Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted

A QoS-Guaranteed Coverage Precedence Routing Algorithm for Wireless Sensor Networks

For mission-critical applications of wireless sensor networks (WSNs) involving extensive battlefield surveillance, medical healthcare, etc., it is crucial to have low-power, new protocols, methodologies and structures for transferring data and information in a network with full sensing coverage capability for an extended working period. The upmost mission is to ensure that the network is fully functional providing reliable transmission of the sensed data without the risk of data loss. WSNs have been applied to various types of mission-critical applications. Coverage preservation is one of the most essential functions to guarantee quality of service (QoS) in WSNs. However, a tradeoff exists between sensing coverage and network lifetime due to the limited energy supplies of sensor nodes. In this study, we propose a routing protocol to accommodate both energy-balance and coverage-preservation for sensor nodes in WSNs. The energy consumption for radio transmissions and the residual energy over the network are taken into account when the proposed protocol determines an energy-efficient route for a packet. The simulation results demonstrate that the proposed protocol is able to increase the duration of the on-duty network and provide up to 98.3% and 85.7% of extra service time with 100% sensing coverage ratio comparing with LEACH and the LEACH-Coverage-U protocols, respectively

Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer

BackgroundSignificant ethnic differences in susceptibility to the effects of chemotherapy exist. Here, we retrospectively analyzed the safety and efficacy of induction chemotherapy (ICT) with dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) in Asian patients with borderline resectable or unresectable head and neck squamous cell carcinoma (HNSCC).MethodsBased on the incidence of adverse events that occurred during daily practice, TPF90 (90% of the original TPF dosage; docetaxel 67.5 mg/m2 on Day 1, cisplatin 67.5 mg/m2 on Day 1, and 5-fluorouracil 675 mg/m2 on Days 1–5) was used for HNSCC patients who were scheduled to receive ICT TPF.ResultsBetween March 2011 and May 2014, 52 consecutive patients with borderline resectable or unresectable HNSCC were treated with ICT TPF90 followed by concurrent chemoradiotherapy. Forty-four patients (84.6%) received at least three cycles of ICT TPF90. The most commonly observed Grade 3–4 adverse events included neutropenia (35%), anemia (25%), stomatitis (35%), diarrhea (16%), and infections (13.5%). In an intention-to-treat analysis, the complete and partial response rates after ICT TPF90 were 13.5% and 59.6%, respectively. The complete and partial response rates following radiotherapy and salvage surgery were 42.3% and 25.0%, respectively. The estimated 3-year overall survival and progression-free survival rates were 41% [95% confidence interval (CI): 25–56%] and 23% (95% CI: 10–39%), respectively. The observed median overall survival and progression-free survival were 21.0 months (95% CI: 13.3–28.7 months) and 16.0 months (95% CI: 10.7–21.3 months), respectively.ConclusionTPF90 is a suitable option for Asian patients with borderline resectable or unresectable HNSCC who are scheduled for ICT

Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Histone Deacetylase as a Therapy for Colorectal Cancer

AbstractStatins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) inhibitors decreasing serum cholesterol and have shown promise in cancer prevention. In this study, we demonstrated the oncogenic role of HMGR in colorectal cancer (CRC) by disclosing increased HMGR activity in CRC patients and its enhancement of anti-apoptosis and stemness. Our previous studies showed that statins containing carboxylic acid chains possessed activity against histone deacetylases (HDACs), and strengthened their anti-HDAC activity through designing HMGR-HDAC dual inhibitors, JMF compounds. These compounds exerted anti-cancer effect in CRC cells as well as in AOM-DSS and ApcMin/+ CRC mouse models. JMF mostly regulated the genes related to apoptosis and inflammation through genome-wide ChIP-on-chip analysis, and Ingenuity Pathways Analysis (IPA) predicted their respective regulation by NR3C1 and NF-κB. Furthermore, JMF inhibited metastasis, angiogenesis and cancer stemness, and potentiated the effect of oxaliplatin in CRC mouse models. Dual HMGR-HDAC inhibitor could be a potential treatment for CRC

Collaborative Localization in Wireless Sensor Networks via Pattern Recognition in Radio Irregularity Using Omnidirectional Antennas

In recent years, various received signal strength (RSS)-based localization estimation approaches for wireless sensor networks (WSNs) have been proposed. RSS-based localization is regarded as a low-cost solution for many location-aware applications in WSNs. In previous studies, the radiation patterns of all sensor nodes are assumed to be spherical, which is an oversimplification of the radio propagation model in practical applications. In this study, we present an RSS-based cooperative localization method that estimates unknown coordinates of sensor nodes in a network. Arrangement of two external low-cost omnidirectional dipole antennas is developed by using the distance-power gradient model. A modified robust regression is also proposed to determine the relative azimuth and distance between a sensor node and a fixed reference node. In addition, a cooperative localization scheme that incorporates estimations from multiple fixed reference nodes is presented to improve the accuracy of the localization. The proposed method is tested via computer-based analysis and field test. Experimental results demonstrate that the proposed low-cost method is a useful solution for localizing sensor nodes in unknown or changing environments

Anti-UVC Irradiation and Metal Chelation Properties of 6-Benzoyl-5,7-dihydroxy-4-phenyl-chromen-2-one: An Implications for Anti-Cataract Agent

Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen- 2-one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was found to have the most potent activity in protecting porcine γ-crystallin against UVC insults. Results of fluorescence assays indicated that compound 7 was capable of decreasing the loss of intensity while lens crystallins and DNA PUC19 were irradiated with UVC. Presence of compound 7 decreased hydroxyl radical levels determined by probe 1b and the free iron concentrations determined by Ferrozine reagent. The chelation assay showed that compound 7 was chelated to metal via 6-CO and 5-OH on the benzopyrone ring. The observed protective effects of compound 7 towards crystallins from insults of UVC and free radicals may be due to its iron-chelating activity and its peak absorption at 254 nm

Study of Coverage Precedence Adaptive Routing Algorithm for Wireless Sensor Networks

無線感測器網路因受到各感測器節點電量、通訊能力及運算能力的限制，使得無線感測器網路系統在實際應用中會有諸多問題需要考量。為改善無線感測器網路的使用壽命，過去許多研究學者利用各種路由演算法來調整節點間的資料傳遞。目前大多數演算法僅多半針對能量平衡、資料傳輸可靠度及節點分群調度方式加以探討。針對軍事偵測、保全系統及老人居家看護等應用，感測器節點在所欲監測的區域內應必須能達到100 % 覆蓋率才能準確偵測任一重要事件，因此覆蓋率因素應當納入感測器網路運作考量之中。因此，吾人提出一高覆蓋率動態路由演算法，透過模擬驗證此演算法能持續維持百分之百覆蓋率且增加網路的運作時間，並透過實作實驗驗證此演算法於實際網路應用之可行性。 在本研究中吾人提出一動態路由演算法，演算法針對能量均衡消耗及高覆蓋率的特性來進行群首挑選機制。利用經過覆蓋率考量後挑選出多餘的節點，讓這些節點主要用於群首節點運作及資料轉傳，藉以延長網路持續維持100 % 覆蓋率的運作時間，並依據傳輸能量消耗與節點剩餘能量來進行動態路由挑選機制。模擬中針對群首挑機制及動態路由挑選機制進行最佳參數分析，並與其他已經發表過的演算法進行性能比較，模擬結果顯示高覆蓋率動態路由演算法有效增加59 %的系統運作時間。 過去大多數所發表的演算法僅透過模擬方式分析性能，為了驗證本演算法確實可於實際應用中使用，本研究之演算法透過NesC語言撰寫，架構於TinyOS 系統上，實際在OctopusII節點上運作。為了驗證及分析本演算法的相關性能，分別於實驗室內及戶外環境進行相關實驗測試，實驗結果顯示動態路由機制確實能有效運作並提升資料回傳率。There are a lot of issues which need to be considered due to the limited power, the communication range, and the programming ability of wireless sensor nodes. In order to improve the lifetime of wireless sensor networks (WSNs), a number of routing algorithms have been proposed to adjust the data transmission between sensor nodes. Besides the energy efficiency, however, reliability of data transmission and cluster forming method, maintenance of the sensing coverage over the entire monitored area are also essential. In construction of projects that involve operational strategies to responds to specific emergency events such as medical healthcare, battlefield surveillance, or illegal smuggling, the primary concern is to preserve all valuable data acquired from the targeted area without any losing. Hence, this work proposed a novel energy-aware coverage-preserving hierarchical routing (ECHR) algorithm. The performance of ECHR algorithm was evaluated by simulations. In simulations, the ECHR algorithm can maximize the on duty time of full coverage. This work also applied the ECHR algorithm in wireless sensor node with OctopusII platform. The basic idea of the proposed ECHR algorithm is to take the remaining energies of the nodes as well as the coverage redundancy of its sensing ranges into consideration while selecting cluster heads. Intuitively, the sensor nodes deployed in a densely populated area have the higher probability to be selected as cluster heads in each round. These nodes are frequently chosen to be cluster heads, because the loss of nodes from the densely populated area is not significant for the network coverage. In addition, an energy-aware hierarchical routing mechanism was also proposed to determine the optimal route. Extensive series simulations were conducted to analyze the performance of the ECHR algorithm applying to the network with different weight factors of the cluster head selection mechanism and the adaptive energy-aware hierarchical routing mechanism. The simulation results demonstrate that the proposed protocol is able to increase the duration of network on duty and provide up to 59 % of extra service time with 100% sensing coverage ratio comparing with other existing protocols. Most presented researches about routing algorithms only evaluated the performance under simulations. In order to evaluate the feasibility of ECHR algorithm in realistic applications, this work has developed the ECHR algorithm with NesC program on TinyOS. All of experimental tests in laboratory and outdoor environment used wireless sensor nodes, OcotpusII. The experimental results demonstrate that the adaptive routing mechanism of the ECHR algorithm is able to reduce the data loss rate.誌謝 i文摘要 ii文摘要 iii錄 v目錄 viii目錄 xi一章 前言 1.1研究背景 1.2文獻探討 3.2.1 WSN路由協定種類─依據網路型態分類 3 1.2.1.1 平面式路由(Flat Routing) 4 1.2.1.2 階層式路由(Hierarchical Routing) 5 1.2.1.3 地理資訊式路由(Geographical Routing) 9 1.2.2無線感測器路由演算法─依據應用狀況分類 9 1.2.2.1集中式路由演算法 10 1.2.2.2分散式路由演算法 11 1.2.3覆蓋率考量路由演算法 12.3研究動機及目的 13 1.4論文架構 15二章 無線感測器網路介紹 16.1無線感測器網路系統架構 16.2無線感測器節點 18.3 ZigBee協定 20 2.4無線感測器網路作業系統—TinyOS 22三章 高覆蓋率動態路由演算法 24 3.1無線通訊模型 24 3.2覆蓋率模型 26 3.3高覆蓋率動態路由演算法 28.3.1群首挑選機制 29 3.3.2動態路由挑選機制 31 3.4演算法相關參數分析 31 3.4.1群首挑選機制參數分析 33 3.4.2動態路由挑選機制參數分析 35 3.5演算法性能驗證分析 38四章 感測器網路建置與性能驗證分析 44 4.1 感測器節點性能測試 44 4.1.1 SuperNode天線指向性測試 44 4.1.2 平台端感測器節點天線適用性測試 46 4.1.3 OctopusII通訊距離及資料回傳率測試 48 4.1.4 多跳路由性能測試實驗 50 4.2 動態路由演算法運作流程與架構 52 4.2.1路由係數 53 4.2.2資訊交換程序 54 4.2.3同步設定程序 56 4.2.4資料回傳程序 57 4.2.5節點重新加入網路機制 59 4.3 室內感測器網路平台實驗 60 4.3.1 節點重新加入網路測試 65 4.4 戶外感測器網路平台實驗 67五章 結論與未來工作 69 5.1 結果討論 69 5.2 未來研究方向 70考文獻 72者簡歷 7