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Federated learning (FL) has been a popular distributed learning framework to reduce privacy risks by keeping private data locally. However, recent work (Hitaj 2017) has demonstrated that sharing model’s parameter updates still leaves FL vulnerable to internal attacks in its training phase. Existing works cannot detect such attacks well. To address this problem, we propose a novel and lightweight detection scheme which selects and analyzes just a few parameter updates of the last convolutional layer in the FL model. Extensive experiments demonstrate that our proposed detection scheme can accurately and efficiently detect the malicious participant in near real time for a scenario with a malicious participant.

Circular Supply Chain Management (CSCM) incorporates the economy concept into supply chain concepts, which gives the supply chain sustainability domain an innovative and convincing viewpoint. The challenging factors in the circular economy are cooperation, trust, and transparency. Therefore, to achieve sustainable results, collaboration, and openness between organizations within networks and value chains are required. This paper explores the sustainability success using the Sustainable Circular Business Model (SCBM) to incorporate the principle at an operational level and suggest a structure for combining Circular Business Model (CBM) and CSCM for sustainable growth. The proposed structure shows how various circular business structures power the global supply chain in multiple loops. The circular business models differ according to the difficulty of the Circular Supply Chain (CSC) and the value proposition. Proposed SCBM shows that circular market and supply chain aid in reaching goals for sustainability has been discussed in this research.

Drug resistance is a constant threat to malaria control efforts making it important to maintain a good pipeline of new drug candidates. Of particular need are compounds that also block transmission...

The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only excellent discrimination versus ALK3 but also high kinome selectivity. In addition, the optimized compound 23 demonstrates good ADME and in vivo pharmacokinetic properties.

Due to technical bottlenecks such as systems vulnerable to attacks and data are easily tampered with, and it is difficult for the distributed power system data storage management to achieve multi-agent integration and development. Known as the "trust machine," the Blockchain has an essential role in promoting the energy Internet construction with its distributed storage, tamper-proof, traceable, and multi-node sharing technical characteristics. Its technical advantages have great potential application value in the power industry. Most of the existing blockchain schemes directly combine the CP-ABE algorithm with the Blockchain. However, due to the lack of permission inheritance, these schemes have permission to redundancy and waste computing resources. In this paper, a new user-controlled on-chain permission management scheme is proposed. The original CP-ABE model is extended in this scheme, and the concept of role assignment and attribute tree is proposed. The attribute tree uses the multi-tree structure to realize the attribute set's specification description. The connectivity between roles in the attribute tree represents the inheritance relationship of permission so that the permission inheritance and permission granting can be realized. In this paper, a sidechain prototype system is developed for evaluating the scheme, and its performance is tested and analyzed. The experimental results show that the prototype system can realize the user-controlled permission assignment and permission inheritance function of data owner on the Blockchain.

In order to solve the security problems existing when power users access power services in different domains, this paper proposes a dynamic authorization model for power users based on master-slave chain. In this model, the slave Blockchain conducts identity authentication in each autonomous domain, and the main Blockchain undertakes identity authentication among autonomous domains. Moreover, by constructing an attribute access control model, a trusted identity cross-domain authorization mechanism is proposed, and an attribute-based allocation strategy in both single-domain and cross-domain scenarios is designed in detail. Through application analysis and security analysis, it is verified that the trusted identity cross-domain authorization mechanism proposed in this paper can be conveniently applied to existing systems, and has better performance in confidentiality, integrity, and availability.

[Image: see text] Drug resistance is a constant threat to malaria control efforts making it important to maintain a good pipeline of new drug candidates. Of particular need are compounds that also block transmission by targeting sexual stage parasites. Mature sexual stages are relatively resistant to all currently used antimalarials except the 8-aminoquinolines that are not commonly used due to potential side effects. Here, we synthesized a new Torin 2 derivative, NCATS-SM3710 with increased aqueous solubility and specificity for Plasmodium and demonstrate potent in vivo activity against all P. berghei life cycle stages. NCATS-SM3710 also has low nanomolar EC(50)s against in vitro cultured asexual P. falciparum parasites (0.38 ± 0.04 nM) and late stage gametocytes (5.77 ± 1 nM). Two independent NCATS-SM3710/Torin 2 resistant P. falciparum parasite lines produced by growth in sublethal Torin 2 concentrations both had genetic changes in PF3D7_0509800, annotated as a phosphatidylinositol 4 kinase (Pf PI4KIIIβ). One line had a point mutation in the putative active site (V1357G), and the other line had a duplication of a locus containing Pf PI4KIIIβ. Both lines were also resistant to other Pf PI4K inhibitors. In addition NCATS-SM3710 inhibited purified Pf PI4KIIIβ with an IC(50) of 2.0 ± 0.30 nM. Together the results demonstrate that Pf PI4KIIIβ is the target of Torin 2 and NCATS-SM3710 and provide new options for potent multistage drug development.

The English education course in China aims to help students establish the English skills necessary to enhance their international competitiveness. However, traditional English classes often lack the linguistic environment to enable students to apply the English skills they have learned from their textbook. Virtual reality (VR) technology can create an immersive English language environment and then encourage the learners to use English by presenting different collaborative communication tasks. Thus, to promote learners in using the target language skills this study applied a spherical video-based virtual reality technology to build a linguistic environment, and a collaborative learning strategy was adopted to promote their communication. Additionally, a mixed-methods research approach was used to analyze students' achievement in a traditional classroom and a virtual reality supported collaborative classroom and to evaluate their perception of the two approaches. The experimental results revealed that the collaborative classroom, supported by virtual reality, was able to enhance students' achievements. Moreover, analysis of student interviews identified their attitudes towards the virtual-reality-supported collaborative class and the use of language learning strategies in those classes. These findings could be a valuable reference for those who intend to create opportunities for students to collaborate and communicate in the target language in their classroom and then improve their language skills.

Hierarchical porous graphene is first fabricated from lotus leaves by naturally CaO in situ self-catalyzing strategy without the utilization of any chemical or physical agent. The intrinsic Ca-containing species in biomass first converses into CaCO3 and then decomposes into CaO during the pyrolysis process, and the imbedded CaO serves as in situ template and catalyst to generate hierarchical structure and graphitic structure. The resultant graphene exhibits 3D structural hierarchy with micro-sized in-plane vacancies, meso-sized channels and macro-sized cavities, contributing to rapid charge transfer, short ion diffusion pathway and robust framework. It has been demonstrated as a high-rate performance supercapacitor electrode (without the addition of any conductive agent) with outstanding rate capability (85.3% retention rate from 1 to 20 A/g) and high scan rate of 3000 mV/s. No obvious deterioration (98.2% capacitance retention) was observed after 10,000 charge-discharge cycles at 20 A/g. The first synthesis of nanoarchitecture graphene via one-step pyrolysis method by taking advantage of the unique natural features of biomass opened up new angle for the green and facile preparation of 3D graphene for energy storage.

Ultrahigh-quality graphene with structural hierarchy has been successfully fabricated through a novel and effective bioinspired in situ self-catalyzing strategy with camphor leaves as a renewable carbon source. The intrinsic Ca-containing species in biomass transfers into CaO via the intermediate of CaCO3 during the pyrolysis process, and the finally imbedded CaO functions as in situ hard template and catalyst to generate hierarchical structure and construct the graphitic structure. The utilization of KOH effectively facilitated the graphene formation and enhanced the porosity of the carbon materials. The resultant graphene possesses many advantages for supercapacitor application, including large surface area, hierarchical porosity (crosslinked micro/meso/macroporous vacancies), well-organized graphene layers and favorable dually co-doping of O/N, thereby contributing to rapid charge transportation on the electrode/electrolyte interface, fast diffusion of electrolyte ions and high conductivity. When directly used as supercapacitor electrode (without the mixture of any conductive agent), as-produced graphene exhibited a specific capacitance of 397F/g at a current density of 1.0 A/g with a high rate retention of 74% from 1 to 20 A/g in a three-electrode system with 6 M KOH aqueous electrolyte. The high-quality graphene prepared from biomass via a readily scalable method opened up new vision towards high performance applications in energy storage and conversion.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of progressive ossification of skeletal muscle, fascia, tendons, and ligaments. Most FOP cases are caused by a heterozygous c. 617G > A mutation in the ACVR1 gene which encodes a gain-of-function of bone morphogenetic protein type I receptor. A human induced pluripotent stem cell (iPSC) line was generated from the dermal skin fibroblasts of a FOP patient who carries the c. 617G > A mutation in the ACVR1 gene. This iPSC line provides an attractive resource for FOP disease modeling.

A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)–intramolecular cyclization–Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual parasites using a growth inhibition assay and gametocytes using a viability assay.

RATIONALE: BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, and downstream effectors have been reported in heritable PAH. OBJECTIVES: To determine how an acquired deficiency of BMP9 signaling might contribute to PAH. METHODS: Plasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH. MEASUREMENTS AND MAIN RESULTS: BMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl4-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone. CONCLUSIONS: BMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.

It is commonly accepted that non-native speakers who immerse themselves in English-speaking countries are most effective at second language acquisition. Nevertheless, the vast majority of elementary school students in China lack the chance to be immersed in an English-speaking environment. At the same time, with recent advancements in technology, virtual reality games are currently a rapidly developing area of interest for researchers, teachers, material writers and application developers in the educational field. Thus, based on the APT model, this paper constructs the design framework of a virtual reality game for English learning. Taking the fourth-grade English materials as an example, the purpose of this study was to design and develop a virtual reality game for fourth-grade students to learn English at an elementary school in Xi'an. The experimental results show that the proposed approach, based on the APT model, effectively satisfied the requirements of a VR learning environment.

CCD (charge-coupled device) is a unique performance of the semiconductor photoelectric device, CCD technology applied to displacement, thickness and other geometric measurement, can achieve high precision, online dynamic detection and non-contact measurement requirements. This system USES the method of combining FPGA and single chip microcomputer to measure the thickness of the object using CCD as the sensor. In this design, the CCD driver pulse circuit, control logic and calculation circuit are all integrated in FPGA chip, thus improving the reliability of the system and creating conditions for the system integration. External display and control circuits such as liquid crystal display, keyboard and EEPROM memory are designed by SCM. The whole system embodies the characteristics of high integration, simple structure and superior performance. This paper introduces the principle, design and implementation of the system in detail.

The development of smart grid will depend on the increased developments of communication technology and advanced measurement technology to support observation and control function. Unfortunately, this also increase the risk from cyber-attacks in communication network and second power equipment. Designing the cyber-attack testbed with hardware-in-loop provides technical support for theoretical research and operational strategy formulation of power cyber-physical system (CPS). This paper provides an overview of smart grid co-simulation platform, including system structure and synchronized methods. It then introduces the classification of cyber-attack. The cyber-attack testbed with hardware-in-loop is then introduced, including the architecture, modeling process, applications, and novel capabilities, such as RT-Lab, OPNET, and the security and stability control device. Finally, several attack scenarios are evaluated using the testbed to explore cyber-physical impacts. In particular, availability and integrity attacks are demonstrated with both isolated and coordinated approaches, these attacks are then evaluated based on the power grid's voltage stability.

BACKGROUND The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. MATERIALS AND METHODS We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. RESULTS No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. CONCLUSIONS Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

Previous studies performed in Kenya have suggested that the C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition; however, no relevant study has been conducted in China. To evaluate the influence of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls. No significant differences in the genotype and allele distributions of this polymorphism were observed among the patient and control groups. Additionally, binary logistic regression analyses adjusted by age and gender revealed that the C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore, when analyses of genotype and allele frequencies were stratified by gender, similar nonsignificant results were found. Our study demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility of HIV-1 acquisition in a Chinese population. Further studies are warranted to confirm these results.

Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues due to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2/ACVR1. From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2 compared with other receptors of the BMP/TGFβ signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducibleACVR1Q207Dtransgenic mouse line, which provides a model of heterotopic ossification, as well as an inducibleACVR1R206Hknock-in, which serves as a genetically and physiologically faithful model of FOP. In both models, saracatinib was well tolerated and potently inhibited the development of heterotopic ossification even when administered transiently following soft tissue injury. Together, these data suggest that saracatinib is an efficacious clinical candidate for repositioning in the treatment of FOP, offering an accelerated path to clinical proof of efficacy studies and potentially significant benefits to individuals with this devastating condition.

Background Blocking malaria transmission is an important step in eradicating malaria. In the field, transmission requires the production of sexual stage Plasmodium parasites, called gametocytes, which are not effectively killed by the commonly used anti-malarials allowing individuals to remain infectious after clearance of asexual parasites. Methods To identify new gametocytocidal compounds, a library of 45,056 compounds with diverse structures was screened using a high throughput gametocyte viability assay. The characteristics of active hits were further evaluated against asexual stage parasites in a growth inhibition assay. Their cytotoxicity were tested against mammalian cells in a cytotoxicity assay. The chemical scaffold similarity of active hits were studied using scaffold cluster analysis. Results A set of 23 compounds were identified and further confirmed for their activity against gametocytes. All the 23 confirmed compounds possess dual-activities against both gametocytes responsible for human to mosquito transmission and asexual parasites that cause the clinical symptoms. Three of these compounds were fourfold more active against gametocytes than asexual parasites. Further cheminformatic analysis revealed three sets of novel scaffolds, including highly selective 4-1H-pyrazol-5-yl piperidine analogs. Conclusions This study revealed important new structural scaffolds that can be used as starting points for dual activity anti-malarial drug development. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1805-0) contains supplementary material, which is available to authorized users.