Search

Radiation therapy benefits more than 50% of all cancer patients and cures 40% of them, where ionizing radiation (IR) deposits energy to cells and tissues, thereby eliciting DNA damage and resulting in cell death. Small GTPases are a superfamily of proteins that play critical roles in cell signaling. Several small GTPases, including RAC1, RHOB, and RALA, were previously shown to modulate radioresistance in cancer cells. However, there is no systematic proteomic study on small GTPases that regulate radioresistance in cancer cells. Herein, we applied a high-throughput scheduled multiple-reaction monitoring (MRM) method, along with the use of synthetic stable isotope-labeled (SIL) peptides, to identify differentially expressed small GTPase proteins in two pairs of breast cancer cell lines, MDA-MB-231 and MCF7, and their corresponding radioresistant cell lines. We identified 7 commonly altered small GTPase proteins with over 1.5-fold changes in the two pairs of cell lines. We also discovered ARFRP1 as a novel regulator of radioresistance, where its downregulation promotes radioresistance in breast cancer cells. Together, this represents the first comprehensive investigation about the differential expression of the small GTPase proteome associated with the development of radioresistance in breast cancer cells. Our work also uncovered ARFRP1 as a new target for enhancing radiation sensitivity in breast cancer.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

Computer-assisted textual enhancement (CATE) technology has been widely used to improve English as foreign language (EFL) learners’ syntactical and grammatical learning. Visual attention, repetition, and prior knowledge are known as the vital factors in CATE-assisted knowledge-acquisition; however, there still lacks a model which can describe those factors’ intrinsic cooperating-mechanism that works in the CATE-based knowledge-acquisition. Therefore, this paper built up a computational model (PESE) of using those factors as variables, by fitting and predicting the data collected from empirical experiments with an average accuracy of 78%, PESE testified and complemented the assumptions proposed by previous studies. PESE suggested that although the efficacy of CATE is majorly decided by learners’ prior-knowledge of the targets, the interactive effects of visual-attention, repetition, and inductive activity could partly compensate for the effect from prior-knowledge, and the efficacy ceiling of repetition also could be estimated according to the ‘easy-perceiving level’ coefficient. At the end of this paper, 3 pedagogical implications were proposed for English teachers who are willing to integrate CATE into their teaching activities.

In marine, aviation and railway transportation, dirt, corrosion, and wear lead to rapid failure of equipment, and organic coating is the main protective means. Epoxy (EP) coating is a widely used film-forming material in organic coating. We report a new modification method — fluorine modified silicon carbide (F–SiC) modified EP coating. The hydrophobicity, wear resistance and corrosion resistance of the EP coating were improved by grafting fluorinated organic compound (F–SiC) onto the surface of silicon carbide particles and adding it to the EP coating. When the content of F–SiC is 3[Formula: see text]wt.%, compared with the EP coating without F–SiC, the contact angle between 3[Formula: see text]wt.% F–SiC EP coating and water increases by 63%, and the friction coefficient decreases by 73%. The corrosion resistance of 3[Formula: see text]wt.% F–SiC EP coating is about three orders of magnitude higher than that of the EP coating soaked for six days.

Small GTPases of the Ras superfamily are master regulators of intracellular trafficking and constitute essential signaling components in all eukaryotes. Aberrant small GTPase signaling is associated with a wide spectrum of human diseases, including cancer. Here, we developed a high-throughput, multiple reaction monitoring–based workflow, coupled with stable isotope labeling by amino acids in cell culture, for targeted quantification of approximately 100 small GTPases in cultured human cells. Using this method, we investigated the differential expression of small GTPases in three pairs of primary and metastatic melanoma cell lines. Bioinformatic analyses of The Cancer Genome Atlas data and other publicly available data as well as cell-based assays revealed previously unrecognized roles of RAB38 in promoting melanoma metastasis. Diminished promoter methylation and the subsequent augmented binding of transcription factor MITF contributed to elevated expression of RAB38 gene in metastatic versus primary melanoma cells. Moreover, RAB38 promoted invasion of cultured melanoma cells by modulating the expression and activities of matrix metalloproteinases-2 and -9. Together, these data establish a novel targeted proteomic method for interrogating the small GTPase proteome in human cells and identify epigenetic reactivation of RAB38 as a contributing factor to metastatic transformation in melanoma.Significance: A novel quantitative proteomic method leads to the discovery of RAB38 as a new driver of metastasis in melanoma. Cancer Res; 78(18); 5431–45. ©2018 AACR.

I. Supplementary Figures Figure S1. LC-MRM-based targeted quantitative proteomic assay revealed differential expression of small GTPases during melanoma metastasis. Figure S2. The scheduled LC-MRM platform provides accurate retention time (RT) prediction of targeted peptides, high sensitivity and excellent reproducibility. Figure S3. Validation of RAB32 expression in WM-115/WM-266-4 and IGR39/IGR37 paired melanoma cell lines. Figure S4. RAB12 and RAB31 were differentially expressed in WM-115 and WM-266-4 cells. Figure S5. Western blots confirmed the overexpression and knockdown of RAB38 in WM-115 and WM-266-4 cells, respectively. Figure S6. RAB38 mediates both the expression levels and activities of MMP2 and MMP9 in metastatic IGR37 and M14 cells. Figure S7. Correlations of mRNA expressions of MITF, RAB38 and RAB27A with different genetic backgrounds of melanoma patients. Figure S8. Up-regulation of MITF in metastatic melanoma cells. Figure S9. RAB38 expressions were highly correlated with MITF in a large number of melanoma cell line and melanoma patient cohorts. Figure S10. Higher levels of expression of RAB38 in metastatic melanoma compared to primary melanoma were observed in melanoma patient with MITF high signature. Figure S11. Occurrence and prognostic values of RAB38 promoter hypomethylation. II. Supplementary Methods and Materials 1) Sample Preparation and LC-MS/MS for Shotgun Proteomic Analysis. 2) Retention time (RT) Prediction for Small GTPase Peptides. 3) Sample Preparation and Scheduled LC-MRM Analysis. 4) Construction and Transfection of FLAG-tagged Fusion Protein Expression Plasmid. 5) siRNA Transfection. 6) Real-time Quantitative PCR (RT-qPCR). III. Supplementary Tables Table S1. A complete list of primers used for real-time quantitative PCR (RT-qPCR) in this study. Table S2. A complete list of small GTPases of the Ras superfamily in the human proteome. Table S3A. A complete list of small GTPases in the Skyline MRM library with their gene names, IPI numbers, and targeted peptides and transitions. 4) Table S3B. A complete list of quantified small GTPase peptides and proteins in three sets of SILAC experiments for WM, IGR and WMLu paired melanoma cell lines.

Epitranscriptomic reader, writer, and eraser (RWE) proteins recognize, install, and remove modified nucleosides in RNA, which are known to play crucial roles in RNA processing, splicing, and stability. Here, we established a liquid chromatography-parallel-reaction monitoring (LC–PRM) method for high-throughput profiling of a total of 152 epitranscriptomic RWE proteins. We also applied the LC–PRM method, in conjunction with stable isotope labeling by amino acids in cell culture (SILAC), to quantify these proteins in two pairs of matched parental/radioresistant breast cancer cells (i.e., MDA-MB-231 and MCF-7 cells and their corresponding radioresistant C5 and C6 clones), with the goal of assessing the roles of these proteins in radioresistance. We found that eight epitranscriptomic RWE proteins were commonly altered by over 1.5-fold in the two pairs of breast cancer cells. Among them, TRMT1 (an m(2,2)G writer) may play a role in promoting breast cancer radioresistance due to its clinical relevance and its correlation with DNA repair gene sets. To our knowledge, this is the first report of a targeted proteomic method for comprehensive quantifications of epitranscriptomic RWE proteins. We envision that the LC–PRM method is applicable for studying the roles of these proteins in the metastatic transformation of cancer and therapeutic resistance of other types of cancer in the future.

Metastasis is a major obstacle in the therapeutic intervention of melanoma, and several GTP-binding proteins were found to play important roles in regulating cancer metastasis. To assess systematically the regulatory roles of these proteins in melanoma metastasis, we employed a targeted chemoproteomic method, which relies on the application of stable isotope-labeled desthiobiotin-GTP acyl phosphate probes in conjunction with scheduled multiple-reaction monitoring (MRM), for profiling quantitatively the GTP-binding proteins. Following probe labeling, tryptic digestion, and affinity pull-down of desthiobiotin-conjugated peptides, differences in expression levels of GTP-binding proteins in two matched pairs of primary/metastatic melanoma cell lines were measured using liquid chromatography–MRM analysis. We also showed that among the top upregulated proteins in metastatic melanoma cells, AK4 promotes the migration and invasion of melanoma cells; overexpression of AK4 in primary melanoma cells leads to augmented migration and invasion, and reciprocally, knockdown of AK4 in metastatic melanoma cells results in repressed invasiveness. In summary, we examined the relative expression levels of GTP-binding proteins in two pairs of primary/metastatic melanoma cell lines. Our results confirmed some previously reported regulators of melanoma metastasis and revealed a potential role of AK4 in promoting melanoma metastasis.

In recent years, with the continuous in-depth research on the pathogenesis of rheumatism and the rapid development of biopharmaceutical technology, the development of targeted drugs for rheumatism is in full swing. In order to better standardize the diagnosis and treatment of rheumatism and the rational application of targeted drugs, the Chinese Rheumatology Association will introduce the targeted drugs for rheumatism that have been approved by the China National Medical Products Administration so far, and provide clinicians with standardized diagnosis and treatment reference.近年来，随着对风湿病发病机制研究的不断深入，及生物制药技术的迅猛发展，风湿病的靶向药物发展如火如荼。中华医学会风湿病学分会为更好地规范风湿病诊疗及靶向药物的合理应用，就目前已取得中国国家药品监督管理局批准应用的风湿病靶向药物逐一介绍，为临床医生规范使用提供参考。.

Objective. The variable flip angle (VFA) method for longitudinal relaxation time (T 1) measurement is inherently sensitive to inaccuracies in the radiofRequency transmit field (B 1) and incomplete spoiling of transverse magnetization. The objective of this study is to devise a computational method that addresses the problems of incomplete spoiling and B 1 inhomogeneity in the estimation of T 1 using VFA method. Approach. Using an analytical expression of the gradient echo signal with account of incomplete spoiling, we first showed that ill-posedness in the simultaneous estimation of B 1 and T 1 can be lifted with the use of flip angles larger than the Ernst angle. We then devised a nonlinear optimization method based on this signal model of incomplete spoiling for simultaneous estimation of B 1 and T 1. Main results. We evaluated the proposed method on a graded-concentration phantom to show that the derived T 1 estimates offers an improvement over the regular VFA method and compares well with reference values measured by inversion recovery. Reduction of the number of flip angles from 17 to 5 yielded consistent results indicating that the proposed method is numerically stable. T 1 estimates derived from in-vivo brain imaging were consistent with literature values for gray and white matter tissues. Significance. Contrary to the common notion that B 1 correction in the VFA method for T 1 mapping should be performed separately, we show that combined estimation of B 1 and T 1 is feasible by the proposed method simply with the acquisition of 5 flip angles, as demonstrated on both phantom and in-vivo imaging data.

With the increasing demand to study the cause of complex diseases, mega cohort has gradually replaced the traditional small sample cohort and become the hotspot of epidemiological research. Follow-up is the essential step in a cohort study to obtain the information about the onset and death of diseases, migration or loss of follow-up of the cases. Its quality has a direct impact on the conclusions of cohort study. Therefore, it is necessary to develop a reasonable follow-up monitoring program for a mega cohort.In this paper, we summarized the contents and methods of the follow-up monitoring program in the mega cohorts at home and abroad, which aimed to provide suggestions for the new cohort and improve the follow-up program for the existing cohort.随着人们对复杂性疾病病因研究需求的日益提升，大型队列研究逐渐替代传统小样本队列研究，成为流行病学研究的热点。随访作为队列研究中的获取疾病发病、死亡以及迁移或失访资料的重要环节，其质量对队列研究的结论有着直接影响。因此，制定合理的随访监测方案成为大型队列研究成功的关键。本文主要针对目前国内外大型队列研究随访监测的内容和方法进行综述，旨在为新建队列研究的随访方案设计和现有队列随访方案改进提供建议和思路。.

Lateral lymph node metastasis (LLNM) has been considered a risk factor of recurrence in papillary thyroid cancer (PTC). Preoperative detecting LLNM accurately is difficult. Solitary lateral lymph node metastasis is a special type of LLNM. We aimed to develop nomograms for predicting LLNM and multiple lateral lymph node metastasis (MLLNM).We retrospectively retrieved 528 classic PTC patients that underwent surgery between March 2019 and May 2020. Sonographic and clinicopathological features were collected. Risk factors of LLNM and MLLNM were determined by univariate and multivariate analysis. Nomograms for predicting LLNM and MLLNM were developed.LLNM was independently associated with tumor size, the number of foci, location, margin, central lymph node metastasis, and lymph node ratio. Independent predictors of MLLNM were age, margin, and the number of metastatic lymph nodes in central compartment. By using above variables, we constructed nomograms for predicting LLNM and MLLNM, with area under curves of 0.864 and 0.748, respectively.Through these accurate and easy-to-use nomograms, we can detect the risk of residual LLNM postoperatively for classic PTC patients who did not receive lateral neck dissection and provide an individualized plan for postoperative management of classic PTC patients.

A compact/SPICE model for normally-off 650 V GaN power switches is presented. The industry standard physics-based ASM-HEMT model is used as the base for modeling the GaN HEMT in the cascode configured power switch. Accurate models for current-voltage (I-V) and capacitance-voltage (C-V) characteristics have been obtained. It is found that the bias-dependent two-dimensional electron gas under the field-plate regions are very important for modelling the complex capacitances of the cascode switch. Field-plates have been modeled with the ASM-HEMT formulations, and accurate models for input, output, and reverse transfer capacitance of the switch is obtained. The compact model for the full switch is created by synthesizing the MOSFET and HEMT models and optimizing model parameters.

Power cable undertakes the important task of power transmission. In recent years, the use of power cables is increasing, and its safe and reliable operation is very important to ensure the stable operation of distribution system. However, the cable is deeply buried in the ground, so it is difficult to find the problem in time and reliably in ordinary daily inspection. In recent years, the number of cable faults has increased greatly, and the fire failure caused by the explosion of cable intermediate joint accounts for more than 80%. Taking a typical large-scale fire accident of distribution cable as an example, this paper deeply analyzes the prominent problems existing in the installation process of cables and accessories, line protection configuration, operation and maintenance of cable operation environment. The case has high learning value and significant guiding significance. It basically covers the prominent problems in technology, process and management of current distribution cable. Through in-depth analysis of the case, targeted and reliable solutions are proposed, which can effectively improve the operation level of distribution network.

The distribution station area is composed of distribution transformer, low-voltage comprehensive distribution box, lowvoltage line, drop out fuse and other medium voltage protection equipment. It undertakes the important tasks of voltage transformation and power distribution in the distribution system, and its safe and reliable operation is very important to ensure the stable operation of the distribution system. With the continuous increase of load capacity, the operation environment of distribution station area is deteriorating day by day. The fire and damage accidents occur frequently in the distribution area, which seriously affect the safe and reliable operation of distribution network and have a very bad social impact. This paper takes a typical high and low voltage equipment comprehensive damage fault in the distribution station area as an example, analyzes the prominent problems existing in the low and medium voltage protection configuration, low voltage equipment installation technology, daily operation and maintenance management, etc. The case has high learning value and significant guiding significance. It basically covers the outstanding problems in technology, technology and management of the current distribution area. Through in-depth analysis of the case, targeted and reliable solutions are proposed, which can effectively improve the operation level of distribution network.

In the study of genetic diversity in non-model species there is a notable lack of the low-cost, high resolution tools that are readily available for model organisms. Genotyping microarray technology for model organisms is well-developed, affordable, and potentially adaptable for cross-species hybridization. The Mouse Diversity Genotyping Array (MDGA), a single nucleotide polymorphism (SNP) genotyping tool designed for Mus musculus, was tested as a tool to survey genomic diversity of wild species for inter-order, inter-genus, and intra-genus comparisons. Application of the MDGA cross-species provides genetic distance information that reflects known taxonomic relationships reported previously between non-model species, but there is an underestimation of genetic diversity for non-Mus samples, indicated by a plateau in loci genotyped beginning 10-15 millions of years divergence from the house mouse. The number and types of samples included in datasets genotyped together must be considered in cross-species hybridization studies. The number of loci with heterozygous genotypes mapped to published genome sequences indicates potential for cross-species MDGA utility. A case study of seven deer mice yielded 159,797 loci (32% of loci queried by the MDGA) that were genotyped in these rodents. For one species, Peromyscus maniculatus, 6,075 potential polymorphic loci were identified. Cross-species utility of the MDGA provides needed genetic information for non-model species that are lacking genomic resources. Genotyping arrays are widely available, developed tools that are capable of capturing large amounts of genetic information in a single application, and represent a unique opportunity to identify genomic variation in closely related species that currently have a paucity of genomic information available. A candidate list of MDGA loci that can be utilized in cross-species hybridization studies was identified and may prove to be informative for rodent species that are known as environmental sentinels. Future studies may evaluate the utility of candidate SNP loci in populations of non-model rodents.Author SummaryThere is a need for a tool that can assay DNA sequence differences in species for which there is little or no DNA information available. One method of analyzing differences in DNA sequences in species with well-understood genomes is through a genotyping microarray, which has demonstrated utility cross-species. The Mouse Diversity Genotyping Array (MDGA) is a tool designed to examine known differences across the genome of the house mouse, Mus musculus. Given that related organisms share genetic similarity, the MDGA was tested for utility in identifying genome variation in other wild mice and rodents. Variation identified from distantly related species that were not of the same genus as the house mouse was an underestimate of the true amount of variation present in the genomes of wild species. Utility of the MDGA for wild species is best suited to mice from the same genus as the house mouse, and candidate variation identified can be tested in rodent populations in future studies. Identifying changes in genetic variation within populations of wild rodents can help researchers understand the links between specific genome changes and the ability to adapt to pressures in the environment, as well as better understand the evolution of rodents.

The purpose of this study was to explore the effect of micro ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis (OA), and to research the association between its targeting on B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling pathway and chondrocyte apoptosis.The mouse model of OA was established via surgery, and chondrocytes were isolated and cultured in vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, with those normally cultured as the control. After that, the expression levels of miR-145 and BNIP3 in cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was detected via flow cytometry, and the apoptosis level was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the target gene sequences were predicted and compared using the software, and the BNIP3 Luciferase reporter vectors containing predicted target sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, Notch1, and P21 were determined through Western blotting.The results of qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than that in normal chondrocytes (p0.05), while the mRNA and protein expressions of BNIP3 were higher than those in normal chondrocytes (p0.05). According to flow cytometry, the apoptosis rate was (4.4±0.6)% in normal cartilage tissues and (29.2±2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly reduced chondrocyte apoptosis (p0.05), while overexpression of BNIP3 markedly increased chondrocyte apoptosis (p0.05). In addition, the Luciferase reporter system showed that miR-145 mimics evidently inhibited BNIP3 (p0.05) and suppressed the Notch signaling pathway (p0.05), while BNIP3 enhanced the expression of Notch signaling pathway (p0.05).MiR-145 can reduce OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and regulation on Notch signaling pathway.

To explore the influences of micro ribonucleic acid (miR)-204 on the rats with diabetic retinopathy by regulating the expressions of B-cell lymphoma 2 (Bcl-2) and sirtuin 1 (SIRT1).A total of 36 Sprague-Dawley rats were randomly assigned into normal group (n=12), model group (n=12), and miR-204 mimics group (n=12). No treatment was performed in the normal group, the diabetic retinopathy model was established in model group, and miR-204 mimics were administered for intervention after modeling in the inhibitor group. After 7 d, materials were sampled for detection. The expressions of Bcl-2 and SIRT1 were detected via immunohistochemistry, and their relative protein expression levels were determined via Western blotting (WB). Quantitative Polymerase Chain Reaction (qPCR) was performed to detect the expression of miR-204, and the content of inflammatory factors interleukin (IL)-6, IL-18, and tumor necrosis factor-α (TNF-α) was measured using enzyme-linked immunosorbent assay (ELISA). Finally, cell apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).Immunohistochemistry results showed that the positive expression levels of Bcl-2 and SIRT1 were substantially lower in the model and miR-204 mimics groups than those in the normal group (p0.05), and their positive expression levels in miR-204 mimics group were notably higher than those in model group (p0.05). According to Western blot (WB) results, the relative protein expression levels of Bcl-2 and SIRT1 markedly declined in the other two groups compared with those in the normal group (p0.05), while miR-204 mimics group exhibited remarkably higher relative protein expression levels of Bcl-2 and SIRT1 than the model group (p0.05). The results of qPCR revealed that the relative expression level of miR-204 was markedly lowered in model and miR-204 mimics groups compared with that in the normal group (p0.05), and its relative expression level in miR-204 mimics group was remarkably higher than that in the model group. It was found through enzyme-linked immunosorbent assay (ELISA) that compared with normal group, the other two groups had substantially increased content of IL-6, IL-18, and TNF-α (p0.05), and the content of IL-6, IL-18, and TNF-α in miR-204 mimics group was markedly lower than that in the model group (p0.05). According to TUNEL results, the apoptosis rate of cells rose substantially in the other two groups compared with that in the normal group (p0.05), while was notably lower in the miR-204 mimics group than that in the model group (p0.05).MiR-204 up-regulates Bcl-2 and SIRT1 expressions to inhibit the inflammation and cell apoptosis in rats with diabetic retinopathy.

HVDC cable has been widely used with the development of flexible HVDC transmission. Cable accessories are the weakest part of HVDC cables, while the most serious problem of DC cable joint is the uneven distribution of electric field caused by space charge accumulation, which may lead to the ageing and failure of joint insulation, especially at the interface between different materials. In this paper, the progress of the interface charge research of the HVDC cable accessories is discussed, the existing theoretical model and the suppression method of the interface charge are analyzed, and the research trend of the interface charge of the accessories in the future is prospected. The results show that space charges accumulate at the interface between different material are closely related to temperature, applied electric field and working conditions such as polarity reversal, etc.; the Maxwell-Wagners-Sillars theory and bipolar charge transport model are discussed in detail, and the method of using quantum chemical theory to calculate and analyze interface charges is introduced; the methods of interface charge suppression based on geometry design, surface modification, field grading materials and material selection are analyzed and compared.

This abstract was not presented at the conference. Citation Format: Zang Y-S, Qi F, Qin W-X. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-23.

RNA contains more than 170 types of chemical modifications, and these modified nucleosides are recognized, installed and removed by their reader, writer, and eraser (RWE) proteins, respectively. Here, we employed a parallel-reaction monitoring (PRM)-based targeted proteomic method, in conjunction with stable isotope labeling by amino acids in cell culture (SILAC), to examine comprehensively the differential expression of epitranscriptomic RWE proteins in a matched pair of primary/metastatic colorectal cancer (CRC) cells, namely SW480/SW620. We were able to quantify 113 nonredundant epitranscriptomic RWE proteins; among them, 48 and 5 were up- and down-regulated by 1.5-fold in SW620 over SW480 cells, respectively. Some of those proteins with marked up-regulation in metastatic CRC cells, including NAT10, hnRNPC, and DKC1, were documented to assume important roles in the metastasis of CRC and other types of cancer. Interrogation of the Clinical Proteomic Tumor Analysis Consortium data revealed the involvement of DUS1L in the initiation and metastatic transformation of CRC. It can be envisaged that the PRM method can be utilized, in the future, to identify epitranscriptomic RWE proteins involved in the metastatic transformations of other types of cancer.

Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). In summary, our targeted kinome profiling method provided by far the most comprehensive dataset for kinome reprogramming associated with melanoma progression, which builds a solid foundation for examining the functions of other kinases in melanoma metastasis. Moreover, our results reveal a role of JAK3 as a potential suppressor for melanoma metastasis.

Through the effort in nearly 40 years of Tanzania, the total number of reported cases, the prevalence of HIV/AIDS and the number of death have declined, while the number of patients receiving antiretroviral therapy has increased significantly in Tanzania. At the same time, however, there are new challenges that require more attention, such as the HIV spread to rural areas, middle and lower social classes, and female teenagers. Although the overall performance of the HIV/AIDS prevention and control response is great, there is still a need to survey the new trends of this disease at the micro-level in Tanzania. In addition, there is a necessity of interdisciplinary concern due to the prevalence of heterosexual anal sex in Tanzania.通过近40年的努力，坦桑尼亚艾滋病疫情出现了新报告数、患病率和死亡数下降，抗病毒治疗数上升的态势，但同时也出现了艾滋病疫情流向农村、中低收入社会阶层、青少年和女性等更值得关注的人群。据此，在整体意义上肯定坦桑尼亚的努力与付出，但同时更应从微观层面来审视其新动向。另外，普遍发生的异性肛交与艾滋病广泛流行的关联亟待加强人类学或者跨学科的关注。.

In this study, a comprehensive comparison in light of the switching behavior has been made to the AlO x dielectrics in Resistive Random Access Memory (RRAM) devices, which were fabricated with solution-processed (SP) and atomic-layer-deposition (ALD) based techniques under the same temperature (250°C). The improved resistive switching properties such as smaller Vset/Vreset (1.2~1.8 V/−0.9~−1.3 V), a narrower RHRs/RLRs distribution (2~80 k Ω /0.8~1 k Ω) and a higher resistance ratio (8~230) under 5 mA compliance current (CC) have been achieved with SP method. The conduction mechanisms of the ON and OFF state for both devices are the ohmic conduction and Frenkel-Poole emission, respectively. Therefore, the solution-based fabrication method has the potential application for the flexible memory, due to the fabrication merits of the low-temperature, low cost, large area implementation and being environmental-friendly.

In this work, the compounds of brominated epoxy resins and antimony trioxide (BER/Sb2O3) additives are analyzed and added into long-glass-fiber reinforced polyamide 6 (PA6/LGF) composites in order to solve the “candle-wick effect” caused by glass fibers. The thermal stability, flammability, and morphology of charred residues of the flame retardant PA6/LGF composites are investigated by thermogravimetric analysis (TGA), limiting oxygen index (LOI), UL-94 test, cone calorimeter test (CCT), and scanning electronic microscopy (SEM). The results show the addition of BER/Sb2O3 provides improvements in flame retardancy by increasing the LOI values, enhancing UL-94 rating, and reducing the heat release rate, total heat release and effective heat of combustion due to the formation of consolidated and thick charred residual structures on the surfaces of the LGF reinforced PA6 composites. When the content of BER/Sb2O3 is increased to 12 wt%, the LOI value and UL-94 rating of BER/PA6/LGF composites reach 24.8 and V-0, respectively. The TGA results exhibit that the decomposition temperature of the PA6/LGF composites decreases with the addition of BER/Sb2O3 additive, resulting in forming some high quality residual char layer. A possible flame retardant mechanism is proposed to illustrate the effect of the gaseous and condensed phases on the flame retardancy of the PA6/LGF composites.

Drought is a major environmental stress that limits potato (Solanum tuberosum L.) production worldwide. The transcription factor DREB1A/CBF3 specifically interacts with the dehydration responsive element (DRE/CRT) and induces expression of genes involved in environmental stress tolerance in Arabidopsis thaliana. In this study, DREB1A of A. thaliana was overexpressed in a potato cultivar Longshu 3 (L3) through Agrobacterium tumefaciens-mediated transformation. The transformation and overexpression of DREB1A were assessed using PCR, Southern blotting and semi-quantitative RT-PCR analysis. The results clearly confirmed that the DREB1A gene was successfully integrated into the genome and expressed. When pot-grown plants with 15–16 leaves were subjected to drought stress treatments by withholding water for 8 days, the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), the MDA content and electrolyte leakage in leaves from both non-transgenic and transgenic L3 plants leaves increased. The average activities of SOD, CAT, and POD in transgenic plant leaves, respectively showed 69.77, 60.78, and 24.60% increase than those of non-transgenic L3. The MDA content and electrolyte leakage in non-transgenic L3 plant leaves, respectively increased 59.09 and 37.63% relative to those of transgenic plant leaves. When water was withheld for 14 days control plants exhibited severe wilting and transgenic plants only partially wilting. These results demonstrated that overexpression of DREB1A resulted in improved drought stress tolerance in S. tuberosum plants.

Metastasis is the leading cause for mortality in melanoma patients. Here, an unbiased mass spectrometry-based quantitative proteomic method is utilized to assess differential protein expression in a matched pair of primary/metastatic melanoma cell lines (i.e., WM-115/WM-266–4) derived from the same patient. It is found that TBC1D7 is overexpressed in metastatic over primary melanoma cells, and elevated expression of TBC1D7 promotes the invasion of these melanoma cells in vitro, partly through modulating the activities of secreted matrix metalloproteinases 2 and 9. Additionally, interrogation of publicly available data show that higher mRNA expression of TBC1D7 predicts poorer survival in melanoma patients. Together, the results suggest TBC1D7 as a driver for melanoma cell invasion, which is an important element in melanoma metastasis. The proteomic data generated from this study may also be useful for exploring the roles of other proteins in melanoma metastasis.

Millimeter-wave(MMW) radar sensing is one of the most promising technologies to provide safe navigation for autonomous vehicles due to its expected high-resolution imaging capability However, driverless cars have higher request for different environment and light conditions. Therefore, millimetre-wave imaging is of paramount importance for complex load scenario. In this paper, we have built models of pavement pits and bulges and analysed their with differences ways of antennas. A comparison of the imaging performance of experimental systems operating at a MMW radar and a Lidar is presented with the analysis of features for initial image interpretation Experimental images of the complex road surface are made by a 94GHz frequency-modulated continuous-wave (FMCW) radar technique with 3mm wavelength.