There is an increasing prevalence of Alzheimer’s disease (AD), which has become a public health issue. However, the underlying mechanisms for the pathogenesis of AD are not fully understood, and the current therapeutic drugs cannot produce acceptable efficacy in AD patients. Previous animal studies have shown that coffee (Coff), caffeine (Caff), and melatonin (Mel) have beneficial effects on AD. Disturbed circadian rhythms are observed in AD, and chronotherapy has shown promising effects on AD. In this study, we examined whether a combination of Coff or Caff plus Mel produced a synergistic/additive effect on amyloid-β (Aβ) generation in Neuro-2a (N2a)/amyloid precursor protein (APP) cells and the possible mechanisms involved. Cells were treated with Coff or Caff, with or without combined Mel, with three different chronological regimens. In regimen 1, cells were treated with Coff or Caff for 12 hours in the day, followed by Mel for 12 hours in the night. For regimen 2, cells were treated with Coff or Caff plus Mel for 24 hours, from 7 am to 7 am the next day. In regimen 3, cells were treated with Coff or Caff plus Mel with regimen 1 or 2 for 5 consecutive days. The extracellular Aβ40/42 and Aβ oligomer levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The expression and/or phosphorylation levels of glycogen synthase kinase 3β (GSK3β), Erk1/2, PI3K, Akt, Tau, Wnt3α, β-catenin, and Nrf2 were detected by Western blot assay. The results showed that regimen 1 produced an additive antiamyloidogenic effect with significantly reduced extracellular levels of Aβ40/42 and Aβ42 oligomers. Regimen 2 did not result in remarkable effects, and regimen 3 showed a less antiamyloidogenic effect compared to regimen 1. Coff or Caff, plus Mel reduced oxidative stress in N2a/APP cells via the Nrf2 pathway. Coff or Caff, plus Mel inhibited GSK3β, Akt, PI3K p55, and Tau phosphorylation but enhanced PI3K p85 and Erk1/2 phosphorylation in N2a/APP cells. Coff or Caff, plus Mel downregulated Wnt3α expression but upregulated β-catenin. However, Coff or Caff plus Mel did not significantly alter the production of T helper cell (Th)1-related interleukin (IL)-12 and interferon (IFN)-γ and Th2-related IL-4 and IL-10 in N2a/APP cells. The autophagy of cells was not affected by the combinations. Taken together, combination of Caff or Coff, before treatment with Mel elicits an additive antiamyloidogenic effects in N2a/APP cells, probably through inhibition of Aβ oligomerization and modulation of the Akt/GSK3β/Tau signaling pathway.

In this study, by analysis of the value of public opinion, the node of the 30 the "PM2.5 Chinese name" event, the network cluster of public opinion, the event found examples to study its propagation characteristics. online public opinion perspective, build the adjacency matrix of a network cluster analysis; using four types of centrality and path calculation and analysis of network clusters presented key milestones, and critical path method. Calculated from the social point of view, the corresponding public opinion through the study guide and the entry point of the network cluster control, laid the foundation to further explore the online public opinion research in network cluster behavior patterns.

In order to detect hacker attacks and take early countermeasures, this paper introduced a novel mobile botnet called CPbot which uses Google Cloud Messaging (GCM) to spread Trojan on Android devices. First, we presented the network model of this GCM based mobile botnet as well as its command and control (C&C) mechanism. Secondly, we illustrated the different roles that this botnet can play. Finally, we setup a simulation model to discuss the topology of this mobile botnet. The MATLAB simulation result shows that CPbot is robust against single point of failures and has good resiliency to shutdown attempts, its command dissemination is highly efficient and the bot App has very low battery consumption. This analysis indicates that mobile botnet is a leading threat to mobile network security; therefore we must deploy defense strategies against this botnet.

The commonly used method for high resolution velocity analysis in seismic data processing and interpreting is based on signal estimation algorithm. However, the numerical realization of this method is complicated and time-consuming due to the process of signal-noise separation requiring enormous loop calculations before constructing the energy function. In this paper, we improved the method on the base of multi-trace signal estimation. This improved method made full use of amplitude information that can enhance the anti-noise ability and improve the resolution greatly. Meanwhile, this method has more economical calculation cost than other methods for it didnt require multiple loop calculations.

Learning outcomes Through the discussion of this case, students will have a better understanding of the managerial dilemma associated with the implementation of management control in an early-stage firm. Students will provide proposals to improving current management control. Finally, this case encourages students to think about the costs and benefits of implementing formal management control systems. Case overview/synopsis As the company grows, it becomes difficult to keep control of the organization. The organizational structure of Majid Al Futtaim (MAF) Carrefour Jordan is too centralized, and the top management is confronted with information overload, which inhibits their ability to pursue strategic goals. The department managers are also confronted with communication problems, and they are evaluated based on the indicators that were out of their control. Processes and rules do not permit managers sufficient autonomy, and neither do these motivate employees towards organizational strategic goals. It is obvious that many control issues needed to be addressed in MAF Carrefour Jordan. However, given the limited budgets, MAF Carrefour Jordan managers need to decide which control systems to implement first. Complexity academic level This case can be used in an introductory cost accounting and management control course at the undergraduate or postgraduate level. The case should be introduced after students attained a baseline understanding of management control system fundamental concepts. However, this case is equally effective in introducing concepts to students who are new to management control systems. Supplementary materials Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes. Subject code CSS 1: Accounting and Finance