Total synthesis of argyrin A and analogues thereof

The cyclin dependent kinase inhibitor p27 is one of the most frequently dysregulated tumour suppressor protein in human cancers. A reduction in the level of cellular p27 is frequently due to increased proteasome-dependent degradation. Recently, studies show that the macrocyclic octapeptide argyrin A induced an increase in cellular p27 levels by preventing the turnover of the protein via inhibition of proteasome function. In order to investigate this interesting biological property, this project embarked on the total synthesis of argyrin A, a naturally occurring macrocyclic peptide originally isolated from myxobacteria Archangium gephyra. Argyrin A is a non-ribosomal octapeptide containing four standard amino acids and three unusual amino acid-based subunits. The synthesis of these three unusual amino acid components was established. In particular, a novel generic synthetic route to access the optically pure N-Fmoc-4-methoxy-tryptophan and analogues thereof was developed. Key features of the synthetic route include the use of chiral Strecker amino acid synthesis and mild conditions to hydrolyse α-amino nitrile to α-amino acid. Furthermore, the total synthesis of argyrin A and analogues was accomplished by the application of modern solid-phase chemistry and macrocyclisation strategies. This platform technology will enable the robust total chemical synthesis of a focused library of argyrin analogues, which will facilitate a comprehensive SAR study. Additionally, the synthesised argyrin A and analogues thereof comprising unique tryptophan analogues were tested in a cytotoxicity assay against HCT-117 human colon cell line. The results showed that all synthetic argyrin derivatives display growth inhibitory effects at nanomolar concentrations. The best result was obtained for the argyrin A and (5-methoxy-Trp4)argyrin with GI50 value at 1.8 and 3.8 nM, respectively. In summary, it became apparent that the methoxy group at 4- or 5-position of tryptophan-5 residue is essential for the biological activity of argyrin

Total synthesis of argyrin A and analogues thereof

The cyclin dependent kinase inhibitor p27 is one of the most frequently dysregulated tumour suppressor protein in human cancers. A reduction in the level of cellular p27 is frequently due to increased proteasome-dependent degradation. Recently, studies show that the macrocyclic octapeptide argyrin A induced an increase in cellular p27 levels by preventing the turnover of the protein via inhibition of proteasome function. In order to investigate this interesting biological property, this project embarked on the total synthesis of argyrin A, a naturally occurring macrocyclic peptide originally isolated from myxobacteria Archangium gephyra. Argyrin A is a non-ribosomal octapeptide containing four standard amino acids and three unusual amino acid-based subunits. The synthesis of these three unusual amino acid components was established. In particular, a novel generic synthetic route to access the optically pure N-Fmoc-4-methoxy-tryptophan and analogues thereof was developed. Key features of the synthetic route include the use of chiral Strecker amino acid synthesis and mild conditions to hydrolyse α-amino nitrile to α-amino acid. Furthermore, the total synthesis of argyrin A and analogues was accomplished by the application of modern solid-phase chemistry and macrocyclisation strategies. This platform technology will enable the robust total chemical synthesis of a focused library of argyrin analogues, which will facilitate a comprehensive SAR study. Additionally, the synthesised argyrin A and analogues thereof comprising unique tryptophan analogues were tested in a cytotoxicity assay against HCT-117 human colon cell line. The results showed that all synthetic argyrin derivatives display growth inhibitory effects at nanomolar concentrations. The best result was obtained for the argyrin A and (5-methoxy-Trp4)argyrin with GI50 value at 1.8 and 3.8 nM, respectively. In summary, it became apparent that the methoxy group at 4- or 5-position of tryptophan-5 residue is essential for the biological activity of argyrin

From Teachers’ Views to Explore the Implementation of Energy Education in Taiwan’s Elementary Schools

This study intended to explore the implementation of promoting “energy education” in Taiwan’s elementary schools. The research adopted a questionnaire (Likert five-point scale) from teachers’ view in three dimensions to construct examination. The 45 participants come from 10 different primary schools distributed across Taiwan, which participate in energy education program in the second period (2015-2017). The data was analyzed by ANOVA, mean and standard deviations of the viewpoints of the participants in the energy education learning achievement of the primary schools. The first findings in this research is, the program of energy education was most effective in “energy attitude” (M=4.282, SD=0.814), followed by “energy awareness” (M=4.049, SD=0.720) and “energy behavior” (M=3.983, SD=0.875). It shows that students have positive energy attitude, but they were relatively weak at energy saving behavior. Secondly, there is statistically significant difference in overall students learning performance with urban areas are higher than rural areas. Finally, it is suggested that in addition to strengthen energy attitudes and energy awareness, we should encourage students to take action in save energy in their daily life. Furthermore, we should invest more resources to rural areas to balance the students’ performances between urban and rural areas

A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues

A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were (S)-methylbenzylamine and related derivatives. To illustrate the robustness of the method, eight optically pure (S)-tryptophan analogues were synthesized, which were subsequently used for the convergent synthesis of a potent antibacterial agent, argyrin A and its analogues

Smart Grid as a Service: A Discussion on Design Issues

Smart grid allows the integration of distributed renewable energy resources into the conventional electricity distribution power grid such that the goals of reduction in power cost and in environment pollution can be met through an intelligent and efficient matching between power generators and power loads. Currently, this rapidly developing infrastructure is not as “smart” as it should be because of the lack of a flexible, scalable, and adaptive structure. As a solution, this work proposes smart grid as a service (SGaaS), which not only allows a smart grid to be composed out of basic services, but also allows power users to choose between different services based on their own requirements. The two important issues of service-level agreements and composition of services are also addressed in this work. Finally, we give the details of how SGaaS can be implemented using a FIPA-compliant JADE multiagent system

Investigating the maxillary buccal vestibule

AbstractBackground/purposeImproper assessment of the maxillary buccal vestibular space can contribute to the fabrication of maxillary dentures with inadequate buccal flange extensions. The purpose of this study was to determine whether a significant difference existed between the anatomic dimensions of the buccal vestibules and the corresponding buccal flanges of maxillary complete dentures in an edentulous population.Materials and methodsThe anterior, middle, and posterior depth and width of the maxillary buccal vestibules in 100 randomly selected subjects were measured with a periodontal probe. Corresponding measurements of the buccal flanges of the subjects' existing dentures were recorded. The differences between buccal vestibule widths and depths and denture flange widths and lengths were statistically compared according to site.ResultsThe difference in the mean depth between the vestibules and the flanges in the posterior area (6.4 mm and 10.3 mm, respectively) was approximately 38% (P < 0.001). The difference in the mean width between the vestibules and the flanges in the posterior area (3.3 mm and 7.9 mm, respectively) was approximately 58% (P < 0.001).ConclusionThe study revealed statistically significant differences between the anatomic depth and width of the buccal vestibules and the corresponding flange dimensions of the existing dentures

The epidemiology of patients with pterygium in southern Taiwanese adults: The Chiayi survey

AbstractPurposeTo investigate patients with pterygium in different geographic regions and the associated risk factors in southern Taiwan.MethodsA clinical observation survey was conducted in Chiayi County, a rural area in southern Taiwan. The subjects aged 40 years and above underwent complete ocular examinations. Associated risks factors were evaluated, including gender, age, occupations, smoking, and geographical living regions by univariant and multivariant logistic regression analysis.ResultsA total of 2197 participants (790 male, 36.0%) from 44 different villages were evaluated. In these, 554 participants (25.2%) have either unilateral or bilateral pterygium. Age is associated with the percentage of pterygium, and those aged between 60 and 69 had the highest percentage of 30.1% (p < 0.0001). The gender effect was higher among men than women (OR = 1.31, 95% CI: 1.08–1.60, p = 0.006). The percentage of pterygium lived in plain, seaside, and mountainous areas were 22.6%, 32.6%, and 14.5% respectively. Geographical regions also showed that seaside area had the highest percentage of pterygium (seaside area OR = 1.65, 95% CI: 1.35-2.03, and mountainous area OR = 0.58, 95% CI: 0.35-0.95 compared with plain areas). Primary outdoor workers and residents with smoking history had relative higher risk for pterygium (OR = 1.47, 95% CI: 1.17-1.86; OR = 1.36, 95% CI: 1.02-1.83).ConclusionsThe percentage of pterygium in southern Taiwan is about 25.2% among adults aged over 40 years in this survey. It is significantly higher in the age of 50 or more and in residents living in villages along the seaside than those living in the mountainous and the plain areas

Temporal Arteritis

Temporal arteritis, a chronic inflammatory vasculitis involving medium- and large-sized arteries, has rarely been reported in Asia. However, we report 2 cases, in which the patients initially presented with headache. Physical examination disclosed engorged, hard and palpable vessels in the temporal areas. Temporal-artery biopsy revealed 2 different types of arteritis: the multinucleated giant cell type and the panarteritis type without multinucleated giant cells. One patient was positive for immunoglobulin G anticardiolipin antibody. The pathologic findings of the different subsets of temporal arteritis, and the relationship between anticardiolipin antibody and the extent of vascular complications of temporal arteritis, are discussed

Rainfall variations in central Indo-Pacific over the past 2,700 y

Tropical rainfall variability is closely linked to meridional shifts of the Intertropical Convergence Zone (ITCZ) and zonal movements of the Walker circulation. The characteristics and mechanisms of tropical rainfall variations on centennial to decadal scales are, however, still unclear. Here, we reconstruct a replicated stalagmite-based 2,700-y-long, continuous record of rainfall for the deeply convective northern central Indo-Pacific (NCIP) region. Our record reveals decreasing rainfall in the NCIP over the past 2,700 y, similar to other records from the northern tropics. Notable centennial- to decadal-scale dry climate episodes occurred in both the NCIP and the southern central Indo-Pacific (SCIP) during the 20th century [Current Warm Period (CWP)] and the Medieval Warm Period (MWP), resembling enhanced El Niño-like conditions. Further, we developed a 2,000-y-long ITCZ shift index record that supports an overall southward ITCZ shift in the central Indo-Pacific and indicates southward mean ITCZ positions during the early MWP and the CWP. As a result, the drying trend since the 20th century in the northern tropics is similar to that observed during the past warm period, suggesting that a possible anthropogenic forcing of rainfall remains indistinguishable from natural variability