[3+2] Annulation of Cyclopropylanilines with Alkynes under Photocatalysis

Over the past decade, pharmaceutical industries have prioritized their focus on discovering new innovative drugs, yet the syntheses are often either inefficient or the approach of environmental sustainability presents a great deal of concern. Moreover, the methodology developments for amine syntheses have continued to flourish due to their important role and wide use in pharmaceutics. Yet their syntheses often lack sustainability and efficiency. Synthetic chemists have continued to explore potential innovative avenues for conducting chemical reactions more effectively and efficiently. One of the most abundant, renewable natural resources is solar energy and to harvest, use, and store it directly is an ongoing development. To reduce our dependency on fossil energy sources, methods of direct and proficient conversion of solar energy to chemical energy become critically important. Recently, visible light photoredox catalysis has become a highly prominent tool in the development of many successful organic transformations. This work describes an innovative approach of using visible light photocatalysis to develop efficient one-step syntheses for the construction of structurally diverse carbocycles substituted with amines from simple starting materials under mild conditions. Under photocatalysis, amines can function as both the sacrificial electron donor and substrate. Incorporating the oxidation of the amine and a subsequent irreversible reaction will allow the amine to posses its dual roles. To accomplish this, cyclopropylanilines were used and subjected to ring opening to form reactive β-carbon radical iminium ions via nitrogen radical cations upon oxidation of the cyclopropylanilines. As a result, an intermolecular [3+2] annulation of cyclopropylanilines with alkynes was developed to afford highly useful synthetic intermediates and motifs such as fused indolines, which are found in various bio-active alkaloids and pharmaceuticals. This method exhibited significant group tolerance particularly with heterocycles. Moreover, the [3+2] annulation enabled rapid assembly of diverse cyclic allylic amine derivatives. Expansion of the [3+2] annulation to include substituted cyclopropylanilines and other types of π-bonds, such as enynes and diynes to afford structurally diverse carbo- and heterocycles were studied. Lastly, a protocol for an oxidative cleavage of N-aryl group was successfully accomplished upon screening various oxidants and installing various removable aryl or heteroaryl group

Review of hydroxypropyl cellulose ophthalmic inserts for treatment of dry eye

Dry eye syndrome is a prevalent disease that affects visual acuity, activities of daily living, and quality of life. A number of contributory factors affect the severity of dry eye syndrome, including autoimmune disease, environmental surroundings, contact lens use, hormonal changes, anatomical features, chronic inflammation, infections, and iatrogenic factors, such as medications or surgery. Symptoms may include intermittent or constant blurry vision, discomfort, burning, foreign body sensation, hyperemia, dryness, and photophobia. The severity of dry eye syndrome can range from very mild disease to extremely severe cases with vision-threatening consequences. A variety of dry eye treatment modalities exist to address the different causes, symptoms, and consequences of ocular surface disease, including artificial tears, lubricating gels, ophthalmic inserts, anti-inflammatory drops, and surgical procedures. In this paper, an assortment of literature pertaining to the treatment of dry eye syndrome, in particular hydroxypropyl cellulose ophthalmic inserts, is reviewed. These inserts can be used effectively as monotherapy, or in conjunction with other therapies, and should be considered in the treatment of dry eye syndrome

India Global Immersion 2018

Undergraduate Clinical/ Cultural Immersion in New Delhi, India 2018https://deepblue.lib.umich.edu/bitstream/2027.42/148305/1/LiLeeNguyen.pd

The Children in Action Pilot Study

Interventions that can successfully alter the trajectory toward obesity among high-risk children are critical if we are to effectively address this public health crisis. The goal of this pilot study was to implement and evaluate an innovative physical activity program with Hispanic-American (HA) preschool children attending Head Start. The Children in Action (CIA) program was a five month physical activity intervention. This intervention was a pilot study with 3- to 5-year-olds enrolled in four HA Head Start centers. After baseline assessment, centers were matched by enrollment and randomly assigned to either the intervention or the control condition. A total of 295 preschool children were randomly selected across the four centers. The primary endpoints of this study were favorable changes in physical activity levels and gross motor skills. Using mixed effect time-series regression models, changes in weight was a secondary endpoint. We did not observe a statistical difference between intervention and control groups in physical activity levels during the awake time, gross motor skills, or weight status. Process evaluation data showed that there was adherence to protocols and the intervention was delivered 92% of the time, four times per week, during the five month intervention. We demonstrated that it is feasible to conduct the SPARK-Early Childhood (EC) curriculum among preschool children attending Head Start centers but that an increased dose and/or longer intervention duration will be required to impact gross motor skills, physical activity levels and weight status during this critical early childhood development stage

Alliance Catering at Deakin: the Economics of University Cafeterias

University cafeterias are a common and crucial component of university life as they provide cheap and convenient meals for students. Ideally, university cafeterias should also be responsible for providing nutritious food at reasonable prices. In practice though, university cafeterias often provide less nutritious food and at high prices. One reason for why this may happen is that cafeterias are aware of their unique market power. For instance, students consider the opportunity and transportation costs in the price they are willing to pay for on-campus services. The costs of preparing meals at home or walking to the alternatives are high, as students may prefer to use the time for studying or socializing. Thus, for a variety of reasons, university cafeterias become more practical in their delivery of services by placing less concern on the health quality of products and the fairness of prices. In this paper, we study the market power of university cafeterias specifically due to a locational advantage by analysing the case of the Alliance Cafeteria operating in Buildings La and Lb at Deakin University’s Burwood campus in Melbourne. We begin by examining Alliance as a monopolistically competitive firm and assess how its location gives market power

Molecular Analysis of Tomato Seed Germination and Tomato Production in Almería, Spain

Tomato is considered to be one of the most important vegetables for its value as a source of nutrients and antioxidants, and as a model crop for biological research, including seed biology. In this thesis, tissue-specific gene expression and its regulation in tomato seeds were analyzed to understand the mechanisms underlying tomato seed germination, which is key to producing a healthy tomato plant. Endosperm cap-specific genes were identified using GeneChip® analysis. Tomato ETHYLENE RESPONSE FACTOR1 (TERF1), a hormone-signaling gene was found to be a potential upstream regulator of multiple endosperm cap-specific genes. In addition to the basic research on tomato seed germination, a case study of tomato production and distribution in Almería, Spain, one of the most important tomato exporting sectors in the world, was performed as part of international degree research. In this case study, the methods and efficiency of the tomato production systems in hundreds of greenhouses, so called ‘mar del plástico’ (sea of plastic) and the tomato distribution systems were analyzed

Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT2B Receptors

G protein-coupled receptors are linked to various intracellular transducers, each pathway associated with different physiological effects. Biased ligands, capable of activating one pathway over another, are gaining attention for their therapeutic potential, as they could selectively activate beneficial pathways whilst avoiding those responsible for adverse effects. We performed molecular dynamics simulations with known β-arrestin-biased ligands like lysergic acid diethylamide and ergotamine in complex with the 5-HT2B receptor and discovered that the extent of ligand bias is directly connected with the degree of closure of the extracellular loop region. Given a loose allosteric coupling of extracellular and intracellular receptor regions, we delineate a concept for biased signaling at serotonin receptors, by which conformational interference with binding pocket closure restricts the signaling repertoire of the receptor. Molecular docking studies of biased ligands gathered from the BiasDB demonstrate that larger ligands only show plausible docking poses in the ergotamine-bound structure, highlighting the conformational constraints associated with bias. This emphasizes the importance of selecting the appropriate receptor conformation on which to base virtual screening workflows in structure-based drug design of biased ligands. As this mechanism of ligand bias has also been observed for muscarinic receptors, our studies provide a general mechanism of signaling bias transferable between aminergic receptors