AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production

Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-kappa B activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36 alpha, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.Peer reviewe

How We Pass From Semigroups to Hypersemigroups

In this paper we show the way we pass from semigroups (without order) to hypersemigroups. Moreover we show that, exactly as in semigroups, in the results of hypersemigroups based on right (left) ideals, quasi-ideals and bi-ideals, points do not play any essential role, but the sets, which shows their pointless character. The aim of writing this paper is not just to add a publication on hypersemigroups but, mainly, to publish a paper which serves as an example to show what an hypersemigroup is and give the right information concerning this structure. © 2018, Pleiades Publishing, Ltd

[[alternative]]On advancing routing protocols in vehicular ad-hoc networks

碩士[[abstract]]在這個資訊爆炸的時代，隨著行動隨意網路架構出現之後，首先便是承襲舊有有線網路架構，需要整個拓樸資訊的之基於拓撲(Topology-based)的路由協定，由於這類的協定是針對有線網路的架構設計的，所以當節點要傳送封包時，必須仰賴是先建立好的路徑來幫助傳送資料封包，這導致在傳送資料之前必須先耗費大量的控制封包來建立路徑。 由於現今的車輛搭載全球定位系統(Global Positioning System，簡稱GPS)已經是現今車輛的基本配備了，也因此在取得車輛即時地理位置的座標是沒有問題的，因此便衍伸出了Position-based的路由協定，而Position-based傳統的做法有限制廣播區域、Greedy Forwarding以及劃分區塊等等，但是在VANET中，由於節點移動速度較快加上城市環境格局的限制，上述的做法可能會遇到控制封包損耗過大，或是最短路徑無法順利到達目的地等等問題。 根據VANET中城市環境的格局限制的特性，近年的研究多半是以街道及路口的特性為基礎而衍伸出來的路由協定我們稱為基於路口(Junction-based)的路由協議，加上近年來圖資系統的普及，使得這類的路由協定不需要再進行是否位於路口的判斷。 我們的研究目標為設計一個倚靠路口位置資訊(Junction-based)建立之依照local端紀錄傳輸路徑的VANET路由協定，以提升VANET傳輸路徑的穩定度，在我們的研究中，利用固定的街道與路口資訊結合動態的節點資訊，使封包的傳輸更有效率，由於在都市環境中，車輛行進的叉路，也就是封包傳遞方向的改變，主要發生在路口處，並非在筆直的街道上，因此可以利用我們提出的方法，將節點與所在路口配對，改善以往方法重新搜尋路徑或是找不到適合節點轉傳的問題，因為將節點與路口做了配對，也能改善雖然指定了路口，但是卻沒有節點可以轉傳的問題。 在我們的模擬中，可以看出我們的方法在VANET這樣節點移動頻繁的環境中，不需要增加額外的網路成本，也能準確的搜尋到可以轉傳的節點，進而增進效率。[[abstract]]Nowadays vehicles are usually equipped with Global Positioning System (GPS). The protocol that uses GPS in VANET is called Position-based. The Position-based approaches include limited broadcast area, greedy forwarding and dividing the blocks, etc. Because nodes move quickly due to characteristics of the city scenario in VANET, the methods described previously may incur high control packet overhead, with the shortest paths unable to reach the destination successfully. According to the characteristics of the city scenario in VANET, the existing routing protocols divide the city scenarios into streets and junctions. These are called Junction-based routing protocols. With digital maps, the Junction-based protocols in more recent literature do not need to judge the junctions. Designing a Junction-based routing protocol for VANET is our researching target. Using junctions and node information to forward packets, this method can enhance the stability of the transmission paths and can reduce the waste of resources caused by searching paths again and again. In city scenarios, packets change path directions at junctions, not on streets. We use the junction and node information to improve the stability of the transmission paths. The simulation of our research proves our method is suitable for frequent use in mobile V2V environments. The results show that our method can find the node to forward the data accurately and enhance transmission efficiently, without increasing network cost.[[tableofcontents]]目錄 第一章、緒論 1 1.1 論文簡介 1 1.2 研究動機 2 1.3 論文架構 5 第二章、背景知識與相關研究 7 2.1 MANET架構 7 2.1.1 Topology-based 8 2.1.2 Position-based 11 2.2 VANET架構 11 2.2.1 Vehicle to RSU(V2R) 12 2.2.2 Vehicle to Vehicle(V2V) 13 2.2.3結合V2V以及V2R之架構 13 2.2.4 Junction-based 14 2.3既有路由協定介紹 17 2.3.1GPSR 17 2.3.1.1貪婪演算法(Greedy Forwarding) 18 2.3.1.2平面圖環繞法(Planer Perimeter) 18 2.3.2 GPCR 21 2.3.2.1 受限制的greedy forwarding 24 2.3.2.2 Repair Strategy 25 2.3.3 JBR 26 2.3.3.1 選擇性的greedy forwarding 28 2.3.3.2 在路口中的轉傳機制 29 2.3.3.3 Recovery mode 30 2.3.4 JMSR 32 2.3.4.1 以路口為主要轉傳基準 35 2.3.4.2 Multipath 35 2.3.4.3 若路口中沒有可轉傳的節點 35 2.4 既有協定之比較 36 第三章、新的VANET路由協定 37 3.1轉傳區域的分類 41 3.2區域的判定 42 3.3路口表單建立之方法 42 3.3.1 Switch Table Learning 42 3.3.2 Routing Table Learning 46 3.4表單的維護 46 3.5整體封包轉傳的演算法 47 第四章、模擬與比較 51 4.1 模擬環境 51 4.2 模擬結果與分析 54 4.2.1 控制封包overhead 54 4.2.2 封包傳輸抵達率 56 4.2.2.1 PDR vs. speed 56 4.2.2.2 PDR vs. connection 59 4.2.3封包傳輸平均延遲時間 60 4.2.3.1 ADT vs. speed 60 4.2.3.2 ADT vs. connection 61 第五章、結論與未來工作 62 第六章、參考文獻 65   圖目錄 圖1. 結合路口與節點資訊之示意圖 4 圖2. 重新搜尋路徑示意圖 5 圖3. RREQ示意圖 9 圖4. RREP示意圖 9 圖5. 路徑損壞示意圖 10 圖6. Vehicle to RSU 12 圖7. Vehicle to Vehicle 13 圖8. 沒有圖資系統之路口判定示意圖 16 圖9. 有圖資系統之路口判定示意圖 17 圖10. greedy forwarding example 18 圖11 .Greedy forwarding failure 19 圖12. The right-hand rule (interior of the triangle) 20 圖13. RNG(Relative Neighborhood Graph) 21 圖14. GG(Gabriel Graph) 21 圖15. Flowchart of the GPCR procedure 22 圖16. GPCR greedy forwarding示意圖 24 圖17. Repair Strategy示意圖 26 圖18. Flowchart of the JBR procedure 27 圖19. JBR Greedy forwarding示意圖 30 圖20. recovery mode示意圖 32 圖21. Flowchart of the JMSR procedure 34 圖22. 以路口節點為主之傳輸示意圖 39 圖23. 節點紀錄示意圖 40 圖24. JMSR規畫路徑示意圖 41 圖25. 規劃路口中沒有節點可以傳輸之示意圖 41 圖26. Switch Port接收封包示意圖 43 圖27. Switch轉送封包示意圖 44 圖28. Switch table紀錄示意圖 44 圖29. Flowchart of the Ours procedure 48 圖30. 模擬場景示意圖 53 圖31. 控制封包消耗 55 圖32. 不同速度下之封包傳輸成功率 56 圖33. 丟棄封包之機率 58 圖34. 不同連線數下封包之傳輸成功率 59 圖35. 不同速度之平均延遲時間 60 圖36. 不同連線數下之平均延遲時間 61   表目錄 表1. 沒有圖資系統的beacon 15 表2. 有圖資系統的beacon: 15 表3. GPCR algorithm 23 表4. JBR algorithm 28 表5. JMSR algorithm 33 表6. Ours algorithm 49 表7. 各項方法之比較 50 表8. 模擬參數設定 53 表9. 各項方法之控制封包size 54[[note]]學號: 600450281, 學年度: 10

TCP-Call Admission Control Interaction in Multiplatform Space Architectures

The implementation of efficient call admission control (CAC) algorithms is useful to prevent congestion and guarantee target quality of service (QoS). When TCP protocol is adopted, some inefficiencies can arise due to the peculiar evolution of the congestion window. The development of cross-layer techniques can greatly help to improve efficiency and flexibility for wireless networks. In this frame, the present paper addresses the introduction of TCP feedback into the CAC procedures in different nonterrestrial wireless architectures. CAC performance improvement is shown for different space-based architectures, including both satellites and high altitude platform (HAP) systems

Ap1s3 mutations cause skin autoinflammation by disrupting keratinocyte autophagy and up-regulating il-36 production

Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-kappa B activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36 alpha, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target