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In this article, an integrated method is proposed for evaluating the requirements of smart manufacturing systems under the era of Industry 4.0 and Industrial Internet of Things. This method uses systematic research on identifying, classifying, and evaluating the requirements of smart manufacturing systems with uncertainty, multi-users, and multi-disciplines. The results of this article provide a procedure to capture the preferential SMSs-R and the framework of SMSs-R. First, this method provides a comprehensive requirement of smart manufacturing identified by questionnaire survey, document reviews, and the affinity diagram method. Second, the classification of SMSs-R considers the multi-user preference by the fuzzy Kano model. Third, the best non-fuzzy performance and fuzzy analytic hierarchy process method is used for evaluating and ranking the SMSs-R factor to solve the uncertain, vague, and preferential questions. Finally, we validated the effectiveness of the method through a real discrete manufacturing enterprise case.

In the tide of smart manufacturing in the world, many countries have put forward their own reference frameworks for smart manufacturing system. Based on the framework of smart manufacturing system (SMS) proposed by China, a reference smart manufacturing integration system (SMIS) from multi-level and multi-perspective was proposed. The reference model of SMIS was analyzed by means of system engineering. Based on this model, the overall architecture of SMIS was proposed. Then, the physics subsystem, information integration subsystem, network integration subsystem, data integration subsystem, and visualization integration subsystem for SMIS were proposed through the overall architecture of SMIS. Finally, the above integrated subsystems were collected together to deduce the implementation path of SMIS. Four reference subsystems for SMIS proposed in this paper have achieved good effects in the projects we participated in, which were organized by the state. The research results of this paper can be used as a reference for industry and government to design, set, and carry out SMIS. At the same time, it has a certain reference value for the improvement and supplement of national smart manufacturing system architecture.

Autophagy is central to the maintenance of intracellular homeostasis across species. Accordingly, autophagy disorders are linked to a variety of diseases from the embryonic stage until death, and the role of autophagy as a therapeutic target has been widely recognized. However, autophagy-associated therapy for human diseases is still in its infancy and is supported by limited evidence. In this review, we summarize the landscape of autophagy-associated diseases and current autophagy modulators. Furthermore, we investigate the existing autophagy-associated clinical trials, analyze the obstacles that limit their progress, offer tactics that may allow barriers to be overcome along the way and then discuss the therapeutic potential of autophagy modulators in clinical applications.

In this paper, we investigate the secure transmission in multigroup multicasting cell-free massive MIMO system in the presence of pilot spoofing attack. With the imperfect uplink and downlink channel estimation, a distributed conjugate beamforming processing with normalized power constraint policy is exploited at access points (APs) for downlink multicasting data transmission. Closed-form expressions for the per-user achievable rate are derived with and without downlink training, respectively. Also, the analytical results of the upper bound on the information leakage to eavesdropper are carried out. Moreover, a mechanism based on the minimum description length (MDL) is presented to detect pilot spoofing attack. Consequently, the achievable ergodic secrecy rate is obtained to evaluate the system's secrecy performance. The numerical results are presented to quantitatively analyze the impacts of eavesdropper's spoofing pilot power and the number of groups on the secrecy performance of the considered systems.

This paper investigates the secure transmission in multi-pair massive multiple-input multiple-output amplify-and-forward (AF) relaying networks under active pilot spoofing attacks. The AF relaying beamforming and the artificial noise generation are designed based on the imperfect estimated channel state information. Exploiting a random matrix theory, we first derive the tractable analytical expressions for the end-to-end signal-to-interference-plus-noise ratios (SINRs) at both the intended user and the eavesdropper. Then, we provide the asymptotic results for derived SINRs with respect to the infinite number of relay antennas, unbounded transmit power, and relay power, which show that the SINRs at intended user and eavesdropper are both limited by specific bounds and the effects of relay noise or received additive noise will be eliminated in these extreme power cases. Moreover, power scaling laws are studied to reveal that only the scaled relay power is effective, while source power has no scaling properties for secure transmission in the considered system. To mitigate the severe information leakage, by superimposing a random detection pilot sequence on the training sequence, a simple method based on the minimum description length criterion is provided to detect the presence of the pilot spoofing attacks. The numerical results are provided to confirm the accuracy of our theoretical derivations and illustrate the effectiveness of the proposed scheme.

Mesothelin (MSLN) is a cell surface glycoprotein that is expressed by most pancreatic ductal adenocarcinoma (PDAC) and is used as a target for anti-cancer therapy. MSLN expression appears to make pancreatic cancer more aggressive. Previously, we found that MSLN KO PDAC cells grow in culture and as subcutaneous tumors similarly to wild-type (WT) cells but form intraperitoneal metastases poorly. MSLN pre-cursor (pre-MSLN) is a 71-kD glycosylphosphatidylinositol (GPI)-anchored protein that is cleaved intracellularly to make the 31-kD secreted protein Megakaryocyte Potentiating Factor (MPF), and a 40-kD mature MSLN (mMSLN) that retains membrane attachment. The mMSLN can be shed from the cell surface by the action of specific proteases, resulting in release of soluble MSLN (sMSLN) to both the tumor microenvironment and serum. The goal of this study is to see if sMSLN promotes cancer cell aggressiveness. We transduced MSLN KO pancreas cancer cells to express: 1) a mutant, secreted-only pre-MSLN (includes WT MPF) with a C-terminal truncation (MSLNΔ599) that prevents GPI-linkage of MSLN to the membrane, and 2) truncated pre-MSLN consisting of MPF only. Results show that complementation of KO cells with MPF or MSLNΔ599 does not rescue the MSLN KO phenotype, while MSLNΔ599 bearing a Y318A point mutation that disrupts the binding of MSLN to MUC16/CA125 does restore growth of peritoneal metastasis. We performed RNA-deep sequencing on MSLN KO cells exposed to WT or Y318A sMSLN from conditioned medium. We identified 2000 genes that were differentially expressed across the treatment groups. Exposure to sMSLN resulted in changes in expression of cell adhesion and sterol biosynthetic synthesis pathway genes. Individual genes that were top hits were also identified and are under investigation. Exposure to sMSLN changes the transcriptomic program of pancreas cancer cells and may promote peritoneal colonization. Citation Format: Theressa Ewa, Leela Avula, Sarah Joseph, Michael Rudloff, Samantha Sevilla, Vishal Koparde, Xianyu Zhang, Christine Alewine. Soluble mesothelin acts as a signaling molecule [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 93.

Enterprise information systems play a significant role in the Industry 4.0 era and are the crucial component to realize smart manufacturing systems. However, traditional enterprise information systems have some limits: (1) lack of complete information, (2) only satisfy limited business needs, and (3) lack of seamless integration, business intelligence, value-driven processes, and dynamic optimization. Clearly, the existing enterprise information systems are unable to satisfy the requirements for smart manufacturing systems: (1) autonomous operation, (2) sustainable values, and (3) self-optimization. In addition, smart manufacturing systems have become more efficient and effective, demanding for seamless information flow in enterprise information systems, knowledge, and data-driven accurately decision. Therefore, a new enterprise information systems framework is needed to bridge gaps between the requirements for traditional manufacturing system and smart manufacturing system. In this article, the integrative framework is proposed based on the business process reengineering, lean thinking, and intelligent management methods, with inclusion of six enterprise information systems aspects to provide upgrading guidelines from traditional manufacturing to smart manufacturing. The procedure of this method contains three steps: (1) it identifies requirements and acquires best practices using AS-IS model, (2) it redesigns six aspects of enterprise information systems using TO-BE model, and (3) it proposes a new enterprise information systems framework. Finally, the proposed framework is validated by real cases.

The present study examined the effect of microRNA (miRNA/miR)-186-3p and its target gene, minichromosome maintenance complex component 2 (MCM2), on cervical cancer. Cervical cancer tissues and corresponding normal tissues were collected from 48 patients and bioinformatics analysis was performed to identify the differentially expressed genes in cervical cancer. TargetScan and TarBase were used to identify miRNAs, and reverse transcription-quantitative PCR was conducted to detect and evaluate mRNA expression levels. Additionally, MTT and 5-bromo-2-deoxyuridine assays were performed to examine cell proliferation. Cell adhesion, cell cycle distribution and apoptosis were assessed using cell adhesion, flow cytometry and caspase-3/7 activity assays, respectively. The results revealed that miR-186-3p expression was downregulated in cervical cancer tissues and cells, and it negatively regulated MCM2 expression by directly targeting its 3′ untranslated region in cervical cancer. Furthermore, MCM2 facilitated cell proliferation and inhibited cell apoptosis, which were reversed by upregulation of miR-186-3p expression. Collectively, the present study suggested that MCM2 and its negative regulator, miR-186-3p, regulate cervical cancer progression.

Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54–99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56–100%), and AUPRC = 0.9220 (95% CI: 91.02–94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72–99.27%), and AUPRC = 0.9111 (95% CI: 88.45–93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07–98.91%), and AUPRC = 0.8640 (95% CI: 82.82–89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72–97.87%) and a specificity of 98.70% (95% CI: 86.36–100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75–99.55%), and AUPRC = 0.9800 (95% CI: 96.6–99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95–96.34%), and AUPRC = 0.9490 (95% CI: 91.7–98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p

Antibody-based therapies designed for human use frequently fail to cross-react with the murine isoform of their target. Because of this problem, preclinical studies of antibody-based mesothelin (Msl)-targeted therapeutics in immunocompetent systems have been limited by the lack of suitable mouse models. Here, we describe two immunocompetent humanized mesothelin transgenic mouse lines that can act as tolerant hosts for C57Bl/6-syngeneic cell lines expressing the human isoform of mesothelin. Thyroid peroxidase (TPO) mice have thyroid-restricted human mesothelin expression. Mesothelin (Msl) mice express human mesothelin in the typical serosal membrane distribution and can additionally be utilized to assess on-target, off-tumor toxicity of human mesothelin–targeted therapeutics. Both transgenic strains shed human mesothelin into the serum like human mesothelioma and patients with ovarian cancer, and serum human mesothelin can be used as a blood-based surrogate of tumor burden. Using these models, we examined the on-target toxicity and antitumor activity of human mesothelin–targeted recombinant immunotoxins. We found that immunotoxin treatment causes acute and chronic histologic changes to serosal membranes in Msl mice, while human mesothelin-expressing thyroid follicular cells in TPO mice are resistant to immunotoxin despite excellent drug delivery. Furthermore, poor delivery of immunotoxin to syngeneic orthotopic human mesothelin-expressing pancreatic adenocarcinoma limits antitumor activity both alone and in combination with immune checkpoint inhibition. In summary, we have developed two high-fidelity, immunocompetent murine models for human cancer that allow for rigorous preclinical evaluation of human mesothelin–targeted therapeutics.

The Facility AO systems at the LBT are based around the two Adaptive Secondary Mirrors (ASM) and the Pyramid Wavefront Sensors (PWFS), the latter being recently upgraded as part of the SOUL project in order to provide improved image quality performance and greater faint target sensitivity, at the LUCI and LBTI ports. These represent operational AO Systems with unique challenges for maintaining their optimal operational status. Based on our experience, especially over the last seven years, we present our approach to provide the readiness of the AO systems at all times including routine calibration, monitoring, and maintenance activities necessary to keep their performance at an optimal level. We also address intervention activities to improve the ASMs’ reliability and robustness.

With the exception of the two prime focus cameras, all the instruments on the Large Binocular Telescope (LBT) use the two advanced 672-voice-coil-actuators adaptive secondary mirrors (ASMs). Based on 10 years of ASMs operation experience, and taking advantage of new technology developments, we decided to upgrade some of the ASMs hardware, to increase their performance and reliability. In this paper, we describe these improvements, i.e., upgrade of the power backplanes used in the ASM electronic control system, integration of an accelerometer-based tip-tilt vibration suppression system and upgrade of the optical calibration interferometers.

The adaptive secondary mirrors (ASMs), being an integral part of the telescope optical train, have huge advantages over other wave-front correctors. At the same time, because of this specific characteristic, high performance and high reliability is required from an ASM. In this paper, we report on algorithm/software developments at the Large Binocular Telescope designed to improve performance and reliability of the two 672-voice-coil-actuators ASMs. By making use of the ASMs telemetry, we are able to intervene when critical condition occurs, monitor the daily operation of the ASMs and review the long-term trends to plan future maintenance activities.

Spermatogonial stem cell (SSC) transplantation is an alternative reproductive method to achieve conservation and production of elite animals in livestock production. Creating a recipient animal without endogenous germ cells is important for effective SSC transplantation. However, natural mutants with depletion of SSCs are difficult to obtain, and drug ablation of endogenous germ cells is arduous to perform for practical use. In this study, we used mouse models to study the preparation of recipients with congenital germ cell ablation. We knocked out (KO) Ets-variant gene 5 (Etv5) in mice using the CRISPR/Cas9 system. The testicular weight of Etv5−/− mice was significantly lower than that of wild-type (WT) mice. The germ cell layer of the seminiferous tubules gradually receded with age in Etv5−/− mice. At 12 weeks of age, the tubules of Etv5−/− mice lacked almost all spermatogenic cells with a Sertoli cell-only phenotype, and sperm were completely absent in the epididymis. We subsequently transplanted allogeneic SSCs with enhanced green fluorescent protein (EGFP) into 3- (immature) or 7-week-old (mature) Etv5−/− mice. Partially restoration of germ cell layers in the seminiferous tubules and spermatogenesis was observed in all immature testes but not in mature adult testes at 2 months post-transplantation. The presence of heterologous genes Etv5 and EGFP in recipient testicular tissue and epididymal sperm by PCR indicated that sperm originated from the transplanted donor cells. Our study demonstrates that, although Etv5−/− mice could accommodate and support foreign germ cell transplantation, this process occurs in a quite low efficiency to support a full spermatogenesis of transplanted SSCs. However, using Etv5−/− mice as a recipient model for SSC transplantation is feasible, and still needs further investigation to establish an optimized transplantation process., Summary: Spermatogonial stem cell transplantation in mice with germline ablation by genetic modification of a specific gene.

Methylation alterations of imprinted genes lead to loss of imprinting (LOI). Although studies have explored the mechanism of LOI in breast cancer (BC) development, the association between imprinted gene methylation in peripheral blood and BC risk is largely unknown. We utilized HumanMethylation450 data from TCGA and GEO (n = 1461) to identify the CpG sites of imprinted genes associated with BC risk. Furthermore, we conducted an independent case-control study (n = 1048) to validate DNA methylation of these CpG sites in peripheral blood and BC susceptibility. cg26709929, cg08446215, cg25306939, and cg16057921, which are located at KCNQ1, KCNQ1OT1, and PHLDA2, were discovered to be associated with BC risk. Subsequently, the association between cg26709929, cg26057921, and cg25306939 methylation and BC risk was validated in our inhouse dataset. All 22 CpG sites in the KCNQ1OT1 region were associated with BC risk. Individuals with a hypermethylated KCNQ1OT1 region (>0.474) had a lower BC risk (OR: 0.553, 95% CI: 0.397−0.769). Additionally, the methylation of the KCNQ1OT1 region was not significantly different among B cells, monocytes, and T cells, which was also observed at CpG sites in PHLDA2. In summary, the methylation of KCNQ1, KCNQ1OT1, and PHLDA2 was associated with BC risk, and KCNQ1OT1 methylation could be a potential biomarker for BC risk assessment.

Objectives Complement 1q binding protein (C1QBP/HABP1/p32/gC1qR) has been found to be overexpressed in triple-negative breast cancer (TNBC). However, the underlying mechanisms of high C1QBP expression and its role in TNBC remain largely unclear. Hypoxia is a tumor-associated microenvironment that promotes metastasis and paclitaxel (PTX) chemoresistance in tumor cells. In this study, we aimed to assess C1QBP expression and explore its role in hypoxia-related metastasis and chemoresistance in TNBC. Materials and Methods RNA-sequencing of TNBC cells under hypoxia was performed to identify C1QBP. The effect of hypoxia inducible factor 1 subunit alpha (HIF-1α) on C1QBP expression was investigated using chromatin immunoprecipitation (ChIP) assay. The role of C1QBP in mediating metastasis, chemoresistance to PTX, and regulation of metastasis-linked vascular cell adhesion molecule 1 (VCAM-1) expression were studied using in vitro and in vivo experiments. Clinical tissue microarrays were used to verify the correlation of C1QBP with the expression of HIF-1α, VCAM-1, and RELA proto-oncogene nuclear factor-kappa B subunit (P65). Results We found that hypoxia-induced HIF-1α upregulated C1QBP. The inhibition of C1QBP notably blocked metastasis of TNBC cells and increased their sensitivity to PTX under hypoxic conditions. Depletion of C1QBP decreased VCAM-1 expression by reducing the amount of P65 in the nucleus and suppressed the activation of hypoxia-induced protein kinase C-nuclear factor-kappa B (PKC-NF-κB) signaling. immunohistochemistry (IHC) staining of the tissue microarray showed positive correlations between the C1QBP level and those of HIF-1α, P65, and VCAM-1. Conclusion Targeting C1QBP along with PTX treatment might be a potential treatment for TNBC patients., Graphical Abstract In TNBC cells, the inhibition of C1QBP suppresses PKC–NF-κB signaling in cytoplasm, upregulating Iκβα expression, thereby decreasing the VCAM-1 expression by lowering p65 level in nucleus in normoxic conditions. When TNBC cells are exposed to hypoxic conditions, HIF-1α upregulates C1QBP expression. The inhibition of C1QBP notably suppresses the activation of hypoxia-induced PKC–NF-κB signaling and decreases VCAM-1 level, resulting in metastasis blocking and PTX drug chemoresistance decreasing of TNBC cells.

The trend towards socialization, personalization and servitization in smart manufacturing has attracted the attention of researchers, practitioners and governments. Social manufacturing is a novel manufacturing paradigm responding to this trend. However, the current cyber&ndash, physical system (CPS) merges only cyber and physical space, social space is missing. A cyber&ndash, physical&ndash, social system (CPSS)-based smart manufacturing is in demand, which incorporates cyber space, physical space and social space. With the development of the Internet of Things and social networks, a large volume of data is generated. A data-driven view is necessary to link tri-space. However, there is a lack of systematical investigation on the integration of CPSS and the data-driven view in the context of social manufacturing. This article proposes a seven-layered framework for a data-driven CPSS (D-CPSS) along the data&ndash, information&ndash, knowledge&ndash, wisdom (DIKW) pyramid under a social manufacturing environment. The evolution, components, general model and framework of D-CPSS are illustrated. An illustrative example is provided to explain the proposed framework. Detailed discussion and future perspectives on implementation are also presented.

Automated warehouse is an important part of modern intelligent logistics distribution center, which is developed from modern logistics technology, warehousing technology and automation technology, and integrates storage, transportation and distribution. However, due to the inconsistency between the information control system of the automated stereoscopic database and the information system of manufacturing enterprises, how to integrate and apply it has become a pain point for many manufacturing enterprises. In this paper, the integration and application of ERP system and WMS system in function, business, data, etc. are solved by using middle table technology. This method can effectively solve the problem that multiple systems cannot be directly connected, and can reduce the repeated work of data entry in different systems. At the same time, it can also avoid the data difference caused by manual operation. It not only makes the data transmission safe, stable and reliable, but also reduces the cost and avoids the repeated development.

The purpose of our article was to probe the influence of GRINA on rectal cancer and how GRINA is regulated in rectal cancer. Based on the public data, we found that GRINA was highly expressed in rectal cancer tissues and related to worse prognosis in rectal cancer patients. MiR-296 was predicted as an upstream regulatory miRNA of GRINA, which was further verified by dual-luciferase reporter assay. Moreover, we revealed that up-regulation/down-regulation of GRINA facilitated/suppressed SW1463/SW837 cell proliferation, migration, and invasion. Rescue assays indicated that the facilitating impact of GRINA on SW1463 cell proliferation and motility was abolished by miR-296 over-expression whilst the suppressing influence of GRINA on SW837 cell proliferation, migration, and invasion was reversed by miR-296 depletion. These consequences indicated that GRINA, which might be regulated by miR-296, acted stimulative important impact on rectal cancer cells, insinuating that GRINA might be a novel potential target for rectal cancer therapy.

Recently the competition between firms is transforming from &ldquo, firm vs. firm&rdquo, to &ldquo, ecosystem vs. ecosystem&rdquo, To fulfil the personalized customer requirements for a high-quality product-service in the age of servitization and sustainability, it is difficult for an individual actor to realize it. The product-service system (PSS) is naturally an integration of product and service. The final product-service of PSS that depends on a tangible product and intangible service, calls for value co-creation of multi-stakeholders. However, most existing related works have investigated PSS from the perspective of a supply chain or network, PSS in the view of an ecosystem of multi-stakeholders lacks sufficient exploration, especially the topic on the relationship between product-service and stakeholders. To fill the gap, this paper proposed a framework for the PSS ecosystem with quality function deployment (QFD) and fuzzy analytic network process (fuzzy ANP) to determine the stakeholders by clarifying the relationship between the final integrated product-service and stakeholders. Firstly, the PSS ecosystem structure was presented, including the stakeholders. Secondly, a model with the three-stage fuzzy ANP-QFD approach to determine stakeholders was employed. Thirdly, the specific process of the three-stage approach was presented. An illustrative case study of the automobile aftermarket was presented to verify the proposed model and approach. Discussions and future directions concluded this paper.

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancers, and patients with this subtype usually have a poor prognosis. Early analyses identified that fibroblast growth factor receptor 4 (FGFR4) was involved in breast cancer, but its prognostic effect on TNBC is unknown. In the present study, we investigated the association between FGFR4 and TNBC prognosis.Methods: FGFR4 protein expression was detected in 282 TNBC patients using immunohistochemistry.Results: FGFR4 was highly expressed in TNBC patients. Lymph node metastasis (LNM) (P=0.033) and p53 status (P=0.019) were associated with high FGFR4 expression. Univariate analysis identified high FGFR4 expression (P=0.016) as a prognostic predictor, and multivariate analysis found that high FGFR4 expression (P=0.016) was an independent prognostic factor. The Kaplan-Meier survival curve showed that high FGFR4 protein expression was correlated with poorer overall survival.Conclusions: The results of our present study show that FGFR4 protein expression is correlated with a worse prognosis in TNBC.

Transplantation of spermatogonial stem cells (SSCs) is an alternative reproductive method to achieve conservation and production of elite animals in livestock production. Creating a recipient animal without endogenous germ cells is important for effective SSC transplantation. However, natural mutants with depletion of SSCs are difficult to obtain, and drug ablation of endogenous germ cells is arduous to perform for practical use. In this study, we used mouse models to study the preparation of recipients with congenital germ cell ablation. We knocked out (KO) Ets-variant gene 5 (Etv5) in mice using the CRISPR/Cas9 system. The testicular weight of Etv5-/- mice was significantly lower than that of wild-type (WT) mice. The germ cell layer of the seminiferous tubules gradually receded with age in Etv5-/- mice. At 12 weeks of age, the tubules of Etv5-/- mice lacked germ cells (Sertoli cell-only syndrome), and sperm were completely absent in the epididymis. We subsequently transplanted allogeneic SSCs with enhanced green fluorescent protein (EGFP) into 3-(immature) or 7-week-old (mature) Etv5-/- mice. Restoration of germ cell layers in the seminiferous tubules and spermatogenesis was observed in all immature testes but not in mature adult testes at 2 months post-transplantation. The presence of heterologous genes Etv5 and EGFP in recipient testicular tissue and epididymal sperm by PCR indicated that sperm originated from the transplanted donor cells. Our study demonstrates that, although Etv5-/- mice could accommodate and support foreign germ cell transplantation, this process occurs in a quite low efficiency to support a full spermatogenesis of transplanted SSCs. However, using Etv5-/- mice as a recipient model for SSC transplantation is feasible, and still needs further investigation to establish an optimized transplantation process.

In the rapid development of marine aquaculture, the water quality of aquatic environments is regarded as a main limiting factor. Therefore, it is necessary to assess the water quality and environmental conditions in marine aquaculture areas and find out the main influencing factors regarding damage to the water quality environment. In the present research, pond aquaculture and cage aquaculture areas were sampled in May, August and November in 2018. Nine water quality indicators were detected, including pH, temperature, salinity, dissolved oxygen, molybdate-reactive phosphorus, chemical oxygen demand, chlorophyll a, inorganic nitrogen and antibiotic resistance genes (ARGs). Principal component analysis (PCA) was used to analyze the water quality conditions, spatial&ndash, temporal changes, and the driving factors in pond and cage aquaculture areas. The results showed that three main components were extracted from the pond aquaculture area, which explained 66.82% of the results, the most relevant factors are salinity, dissolved oxygen and ARGs. For the cage aquaculture area, three main components were extracted which can account for 72.99% of the results, the most relevant factors are chlorophyll a, salinity and dissolved oxygen. The comprehensive scores of the principal components indicated that the heaviest polluted months in pond and aquaculture areas were August and November, respectively. The water quality of the pond aquaculture area is mainly limited by the volume of the pond, while aquaculture activities and seasonality are the main factors for cage aquaculture. ARGs in cage culture areas showed more variety and frequency compared with pond culture areas, which indicated that terrestrial input might be one of the sources for ARGs occurrence. The results would be helpful for the relevant authorities to select water quality monitoring parameters in marine aquaculture areas.

Introduction Spinal cord injury (SCI) leads to abnormal expression of miRs, leading to secondary responses such as oxidative stress, inflammation and apoptosis. In the present work, we screened the miRs involved and the associated pathway. Methods In a rat model of SCI, the microarray analysis for expression of miRs at various time points post-SCI was done. The locomotor analysis was done by Basso, Beattie and Bresnahan score, and Cresyl violet staining was done for lesion volume and TUNEL assay was done for apoptosis in neuronal cells. The expression of apoptotic proteins was done by the western blot study. Results It was evidenced that the expression of the number of miRs was altered on the 14th day post-SCI, and miR-142-3p was found to be the most significantly suppressed miR. The results suggested that overexpression of miR-142-3p by its agomir-attenuated functional recovery decreased lesion size and apoptosis of neuronal cells in rats subjected to SCI. The luciferase assay indicated that miR-142-3p blocked the levels of Bax, which is a significant activator of the mitochondrial apoptotic pathway (MAP) via targeting the 3′UTR region of BV-2 cells, and in addition, pc-DNA-Bax restored Bax and inhibited the correcting role of miR-142-3p in hydrogen peroxide-treated BV-2 cells. The findings suggested that miR-142-3p may inhibit the MAP by inhibiting the expression of cleaved-caspase-3/-9 and Bax in SCI rats. Conclusion This study concludes that miR-142-3p may attenuate the functional recovery and decrease apoptosis in neuronal cells via inhibiting the MAP in the spinal cord-injured rats, confirming miR-142-3p as a potential therapeutic target in treating SCI.

In order to enhance competitiveness, modern enterprises constantly pursue product based innovation, such as the innovation of manufacturing model, service model, and networked collaborative model based on products. Based on these model innovations, this paper is intended for the complex networked product service system, and focuses on the form of network collaboration, organization, mechanism, kernel, etc. The purpose of this paper is to build the comprehensive framework and network model of N-PSS, realize the coordination and value-added of products and services within and outside the company, and improve the efficiency of products and services. Firstly, an integrated collaborative network integrating vertical and horizontal services is constructed, which is helpful to analyze the degree of association, closeness and collaboration of each service item in the whole N-PSS system. Secondly, the system and subsystem architecture of N-PSS proposed in this paper is helpful for enterprises to set up, plan, build and implement product service system for networked collaborative manufacturing. At last, it can empower the product service innovation and digital transformation and upgrading for enterprises, and provide decision-making and reference value for enterprise managers.

With the breakthroughs in artificial intelligence technology and the rapid development of intelligent manufacturing, industry and artificial intelligence (AI) are gradually being deeply integrated. On the basis of artificial intelligence, we systematically expounded the generation, definition, characteristics, classification, technical system, and current situation of industrial artificial intelligence (I-AI). Combining existing research and industrial projects, we propose a detailed framework and a reference model for I-AI in industry. The framework contains seven dimensions: objects of I-AI, domain of I-AI, application stages of I-AI, application requirements of I-AI, intelligent technology of I-AI, intelligent function of I-AI, and solutions of I-AI. Secondly, based on the application scenarios of artificial intelligence and industrial convergence, we propose a detailed overall planning for I-AI. Finally, five typical industrial fields are selected, and the I-AI solutions based on TFV (technology and function integration in industrial value chain) unit and 6W1H method are used for new application scenarios of the proposed framework. In addition, a detailed case of implementing for I-AI in port equipment industry is given. The research results of this paper have achieved good results in the related industrial field and can provide some reference for other industrial enterprises to plan, design, implement, and apply artificial intelligence.

Taking smart manufacturing as a strategy for industrial development, China has put forward a people-oriented policy and launched a series of plans for smart manufacturing talent education (SMTE). The demand for smart manufacturing talents in ten priority areas and the industrial applications in China is very huge. Therefore, in this paper, a reference system of SMTE in China is presented, which includes discipline system, training system, practice system, and assessment system. In order to further refine the architecture of smart manufacturing system, a reference course system was proposed; the system contains seven layers, which are basic layer, technique layer, implementation layer, management layer, platform layer, application layer, and industrialization layer. Finally, nine stakeholders of the common operation body were investigated, and a reference implementation of SMTE in China was put forward. In this paper, the smart manufacturing talent education reference system, reference model, and related reference subsystems can be a very useful guideline for Chinese industry and education to design, set, and carry out the smart manufacturing talent education system. At the same time, the system has its reference value for the improvement of China’s smart manufacturing system architecture.

In this paper, we investigate the secure downlink transmission in a multi-user massive multiple-input multiple-output system assuming there is a passive multi-antenna eavesdropper (Eve) that intends to intercept information of a target user. Specifically, we employ the distributed massive antenna sets at the base station, which are known as remote radio heads (RRHs). With cooperative maximum-ratio transmission beamforming, artificial noise (AN) generation and autonomous power allocation at each RRH, the closed-form deterministic lower bound of the ergodic secrecy rate is derived by random matrix theory. Based on a simplified channel model, the impacts of various parameters on secrecy performance, such as uplink training energy, eavesdropper’s antennas number, power allocation factor, have been analyzed in detail, which provide intuitive insights for optimization and performance evaluation. Moreover, by exploiting complementary geometric programming, an power optimization algorithm over signal and AN power is derived subject to total power and Eve’s signal-to-interference-plus-noise ratio constraints. Numerical results have been presented to reveal the system’s secrecy performance and confirm all analysis results in this paper.

Edwardsiella Ictaluri is known as the etiological agent of enteric septicaemia of channel catfish, causing heavy economic losses in the aquaculture industry. In this study, a colloidal gold-based immunochromatography assay (GICA) was developed for rapid detection of E. ictaluri. Briefly, monoclonal antibody (MAbs) and polyclonal antibody (PAbs) against E. ictaluri were prepared. Sensitivity of MAbs and PAbs to E. ictaluri was analyzed by Dot ELISA. Mouse MAb5D11 against E. ictaluri was conjugated with the 20 nm colloidal gold particles as the detector. Rabbit PAbs of E. ictaluri and goat anti-mouse IgG antibody was sprayed on nitrocellulose membranes as test line (T) and control line (C) respectively. The minimum detectable amount of this method to E. ictaluri was 5 × 106 CFU/mL. Cross reactions wouldn't occur when detecting E. tarda, Aeromonas hydrophila, V. parahaemolyticus and other several common standard strains. The result could be got in only 5 to 10 minutes. It didn't need professional technologies and testing experience. So this assay was very suitable for basic departments of aquatic product companies.

This paper investigates the secure communication in a multi-pair massive multiple-input multiple-output (MIMO) amplify-and-forward (AF) relay network over Ricean fading channels in the presence of an eavesdropper. With the imperfect estimated channel state information, maximum ratio combining (MRC)/maximal ratio transmission (MRT) are employed for AF relaying. Based on random matrix theory, we first derive tractable analytical expressions of the end-to-end signal-to-interference-plus-noise ratios (SINRs) at the intended user and Eve, respectively. Then, some asymptotic results for infinite Ricean K-factor, unbounded transmit power, and relay power are provided, which show that the SINRs at target user and Eve are both limited by some bounds and the effects of estimation error, relay noise, or received additive noise will be eliminated in these extreme cases. Meanwhile, power scaling laws for transmit power and relay power are studied that they should satisfy to maintain a desirable rate level. Analytical results indicate that the power can largely be cut down in inverse proportion to the number of relay antennas in Ricean fading channels. Moreover, by exploiting successive approximations, geometric programming, and iterative computation, a power control scheme is proposed to maximize the achievable sum secrecy rate. Numerical results are presented to demonstrate the effectiveness of this secure multi-pair massive MIMO relaying system.

Background/Aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P

The authors investigate the secure communication in multigroup multicasting cell-free massive MIMO systems in the presence of an active pilot spoofing attack. With the imperfect estimated local channels at access points, a distributed conjugate beamforming with normalised power constraint policy is exploited for downlink multicasting transmission. Closed-form expressions for the per-user achievable rate and information leakage to eavesdropper are derived, respectively. Numerical results are presented to verify the correctness of their analytical results and quantitatively analyse the impacts of eavesdropper's spoofing pilot power and a number of groups on the secrecy performance of the considered systems.

Manufacturers are adding service offerings to satisfy customers’ needs in various markets. Effective strategies for servitization can improve the competitiveness of manufacturers during cooperation. The Belt and Road Initiative (BRI) established by China offers opportunities for economic cooperation and regional integration for the involved countries. Now, many manufacturing firms are expanding their businesses into Belt and Road countries, most firms are facing the “how to do” problems in improving sustainability during their cooperation. They urgently require methodical assistance on both improving competitiveness through servitization and addressing sustainability challenges. This necessitates the firms to develop successful service models for their industrial initiatives and investigate ways to produce long-term sustainable value through services. In addition to the firm’s economic worth, it also entails lowering the project’s negative environmental impact. The results provided effective strategies for manufacturers from two perspectives. The first perspective is the study discovered innovative service models at both the product and project levels. Project-service systems are critical, and manufacturing firms should use innovative service models to deliver projects. The operation method of holistic solution and localization integration project service was addressed in particular in this study. In the second perspective, there are suggestions for achieving sustainability through innovative service models. The methods for preserving sustainable value on the industrial project level were the subject of our study, which included significant criteria and detailed descriptions. The effective project service system should bring sustainable value to the lifespan of an industrial project. This study has determined four major paths to improving sustainable value creation through servitization: improving resource allocation capabilities, reduce carbon emissions through energy project service, technological outputs, and standards exportation. Useful recommendations are provided for manufacturing firms planning to develop their business overseas, especially in BRI countries.

With the upgrading of industrial era, the rise of industrial Internet environment and the development of intelligent technology, enterprises will pay more attention to the system platform, information sharing, network collaboration, personalized customization and recommendation of services when designing, implementing and operating an industrial information platform, which is called Industrial Internet Platform (IIP). In the existing literature, scholars focus on a local dot, such as: technology, function, elements and application based on IIP. However, there is a lack of an overall framework to study the top-level planning of IIP implementation from a systematic perspective. Moreover, there are few studies on the detailed path and steps of IIP implementation in a specific industry. The research objective is to study the general model, reference architecture, service evaluation index system, implementation path, application verification, etc. for IIP which meets the needs of industry on the basis of existing theory and industrial practice, and to provide reference for government and industry planning, design, implementation and promotion of IIP. From a case study, the comprehensive performance rate of comprehensive ability for IIP in a pharmaceutical manufacturing industry enterprise is calculated. It can reflect the comprehensive ability for IIP in enterprise from the ability of the IIP’s resource management, platform technology, industrial application, and etc. In addition, the general model, reference architecture, implementation path and service evaluation system of IIP can improve the enterprise's resource management ability, platform service ability, industrial application ability, and enhance the core value of the enterprise and increase benefits.

Increasing complexity of industrial products and manufacturing processes have challenged conventional statistics based quality management approaches in the circumstances of dynamic production. A Bayesian network and big data analytics integrated approach for manufacturing process quality analysis and control is proposed. Based on Hadoop distributed architecture and MapReduce parallel computing model, big volume and variety quality related data generated during the manufacturing process could be dealt with. Artificial intelligent algorithms, including Bayesian network learning, classification and reasoning, are embedded into the Reduce process. Relying on the ability of the Bayesian network in dealing with dynamic and uncertain problem and the parallel computing power of MapReduce, Bayesian network of impact factors on quality are built based on prior probability distribution and modified with posterior probability distribution. A case study on hull segment manufacturing precision management for ship and offshore platform building shows that computing speed accelerates almost directly proportionally to the increase of computing nodes. It is also proved that the proposed model is feasible for locating and reasoning of root causes, forecasting of manufacturing outcome, and intelligent decision for precision problem solving. The integration of bigdata analytics and BN method offers a whole new perspective in manufacturing quality control.

// Ying Lu 1 , Xianyu Zhang 1 , Nicolas Bouladoux 2 , Saransh Neel Kaul 3 , Kangxin Jin 4 , Derek Sant’Angelo 5 , Yasmine Belkaid 2 and Damian Kovalovsky 1,6 1 Experimental Immunology Branch, NCI, NIH, Bethesda, MD, USA 2 Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA 3 University of Maryland, College Park, MD, USA 4 Zhongshan Ophthalmic Center, State Key Laboratory for Ophthalmic Researches, Sun Yat-Sen University, Guangzhou, Guangdong, China 5 Cancer Metabolism and Growth Program, Rutgers, Child Health Institute of New Jersey, New Brunswick, NJ, USA 6 Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD, USA Correspondence to: Damian Kovalovsky, email: // Keywords : innate lymphoid cells, ILC, ILC3, Zbtb1, IFN-γ, Immunology and Microbiology Section, Immune response, Immunity Received : May 16, 2017 Accepted : July 14, 2017 Published : July 27, 2017 Abstract Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt + ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46 + ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46 + ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt + CCR6 - NKp46 - ILC3s didn’t generate NKp46 + ILC3s in co-cultures with OP9-DL1 stroma. In correlation with this impairment, Zbtb1-deficient ILC3 cells failed to upregulate T-bet expression, and to acquire IFN-γ production characteristic of NKp46 + cells. Finally, absence of NKp46 + ILC3 cells combined with the absence of T-cells in Zbtb1-deficient mice, led to a transient susceptibility to C. rodentium infections. Altogether, these results establish that Zbtb1 is essential for the development of NKp46 + ILC3 cells.

// Xianan Bai 1 , Jingjing Xie 1 , Shanshan Sun 1 , Xianyu Zhang 1 , Yongdong Jiang 1 , Da Pang 1 1 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin150040, China Correspondence to: Da Pang, email: pangda@ems.hrbmu.edu.cn Yongdong Jiang, email: jiangyongdonghmu@126.com Keywords: SNP, CYP1A2, CYP3A4, breast cancer, prognosis indicator Received: December 06, 2015 Accepted: February 27, 2017 Published: March 18, 2017 ABSTRACT Background: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. Results: Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model ( P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan–Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model ( P < 0.001, P < 0.001, respectively). Materials and Methods: Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson’s chi-square test. The Cox hazard regression analysis and Kaplan–Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. Conclusions: CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma.

With a focus on the aero-engine distributed control system (DCS) with parameter perturbation, Markov time delay, data packet dropout and external disturbance, a research has been carried out on DCS fault-tolerant control on condition of partial failure of actuator. First, a quantitative description of the system parameters is given, and the augmented model of the entire closed-loop system is established. Then the stability of the closed-loop system constrained by \(H_\infty \) and cost performance index is analyzed, and the method of designing optimal guaranteed cost fault-tolerant controller is proposed based on dynamic output feedback. Finally, the consistency theory of bi-index constraints is introduced, based on which the fault-tolerant controller is designed. The simulation results show that the designed controller can effectively reduce the controlling cost of the system while guaranteeing its \(H_\infty \) performance.

The transformation to service economy and rapid development of smart technologies have greatly changed traditional commodity trading based business models. There is an irresistible trend developing to the new business paradigm of Smart Product Service Ecosystem (SPSE), which integrates value co-creation network, service ecological thinking and Information & Communication Technologies (ICT). A conceptual framework of SPSE is proposed, covering the study on its definition, characters, components, mutual interactions and development roadmap. Business model innovations of SPSE are analysed from three aspects, including interaction modes, resource allocation principles and cooperation mechanisms. First, smart interactions offer new approaches and opportunities for manifest customer demand acquiring and implicit demand reasoning. Then, the dynamic sharing resource pool is introduced for service resource allocation optimization. The integration of distributed layout and centralized management and scheduling of resources will significantly reduce operation costs, improve resource utilization efficiency, and accelerate service response speed. Last, cooperative mechanisms will be developed based on risk sharing, ecological diversification and node association multi-polarization, to achieve a win-win situation and improve the stability, reliability and competitiveness of SPSE. The proposed theory is expected to offer possible guidelines and roadmaps for those transforming and emerging industries.

Astrocytes respond to central nervous system (CNS) insults with varieties of changes, such as cellular hypertrophy, migration, proliferation, scar formation, and upregulation of glial fibrillary acidic protein (GFAP) expression. While scar formation plays a very important role in wound healing and prevents further bleeding by forming a physical barrier, it is also one of key features of CNS injury, resulting in glial scar formation (astrogliosis), which is closely related to treatment resistant epilepsy, chronic pain, and other devastating diseases. Therefore, slowing the astrocytic activation process may give a time window of axonal growth after the CNS injury. However, the underlying mechanism of astrocytic activation remains unclear, and there is no effective therapeutic strategy to attenuate the activation process. Here, we found that methimazole could effectively inhibit the GFAP expression in physiological and pathological conditions. Moreover, we scratched primary cultures of cerebral cortical astrocytes with and without methimazole pretreatment and investigated whether methimazole could slow the healing process in these cultures. We found that methimazole could inhibit the GFAP protein expression in scratched astrocytes and prolong the latency of wound healing in cultures. We also measured the phosphorylation of extracellular signal-regulated kinase (ERK) in these cultures and found that methimazole could significantly inhibit the scratch-induced GFAP upregulation. For the first time, our study demonstrated that methimazole might be a possible compound that could inhibit the astrocytic activation following CNS injury by reducing the ERK phosphorylation in astrocytes.