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DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

Electrowetting technology, one of the microfluidic technologies, has attracted more and more attentions in recent years, and it has a broad prospect in terms of microdroplet drive. In this paper, the dynamic contact angle theory is used to develop a numerical model to predict the droplet dynamic contact behavior and the internal flow field under electrowetting. In particular, based on the established computational model of droplet force balance, the dynamic process of a droplet under electrowetting is analyzed, with the perspective of pressure variation and force balance inside the droplet. The results show that when the alternating current frequency increases from 50Hz to 500Hz, the amplitude of the oscillation waveform after droplet stabilization is 0.036mm, 0.016mm, 0.013mm, 0.002mm, while the relevant droplet oscillation periods T are 11ms, 4ms, 2ms, 1ms, respectively. It is also found that the initial phase angle does not affect the droplet oscillation amplitude. In addition, the pressure on the droplet surface under alternating current electrowetting increases rapidly to the maximum value, with resonant waveform oscillation, and the droplet will present different resonance modes under voltage stimulation. The higher the resonance mode is, the smaller the droplet oscillation amplitude is, and the streamline at the interface will present eddy current, in which the number of vortices matches the resonance mode. The high resonance mode corresponds to the small droplet amplitude, while there are more vortices with smaller size.

Lysine-specific demethylase 1 (LSD1) is a well characterized transcriptional regulator functioning on the chromatin to remove mono- and di-methyl groups from lysine 4 or lysine 9 of histone 3 (H3K4 or H3K9). LSD1 also has non-transcriptional activities via targeting non-histone substrates that participate in diverse biological processes. In this report, we determined that LSD1 negatively regulates autophagy in skeletal muscle cells by promoting PTEN degradation in a transcription-independent mechanism. In C2C12 cells, LSD1 inhibition or depletion significantly induced the initiation of autophagy; and autophagy resulted from LSD1 inhibition is associated with AKT/mTORC1 inactivation. Notably, the proteins of PTEN, a prominent repressive AKT modulator, are stabilized by LSD1 inhibition despite a decrease of its mRNA levels. Further data demonstrated that LSD1 interacts with PTEN protein and enhances its ubiquitination and degradation. Together, our findings identify a novel biological function of LSD1 in autophagy, mediated by regulating the stability of PTEN and the activity of AKT/mTORC1.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Aim To confirm non-inferiority and test potential superiority of capecitabine/cisplatin (XP) over 5-fluorouracil (5-FU)/cisplatin (FP) as first-line treatment for advanced gastric cancer (AGC) in Chinese patients. Methods In open-label phase III ML17032 trial, AGC (stage IIIA-IV) patients with or without metastases were randomized 1:1 to receive cisplatin (80 mg/m2 /day intravenous [IV] day 1) with either capecitabine (1000 mg/m2 /day oral [PO] twice daily [BID], days 1-14; XP) or 5-FU (800 mg/m2 /day continuous IV days 1-5; FP) every 3 weeks. The primary objective was to confirm the non-inferiority of XP over FP for progression-free survival (PFS). Results The intent-to-treat (ITT) population included 126 Chinese patients (XP-62, FP-64; 67.5% male, mean age 54.7 years). The primary analysis was performed on the per-protocol (PP) population (105 patients; XP-51, FP-54; 65.7% male). Median PFS in the XP and FP groups was 7.2 and 4.5 months, respectively. The adjusted hazard ratio (HR) for PFS was 0.52 (95% confidence interval [CI]: 0.32-0.83, P = 0.006). Unadjusted HR for PFS in the ITT population was 0.63 (95% CI, 0.42-0.94, P = 0.022). The most frequent drug-related grade 3/4 adverse events (AEs) were neutropenia (XP-20.7%, FP-17.7%) and gastrointestinal disorders (XP-19.0%, FP-19.4%). The overall incidence of grade 3/4 AEs (XP-43.1%, FP-46.8%), serious AEs (XP-1.7%, FP-3.2%), and AEs related to treatment discontinuation (XP-10.3%, FP-16.1%) were comparable. Conclusion XP had a similar safety profile and may demonstrate superiority for PFS compared to FP as first-line treatment of Chinese patients with AGC (NCT02563054).

The drying system plays an important role in printing speed and energy consumption of gravure printing machine. Nozzle is a factor which decides heated air distribution in drying system finally. This research makes a model for the structure of nozzle and takes a numerical simulation analysis of heated air field with hydrodynamic theory. The defect of structure is found through the distribution of velocity, temperature and trajectories. A crosswind landing area is added around outlet area of nozzle. In this study, it is evaluated that the distribution of the wind field. It is found that the velocity and pressure of heated air in the vortex area between substrate and nozzle by the cross-wind board can be improved from the simulation results. The study has significance on optimizing the structure of nozzle and improving efficiency of drying system.

We studied the shutdown state of natural gas engine on a modified GW4B13 direct injection engine. The result shows that when the engine is cold, high speed hold a dominant factor, causing the engine spends longer time shutting down than the time under the hot engine situation; stop position of the engine is normal distribution, and the majority of the stop position is located before the top dead center between 70° to 90°; when the stop position before the top dead center 90° and 120 ° , the engine spends shortest time, less than 0.3s, reaching the target speed, i.e. the idle speed 400rpm.

Take the traction wire rope cleaning and detection line of pay-off unit as an example, investigate the general law of the change during paying off of traction wire rope cleaning and detection line and build the mathematical model in each step of the paying off tension control system. Build the simulation model using MATLAB on the foundation of the mathematical model and research on the model. Afterwards, it is proved that the demand of keeping the tension of pay-off unit constant can be meet through regulating magnetic braking torque of pay-off unit.

This paper puts forth an overall plan of integrated control system based on PLC and touch screen according to the technological requirements of wire ropes cleaning and detection line. It introduces an automation control system composed of two parts by touch screen and PLC automation control system. The core of the control system is the PLC which uses I/O to achieve the control of the switch. Touch screen communicates with PLC by means of RS232 to complete all parameters input and actuators operations. First, it designs various modules of the hardware circuit according to the general scheme. PLC controls rough brush motor, high-pressure water cleaning motor, water drying valve, oil drying valve through I/O module. PLC controls take-up motor by D/A output module. It uses temperature controller to realize automatic heating control in the process of water heating and oil heating. At the same time the temperature controller communicates with PLC by means of RS485. Then, it designs the software of PLC control system which adopts the idea of modular design. As to the software of PLC control system, many programs are designed such as manual control function, automatic control function, communicating function and so on. Finally, it designs the Human Machine Interface system which completes many functions such as manual control operation, automatic control operation, parameter setting, system diagnosis, historical records and help system. The system makes the automation and intellectualization to be realized. It can monitor parameters real-time and improves production efficiency.

The molecularly imprinted polymers (MIPs) are used as the base material of solid phase extraction (SPE) for the separation and concentration of the propachlor herbicide (Prop) in different environmental matrix. Accordingly, we prepared MIPs on the surface of modified silica gel using propachlor as a template, acrylamide (AA) as functional monomers, ethylene glycol dimethacrylate (EGDMA) as a cross-linker and 2,2-azo-bis-isobutyronitrile (AIBN) as an initiator. The MIP structure was characterised using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Synthesised MIPs had a specific ability to detect the template Prop. The high selectivity solid phase extraction cartridges of molecularly imprinted polymers (MISPE) containing MIP Prop particles were prepared. The optimised Prop-MISPE procedure was developed for enrichment or clean-up of propachlor residues in water, soil and rice samples. Concentrations of propachlor in the samples were analysed by high performance liquid chromatography. Overall, the newly developed technique provides an analytical platform to quantify the trace amount of propachlor residues in multi or complex environmental and food media.

In augmented reality (AR) systems, virtual objects, graphics or texts are added to the real scene to improve the person's perception. Virtual and real information must be aligned strictly in the combination of scenes. The key of augmented reality is 3D registration technology which is based on tracking the artificial marker in the scene effectively. Using linear programming theory, this paper presents a tracking method which can recognize the vertices of any convex polygon in augmented reality system since most of the markers are squares. The transformation matrix of camera can be estimated at the aid of coordinates of the four vertices.

Aneuploidy and chromosomal instability are major characteristics of human cancer. These abnormalities can result from defects in the spindle assembly checkpoint (SAC), which is a surveillance mechanism for accurate chromosome segregation through restraint of the activity of the anaphase-promoting complex/cyclosome (APC/C). Here, we show that a CUE-domain-containing protein, CUEDC2, is a cell-cycle regulator that promotes spindle checkpoint inactivation and releases APC/C from checkpoint inhibition. CUEDC2 is phosphorylated by Cdk1 during mitosis. Depletion of CUEDC2 causes a checkpoint-dependent delay of the metaphase-anaphase transition. Phosphorylated CUEDC2 binds to Cdc20, an activator of APC/C, and promotes the release of Mad2 from APC/C-Cdc20 and subsequent APC/C activation. CUEDC2 overexpression causes earlier activation of APC/C, leading to chromosome missegregation and aneuploidy. Interestingly, CUEDC2 is highly expressed in many types of tumours. These results suggest that CUEDC2 is a key regulator of mitosis progression, and that CUEDC2 dysregulation might contribute to tumour development by causing chromosomal instability.

Endocrine resistance is a major obstacle to hormonal therapy for breast cancers. Although reduced expression of estrogen receptor-α (ER-α) is a known contributing factor to endocrine resistance, the mechanism of ER-α downregulation in endocrine resistance is still not fully understood. Here we report that CUE domain-containing protein-2 (CUEDC2), a ubiquitin-binding motif-containing protein, is a key factor in endocrine resistance in breast cancer. We show that CUEDC2 modulates ER-α protein stability through the ubiquitin-proteasome pathway. Through the study of specimens from a large cohort of subjects with breast cancer, we found a strong inverse correlation between CUEDC2 and ER-α protein expression. Notably, subjects with tumors that highly expressed CUEDC2 had poor responsiveness to tamoxifen treatment and high potential for relapse. We further show that ectopic CUEDC2 expression impaired the responsiveness of breast cancer cells to tamoxifen. Therefore, our findings suggest that CUEDC2 is a crucial determinant of resistance to endocrine therapies in breast cancer.

Tracking and registration is one key issue for an augmented reality (AR) system. For the marker-based AR system, the research focuses on detecting the real-time position and orientation of camera. In this paper, we describe a method of tracking and registration using the vector operations. Our method is proved to be stable and accurate, and have a good real-time performance.

Intensive remediation of abandoned former organochlorine pesticides (OCPs) manufacturing areas is necessary because the central and surrounding soils contaminated by OCPs are harmful to crop production and food safety. Organochlorine and its residues are persistent in environments and difficult to remove from contaminated soils due to their low solubility and higher sorption to the soils. We performed a comprehensive study on the remediation of OCPs-contaminated soils using thermal desorption technique and solvent washing approaches. The tested soil was thermally treated at 225, 325, 400, and 500 °C for 10, 20, 30, 45, 60, and 90 min, respectively. In addition, we tested soil washing with several organic solvents including n-alcohols and surfactants. The optimal ratio of soil/solvent was tested, and the recycling of used ethanol was investigated. Finally, activities of polyphenol oxidase (PPO), urease (URE), alkaline phosphatase, acid phosphatase (ACP), and invertase (INV) were assayed in the treated soils. The tested soil was thermally treated at 500 °C for 30 min, and the concentration of contaminants in soil was decreased from 3,115.77 to 0.33 mg kg(-1). The thermal desorption in soil was governed by the first-order kinetics model. For the chemical washing experiment, ethanol showed a higher efficiency than any other solvent. Using a 1:20 ratio of soil/solvent, the maximum removal of OCPs was achieved within 15 min. Under this condition, approximately 87 % of OCPs was removed from the soils. More than 90 % of ethanol in the spent wash fluid could be recovered. Activities of some enzymes in soils were increased after ethanol treatment. But ALP, ACP, and INV activities were decreased and PPO and URE showed slightly higher activities following remediation by thermal treatment. Both heating temperature and time were the key factors for thermal desorption of OCPs. The n-alcohol solvent showed higher removal of OCPs from soils than surfactants. The highly efficient removal of OCPs from soil was achieved using ethanol. More than 90 % of ethanol could be recovered and be reused following distillation. This study provides a cost-effective and highly efficient way to remediate the OCPs-contaminated soils.

In the last decade, Support vector machine (SVM) has been deeply investigated and it is often used in Hilbert space by the measure of Euclidean distance. In this paper, we present the SVM with mahalanobis distance, and the details of how to compute the mahalanobis distance in the input and the feature space are described. Finally, we apply it to the image classification and compare the results of them. By this, we obtain a sound conclusion.

Considering that the high-frequency sub-band can gather most energy of noise by the wavelet decomposition, and the local variances in edge and noise change inconsistently, the real edges of images are separated from the noise by choosing an appropriate threshold value in each high-frequency sub-bands of wavelet domain, while the WGMAP method is used to restore the images. Experimental results show that the images reconstructed by the improved algorithm reproduce preferably the edge structures of original images; and the signal to noise ratio and the visual effect are significantly improved.

Despite rapid progress in elucidating the molecular mechanisms of activation of the kinase IKK, the processes that regulate IKK deactivation are still unknown. Here we demonstrate that CUE domain-containing 2 (CUEDC2) interacted with IKKalpha and IKKbeta and repressed activation of the transcription factor NF-kappaB by decreasing phosphorylation and activation of IKK. Notably, CUEDC2 also interacted with GADD34, a regulatory subunit of protein phosphatase 1 (PP1). We found that IKK, CUEDC2 and PP1 existed in a complex and that IKK was released from the complex in response to inflammatory stimuli such as tumor necrosis factor. CUEDC2 deactivated IKK by recruiting PP1 to the complex. Therefore, CUEDC2 acts as an adaptor protein to target IKK for dephosphorylation and inactivation by recruiting PP1.

Background Gankyrin was originally purified and characterized as the p28 component of the 26S proteasome, and later identified as an oncogenic protein in hepatocellular carcinomas (HCC). It has recently been found to be highly expressed in several other malignancies, and compelling evidence show gankyrin plays important roles in tumorigenesis. However, its mechanism of action remains unclear. Methods In order to further clarify the functions of gankyrin and better understand its molecular mechanisms, we generated a gankyrin null cell line, HCT116 gankyrin−/− , by targeted homologous recombination in human colon cancer cells, and then employed two-dimensional electrophoresis (2-DE) based proteomic approaches followed by MS identification to investigate alterations in the proteome due to the gankyrin knockout. Western blot and qRT-PCR assays were also used to examine the protein and mRNA levels of some identified proteins. Results Compared with wild-type control cells, gankyrin null cells were impaired in terms of their proliferation, migration and anchorage-independent growth. A total of 21 altered proteins were identified, which included 18 proteins that had not previously been reported to be related to gankyrin. Notably, eight metastasis-related proteins were identified. Western blot analyses confirmed that the changes in three examined proteins were consistent with 2-DE gel analysis. Conclusions In summary, we have generated a useful cell tool to clarify the functions of gankyrin. Our proteomic data provide novel information to better understand the roles and underlying mechanisms by which gankyrin is involved in tumorigenesis and cancer metastasis.