Effects of different ceramic and dentin thicknesses on the temperature rise during photocuring

AbstractBackground/purposeThe aims of this investigation were to describe the effect of different ceramic and remaining dentin thicknesses on substrate temperature during photocuring, and investigate whether the temperature increased by >5.5°C for different dentin/ceramic combinations.Materials and methodsThree groups of dentin thicknesses of 1.0 (D1.0), 1.5 (D1.5), and 2.0 mm (D2.0), and three groups of ceramic thicknesses of 1.5 (C1.5), 2.5 (C2.5), and 3.5 mm (C3.5) were examined. Temperature changes and the maximum temperature were observed under a high-intensity halogen light (QTH-Atralis 10 ECS program at 1200mW/cm2 for 30 seconds, Ivoclar Vivadent AG, Schaan, Liechtenstein). Four groups, D1.0–C1.5 (+11°C), D1.5–C1.5 (+7.2°C), D1.0–C2.5 (+6.7°C), and D2–0C1.5 (+5.8°C), demonstrated temperature changes of >5.5°C.Results and ConclusionsA statistical analysis showed that separate individual thicknesses and combinations of dentin and ceramic had significant effects on temperature changes (P<0.01). It was observed that the ceramic exhibited a smaller temperature shielding effect than dentin. Clinically, it would be optimal to preserve the dentin to avoid damaging pulp tissues. Where there is insufficient overall thickness (≤3.5mm), continuous high-energy output photocuring should be avoided to protect pulp tissues from thermal injury

Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target

Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein's N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5'-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein's RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD-PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs

Experimental Investigation on Thermoelectric Chiller Driven by Solar Cell

This paper presents experimental explorations on cooling performance of thermoelectric chillers being driven by solar cells, as well as comparison results to the performance being driven by fixed direct current. Solar energy is clear and limitless and can be collected by solar cells. We use solar cells to drive thermoelectric chillers, where the cold side is connected to the water tank. It is found that 250 mL of water can be cooled from 18.5°C to 13°C, where the corresponding coefficient of performance (COP) is changed between 0.55 and 1.05, when solar insolation is changed between 450 W/m2 and 1000 W/m2. The experimental results demonstrate that the thermoelectric chiller driven by solar cell is feasible and effective for energy saving issues

Analysis of Surgically Treated Intraspinal Tumors in Southern Taiwan

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), menin-giomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61–70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64–86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer)

Developing a Series of AI Challenges for the United States Department of the Air Force

Through a series of federal initiatives and orders, the U.S. Government has been making a concerted effort to ensure American leadership in AI. These broad strategy documents have influenced organizations such as the United States Department of the Air Force (DAF). The DAF-MIT AI Accelerator is an initiative between the DAF and MIT to bridge the gap between AI researchers and DAF mission requirements. Several projects supported by the DAF-MIT AI Accelerator are developing public challenge problems that address numerous Federal AI research priorities. These challenges target priorities by making large, AI-ready datasets publicly available, incentivizing open-source solutions, and creating a demand signal for dual use technologies that can stimulate further research. In this article, we describe these public challenges being developed and how their application contributes to scientific advances

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Structure basis for identification of the N-terminal domain of coronavirus nucleocapsid protein as a potent antiviral target for drug development

西元2003年，嚴重呼吸道症候群 (Severe Acute Respiratory Syndrome,SARS)大流行，造成各個年齡層患者7%-15%的死亡，其中六十五歲以上的患者死亡率更是超過了50%；嚴重呼吸道症候群的爆發造成世界各國的恐慌，直接地對各國人民的健康造成影響，更間接地引起經濟上的損失。而嚴重呼吸道症候群是由一冠狀病毒所引起，同時冠狀病毒也會造成一般的感冒，在某些情況下還會引發神經系統的疾病，因此研究如何治療冠狀病毒所引起的疾病，成為了各國研究的熱門議題。在治療冠狀病毒所引起的疾病方法中，以抗病毒藥物最為常見，但是由於病毒快速的變異，以致迅速產生抗藥性，進而使抗病毒藥物在治療上更形困難，為了克服病毒的突變，在病毒所含有的蛋白中，具有演化高度保留性並在病毒複製過程中扮演重要角色的核殼蛋白 (nucleocapsid protein, NP)因而成為了抗病毒藥物的目標。本篇即是針對人類冠狀病毒OC43 (HCoV-OC43)的核殼蛋白為目標，分別以四種單核苷核酸 (A、U、G、C nucleoside monophosphate)利用共結晶實驗的方式，研究此核殼蛋白和病毒遺傳物質(RNA)之間的結合情形，發現一個以胺基酸R122、Y124、Y126和R164為主所構成的RNA結合凹槽，同時利用表面膜共振分析實驗，研究分析核殼蛋白和四個不同單核苷核酸之間結合能力上的差異；並在病毒遺傳訊息中比對四個核酸的數量的不同解釋所可能的產生專一性的原因；分析此一結晶結構，以單核苷核酸和核殼蛋白的結合位置為中心，利用電腦模擬分子對接的方式，從各大藥廠龐大的小分子資料庫中，篩選出具有高潛力和核殼蛋白結合的化合物NSC663284、Dicumarol以及PJ34，並利用結晶結構解析其結合方式。本篇研究提出更深入了解冠狀病毒核殼蛋白和其遺傳物質之間結合的方式，以及其重要結合區，並利用電腦模擬分子對接和抗病毒活性實驗，希望可以找出對抗冠狀病毒的抗病毒藥物，並透過抗病毒藥物的開發，以降低人類感染的死亡率和社會成本的增加，期能藉此減少冠狀病毒對於人類社會影響。Coronaviruses (CoV) cause a number of diseases often causing significant economic and health-related consequences. In humans, they are responsible for the common cold and severe acute respiratory syndrome (SARS), the first pandemic of the 21st century. The recent outbreak of a new coronavirus disease in the Middle East further highlights its importance as a human pathogen. CoVs encode the nucleocapsid (N) protein, a major structural protein that play multiple roles in the virus cycle and form a ribonucleoprotein (RNP) complex with viral RNA via its N-terminal domain. By using HCoV-OC43 as an experimental model for CoV research, we present the crystal structures of HCoV-OC43 N-NTD complexed with nucleoside 5’ monophosphates (AMP, CMP, GMP, and UMP) to identify one RNA-binding core that is comprised of R122, Y124, Y126, and R164 at NTD. Furthermore, we obtained a potent N protein inhibitor, PJ34 and NSC663284, via virtual screening in which perform the ability to inhibit viral replication. We also determined the crystal structure of the N-NTD-PJ34 and N-NTD-NSC663284 complexes. According to the results of the complex structures we use surface plasmon resonance to futher invesgate the ability of NP-RNA binding affinity in the present of PJ34 and NSC663284. We also compare the structure of N-NTD with and without ligand to find out the conformation change of prtoein after ligand binding. In summary, we report the first CoV N-NTD structure complexed with ribonucleoside 5’ monophosphate and its inhibitor to identify a distinct drug-targeting pocket. Based on these findings, we propose design guidelines for development of new anti conronaviruse agents.目次 第一章、 緒論 1 一、 冠狀病毒 1 (一) 冠狀病毒概述 1 (二) 冠狀病毒分類 2 (三) 病毒基因體 2 (四) 冠狀病毒感染模式及生命週期 3 (五) 冠狀病毒之核殼蛋白介紹 4 (六) 核殼蛋白N端功能區之結晶結構 5 二、 研究動機與目的 6 第二章、 材料與方法 8 一、 實驗流程 8 二、 實驗材料及儀器設備 9 (一) 化學藥品 9 (二) 有機溶劑 9 (三) 載體(vector)和勝任細胞(competent cell) 9 (四) 培養基 10 (五) 緩衝溶液、染劑及相關材料 10 (六) 蛋白質濃度定量商業套組 10 (七) 感應晶片 10 (八) 單股RNA序列 10 (九) 實驗儀器設備 10 三、 實驗方法 11 (一) HCoV-OC43核殼蛋白N端功能區之純化與製備 11 (二) 共結晶 (co-crystal)實驗 17 (三) 電腦模擬分子對接 (molecular docking)實驗 18 (四) 結晶浸泡 (Soaking)實驗 18 (五) 生物分子交互作用分析系統 (Biomolecular interaction analysis,BIAcore) 19 (六) 利用Ramachandran plot分析結晶結構之正確性 22 第三章、 實驗結果 23 一、 人類冠狀病毒OC43核殼蛋白N端功能區 (HCOV-OC43 N-NTD)純化 23 二、 HCOV-OC43 N-NTD的濃縮與透析 23 三、 單磷酸核苷酸和HCOV-OC43 N-NTD之複合體結晶結構解析 23 (一) X-ray繞射數據分析 23 (二) 複合體之結晶結構解析 24 四、 HCOV-OC43核殼蛋白 (FULL LENGTH)純化 28 五、 以表面膜共振實驗探討冠狀病毒核殼蛋白與不同序列之單股RNA結合能力差異 29 六、 以電腦模擬分子對接尋找有潛力競爭RNA結合位的小分子藥物 29 七、 PJ34和HCOV-OC43 N-NTD之複合體結晶結構解析 31 (一)X-ray繞射數據分析 31 (二)複合體之結晶結構解析 31 八、 以表面膜共振實驗探討PJ34抑制冠狀病毒核殼蛋白結合單股RNA序列的能力 32 九、 NSC663284和HCOV-OC43 N-NTD之複合體結晶結構 33 (一) X-ray繞射數據分析 33 (二) 複合體之結晶結構解析 34 第四章、 討論 35 一. HCOV-OC43 核殼蛋白N端功能區結合NMP時的結構差異 35 二. HCOV-OC43 N-NTD-PJ34複合體結晶結構 36 三. 開發抗冠狀病毒藥物方針 36 四. HCOV-OC43 核殼蛋白與單股RNA序列結合能力分析及探討 37 五. PJ34在不同冠狀病毒核殼蛋白N端功能區上的應用 38 第五章、 結論 41 第六章、 表次 43 表一(A)、 HCOV-OC43 N-NTD-NMPS複合體X-RAY繞射數據分析 43 表一(B)、 HCOV-OC43 N-NTD-NMPS複合體X-RAY繞射數據分析 44 表 二(A)、 HCOV-OC43 N-NTD-COMPOUNDS複合體X-RAY繞射數據分析 45 表 二(B)、 HCOV-OC43 N-NTD-COMPOUNDS複合體X-RAY繞射數據分析 46 表三、 以SPR實驗數據分析HCOV-OC43核殼蛋白與不同單一核酸多重複序列之解離常數 47 表四、 以SPR實驗數據分析HCOV-OC43核殼蛋白在不同濃度PJ34存在下之解離常數 48 第七章、 圖次 49 圖 一、AMP複合體之RAMACHANDRAN PLOT 49 圖 二、UMP複合體之RAMACHANDRAN PLOT 50 圖 三、GMP複合體之RAMACHANDRAN PLOT 51 圖 四、CMP複合體之RAMACHANDRAN PLOT 52 圖 五、PJ34複合體之RAMACHANDRAN PLOT 53 圖 六、NSC663284複合體之RAMACHANDRAN PLOT 54 圖 七、HCOV-OC43 N-NTD截切蛋白純化膠體電泳圖 55 圖 八、HCOV-OC43 N-NTD凹槽 (CAVITY) 56 圖 九、AMP與UMP在結晶中的電子密度雲圖 57 圖 十、AMP與UMP在結晶中的電子密度雲圖 58 圖 十一、GMP與CMP在結晶中的電子密度雲圖 59 圖 十二、GMP與CMP在結晶中的電子密度雲圖 60 圖 十三、HCOV-OC43 N-NTD二級結構圖 61 圖 十四、AMP與HCOV-OC43 N-NTD結合示意圖 62 圖 十五、 AMP之鍵結作用力示意圖 63 圖 十六、HCOV-OC43 N-NTD與AMP複合體表面電荷圖 64 圖 十七、AMP複合體與NATIVE結構比較 65 圖 十八、AMP複合體F57之結構變化 66 圖 十九、UMP與HCOV-OC43 N-NTD結合示意圖 67 圖 二十、 UMP之鍵結作用力示意圖 69 圖 二十一、HCOV-OC43 N-NTD與UMP複合體表面電荷圖 70 圖 二十二、UMP複合體NATIVE結構比較 71 圖 二十三、UMP複合體R164之結構變化 72 圖 二十四、GMP與HCOV-OC43 N-NTD結合示意圖 73 圖 二十五、 GMP之鍵結作用力示意圖 74 圖 二十六、HCOV-OC43 N-NTD與GMP複合體表面電荷圖 75 圖 二十七、GMP複合體與NATIVE結構比較 76 圖 二十八、GMP複合體F57之結構變化 77 圖 二十九、CMP與HCOV-OC43 N-NTD結合示意圖 78 圖 三十、 CMP之鍵結作用力示意圖 79 圖 三十一、HCOV-OC43 N-NTD與CMP複合體表面電荷圖 80 圖 三十二、CMP複合體與NATIVE結構比較 81 圖 三十三、CMP複合體R164之結構變化 82 圖 三十四、HCOV-OC43核殼蛋白純化膠體電泳圖 83 圖 三十五、HCOV-OC43核殼蛋白全長與富含ADENOSINE、URIDINE、GUANOSINE和CYTIDINE RNA序列之結合SENSORGRAM 84 圖 三十六、電腦模擬分子對接小分子結構圖 85 圖 三十七、電腦模擬分子對接PJ34結合示意圖 86 圖 三十八、電腦模擬分子對接DICUMAROL結合示意圖 87 圖 三十九、電腦模擬分子對接NSC663284結合示意圖 88 圖 四十、結晶浸泡圖 89 圖 四十一、PJ34在結晶中的電子密度雲圖 90 圖 四十二、PJ34與HCOV-OC43 N-NTD結合之表面電荷圖 91 圖 四十三、PJ34與HCOV-OC43 N-NTD結合示意圖 92 圖 四十四、 PJ34之鍵結作用力示意圖 93 圖 四十五、PJ34複合體與NATIVE結構比較 94 圖 四十六、PJ34複合體F57之結構變化 95 圖 四十七、PJ34複合體H104與R106之結構變化 96 圖 四十八、PJ34複合體LOOP端結構變化 97 圖 四十九、PJ34複合體R164結構變化 98 圖 五十、HCOV-OC43核殼蛋白加入PJ34混合後測量與RNA的結合活性的SENSORGRAM結果圖 99 圖 五十一、HCOV-OC43 N-NTD截切蛋白晶體 100 圖 五十二、NSC663284在結晶中的電子密度雲圖 101 圖 五十三、NSC663284與HCOV-OC43 N-NTD結合示意圖 102 圖 五十四、NSC663284與HCOV-OC43 N-NTD結合之表面電荷圖 103 圖 五十五、 NSC663284之鍵結作用力示意圖 104 圖 五十六、 HCOV-OC43 核殼蛋白NATIVE結構之電子雲圖和HCOV-OC43核殼蛋白-NSC663284複合體比較 105 第八章、 附圖 106 附圖 一 冠狀病毒全基因序列核酸分布 106 附圖 二 各種冠狀病毒核殼蛋白N端功能區結構重疊圖 107 附圖 三 電腦模擬分子對接PJ34與SARS核殼蛋白N端功能區模擬結合圖 108 附圖 四 電腦模擬分子對接PJ34與IBV核殼蛋白N端功能區模擬結合圖 109 附圖 五 電腦模擬分子對接PJ34與229E核殼蛋白N端功能區模擬結合圖 110 附圖 六 電腦模擬分子對接PJ34與EMC核殼蛋白N端功能區模擬結合圖 111 附圖 七 冠狀病毒核殼蛋白N端功能區結構保留性分析 112 附圖 八 冠狀病毒SARS核殼蛋白N端功能區與PJ34電腦模擬分子對接結果 113 附圖 九 冠狀病毒IBV核殼蛋白N端功能區與PJ34電腦模擬分子對接結果 114 附圖 十 冠狀病毒MHV核殼蛋白N端功能區與PJ34電腦模擬分子對接結果 115 附圖 十一 PJ34與PARP之作用力分析 116 附圖 十二 小分子藥物抑制HCOV-OC43病毒活性實驗 117 附圖 十三 HCOV-OC43核殼蛋白全長與四條RNA序列之結合SENSORGRAM 118 附圖 十四 HCOV-OC43核殼蛋白全長在不同濃度PJ34存在下與RNA序列之結合SENSORGRAM 119 附圖 十五 HCOV-OC43核殼蛋白全長在不同濃度PJ34存在下與RNA序列之結合SENSORGRAM的FITTING 120 第九章、 參考文獻 12