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Background: By associated with inflammation intraplaque, Trimethylamine N-oxide (TMAO) increase the risk of atherosclerotic plaque rupture and has been identified as the independent predictor of cardiovascular events. However, the underlying mechanism is yet unclarity. Accumulating studies have established the critical role of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in mediating intraplaque inflammation and plaque progression. Here, we discussed the role of NLRP3 inflammasome in aggravating ox-LDL-induced macrophage inflammation response to TMAO and its potential mechanism. Results: Our results showed that TMAO enhanced ox-LDL-induced inflammation in THP-1cells. Adding to TMAO remarkably upregulated the expression or mRNA level of NLRP3, Cysteinyl aspartate specific proteinase 1(caspase-1) p20 and Apoptosis associated speck-like protein containing CARD(ASC) and enhanced the activity of caspase-1. An NLRP3 inhibitor (MCC950) reversed the promoting effect of NLRP3 inflammasome activation by TMAO and subsequently macrophage inflammation. Significantly, TMAO also boosted the activation of endoplasmic reticulum stress (ERS) and nuclear factor-kappa B (NF-kB) pathway in ox-LDL-induced cells, manifested as the increasing expression of p-NF-κB, Bip and phosphorylated protein kinase R-like ER kinase (p-PERK). Activation of the NLRP3 inflammasome by TMAO was reversed by the ERS inhibitor 4-PBA or the NF-κB phosphorylation inhibitor JSH-23. Meanwhile, 4-PBA further inhibited the NF-κB phosphorylation and alleviated the NLRP3 inflammasome activation. Conclusions: We concluded that TMAO exacerbates ox-LDL-induced NLRP3 inflammasomes activation and subsequently interleukin (IL)-18 and IL-1b release in THP-1 macrophages, which partly regulated by the activating of the PERK/NF-κB signaling pathway.

Acute myeloid leukemia (AML) is a highly heterogenous cancer in hematopoiesis, and its subtype specification is greatly important in the clinical practice for AML diagnosis and prognosis. Increasing evidence has shown the association between microRNA (miRNA) phenotype and AML therapeutic outcomes, emphasizing the need for novel techniques for convenient, sensitive, and efficient miRNA profiling in clinical practices. Here, we describe a nanoneedle-based discrete single-cell microRNA profiling technique for multiplexed phenotyping of AML heterogeneity without the requirement of sequencing or polymerase chain reaction (PCR). In virtue of a biochip-based and non-destructive nature of the assay, the expression of nine miRNAs in large number of living AML cells can be simultaneously analyzed with discrete single-cell level information, thus providing a proof-of-concept demonstration of an AML subtype classifier based on the multidimensional miRNA data. We showed successful analysis of subtype-specific cellular composition with over 90% accuracy and identified drug-responsive leukemia subpopulations among a mixed suspension of cells modeling different AML subtypes. The adoption of machine learning algorithms for processing the large-scale nanoneedle-based miRNA data shows the potential for powerful prediction capability in clinical applications to assist therapeutic decisions. We believe that this platform provides an efficient and cost-effective solution to move forward the translational prognostic usage of miRNAs in AML treatment and can be readily and advantageously applied in analyzing rare patient-derived clinical samples.

To improve the intrinsic electronic conductivity of Na3V2(PO4)2F3 (NVPF), zirconium (Zr) was introduced into the NVPF/C compound through a carbothermal reduction reaction with citric acid as the carbon source. The effects of Zr4+ doping on the crystal structure and morphology of the as-prepared materials were analyzed. Electrochemical and kinetic properties of the samples were investigated by galvanostatic charge-discharge, CV and EIS test. It is confirmed that moderate Zr4+ doping can improve the electrochemical performance of NVPF. Among all Na3V2-xZrx(PO4)2F3/C (x = 0, 0.01, 0.05, 0.1) samples, Na3V1·95Zr0·05(PO4)2F3/C shows the best rate and cycle performance. It exhibits the highest specific capacity of 121.8 and 110.3 mAh/g at 0.2 and 10 C, respectively, and maintains a capacity retention of approximately 83.6% after 1000 cycles at 5 C. The kinetic properties results show that the excellent electrochemical performance of Na3V1·95Zr0·05(PO4)2F3/C can be attributed to the increase in electronic conductivity and ion diffusion coefficient.

The ICT infrastructures of medium and large organisations that offer ICT services (infrastructure, platforms, software, applications, etc.) are becoming increasingly complex. Nowadays, these environments combine all sorts of hardware (e.g., CPUs, GPUs, storage elements, network equipment) and software (e.g., virtual machines, servers, microservices, services, products, AI models). Tracking, understanding and acting upon all the data produced in the context of such environments is hence challenging. Configuration management databases have been so far widely used to store and provide access to relevant information and views on these components and on their relationships. However, different databases are organised according to different schemas. Despite existing efforts in standardising the main entities relevant for configuration management, there is not yet a core set of ontologies that describes these environments homogeneously, and which can be easily extended when new types of items appear. This paper presents an ontology network created with the purpose of serving as an initial step towards an homogeneous representation of this domain, and which has been already used to produce a knowledge graph for a large ICT company.

Background: Delirium is associated with increased morbidity and mortality in critically ill patients. Research on risk factors for delirium allows clinicians to identify high-risk patients, which is the basis for early prevention and diagnosis. Besides the risk factors for delirium that are commonly studied, here we more focused on the less-studied therapeutic interventions for critically ill patients which are potentially modifiable. Materials and methods: A total of 320 non-comatose patients admitted to the ICU for more than 24 hrs during 9 months were eligible for the study. Delirium was screened once daily using the CAM-ICU. Demographics, admission clinical data, and daily interventions were collected. Results: Ninety-two patients (28.75%) experienced delirium at least once. Delirious patients were more likely to have longer duration of mechanical ventilation, ICU stay, and hospital stay. Most of the less-studied therapeutic interventions were linked to delirium in the univariate analysis, including gastric tube, artificial airway, deep intravenous catheter, arterial line, urinary catheter, use of vasoactive drugs, and sedative medication. After adjusting with age and ICU length of stay, mechanical ventilation (OR: 5.123; 95% CI: 2.501-10.494), Acute Physiology and Chronic Health Evaluation (APACHE) II score≥20 at admission (OR: 1.897; 95% CI: 1.045-3.441), and gastric tube (OR: 1.935, 95% CI: 1.012-3.698) were associated with increased risk of delirium in multivariate analysis. Conclusion: Delirium was associated with prolonged mechanical ventilation, ICU stay, and hospital stay. Multivariate risk factors were gastric tube, mechanical ventilation, and APACHE II score. Although being a preliminary study, this study suggests the necessity of earliest removal of tubes and catheters when no longer needed.

Na3V2(PO4)2F3 (NVPF) with NASCION (Na superionic conductor) is recognized as a potential cathode material owing to its high theoretical capacity. However, the electronic conductivity of NVPF is much lower than its ionic conductivity, which seriously affects the properties of this material. The carbon layer can be used as the conductive medium to enhance the conductivity of NVPF. In this study, we propose a single-step solid-state reaction method based on mechanical activation with pitch as the carbon source to synthesize NVPF/C composites. The crystallographic structure and morphology of all as-prepared samples were investigated by XRD, Raman spectroscopy, BET measurement, thermal analysis, SEM and TEM. Furthermore, the electrochemical performance and kinetic properties were analyzed by CV, galvanostatic charge–discharge and EIS tests. These tests outcomes demonstrated that the NVPF/C-2 composite with a carbon content of 12.14 wt% showed an excellent rate performance and cycle stability. It presented reversible capacities of 103 and 95 mA h g−1 at 0.2 and 10C, respectively, and an outstanding retention of 91.9% after 500 cycles at 5C. These excellent properties of the NVPF/C-2 composite are attributed to its high ion diffusion coefficient and small charge transfer impedance.

In urban renewal, the leaving and rebuilding of markets is a topic that is frequently discussed. Fairs are usually difficult to manage due to open air and non-fixed conditions, they are gradually unable to meet the needs of modern business. But European markets have a long history and show a Forward loop. The article hopes to explore the formation mechanism of European markets, select ten typical cases among them, and analyze the process and main points of the formation from stalls to markets. Finally, it summarizes the appropriate market development form in the urban expansion and renewal.

Autoimmune hepatitis (AIH) is a liver inflammatory disease via induction of debris-like necrosis in the liver portal area, which is characterized by hypergammaglobulinemia and a variety of autoantibodies. And its performance is very similar to viral hepatitis, but with absolutely different treatment. The pathogenesis of AIH is not clear, genetic susceptibility is considered to be the main factor. AIH is a cause of multiple pathogenic disease, and can induce viruses, bacteria, chemicals and drugs which are potential causes for genetic sensitive individuals, to participate in inflammatory disease processes. Due to the destruction of immune tolerance, liver-specific membrane proteins were expressed on the surface of liver cells, asialoglycoprotein receptor (ASGP-R) and microsomal cytochrome P4502D6 are considered to be more clearly present to stimulate AIH antigen. Activation of CD4+ T cells by direct exposure and release of cytokines stimulates B cells to produce antibodies that initiate immune injury responses. At the same time cytokine activation of CD8+ T cells mediates antibody-dependent cell-mediated cytotoxicity (ADCC) effect to kill hepatocytes, activating tumour necrosis factor (TNF) or Fas-mediated hepatocellular death. However, AIH patients are always proved to be lack of immunoregulatory function, which is newly considered to be the cardinal cause of AIH. Genetic susceptibility, molecular simulation theory, and immune pathogenesis are main points of this review article. Especially, in-depth statement has been made from several aspects of AIH’s immune pathogenesis such as cellular immune mechanism, humoral immunity with ADCC, immunosuppressive effects of regulatory T cells, and cytokine theory. Thus, a better understanding of the pathogenesis of AIH is of great importance. Keywords: Autoimmune hepatitis, Molecular simulation theory, Immune pathogenesis

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Scientific evaluation of the main transformer equipment suppliers is the premise to ensure the cost control and safe operation of the power grid. Based on the analysis of various factors affecting the main transformer equipment supplier, the evaluation index of the main transformer equipment supplier is constructed. Considering the fuzziness of the evaluation index, the index weight is determined by AHP, and the evaluation model of main transformer equipment supplier based on fuzzy comprehensive evaluation is established. The example calculation shows that the fuzzy comprehensive evaluation method can fully reveal the evaluation index information and reflect the actual situation of main transformer equipment suppliers scientifically and reasonably.

As an important state-owned energy backbone enterprise related to national energy security and the lifeline of national economy, power grid enterprises are responsible for ensuring the quality and safety of equipment and promoting the development of equipment quality. Therefore, continuously improving the quality evaluation of main transformer equipment is very important to improve the quality of power grid main transformer equipment. This paper first constructs the main transformer equipment quality evaluation index system from equipment procurement, equipment installation, equipment use and equipment decommissioning and scrapping; on this basis, the scoring method of each evaluation index is given, and the final main transformer equipment quality evaluation score is calculated by combining subjective and objective weight determination method; Finally, according to the evaluation of 500kV main transformer equipment of provincial power grid company price score, to evaluate the performance of equipment quality provided by suppliers.

Service-based business processes are often developed and deployed by single organizations. In distributed, shared resource environments like the cloud on the other hand, consumers share resources owned by cloud providers. %Higher levels of resource sharing gives more economy of scale for providers in the software-as-a-service (SaaS) or business process-as-a-service (BPaaS) space. This requires multi-tenancy capability for service processes that provides customized behaviour for on shared process implementations to meet the varying needs of different process consumers as tenants of the process resource. In this paper, we define a distributed multi-tenant architecture for BPEL processes provided as a service. A single-version BPEL process is deployed by a provider and offered for all process consumers, combined with a customization and management functionality to create a unique experience for different consumers (process tenants). We provide two core components: a policy model for consumers to express customization/business requirements of service processes and a coordination framework for policy enforcement between consumers and providers to achieve on-the-fly customization of service processes.

Services are offered in an execution context that is determined by how a provider provisions the service and how the user consumes it. The need for more flexibility requires the provisioning and consumption aspects to be addressed at run-time. We propose an ontology-based context model providing a framework for service provisioning and consumption aspects and techniques for managing context constraints for Web service processes where dynamic context concerns can be monitored and validated at service process run-time. We discuss the contextualisation of dynamically relevant aspects of Web service processes as our main goal, i.e. capture aspects in an extended context model. The technical contributions of this paper are a context model ontology for dynamic service context and an operator calculus for integrated and coherent context manipulation, composition and reasoning. The context model ontology formalises dynamic aspects of Web services and facilitates reasoning. We present the context ontology in terms of four core dimensions--functional, QoS, domain and platform--which are internally interconnected.

Service processes are often enacted across different boundaries such as organisations, countries or even languages. Specifically, looking at the quality and governance of data or content processed by services in this context is important to control different constraints in this cross-boundary processing. In order to provide a context-aware solution that takes into account data and data processing requirements, a rule-based constraints specification and adaptation of processes shall be proposed. A domain ontology shall capture the key data/content data types, activities and constraints, which forms the basis of a rule-based policy monitoring solution. A provenance model is at the core of this ontology solution. The key contribution is a domain-specific model and specification template for constraint policy definition, which can be applied to adapt service processes to domain-specific needs.

Cloud computing needs end-user customisation and personalisation of multi-tenant cloud service offerings. Particularly, QoS and governance policy management and monitoring is needed. We propose a user-customisable policy definition solution that can be enforced in multitenant cloud offerings through automated instrumentation and monitoring. Service processes run by cloud and SaaS providers can be made policy-aware in a transparent way.

With software services becoming a strategic capability for the software sector, service engineering needs to address integration problems based on support that helps services to collaborate and coordinate their activities. The increasing need to address dynamic and automated changes - caused by on-demand environments and changing requirements - shall be answered through a service coordination architecture based on event-based collaboration. The solution is based on a service coordination space architecture that acts as a passive infrastructure for event-based collaboration. We discuss the information architecture and the coordination principles of such a collaboration environment.

Service engineering needs to address integration problems allowing services to collaborate and coordinate. The need to address dynamic automated changes - caused by on-demand environments and changing requirements - can be addressed through service coordination based on ontology-based composition and matching techniques. Our solution to composition and matching utilises a service coordination space that acts as a passive infrastructure for collaboration. We discuss the information models and the coordination principles of such a collaboration environment in terms of an ontology and its underlying description logics. We provide ontology-based solutions for structural composition of descriptions and matching between requested and provided services.

peer-reviewed Service-oriented architecture is an architectural approach that can be applied for building autonomous service systems dynamically to satisfy on-demand business requests. During the execution of service compositions, architectural constraint violations relating to functional and non-fucntional system properties need to be handled intelligently and autonomously, possibly requiring architectural reconfigurations. We propose integrated architectural constraint violation handling to deal with architectural quality problems through dynamic reconfiguration. We concentrate on service replacement selection as a remedial strategy for a possible quality violation requiring architectural remedies.

With the emergence of Business Process Outsourcing and Cloud Computing, enterprises are looking for available business processes outside of their organizations to quickly adopt to new business requirements and also reduce process development and maintenance costs. The process execution needs to be governed as policy enforcement might differ between different clients. Since a process is deployed outside of the organizations and serves multiple process clients, distribution and multi-tenancy have become two requirements for runtime governance of service processes. We address this problem by introducing a policy-oriented aspectual business process framework. The runtime governance constraints from process clients are integrated as aspects through dynamic weaving into rpcess execution.

Service-Oriented Architecture (SOA) offers a technical foundation for Enterprise Application Integration and business collaboration through service-based business components. With increasing process outsourcing and cloud computing, enterprises need process-level integration and collaboration (process-oriented) to quickly launch new business processes for new customers and products. However, business processes that cross organisations’ compliance regulation boundaries are still unaddressed. We introduce a distributed aspect-oriented service composition approach, which enables multiple process clients hot-plugging their business compliance models (business rules, fault handling policy, and execution monitor) to BPEL business processes.

Dynamic service composition is suitable for on-demand business requests. For autonomic computing, service composition needs to deal with runtime environment faults, but also with business constraint violations which result from business requirements. We propose an approach for integrated handling of business constraint violations and runtime environment faults for dynamic service composition. We introduce a loosely coupled implementation architecture to maintain the platform-independent nature.

Autonomic, i.e. dynamic and fault-tolerant Web service composition is a requirement resulting from recent developments such as on-demand services. In the context of planning-based service composition, multi-agent planning and dynamic error handling are still unresolved problems. Recently, business rule and constraint management has been looked at for enterprise SOA to add business flexibility. This paper proposes a constraint integration and violation handling technique for dynamic service composition. Higher degrees of reliability and fault-tolerance, but also performance for autonomously composed WS-BPEL processes are the objectives.

Web service composition is a technology that has received considerable attention in the last number of years. Languages and tools to aid in the process of creating composite Web services have been received specific attention. Web service composition is the process of linking single Web services together in order to accomplish more complex tasks. One area of Web service composition that has not received as much attention is the area of dynamic error handling and re-planning, enabling autonomic composition. Given a repository of service descriptions and a task to complete, it is possible for AI planners to automatically create a plan that will achieve this goal. If however a service in the plan is unavailable or erroneous the plan will fail. Motivated by this problem, this paper suggests autonomous re-planning as a means to overcome dynamic problems. Our solution involves automatically recovering from faults and creating a context-dependent alternate plan. We present an architecture that serves as a basis for the central activities autonomous composition, monitoring and fault handling.

Resistance to RAF-MEK targeted therapy is a major clinical challenge. RAF-MEK inhibitors are initially but only transiently effective in some but not all BRAF mutant patients, and largely ineffective in RAS mutant patients because of resistance. Through a genetic screen in BRAF mutant tumor cells, we show that the Hippo pathway effector YAP acts as a parallel survival input to promote resistance to RAF-MEK inhibitor therapy. Combined YAP and RAF-MEK inhibition was synthetically lethal not only in several BRAF mutant tumor types but also in RAS mutant tumors. Increased YAP in BRAFV600E patient tumors was a biomarker of worse initial response to RAF inhibition in patients, establishing the clinical relevance of our findings. Our data uncover YAP as a novel mechanism of resistance to RAF-MEK targeted therapy. The findings unveil the synthetic lethality of YAP and RAF-MEK co-suppression as a promising strategy to enhance response and patient survival. Citation Format: Luping Lin, Amit Sabnis, Elton Chan, Victor Olivas, Lindsay Cade, Evangelos Pazarentzos, Saurabh Asthana, Dana Neel, Jenny Jiacheng Yan, Xinyuan Lu, Luu Pham, Mingxue Wang, Niki Karachaliou, Maria G. Cao, Jose L. Manzano, Jose L. Ramirez, Jose M. Torres, Fiamma Buttitta, Charles M. Rudin, Eric A. Collisson, Alain Algazi, Eric Robinson, Iman Osman, Eva Munoz-Couselo, Javier Cortes, Dennie T. Frederick, Zachary A. Cooper, Martin McMahon, Antonio Marchetti, Rafael Rosell, Keith T. Flaherty, Jennifer A. Wargo, Trever G. Bivona. The Hippo effector YAP promotes resistance to RAF and MEK targeted therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-239. doi:10.1158/1538-7445.AM2015-LB-239

Recent cross-organisational software service offerings, such as cloud computing, create higher integration needs. In particular, services are combined through brokers and mediators, solutions to allow individual services to collaborate and their interaction to be coordinated are required. The need to address dynamic management - caused by cloud and on-demand environments - can be addressed through service coordination based on ontology-based composition and matching techniques. Our solution to composition and matching utilises a service coordination space that acts as a passive infrastructure for collaboration where users submit requests that are then selected and taken on by providers. We discuss the information models and the coordination principles of such a collaboration environment in terms of an ontology and its underlying description logics. We provide ontology-based solutions for structural composition of descriptions and matching between requested and provided services.