Background The protein high-mobility group AT-hook 1 (HMGA1) has been demonstrated that modulated cellular proliferation, invasion, and apoptosis with a poor prognosis in miscellaneous carcinomas. However, the mechanism of circumstantial carcinogenesis and association with the immune microenvironment of HMGA1 in hepatocellular carcinoma (HCC) had not been extensively explored. Methods The gene expression, clinicopathological correlation, and prognosis analysis were performed in the data obtained from TCGA. The results were further validated by ICGC and GEO database and external validation cohort from Guangxi. The HMGA1 protein expression was further examined in the HPA database. Biological function analyses were conducted by GSEA, STRING database, and Coexpedia online tool. Using TIMER and CIBERSORT method, the relationship between immune infiltrate and HMGA1 was investigated. Results In HCC, HMGA1 had much higher transcriptional and proteomic expression than in corresponding paraneoplastic tissue. Patients with high HMGA1 expression had a poor prognosis and unpromising clinicopathological features. High HMGA1 expression was closely related to the cell cycle, tumorigenesis, substance metabolism, and immune processes by regulating complex signaling pathways. Notably, HMGA1 may be associated with TP53 mutational carcinogenesis. Moreover, increased HMGA1 expression may lead to an increase in immune infiltration and a decrease in tumor purity in HCC. CIBERSORT analysis elucidated that the amount of B cell naive, B cell memory, T cells gamma delta, macrophages M2, and mast cell resting decreased when HMGA1 expression was high, whereas T cells follicular helper, macrophages M0, and Dendritic cells resting increased. Conclusion In conclusions, HMGA1 is a potent prognostic biomarker and a sign of immune infiltration in HCC, which may be a potential immunotherapy target for HCC.

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Narrow-band control theory is applied experimentally to the Hughes Stirling-cycle cryocooler expander. The cryocooler expander designed and W t by Hughes consists of a displacer and a balancer, which are mechanically placed in a back-to-back configuration and commanded BD move in opposite directions in order to cancel the vibration forces produced by the motions of the displacer and the balancer. The existing control design employing the position loop servos failed to provide adequate attenuation for the high-order harmonic vibration forces. A vibration control algorithm based on narrow-band control theory is developed to actively control the high-order vibrations. In this control concept, a load cell measuring the high-order vibration forces is used as a feedback element and a servo compensator is designed to produce an infinite open loop gain at each harmonic frequency. The developed vibration control algorithm is implemented with a digital signal processor, and integrated and tested on the crywooler expander. Peak vibration at the second harmonic frequency was reduced by more than a factor of 25 in the test. After extensive testing we believe that we have demonstrated the technical feasibility of applying the proposed active vibration control to meet the next generation cryocooler vibration spedications. IntroductionA Stirling-cycle cryogenic.cooler has been designed and built by Hughes under company funded IR&D program to support the divelopment of near-term long-life space cryocoolers. In addition to achieve the required tkrmodynamic effeciency, the low froce vibration has been identified to be one of the key technical challenges for these coolers.The designed Stirling-cycle cryocooler consists of three basic modules: (1) the compressor module, (2) the expander module, and (3) the servo control module. Both the compressor and expander modules have been designed to achieve a low vibration level by incorporating an opposed reaction masdactuator within the same housing to obtain a near perfect balance in all active forces, such as pressure forces, dynamic reaction of the moving masses, diaghragm spring forces, motor current lead spring forces, dissipative forces due to eddy currents in the motor, dissipative regenerator pressure drop forces, and motor elcctromechanical forces. The imbalance forces are then controlled by a simple position matching servo control system.Because of nonlinearities in the motor drive electronics, the piston suspension flexures, and gas thermodynamics, the resulting vibrations contain high-order harmonics in addition to the fundamental drive frequency. At these high-order harmonic frequencies, the above dynamic balance condition does not hold any more. Hence one has to rely on the position loop servos to attenuate these high-order harmonic vibrations.This force imbalance bemmes much worse in the expander moduIe due to the absence of pressure forces on the balancer. Our Itcent test data on the IR8cD cooler had indicated that the pure position loop servos failed to provide adequate atte...

Background Hepatocellular carcinoma (HCC) was frequently considered as a kind of malignant tumor with a poor prognosis. Cyclin-dependent kinases (CDK) 4 was considered to be cell-cycle-related CDK gene. In this study, we explored the clinical significance of CDK4 in HCC patients. Methods Data of HCC patients were obtained from The Cancer Genome Atlas database (TCGA) and the Gene Expression Omnibus (GEO) database. Kaplan–Meier analysis and Cox regression model were performed to calculate median survival time (MST) and the hazard ration (HR), respectively. The joint-effect analysis and prognostic risk score model were constructed to demonstrate significance of prognosis-related genes. The differential expression of prognostic genes was further validated using reverse transcription-quantitative PCR (RT-qPCR) of 58 pairs of HCC samples. Results CDK1 and CDK4 were considered prognostic genes in TCGA and GSE14520 cohort. The result of joint-effect model indicated patients in CDK1 and CDK4 low expression groups had a better prognosis in TCGA (adjusted HR = 0.491; adjusted P = 0.003) and GSE14520 cohort (adjusted HR = 0.431; adjusted P = 0.002). Regarding Kaplan–Meier analysis, high expression of CDK1 and CDK4 was related to poor prognosis in both the TCGA (P < 0.001 and = 0.001 for CDK1 and CDK4, respectively) and the GSE14520 cohort (P = 0.006 and = 0.033 for CDK1 and CDK4, respectively). However, only CDK4 (P = 0.042) was validated in RT-qPCR experiment, while CDK1 (P = 0.075) was not. Conclusion HCC patients with high CDK4 expression have poor prognosis, and CDK4 could be a potential candidate diagnostic biomarker for HCC.

Objective The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC. Materials and Methods Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 ( PUS1 ), was used for further research. The clinicopathological feature of PUS1 was analyzed by Student’s t -test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of PUS1 . A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of PUS1 . Results PUS1 was significantly overexpressed in HCC tissues, and patients with high PUS1 were related to unpromising clinicopathological features. Survival analysis revealed high PUS1 expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that PUS1 had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that PUS1 may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of PUS1 significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells. Conclusion PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.