Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells

The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers

CIP2A facilitates the G1/S cell cycle transition via B-Myb in human papillomavirus 16 oncoprotein E6-expressing cells

Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer. However, the regulation of CIP2A by HPV-16E6 remains to be elucidated. In this study, we demonstrated that HPV-16E6 significantly up-regulated CIP2A mRNA and protein expression in a p53-degradation-dependent manner. Knockdown of CIP2A by siRNA inhibited viability and DNA synthesis and caused G1 cell cycle arrest of 16E6-expressing cells. Knockdown of CIP2A resulted in a significant reduction in the expression of cyclin-dependent kinase 1 (Cdk1) and Cdk2. Although CIP2A has been reported to stabilize c-Myc by inhibiting PP2A-mediated dephosphorylation of c-Myc, we have presented evidence that the regulation of Cdk1 and Cdk2 by CIP2A is dependent on transcription factor B-Myb rather than c-Myc. Taken together, our study reveals the role of CIP2A in abrogating the G1 checkpoint in HPV-16E6-expressing cells and helps in understanding the molecular basis of HPV-induced oncogenesis

Research on Water Ingress Lithium Battery for Forklift Based on High Resolution Industrial CT

In recent years, with the development of power battery technology, an increasing number of manufacturers have favored lithium batteries as forklift power sources. However, there has been a lack of relevant research on the safety performance of lithium batteries for forklifts, especially on the nondestructive inspection of faulty batteries, which is rarely performed. Therefore, this study adopted high-resolution industrial computed tomography (CT) to study faulty lithium batteries for forklifts, scanning the internal structure and analyzing the relationship between the performance attenuation of the lithium battery and the internal structure, thereby combining with the charging and discharging conditions, to provide a solution for the nondestructive inspection of lithium batteries in forklifts

Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease

Status and future of the soft X-ray free-electron laser beamline at the SHINE

The Shanghai High repetition rate XFEL and Extreme light facility (SHINE) is under construction and aims at generating X-rays between 0.4 and 25 keV with three FEL beamlines at repetition rates of up to 1 MHz. The soft X-ray FEL beamline, FEL-II, will be ready for commissioning in 2025. It is designed to cover the photon energy from 0.4 to 3 keV, in which the baselines of the FEL operation modes are self-amplified spontaneous emission (SASE), self-seeding, echo-enabled harmonic generation (EEHG), and polarization control. Therefore, a high repetition-rate external seed laser, large period length modulator, soft X-ray monochromator, planar undulator, and elliptically polarized undulator have been adopted in the FEL-II beamline. Several potentials such as an ultra-short pulse mode and a multi-color mode are also foreseeable without significant equipment changes in the follow-up operation. A dual-period undulator design is suggested for the echo-enabled harmonic generation (EEHG) commissioning, and it has great potential to break through the unreachable energy of the fully coherent X-ray in the future. The FEL-II beamline will deliver SASE radiation and fully coherent radiation in all the wavelengths of interest

An investigation into evaluating laptop computers using The Triple Bottom Line (Environmental)

Laptop computer is essential in the university among students and staff members; however, there is little information provided on the economic, environmental, and social assessments when it comes to purchasing laptop computers. This report investigates the analysis of environmental impacts on the laptop computers in order to select the environmentally friendly technology. The environmental impacts are analyzed by looking into the manufacturing process, energy consumption of laptop, and the disposal of the laptop computers. This report makes an thorough examination of laptop’s energy consumption in use, the manufacturing phases, and the necessity and benefit of recycling laptops. In addition, a survey is completed to investigate the reason of purchasing a new laptop and the average lifespan of a laptop. Advantages and disadvantages of the individual brands are illustrated, and will follow with a recommendation into the selection of laptops in terms of its environmental aspect. Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Applied Science, Faculty ofUnreviewedUndergraduat

Experimental and Numerical Study of Polymer-Retrofitted Masonry Walls under Gas Explosions

Unreinforced masonry walls are extensively used in the petrochemical industry and they are one of the most vulnerable components to blast loads. To investigate the failure modes and improve the blast resistances of masonry walls, four full-scale field tests were conducted using unreinforced and spray-on polyurea-reinforced masonry walls subjected to gas explosions. The results suggested that the primary damage of the unreinforced masonry wall was flexural deformation and the wall collapsed at the latter stage of gas explosion. The presence of polyurea coatings could effectively improve the anti-explosion abilities of masonry walls, prevent wall collapses, and retain the flying fragments, which would reduce the casualties and economic losses caused by petrochemical explosion accidents. The bond between the polymer and masonry wall was critical, and premature debonding resulted in a failure of the coating to exert the maximum energy absorption effect. A numerical model for masonry walls was developed in ANSYS/LS-Dyna and validated with the test data. Parametric studies were conducted to explore the influences of the polyurea-coating thickness and spray pattern on the performances of masonry walls. The polyurea-coating thickness and spray pattern affected the resistance capacities of masonry walls significantly

Outlier Detection with the Kernelized Spatial Depth Function

Statistical depth functions provide from the “deepest ” point a “center-outward ordering” of multidimensional data. In this sense, depth functions can measure the “extremeness” or “outlyingness” of a data point with respect to a given data set. Hence they can detect outliers – observations that appear extreme relative to the rest of the observations. Of the various statistical depths, the spatial depth is especially appealing because of its computational efficiency and mathematical tractability. In this article, we propose a novel statistical depth, the kernelized spatial depth (KSD), which generalizes the spatial depth via positive definite kernels. By choosing a proper kernel, the KSD can capture the local structure of a data set while the spatial depth fails. We demonstrate this by the half-moon data and the ring-shaped data. Based on the KSD, we propose a novel outlier detection algorithm, by which an observation with a depth value less than a threshold is declared as an outlier. The proposed algorithm is simple in structure: the threshold is the only one parameter for a given kernel. It applies to a one-class learning setting, in which “normal ” observations are given as the training data, as well as to a missing label scenario where the training set consists of a mixture of normal observations and outliers with unknown labels. We give upper bounds on the false alarm probability of a depth-based detector. These upper bounds can be used to determine the threshold. We perform extensive experiments on synthetic data and data sets from real applications. The proposed outlier detector is compared with existing methods. The KSD outlier detector demonstrates competitive performance

Sulfoxaflor Applied via Drip Irrigation Effectively Controls Cotton Aphid (Aphis gossypii Glover)

Aphis gossypii Glover is a major pest of cotton and can severely affect cotton yield and lint quality. In this study, the efficacy of sulfoxaflor applied via drip irrigation and foliar spray on controlling cotton aphids was evaluated in 2016 and 2017 in Xinjiang, China. The distribution of sulfoxaflor in cotton roots, stems, leaves, and aphids, as well as its effects on two natural enemies of aphids, were also investigated. Results showed that sulfoxaflor applied through drip irrigation mainly concentrated in leaves and provided effective control of cotton aphids for 40 days, compared to 20 days when applied through foliar spray. Furthermore, drip application resulted in much lower sulfoxaflor concentrations in aphids than foliar spray. As a result, ladybird beetle and lacewing populations were higher in drip applied plants than in foliar sprayed plants. Additionally, the cost of drip irrigation was lower than foliar spray as cotton plants are commonly irrigated via drip irrigation in Xinjiang. Our results showed that application of sulfoxaflor through drip irrigation is an effective way of controlling cotton aphids in Xinjiang due to a prolonged control period, safety to two natural enemies, and lower cost of application