Awareness of Complications of Dental Treatment in Patients Treated with Drugs Affecting the Immune System : A Nationwide Questionnaire Survey of Dental Practitioners in Japan

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited

Rhodacyanine Derivative Selectively Targets Cancer Cells and Overcomes Tamoxifen Resistance

MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Development of Chemical Modulators for Heat Shock Protein 70 (Hsp70): a Potential Therapeutic Target for Tauopathies.

Tauopathies are a class of neurodegenerative disorders, which affect millions of people worldwide. These diseases are characterized by the accumulation of protein aggregates composed of abnormally modified variants of the microtubule-binding protein tau. Despite extensive efforts, there is currently no cure for these devastating diseases. The goal of this study is to understand whether heat shock protein 70 (Hsp70) may be an under-explored target for tauopathies. Hsp70 is a molecular chaperone that plays important roles in protein quality control, including the turnover of misfolded polypeptides. However, the molecular mechanisms of tau quality control were not known and it wasn’t clear how pharmacological inhibition of Hsp70 might impact tau accumulation. In this thesis, we review the literature linking Hsp70 to tau and hypothesize that inhibiting the ATPase activity of Hsp70 might lead to the degradation of aberrant tau by favoring the triage pathway. To test this hypothesis, we developed a new high-throughput screen platform and identified promising inhibitors, including methylene blue (MB). MB inhibited the ATPase activity of Hsp70 and, consistent with the major hypothesis, caused a dramatic, Hsp70-dependent reduction in the accumulation of tau in cellular and animal models of tauopathy. In mechanistic studies, we found that MB inhibits Hsp70 by selectively oxidizing two key cysteine residues in the chaperone. To further explore this process, we developed a parallel chemical series of Hsp70 inhibitors based on the known anti-cancer agent, MKT-077. We found that these compounds inhibit the ATPase activity of Hsp70 and, like MB, they dramatically reduce tau levels. However, the MKT-077 analogs acted by a distinct mechanism: binding to the ADP-bound form of Hsp70 and allosterically blocking nucleotide cycling. Together, these studies suggest that Hsp70 normally protects tau from degradation, while inhibitors lead to its rapid degradation. In summary, we have used a chemical biology approach to show that Hsp70 plays a critical role in tau stability and inhibitors reduce tau levels. Thus, this work suggests a potential path towards new treatments for tauopathies. In addition, these findings provide molecular insights into how Hsp70 mediates protein quality control.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/94080/1/ymiyata_1.pd