags for English CFL learners due to the syntactic complexity of canonical tags and irregularity in formation in non-canonical tags.
Mandarin compound verbs containing si ‘die’ are numerous and intriguing with varying meanings of si. This study investigates the meanings, functions, and thematic structures of all si-compounds. It ...was found that there are five basic categories of verbal si-compounds. The most common type is the resultative si-compound with the prototypical meaning of ‘to die.’ The three types have the grammaticalized si meaning of ‘to the extreme degree,’ ‘persistence,’ and ‘motionless and fixed state.’ The last type is one derived through a process of causative construction either from unaccusative si-compounds or from lexical re-mapping of theta roles in a composite causal-caused event. The five types of si-compounds all show a systematic relation among themselves either via the grammaticalization of si, or via the syntactic process of resultativity and causativity. The former causes the meaning of si to change, and the latter, the thematic structure alternation in compound verbs., 中文複合詞裡含有死字的複合動詞十分繁多而且語意變換奧妙有趣，本研究即探討這些複合動詞裡死字的意義、功能、及論旨結構。研究結果為中文裡有基本五類的動詞性死複合詞，首先最普遍的為表結果的死複合動詞，死的含意為最原始的「死掉」意義；之後的三種死複合詞都具有語法化的死，意義各為「致極端的程度」、「執著持續」、「無動靜僵住狀態」；最後一種死複合動詞是由經由句法使動結構過程形成，它可以是從非受格性的死複合動詞變化而來，或是由原因-結果兩事件合併過程經由詞彙論旨角色的重新分配而成。這五類死複合動詞看似不同但彼此有系統性關聯，或由語法化的關係相連接，或經由結果結構或使動結構的句法過程相連接；前者造成死字語意的些微變換，後者造成複合動詞內部論旨結構的換位
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