115 research outputs found
Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling
From PMC: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.An efficient total synthesis of the annulated indole natural product (±)-cis-trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal-halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber-Batcho indole synthesis
Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism
Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism. Available data indicate that insulin secretion is impaired with aging. Almost all the studies that examined insulin secretion by old animals did not take into consideration the state of renal function or the blood levels of parathyroid hormone (PTH). Old animals may have chronic renal failure (CRF) and secondary hyperparathyroidism, and both of these conditions impair insulin secretion. It is possible, therefore, that the impaired insulin secretion of aging is not due to old age per se, but rather to associated CRF and excess PTH. The present study examined this issue in adult (6 month old) and senescent rats (2 years old) with and without CRF and excess PTH. Senescent rats without CRF had normal renal function and normal blood levels of PTH, and the values were not different from those observed in adult rats. Creatinine clearance in senescent rats with CRF was significantly (P < 0.01) lower and serum levels of PTH were significantly (P < 0.01) higher than in senescent animals without CRF and than in the adult rats as well. Only the senescent rats with CRF displayed glucose intolerance during intravenous glucose tolerance test. For any given level of blood glucose, plasma insulin levels were lower in senescent rats with CRF than in the adult rat or senescent animals without CRF. Both initial phase (139 ± 45 pg/islet · 8 min) and total (808 ± 216 pg/islet · 33 min) insulin secretion from pancreatic islets of the senescent rats with CRF and excess PTH were significantly lower than those in senescent rats with normal renal function (658 ± 117 pg/islet · 8 min and 3294 ± 290 pg/islet · 33 min, respectively) or in adult rats (710 ± 134 pg/islet · 8 min and 3183 ± 366 pg/islet · 33 min, respectively). There were no significant differences in insulin secretion between the adult rats and the senescent ones with normal renal function. The data demonstrate that the impaired insulin secretion by the pancreatic islets in old rats is not necessarily related to the higher age per se, but is due to the associated CRF and secondary hyperparathyroidism that develops in many, but not all old animals. Our results indicate that studies examining the effect of aging on body function should take into consideration the level of renal function and of the serum PTH, since both CRF and excess PTH adversely affect the functional integrity of many organs
CD1a expression by Barrett's metaplasia of gastric type may help to predict its evolution towards cancer
As emerging in the recent literature, CD1a has been regarded as a molecule whose expression may reflect tumour evolution. The aim of the present work was to investigate the expression of CD1a in a series of Barrett's metaplasia (BM), gastric type (GTBM), with and without follow-up, in order to analyse whether its expression may help to diagnose this disease and to address the outcome. Indeed, GTBM may be confused sometimes with islets of ectopic gastric mucosa and its evolution towards dysplasia (Dy) or carcinoma (Ca) could not be foreseen. We showed a significant higher expression of CD1a in GTBM than in both Dy and Ca; nevertheless, the number of positive GTBM was significantly lower in the group of cases that at follow-up underwent Dy or Ca. Our data address that CD1a may be a novel biomarker for BM and that its expression may help to predict the prognosis of this pathology
Analysis of arterial intimal hyperplasia: review and hypothesis
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign " intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl
Intertextualizing interactive texts for critical thinking: A South Korean EFL experience
© 2018 Taylor & Francis Group, LLC. In the past three decades or so, the conceptual rigor of intertextuality has exercised enormous influence on pedagogical practices. In this context, intertextuality can also be used as a means of harnessing students’ critical stances that are crucial for teaching language skills. Based on eight qualitative student interviews at a university in South Korea, the authors introduce a case study in which English as a foreign lanugage students develop their critical thinking by responding to an interactive (oral/visual) text in a listening comprehension/speaking class. Critical thinking is a specific learning outcome of this English as a foreign lanugage program. A typology of intertextuality has also been introduced here to illustrate how various intertextual links can stimulate students’ critical observation. The theoretical framework of this research is informed by the concept of intertextuality, which prescribes that texts are populated with other texts, and that they have textual as well as contextual links with each other. As the findings of this empirical investigation demonstrate, Discourse emerging from intertextual resources could be utilized as a textual space where, with appropriate pedagogical intervention, students have immense opportunities for developing critical stances
ESL curriculum with a heuristic anchorage: Tokenist discourses and the epistemology of community service education
Community service education (CSE) in developing countries still remains under-represented in research. Addressing this gap, this article reports a study that investigated a CSE activity at a secondary school in Sri Lanka. The participants of this study comprised 10 English as a second language (ESL) teachers from four secondary schools, 68 Grade 10 students from a secondary school located in a semi-urban area and the author as participant observer. Based on this qualitative case study in the context of ESL writing pedagogy, the article conceptualises the epistemology of CSE in terms of four dimensions: experiential learning, knowledge/skills application, community participation and critical judgement. It also emphasises the futility of tokenist discourses and suggests that an ESL curriculum needs to have a heuristic orientation in CSE not as a mere extra-curricular exercise but as a mandatory component of social interaction where mutually constitutive benefits for students, teachers and the community are foregrounded. This article highlights how the student writer participants in this study were disadvantaged as a result of tokenist discourses and their teachers demoralised due to an inadequate grasp of the epistemology of CSE, curricular deficiencies, politically driven constraints and poorly resourced classrooms
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