3,234 research outputs found

    Synthesis and Cyclotrimerization of Sulfonyl Enynes

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    The synthesis of complex, polysubstituted aromatic rings from simple, non-aromatic building blocks is a consistent challenge to the synthetic community. Neopentylene ring fusions are found in several natural products but are largely absent from synthetic compound libraries. This discrepancy reflects the limitations in modern chemical synthesis. Utilizing, in part, a thoroughly developed fragmentation/olefination methodology from the Dudley Lab, a library of novel 1-sulfonyl-1,6-enynes have been developed. In this methodology, they are prepared in three steps from dimedone (5,5-dimethyl-1,3-cyclohexanedione), an inexpensive starting material. A total of 14 novel 1-sulfonyl-1,6-enynes were synthesized. These substrates were subjected to a novel benzannulation reaction based on metal-catalyzed [2 + 2 + 2] cyclotrimerization methodology. The nickel-catalyzed reaction of sulfonyl enyne with an exogenous alkyne partners and in situ elimination of phenylsulfinic acid provides neopentylene-fused indane cores. The novel methodologies presented herein were used to shorten the synthesis of neoprofen, a synthetic analogue of ibuprofen, from ten steps to seven. Improved access to neopentylene-tethered 1,6-enynes advances target- and diversity-oriented synthesis, expanding synthetic libraries

    A Research Note on Time With Children in Different-and Same-Sex Two-Parent Families

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    Abstract Public debate on same-sex marriage often focuses on the disadvantages that children raised by same-sex couples may face. On one hand, little evidence suggests any difference in the outcomes of children raised by samesex parents and different-sex parents. On the other hand, most studies are limited by problems of sample selection and size, and few directly measure the parenting practices thought to influence child development. This research note demonstrates how the 2003-2013 American Time Use Survey (n = 44,188) may help to address these limitations. Two-tier Cragg's Tobit alternative models estimated the amount of time that parents in different-sex and same-sex couples engaged in child-focused time. Women in same-sex couples were more likely than either women or men in different-sex couples to spend such time with children. Overall, women (regardless of the gender of their partners) and men coupled with other men spent significantly more time with children than men coupled with women, conditional on spending any childfocused time. These results support prior research that different-sex couples do not invest in children at appreciably different levels than same-sex couples. We highlight the potential for existing nationally representative data sets to provide preliminary insights into the developmental experiences of children in nontraditional families

    Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity

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    Objective: Angiotensin II (Ang II), endothelin-1 (ET-1) and reactive oxygen species (ROS) have been implicated in the development of pathologic changes associated with obesity including hypertension and atherosclerosis. The aim of this study was to investigate the effects of dietary fat content on vasoreactivity and receptor expression at the level of gene and protein expression. Methods: C57BL/6 mice were fed diets of normal (Control, 12.3% kcal from fat), high (HF, 41% kcal from fat) and very high (VHF, 58% kcal from fat) fat content for 15weeks. Glucose tolerance tests were performed, and aortic rings were exposed to ET-1 (0.01-300nM) and Ang II (100nM) in the presence of l-nitro-arginine-methyl ester (l-NAME; 300μM). Gene and protein expressions of angiotensin and endothelin receptors were examined by real-time PCR and immunoblotting, respectively. The effects of diet on responses to acetylcholine (ACh 0.1-300μM), in the absence or presence of l-NAME, and to exogenous ROS/·OH were also investigated. Results: Both high fat diets similarly impaired glucose tolerance (P<0.05). Increasing dietary fat augmented contractions to Ang II in a step-wise manner (P<0.05). Conversely, increasing dietary fat had no effect on contractions to ET-1. Exposure to ROS/·OH resulted in a rapid vasodilation that was markedly augmented in a step-wise manner with increasing dietary fat (P<0.05). Endothelium-dependent relaxation to ACh was unaffected whereas vasoconstriction to high concentrations of ACh was enhanced in VHF animals (P<0.05 vs. control). Gene expression of the AT1B receptor was increased in the aorta of VHF mice, and aortic ETA receptor protein expression was increased after both high fat diets. Conclusions: These findings demonstrate that changes in dietary fat intake modulate vascular reactivity in response to Ang II and ROS, as well as expression of vascular angiotensin and endothelin receptors. Dietary fat intake may thereby directly affect cardiovascular ris

    Sustainable Polymers: New 4-H STEM Curricula

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    There are many environmental issues surrounding the global production and use of plastics. Three science curricula (Grades K-2, 3-5, and 6-8) were developed to introduce youth to the past, present, and future of plastics. Designed using research-based methods and grounded in effective science pedagogy, the curricula provide young people opportunities to explore viable alternatives to plastics and develop knowledge and skills necessary to help mitigate environmental impacts associated with the production, use and disposal of plastics. Evaluation results demonstrated that youth improved their understanding of polymers and intention to help reduce impacts of plastics on the environment

    Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial.

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    BACKGROUND Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. METHODS All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. INTERVENTION Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. ETHICS AND DISSEMINATION The study was approved by the respective ethical committees (No 2020-02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT04931485

    The Influence of HIV on the Evolution of Mycobacterium tuberculosis.

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    HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates

    Accelerated functional brain aging in pre-clinical familial Alzheimer's disease

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    Alzheimer's disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer's disease. Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer's disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (A beta) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18-94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant A beta pathology

    Neutron charge form factor at large q2q^2

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    The neutron charge form factor GEn(q)G_{En}(q) is determined from an analysis of the deuteron quadrupole form factor FC2F_{C2} data. Recent calculations, based on a variety of different model interactions and currents, indicate that the contributions associated with the uncertain two-body operators of shorter range are relatively small for FC2F_{C2}, even at large momentum transfer qq. Hence, GEn(q)G_{En}(q) can be extracted from FC2F_{C2} at large q2q^2 without undue systematic uncertainties from theory.Comment: 8 pages, 3 figure

    Point-Form Analysis of Elastic Deuteron Form Factors

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    Point-form relativistic quantum mechanics is applied to elastic electron-deuteron scattering. The deuteron is modeled using relativistic interactions that are scattering-equivalent to the nonrelativistic Argonne v18v_{18} and Reid '93 interactions. A point-form spectator approximation (PFSA) is introduced to define a conserved covariant current in terms of single-nucleon form factors. The PFSA is shown to provide an accurate description of data up to momentum transfers of 0.5 GeV2{\rm GeV}^2, but falls below the data at higher momentum transfers. Results are sensitive to the nucleon form factor parameterization chosen, particularly to the neutron electric form factor.Comment: RevTex, 31 pages, 1 table, 13 figure
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