Attractive aerobic access to the α,β-unsaturated acyl azolium intermediate: oxidative NHC catalysis via multistep electron transfer

To replace high molecular weight oxidants with air (O2) we introduce multistep electron transfer NHC catalysis. The method provides a general and selective oxidation of the α,β-unsaturated aldehyde derived homoenolate to the synthetically useful α,β-unsaturated acyl azolium intermediate. Several independent oxidative NHC-catalyzed reactions are viable with this strategy and the products can be isolated in high to excellent yields

Ionic Liquids as Carbene Catalyst Precursors in the One-Pot Four-Component Assembly of Oxo Triphenylhexanoates (OTHOs)

Ionic liquids (ILs) are a convenient and inexpensive source of N-heterocyclic carbenes (NHCs). In this study, dialkyl imidazolium-based ILs are used as carbene precursors in a four-component synthesis of oxo triphenylhexanoates (OTHOs), where it was found that IL outperformed commonly used NHC precatalysts in terms of reaction efficiency. The reaction is highly stereoselective, delivering the anti-diastereomer (20:1 dr), and the OTHOs can be obtained in high-to-excellent yields. By virtue of the four-component reaction-setup, facile construction of the OTHO scaffold with a diverse set of functional groups (21 examples) can be achieved. In the context of sustainability, the IL can be recovered and reused several times without affecting selectivity or yield. Moreover, most compounds can be isolated by precipitation and filtration, mitigating the use of solvent-demanding chromatograph

N-Heterocyclic Carbene Catalysis in Organic Synthesis - A Green Chemistry Approach

The twelve principles of green chemistry were created as a response to the multiple environmental issues caused by the release of waste from the chemical industry. The principles acts as a guide in the development of sustainable chemical processes for the syntheses of important molecules needed to sustain our living standards. This thesis will focus on the most important principle, catalysis, which can aid in making reactions more efficient and atomeconomic, hence reducing the formation of chemical waste. One type of catalyst is the N-heterocyclic carbene (NHC), a type of organocatalyst that has become an attractive tool for the synthesis of various interesting compounds. Two different methods of using NHC catalysis are presented.The first method uses an imidazolium-based ionic liquid as an NHC-precatalyst for the synthesis of oxo triphenylhexanoates (OTHOs) in a highly stereo- and regioselective manner. The scope of the reaction is broad, with multiple functional groups tolerated. With this method, the selective modification of complex polyols, such as carbohydrates is possible. The reaction operates under mild conditions, can be performed in a one-pot multicomponent reaction without the use of protecting groups, and omits the use of solvent-demanding chromatography by a simple filtration work-up procedure.The second method employs oxidative NHC catalysis for the synthesis of various α,β unsaturated esters, lactones, and acylated N-heterocyclic compounds such as indoles and oxazolidinones. An aerobic protocol was developed with the help of electron transfer mediators (ETMs) enabling the use of molecular oxygen as the terminal oxidant. This aerobic protocol allows for the substitution of a high molecular weight oxidant frequently associated with oxidative NHC catalysis. The developed method facilitates scale-up reactions and reduction of the chemical waste generated. The obtained products were also applied in further functionalization towards commercially interesting compounds. This thesis demonstrates the use of catalysis for the development of reactions that are atomeconomic, energy efficient and avoid the creation of chemical waste. Moreover, with NHC catalysis readily available reagents could be utilized as starting materials, thus avoiding hazardous substrates. By the guidance of the principles of green chemistry more sustainable and benign reactions can be designed

Asymmetric aerobic oxidative NHC-catalysed synthesis of dihydropyranones utilising a system of electron transfer mediators

In the context of green chemistry, the replacement of high molecular weight stoichiometric oxidants with O2 is most desirable but difficult. Here, we report the asymmetric aerobic oxidative synthesis of dihydropyranones. The oxidation is aided by a system of electron transfer mediators and is selective toward the homoenolate. The dihydropyranones can be isolated in high to excellent yields, with high ee (up to 95%)

Finding Happiness Through Globetrotting: Push Factors of Long-Term Travellers

INTRODUCTION: In addition to attitude, perception, personality/self-concept and learning, motivation is a crucial psychological factor that impacts tourist behaviour (Boo & Jones, 2009; Chen & Uysal, 2003; Fodness, 1994; Jang & Cai, 2002; Maslow, 1943; Yuan & McDonald, 1990). Since people have travelled more and more in recent years, the necessity of understanding the motivational factors of travel has also become increasingly important (Yuan & McDonald, 1990). Knowledge, in return, helps stakeholders better accommodate the needs of future travellers of all kinds, in the planning of transportation infrastructures, accommodation, retailing, dining and entertainment (Li, Law & Wang, 2010). Thus, tourism research benefits the economic, environmental and cultural sustainability of touristic destinations, especially in rural areas and in developing countries (World Travel & Tourism Council, 2015). LITERATURE: Travelling in general is commonly linked to happiness, a search for a ‘getaway’ or a recurrent modern way of escaping from daily stress. Many believe that it increases quality of life due to the many benefits travelling induces (Hsu & Huang, 2008; Cai & Jang, 2002; Chick, Durrenberger, Ribeiro & Yarnal, 2009). But while most studies have put focus on the mainstream travellers, almost none have shown interest for the long-term travellers that dedicate a big part of their life to exploring the world. The term long-term traveller refers to a person who travels widely (Merriam- Webster Dictionary) and spends more time travelling than a traditional holiday period would allow, most often longer than a year (Elsrud, 2001, cited in Brun, Larsen & Øgaard, 2011). This particular way of extended holidaying has gained popularity since the 1960s (Brun, Larsen & Øgaard, 2011), but because this trend is relatively new, literature on the topic is still rare. METHODS: The current study was inspired mainly by the work of Brun, Larsen & Øgaard (2011) who conducted one of only few studies on backpackers and other individualist travellers, and Klenosky’s (2002) unique qualitative study on the push and pull factors of travellers. It was intended to pursue the exploration of long-term travellers’ motivation and help clarify how long-term travel affects their subjective wellbeing. There were two research questions: 1) Why do people travel long-term? and 2) How does long-term travel contribute to happiness? Semi-structured interviews were conducted with 22 participants using a purposive sample. Interview transcripts were triangulated to external sources (participants’ websites and blogs). Data were coded and analyzed in the NVivo qualitative software program using a mixture of intuitive and methodological (constant comparison) processes. FINDINGS: Findings revealed that old misconceptions surrounding long-term travel still exist. For example, misconceptions such as dated definitions, that this type of travel is best suited for single men, journey as an escape and as a way to achieve fame and glory) still persist. The current study contributes to existing findings by shedding a new light on what long-term travel is, why long-term travellers prefer the road to the modern Western lifestyle, and how the journey enriches their lives. The study highlights the pursuit of freedom and personal growth, open-mindedness to the world and its incredible diversity, and a life path for a self-fulfilling life. CONCLUSION: Although long-term travellers represent a marginal percentage of the total number of travellers worldwide, their impact is nevertheless significant, particularly in rural areas and developing countries. Long-term travellers are more likely to travel to remote areas than the mainstream tourists, they are more willing to endure hardship, and they spend more time travelling than any other types of travellers. Findings on this utopian alternative to the modern Western life increase our understanding of travel and, maybe most importantly, on humankind’s pursuit of happiness. REFERENCES: Boo, S. &, Jones, D.L. (2009). Using a validation process to develop market segmentation based on travel motivation for major metropolitan areas. Journal of Travel & Tourism Marketing, 26(1), 60-79. Brun, W., Larsen, S. & Øgaard, T. (2011). Backpackers and Mainstreamers; Realities and Myths. Annals of Tourism Research, 38(2), 690-707. Cai, L. A. & Jang, SC. S. (2002). Travel Motivations and Destination Choice: A Study of British Outbound Market. Journal of Travel and Tourism Marketing, 13(3), 111-133. Chen, J.S., & Uysal, M. (2003). Leisure traveler typology: A case of ten Eastern States. Journal of Hospitality & Leisure Marketing, 10(1-2), 51-62. Chick, G.E., Durrenberger, E.P., Ribeiro, N.F. & Yarnal, C.M. (2009). “I Just Wanted to Get Away”: An Analysis of Spring Breakers Travel Motivations. Proceedings of the 2009 Northeastern Recreation Research Symposium, 272-276. Fodness, D. (1994). Measuring tourist motivation. Annals of Tourism Research, 21(3), 555-581. Hsu, C. H.C. & Huang, S. S. (2008). Travel Motivation: a Critical Review of the Concepts’ Development. In Martin D. & Woodside, A., Tourism Management; Analysis, Behavior and Strategy, pp.14-27. Oxfordshire, UK: CAB International. Jang, S.S., & Cai, L.A. (2002). Travel motivations and destination choice: A study of British outbound market. Journal of Travel & Tourism Marketing, 13(3), 111-133. Klenosky, D.B. (2002). The ‘Pull’ of Tourism Destinations: A Means-end Investigation. Journal of Travel Research, 40(4), 385-395. Li, G., Law, R., & Wang, J. (2010). Analyzing international travelers’ profile with self-organizing maps. Journal of Travel & Tourism Marketing, 27, 113–131. Maslow, A.H. (1943). A theory of human motivation. Psychological Review, 50, 370-396. Merriam-Webster Encyclopedia Britannica. Retrieved from http://www.merriam- webster.com/dictionary/globe-trotter. Yuan. S., & McDonald, C. (1990). Motivational determinates of international pleasure time. Journal of Travel Research, 29(1), 42-44. World Travel & Tourism Council (2015). Economic impact of travel & tourism: 2015 annual up-date -summary. Retrieved from http://www.wttc.org/- /media/files/reports/economic%20impact%20research/economic%20impact%202 015%20summary_web.pd

Lipids promote survival, proliferation, and maintenance of differentiation of rat liver sinusoidal endothelial cells in vitro

Primary rat liver sinusoidal endothelial cells (LSEC) are difficult to maintain in a differentiated state in culture for scientific studies or technological applications. Relatively little is known about molecular regulatory processes that affect LSEC differentiation because of this inability to maintain cellular viability and proper phenotypic characteristics for extended times in vitro, given that LSEC typically undergo death and detachment around 48–72 h even when treated with VEGF. We demonstrate that particular lipid supplements added to serum-free, VEGF-containing medium increase primary rat liver LSEC viability and maintain differentiation. Addition of a defined lipid combination, or even oleic acid (OA) alone, promotes LSEC survival beyond 72 h and proliferation to confluency. Moreover, assessment of LSEC cultures for endocytic function, CD32b surface expression, and exhibition of fenestrae showed that these differentiation characteristics were maintained when lipids were included in the medium. With respect to the underlying regulatory pathways, we found lipid supplement-enhanced phosphatidylinositol 3-kinase and MAPK signaling to be critical for ensuring LSEC function in a temporally dependent manner. Inhibition of Akt activity before 72 h prevents growth of SEC, whereas MEK inhibition past 72 h prevents survival and proliferation. Our findings indicate that OA and lipids modulate Akt/PKB signaling early in culture to mediate survival, followed by a switch to a dependence on ERK signaling pathways to maintain viability and induce proliferation after 72 h. We conclude that free fatty acids can support maintenance of liver LSEC cultures in vitro; key regulatory pathways involved include early Akt signaling followed by ERK signaling.National Science Foundation (U.S.) (Grant EFRI-0735997)National Institutes of Health (U.S.) (Grant R01 GM069668

Oxidative organocatalytic chemoselective: N -acylation of heterocycles with aromatic and conjugated aldehydes

Selective acylation of indoles is cumbersome often involving the need for sensitive and reactive acyl chloride derivatives or coupling reagents. Here we report a mild, functional group tolerant and highly chemoselective oxidative carbene catalyzed N-acylation of indoles with aldehydes. The acylation has a broad substrate scope and is compatible with substituents on both the aldehyde and the indole reaction partner. Furthermore, aza-heterocycles such as pyrrole and indazole can also be used as nucleophiles in this reaction providing the corresponding amide congeners in good yield

Ionic Liquids as Carbene Catalyst Precursors in the One-Pot Four-Component Assembly of Oxo Triphenylhexanoates (OTHOs)

Abstract: Ionic liquids (ILs) are a convenient and inexpensive source of N-heterocyclic carbenes (NHCs). In this study, dialkyl imidazolium-based ILs are used as carbene precursors in a four-component synthesis of oxo triphenylhexanoates (OTHOs), where it was found that IL outperformed commonly used NHC precatalysts in terms of reaction efficiency. The reaction is highly stereoselective, delivering the anti-diastereomer (20:1 dr), and the OTHOs can be obtained in high-to-excellent yields. By virtue of the four-component reaction-setup, facile construction of the OTHO scaffold with a diverse set of functional groups (21 examples) can be achieved. In the context of sustainability, the IL can be recovered and reused several times without affecting selectivity or yield. Moreover, most compounds can be isolated by precipitation and filtration, mitigating the use of solvent-demanding chromatography

Conserved Transcriptional Unit Organization Of The Cag Pathogenicity Island Among Helicobacter Pylori Strains

The Helicobacter pylori cag pathogenicity island (cag PAI) encodes a type IV secretion system that is more commonly found in strains isolated from patients with gastroduodenal disease than from those with asymptomatic gastritis. Genome-wide organization of the transcriptional units in H. pylori strain 26695 was recently established using RNA sequence analysis (Sharma et al., 2010). Here we used quantitative reverse-transcription polymerase chain reaction of open reading frames and intergenic regions to identify putative cag PAI operons in H. pylori; these operons were analyzed further by transcript profiling after deletion of selected promoter regions. Additionally, we used a promoter-trap system to identify functional cag PAI promoters. The results demonstrated that expression of genes on the H. pylori cag PAI varies by nearly five orders of magnitude and that the organization of cag PAI genes into transcriptional units is conserved among several H. pylori strains, including, 26695, J99, G27, and J166. We found evidence for 20 transcripts within the cag PAI, many of which likely overlap. Our data suggests that there are at least 11 operons: cag1-4, cag3-4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22, and cag25-24, as well as five monocistronic genes (cag4, cag13, cag14, cag15, and cag26). Additionally, the location of four of our functionally identified promoters suggests they are directing expression of, in one case, a truncated version of cag26 and in the other three, transcripts that are antisense to cag7, cag17, and cag23. We verified expression of two of these antisense transcripts, those antisense to cag17 and cag23, by reverse-transcription polymerase chain reaction. Taken together, our results suggest that the cag PAI transcriptional profile is generally conserved among H. pylori strains, 26695, J99, G27, and J166, and is likely complex

Racial Bias Beliefs Related to COVID-19 Among Asian Americans, Native Hawaiians, and Pacific Islanders: Findings From the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS)

Background: During the COVID-19 pandemic, there have been increased reports of racial biases against Asian American and Native Hawaiian and Pacific Islander individuals. However, the extent to which different Asian American and Native Hawaiian and Pacific Islander groups perceive and experience (firsthand or as a witness to such experiences) how COVID-19 has negatively affected people of their race has not received much attention. Objective: This study used data from the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS), a nationwide, multilingual survey, to empirically examine COVID-19-related racial bias beliefs among Asian American and Native Hawaiian and Pacific Islander individuals and the factors associated with these beliefs. Methods: COMPASS participants were Asian American and Native Hawaiian and Pacific Islander adults who were able to speak English, Chinese (Cantonese or Mandarin), Korean, Samoan, or Vietnamese and who resided in the United States during the time of the survey (October 2020 to May 2021). Participants completed the survey on the web, via phone, or in person. The Coronavirus Racial Bias Scale (CRBS) was used to assess COVID-19-related racial bias beliefs toward Asian American and Native Hawaiian and Pacific Islander individuals. Participants were asked to rate the degree to which they agreed with 9 statements on a 5-point Likert scale (ie, 1=strongly disagree to 5=strongly agree). Multivariable linear regression was used to examine the associations between demographic, health, and COVID-19-related characteristics and perceived racial bias. Results: A total of 5068 participants completed the survey (mean age 45.4, SD 16.4 years; range 18-97 years). Overall, 73.97% (3749/5068) agreed or strongly agreed with ≥1 COVID-19-related racial bias belief in the past 6 months (during the COVID-19 pandemic). Across the 9 racial bias beliefs, participants scored an average of 2.59 (SD 0.96, range 1-5). Adjusted analyses revealed that compared with Asian Indians, those who were ethnic Chinese, Filipino, Hmong, Japanese, Korean, Vietnamese, and other or multicultural had significantly higher mean CRBS scores, whereas no significant differences were found among Native Hawaiian and Pacific Islander individuals. Nonheterosexual participants had statistically significant and higher mean CRBS scores than heterosexual participants. Compared with participants aged ≥60 years, those who were younger (aged \u3c30, 30-39, 40-49, and 50-59 years) had significantly higher mean CRBS scores. US-born participants had significantly higher mean CRBS scores than foreign-born participants, whereas those with limited English proficiency (relative to those reporting no limitation) had lower mean CRBS scores. Conclusions: Many COMPASS participants reported racial bias beliefs because of the COVID-19 pandemic. Relevant sociodemographic contexts and pre-existing and COVID-19-specific factors across individual, community, and society levels were associated with the perceived racial bias of being Asian during the pandemic. The findings underscore the importance of addressing the burden of racial bias on Asian American and Native Hawaiian and Pacific Islander communities among other COVID-19-related sequelae