Abstract
Introduction: Oral mucositis (OM) represents one of the most debilitating and troublesome adverse effects of chemoradiotherapy frequently encountered in patients. Most ionizing ...radiation-induced oral mucosa cell death results from radiation-induced reactive oxygen species (ROS) attack of DNA bases and molecular oxygen (O2) “fixation” of the ROS damage, which results in DNA breakage. Our earlier work showed complete suppression of radiation-induced oral mucositis in rodents by transient reduction of ROS related DNA damage when the animals were pre-treated with a topically-applied vasoconstrictor before irradiation. In this study, we have initiated a Phase IIa clinical investigation to determine whether orotopical vasoconstrictor application conferred the same resistance to radio-damage in normal oral mucosa of patients receiving whole-body radiation prior to bone marrow transplantation. Patients and Methods: In two years, 58 patients received the cyclophosphamide +TBI conditioning regimen. A clinical trial (NCT02434146) was approved by the University of Wisconsin Review Board to test the ability of five increasing doses of the NG-11-1 topical vasoconstrictor formulation to suppress the incidence and severity of OM. For a control cohort, records of five patients who received the cyclophosphamide+TBI regimen at UW were analyzed, records including weights, daily OM scores, use of total parenteral nutrition (TPN) were collected for comparison to the NG-11-1 treatment group. For the “topical NG-11-1 treated” group, each patient received the lowest of the five projected concentrations of NG-11-1 vasoconstrictor. The study physician directed 30 spray pulses to the buccal, lingual and sub-lingual surfaces. The formulation contains a blue coloring that enables directing and judging drug coverage. Orotopical NG-11-1 was applied: i) 15-20 min before IV cyclophosphamide was initiated, ii) 25-30 min after IV cyclophosphamide was initiated, and iii) 15-20 min before every 1.5 Gy irradiation. Pain score and OM score were collected before and after treatments and during follow-up clinic re-visits for 2 weeks. Results: The mean of “Grade 3 oral mucositis duration (days)” in NG-11-1 vasoconstrictor drug treated patients was significantly lower (P=0.047) than that of control patients. And, the mean of “total mucositis duration (days)” in NG-11-1 treated patients was significantly lower (P=0.043) than the level of control patients. Thirdly, either nasogastric feeding or total parenteral nutrition was required in 60% of control patients, however, none of the NG-11-1-treated patients required this intervention. Conclusions: These clinical results showing significant suppression of OM severity are consistent with the same degree of NG-11-1 dose-dependent suppression of radiation-induced oral mucositis that we observed in our previous mouse OM model studies.
Citation Format: Amanda Graul-Conroy, Margo Hoover-Regan, Paul M. Sondel, Natalie S. Callander, Walter L. Longo, Ningfeng F. Li, William E. Fahl. A new orotopically applied vasoconstrictor drug significantly confers normal oral mucosa resistance to radio-damage abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4160.
Dwarf bamboo
Sasa argenteostriata
(Regel) E.G. Camus has previously been considered as potential plant for metal phytoremediation. However, the dynamic responses and correlations among physiological ...resistances to high-concentration Pb exposure have not been described to date. This study conducted four Pb treatments (0, 1500, 3000, and 4500 mg kg
–1
) to examine the physiological resistance responses at days 7, 14, and 21. The findings showed that
S. argenteostriata
can regulate both the enzymatic system and the nonenzymatic system to synergistically overcome Pb damage. In addition, a significant positive correlation was found between enzymes and nonenzymatic substances, which were particularly apparent with regard to the superoxide dismutase (SOD) activities with phytochelatins (PCs) levels, peroxidase (POD), and glutathione reductase (GR) activities with glutathione (GSH) levels, as well as catalase (CAT) and ascorbate peroxidase (APX) activities with soluble protein (SP) levels. Furthermore, Pb concentration was the main factor that induced the physiological responses of
S. argenteostriata
to Pb stress. The antioxidant enzyme system and the AsA–GSH cycle were dominant resistance mechanisms under 1500 mg kg
–1
Pb. AsA–GSH cycle and plant cell chelation were dominant resistance mechanisms under 3000 mg kg
–1
Pb. Antioxidant enzymes and plant cell chelation were dominant resistance mechanisms under 4500 mg kg
–1
Pb. This study provides comprehensive evidence regarding how both enzymatic and nonenzymatic systems of
S. argenteostriata
cooperate to alleviate the high-concentration soil Pb stress. The results highlight the environmental remediation potential of this species for Pb-contaminated media.
The consensus protocol is a crucial mechanism to ensure the consistency and security of distributed systems. In this paper, an improved PBFT consensus protocol is proposed, which incorporates node ...contribution incentives. A reliable consensus node set is formed by dynamically selecting nodes based on their historical involvement in consensus, thereby reducing the presence of malicious nodes. Additionally, we develop a mechanism to incentivize node contribution by distributing consensus income fairly using Shapley value calculation. Moreover, we perform periodic evaluations of node contribution, considering both their consensus income and performance, to enhance node engagement in consensus. Finally, we simulate and analyze the improved PBFT algorithm, demonstrating its benefits in terms of enhancing consensus speed, minimizing communication overhead, and bolstering system resilience against attacks.
Microgrid's smooth transition between island mode and grid-connected mode is a hot topic. Academic circles attach great importance to this, but the concept of smooth transition is not clear and the ...comprehension of it is also different. According to analyse the control process of transition,adjusting the run mode of distributed generations(DG) and storage devices to realize the transition is essential. The run modes of DG and storage devices include PQ,V/f and droop, that is to say, how to choose the run mode is related to run steadily of microgrid. Combined with the control method of voltage outer loop and current inner loop, an improved method of following the control of outer loop to avoid the fluctuation of voltage and frequency is presented to realize the transition smoothly between island mode and grid-connected mode. The effectiveness of this method is confirmed on the platform of simulation.
Distributed energy trading is a bilateral transaction of electricity directly involved by power-producers, operators, power-sellers, and power-large-users. The blockchain essence is a decentralized, ...distributed storage technology with natural adaptability in distributed energy transactions. Applying blockchains to distributed energy transactions requires addressing data desensitization first. Aiming at the data characteristics in energy trading, this paper proposes an energy blockchain data desensitization algorithm based on differential privacy. The algorithm randomizes the query results by adding different distributed noise data. Experiments show that the algorithm can better integrate distributed energy services and improve the security and data storage efficiency of blockchain system data.
The virtual power plant integrates all the distributed power supplies within the communication domain through advanced communication technology, and adopts multiple coordinated control strategies to ...optimize the power supply operation. It is a very competitive new format in the power market. In practical applications, the virtual power plant must meet the needs of market participants, and on the other hand, it also should ensure the safe and reliable operation of the VPP system. It has great difficulty no matter in the designing of operating mechanism or the realization of technology. Blockchain technology has the characteristics of decentralizat distributed storage, and intelligent contracts. This is highly compatible with the distributed control architecture of virtual power plants, providing a new solution for the power trading and coordinated control of virtual power plants. By researching the characteristics of virtual power plant and blockchain technology, this paper uses a distributed calculation based on blockchain to establish a multi-coordinated control model of virtual power plant. The simulation operation of the model shows that the coordinated control under blockchain technology can improve the efficiency of the virtual power plant control calculation, and promote the rapid and accurate release of the control strategy, It also improves the economic benefit.
Along with the energy revolution and the environmental movement, the energy industry is transforming into a clean, distributed energy sector with a new energy structure featuring multiple energy ...flows complementing each other. Blockchain is a distributed database that is jointly maintained by the consensus of the whole network and maintains all historical transaction data. It provides a feasible path for the transaction demand of distributed energy, high frequency and low cost. Firstly the problems brought by distributed energy transaction and the business positioning of each subject is analyzed. Based on the core demand of distributed energy transaction, the fit between Blockchain technology and distributed energy transaction is analyzed. On this basis, Fabric distributed energy transaction architecture and transaction flow are proposed, and the key technologies of distributed data storage, consensus mechanism and intelligent contract are analyzed.
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