ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma

Supplemental Figure S1. The confirmation of ATF2 knockdown and overexpression. Supplemental Figure S2. qRT-PCR analysis of indicated genes expression upon ATF2 knockdown and overexpression. Supplemental Table S1. Sequences of primers used for plasmid construction. Supplemental Table S2. Sequences of primers used for qRT-PCR. Supplemental Table S3. Sequences of primers used for ChIP-qPCR. Supplemental Table S4. Correlation of ATF2 expression and clinical characteristics in RCC patients. Supplemental Table S5. Univariate and multivariate analyses of factors associated with overall survival in RCC patients. Supplemental Table S6. Univariate and multivariate analyses of factors associated with disease-free survival in RCC patients. (DOCX 625 kb

EMMNet: Sensor Networking for Electricity Meter Monitoring

Smart sensors are emerging as a promising technology for a large number of application domains. This paper presents a collection of requirements and guidelines that serve as a basis for a general smart sensor architecture to monitor electricity meters. It also presents an electricity meter monitoring network, named EMMNet, comprised of data collectors, data concentrators, hand-held devices, a centralized server, and clients. EMMNet provides long-distance communication capabilities, which make it suitable suitable for complex urban environments. In addition, the operational cost of EMMNet is low, compared with other existing remote meter monitoring systems based on GPRS. A new dynamic tree protocol based on the application requirements which can significantly improve the reliability of the network is also proposed. We are currently conducting tests on five networks and investigating network problems for further improvements. Evaluation results indicate that EMMNet enhances the efficiency and accuracy in the reading, recording, and calibration of electricity meters

Clinical Study Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma

The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric ( mean , 1 , and 50 ) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm 3 and 35%, respectively. The interweekly parotid volume varied significantly ( < 0.05). The parotid mean , 1 , and 50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid mean , and weight loss rate are valuable indicators for parotid protection-based replanning

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs).Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy.Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child–Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs.Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy

The role of vimentin in regulating cell-invasive migration in dense cultures of breast carcinoma cells

Cell migration and mechanics are tightly regulated by the integrated activities of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations have been implicated in the loss of tissue integrity, and acquisition of an invasive phenotype. In epithelial cancers, for example, increased expression of the cytoskeletal filament protein vimentin correlates with metastatic potential. Nonetheless, the exact mechanism whereby vimentin affects cell motility remains poorly understood. In this study, we measured the effects of vimentin expression on the mechano-elastic and migratory properties of the highly invasive breast carcinoma cell line MDA231. We demonstrate here that vimentin stiffens cells and enhances cell migration in dense cultures, but exerts little or no effect on the migration of sparsely plated cells. These results suggest that cell-cell interactions play a key role in regulating cell migration, and coordinating cell movement in dense cultures. Our findings pave the way towards understanding the relationship between cell migration and mechanics, in a biologically relevant context.Comment: 26+21 pages, 6+11 figures, supplementary movies available at http://doi.org/10.6084/m9.figshare.5480149, submitted to Nano Letters journa

Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC

Fundamental issues, mechanisms and models of flow boiling heat transfer in microscale channels

This paper presents state-of-the-art review on the fundamental and frontier research of flow boiling heat transfer, mechanisms and prediction methods including models and correlations for heat transfer in microscale channels. First, fundamental issues of current research on flow boiling in microscale channels are addressed. These mainly include the criteria for macroscale and microscale channels. Then, studies on flow boiling heat transfer behaviours and mechanisms in microscale channels are presented. Next, the available correlations and models of flow boiling heat transfer in microscale channels are reviewed and analysed. Comparisons of 12 correlations with a database covering a wide range of test parameters and 8 fluids are presented. It shows that all correlations poorly agree to the database. No generalized model or correlation is able to predict all flow boiling heat transfer data. Furthermore, comparisons of the mechanistic flow boiling heat transfer models based on flow patterns including the Thome et al. three-zone heat transfer model for evaporation in microchannel and the flow pattern based model combining the Thome et al. three zone heat transfer models with the Cioncolini-Thome annular flow model for both macro- and microchannel to the database are presented. It shows that the flow pattern based model combining the three zone model with the annular flow model gives better prediction than the three zone heat transfer model alone. The flow pattern based heat transfer model favourably agrees with the experimental database collected from the literature. According to the comparison and analysis, suggestions have been given for improving the prediction methods in the future. Next, flow patterned based phenomenological models and their applications to microscale channels are presented. Finally, as an important topic, unstable and transient flow boiling phenomena in microscale channels are briefed and recommendations for future research are given. According to this comprehensive review and analysis of the current research on the fundamental issues of flow boiling, mechanisms and prediction methods in microscale channels, the future research needs have been identified and recommended. In general, systematic and accurate experimental data of flow boiling heat transfer in microscale channels are still needed although a large amount of work has been done over the past decades. The channel size effect on the flow boiling behaviours should be systematically investigated. Heat transfer mechanisms in microscale channels should be further understood and related to the corresponding flow patterns. Furthermore, effort should be made to develop and improve generalized mechanistic prediction methods and theoretical models for flow boiling heat transfer in microscale channels according to the physical phenomena/mechanisms and the corresponding flow structures. The effects of the channel size and a wide range of test conditions and fluid types should be considered in develop new methods. Furthermore, systematic experimental, analytical and modeling studies on unstable and transient flow boiling heat transfer in microscale channels should be conducted to understand the physical mechanisms and theoretical models

Diversification of importin-α isoforms in cellular trafficking and disease states.

The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases

Understanding watershed hydrogeochemistry: 2. Synchronized hydrological and geochemical processes drive stream chemostatic behavior

This article is a companion to Bao et al. [2017], doi: 10.1002/2016WR018934.Why do solute concentrations in streams remain largely constant while discharge varies by orders of magnitude? We used a new hydrological land surface and reactive transport code, RT‐Flux‐PIHM, to understand this long‐standing puzzle. We focus on the nonreactive chloride (Cl) and reactive magnesium (Mg) in the Susquehanna Shale Hills Critical Zone Observatory (SSHCZO). Simulation results show that stream discharge comes from surface runoff (Qs), soil lateral flow (QL), and deeper groundwater (QG), with QL contributing >70%. In the summer, when high evapotranspiration dries up and disconnects most of the watershed from the stream, Cl is trapped along planar hillslopes. Successive rainfalls connect the watershed and mobilize trapped Cl, which counteracts dilution effects brought about by high water storage (Vw) and maintains chemostasis. Similarly, the synchronous response of clay dissolution rates (Mg source) to hydrological conditions, maintained largely by a relatively constant ratio between “wetted” mineral surface area Aw and Vw, controls Mg chemostatic behavior. Sensitivity analysis indicates that cation exchange plays a secondary role in determining chemostasis compared to clay dissolution, although it does store an order‐of‐magnitude more Mg on exchange sites than soil water. Model simulations indicate that dilution (concentration decrease with increasing discharge) occurs only when mass influxes from soil lateral flow are negligible (e.g., via having low clay surface area) so that stream discharge is dominated by relatively constant mass fluxes from deep groundwater that are unresponsive to surface hydrological conditions.EAR 07‐25019EAR 12‐39285EAR 13‐3172