Impaired epithelial regeneration is a crucial pathophysiological feature of ulcerative colitis (UC). Yes-associated protein (YAP1) appears to control cell proliferation and differentiation. In this study, we sought to identify the roles of YAP in intestinal epithelial cell (IEC) self-renewal, regeneration and tumorigenesis. We first observed that YAP was significantly reduced in 62.5% (45/72) of human UC tissues and it was dramatically enhanced during epithelial regeneration in a murine colitis model. Using lentiviral infection, we established a YAP-overexpression (YAPWT) mouse model. We then found that after tissue injury, YAPWT mice had increased epithelial cell self-renewal capacity and drastically restored intestinal crypt structure. Strikingly, these mice were more susceptible to colitis-associated cancer (CAC) in chemically induced carcinoma. Mechanistically, YAP and β-catenin showed increased nuclear co-localization during regeneration after inflammation. Overexpressing YAP significantly improved IEC ‘wound-healing’ ability and increased the expression of both β-catenin and the transcriptional targets of Wnt signalling Lgr5 and cyclin D1, whereas silencing β-catenin in YAPWT cells attenuated this effect. Remarkably, we observed that YAP could directly interact with β-catenin in the nucleus and formed a transcriptional YAP/β-catenin/TCF4 complex; Lgr5 and cyclin D1 were confirmed to be the target genes of this complex. In contrast, cancer cell proliferation and tumour development were suppressed by the phospho-mimetic YAP mutant. In summary, nuclear YAP-driven IEC proliferation could control epithelial regeneration after inflammation and may serve as a potential therapeutic target in UC. However, excessive YAP activation promoted CAC development.
Storage clouds, such as Amazon S3, are being widely used for web services and Internet applications. It has been observed that the delay for retrieving data from and placing data into the clouds is quite random, and exhibits weak correlations between different read/write requests. This inspires us to investigate a key problem: can we reduce the delay by transmitting data replications in parallel or using powerful erasure codes?In this paper, we study the problem of reducing the delay of downloading data from cloud storage systems by leveraging multiple parallel threads, assuming that the data has been encoded and stored in the clouds using fixed rate forward error correction (FEC) codes with parameters (n, k). That is., each file is divided into k equal-sized chunks, which are then expanded into n chunks such that any k chunks out of the n are sufficient to successfully restore the original file. The model can be depicted as a multipleserver queue with arrivals of data retrieving requests and a server corresponding to a thread. However, this is not a typical queueing model because a server can terminate its operation, depending on when other servers complete their service (due to the redundancy that is spread across the threads). Hence, to the best of our knowledge, the analysis of this queueing model remains quite uncharted.Real traces from Amazon S3 show that the time to retrieve a fixed size chunk is random and can be accurately approximated as an i.i.d. exponentially distributed random variable. We show that any work-conserving scheme is delay-optimal when k = 1. When k > 1, we find that a simple greedy scheme, which allocates all available threads to the head of line request, is delay optimal, which appears surprising.
The drone's open and untrusted environment may create problems for authentication and data sharing. To address this issue, we propose a blockchain-enabled efficient and secure data-sharing model for 5G flying drones. In this model, blockchain and attribute-based encryption (ABE) are applied to ensure the security of instruction issues and data sharing. The authentication mechanism in the model employs a smart contract for authentication and access control, public-key cryptography for providing accounts and ensuring accounts security, and a distributed ledger for security audit. In addition, to speed up outsourced computations and reduce electricity consumption, an ABE model with parallel outsourced computation (ABEM-POC) is constructed, and a generic parallel computation method for ABE is proposed. The analysis of the experimental results shows that parallel computation significantly improves the speed of outsourced encryption and decryption compared with serial computation.
Abstract-In this paper, we investigate the problem of maximizing the throughput over a finite-horizon time period for a sensor network with energy replenishment. The finite-horizon problem is important and challenging because it necessitates optimizing metrics over the short term rather than metrics that are averaged over a long period of time. Unlike the infinite-horizon problem, the fact that inefficiencies cannot be made to vanish to infinitesimally small values, means that the finite-horizon problem requires more delicate control. The finite-horizon throughput optimization problem can be formulated as a convex optimization problem, but turns out to be highly complex. The complexity is brought about by the "time coupling property," which implies that current decisions can influence future performance. To address this problem, we employ a three-step approach. First, we focus on the throughput maximization problem for a single node with renewable energy assuming that the replenishment rate profile for the entire finite-horizon period is known in advance. An energy allocation scheme that is equivalent to computing a shortest path in a simply-connected space is developed and proven to be optimal. We then relax the assumption that the future replenishment profile is known and develop an online algorithm. The online algorithm guarantees a fraction of the optimal throughput. Motivated by these results, we propose a lowcomplexity heuristic distributed scheme, called NetOnline, in a rechargeable sensor network. We prove that this heuristic scheme is optimal under homogeneous replenishment profiles. Further, in more general settings, we show via simulations that NetOnline significantly outperforms a state-of-the-art infinite-horizon based scheme, and for certain configurations using data collected from a testbed sensor network, it achieves empirical performance close to optimal.
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