Development and application of metal catalyzed transfer hydrogenative C-C bond forming reactions

While polyketides display a diverse range of biological properties and are used extensively in human medicine, a lack of methods for the concise preparation of these complex structures still poses a significant challenge in the field of synthetic organic chemistry. To address this issue, metal catalyzed methods for transfer hydrogenative C-C bond formation have been developed. These methods construct products of carbonyl addition through direct C-H bond functionalization, which provides a more atom economic and efficient approach to carbonyl addition products and circumvents the need for stoichiometric use of chiral auxiliaries, premetallated C-nucleophiles, and discrete alcohol-to-carbonyl redox reactions. Efforts have been focused on the development of ruthenium-catalyzed coupling reactions of secondary alcohols to basic chemical feedstocks as well as the application of iridum-catalyzed couplings of primary alcohols with π-unsaturates in the context of the total syntheses of (−)-cyanolide A and (+)-cryptocaryol A. These total syntheses represent the most concise route reported to date for each natural product and illustrate the synthetic utility of transfer hydrogenative C-C bond forming methodology.Chemistr

The Acceptance and Action Questionnaire-II (AAQ-II) as a measure of experiential avoidance: Concerns over discriminant validity

Psychological inflexibility and experiential avoidance are key constructs in the Acceptance and Commitment Therapy (ACT) model of behavior change. Wolgast (2014) questioned the construct validity of the Acceptance and Action Questionnaire-II (AAQ-II), the most used self-report instrument to assess the efficacy of ACT interventions. Wolgast suggested that the AAQ-II measured psychological distress rather than psychological inflexibility and experiential avoidance. The current study further examined the construct validity of the AAQ-II by conducting an online cross-sectional survey (n = 524), including separate measures of experiential avoidance and psychological distress. Confirmatory factor analyses indicated that items from the AAQ-II correlated more highly with measures of depression, anxiety, and stress than the Brief Experiential Avoidance Questionnaire (BEAQ). Implications include that, as broad measures of experiential avoidance, the AAQ-II and BEAQ may not measure the same construct. In terms of psychological distress, the BEAQ has greater discriminant validity than the AAQ-II, and perhaps an alternative instrument of psychological inflexibility might be needed to assess core outcomes in ACT intervention research

Profiles of psychological flexibility: A latent class analysis of the Acceptance and Commitment Therapy model

There exists uncertainty for clinicians over how the separate sub-component processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (i) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key sub-component process, and (ii) to examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (i) High Psychological Flexibility, (ii) Moderate Psychological Flexibility, and (iii) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class subgroup reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients

An investigation of the dynamics of intramammary infections acquired during the dry period on European dairy farms

The dry period is acknowledged as playing a key role in mastitis epidemiology and yet surprisingly few studies have explored dry period infection dynamics in detail. The aim of this study was to investigate the dynamics of intramammary infection across a cohort of dairy herds in Europe. Five hundred and twenty-two cows were recruited from 12 farms in 6 European countries. All cows received antibiotic dry cow therapy but teat sealants were not used. All quarters of all cows were sampled for bacteriology at drying off and in the week immediately postcalving. Two ipsilateral quarters were also sampled for bacteriology in each cow 2 and 6 wk after drying off. Cows were body condition scored and teats assessed for cleanliness at all sampling time points and for the presence of a keratin plug during the dry period. Other cow-level parameters such as historic somatic cell counts and milk yields before drying off were collated from farm records. Univariable and multivariable analyses were undertaken to investigate the etiology, prevalence, and dynamics of infection during the dry period and associated influential factors. In summary, environmental mastitis pathogens predominated. Although gram-positive major pathogens were typically well controlled and did not increase in prevalence across the dry period, gram-negative pathogens generally increased in prevalence. There was an increase in the number of quarters that yielded no growth across the dry period, although this was driven by minor rather than major mastitis pathogen control. Other than the presence of a gram-positive or gram-negative pathogen 6 wk after drying off, the measured parameters were not influential when considering their effect on the presence of pathogens postcalving. Analysis also suggested that the early and mid dry period may be more important with respect to the timing of acquisition of infection than previously thought. We observed substantial variation in the etiology and prevalence of different pathogens on different farms with, in all cases, at least one of the 12 herds experiencing the opposite of the others with respect to increases and decreases in pathogen prevalence. Overall, this study confirms the importance of the dry period in mastitis epidemiology but highlights the importance of assessing and understanding infection dynamics on individual units. The lack of influence of the cow and quarter factors measured in this study suggests that herd and management factors may be more influential

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Aakideh: The Art & Legacy of Carl Beam

Carl Beam, one of Canada’s most influential and significant artists, earned a reputation for being fearless, visionary and ultimately, unforgettable. From his early years spent at a residential school, this documentary explores how these early experiences not only impacted Beam’s life but also his art. Personal remembrances along with insights about his art and ideas are vividly illustrated through Beam’s artworks, family photos, interviews, performance videos, and journals. This award-winning documentary, co-directed by Robert Waldeck and Paul Eichhorn, was over six years in the making. It features unique digital animations inspired by Beam\u27s art and an original soundtrack by Dan Drysdale. Aakideh premiered at the National Gallery of Canada in November 2010 and has since been screen throughout North America including at the Bell TIFF Lightbox (Toronto), International Festival of Film on Art (Montreal), and Smithsonian National Museum of American Indian (New York City).https://source.sheridancollege.ca/ccg_exhibitions_cb_doc/1000/thumbnail.jp

Effects of 4-Aminopyridine on Muscle and Motor Unit Force in Canine Motor Neuron Disease

Hereditary Canine Spinal Muscular Atrophy (HCSMA) is an autosomal dominant disorder of motor neurons that shares features with human motor neuron disease. In animals exhibiting the accelerated phenotype (homozygotes), we demonstrated previously that many motor units exhibit functional deficits that likely reflect underlying deficits in neurotransmission. The drug 4-aminopyridine (4AP) blocks voltage-dependent potassium conductances and is capable of increasing neurotransmission by overcoming axonal conduction block or by increasing transmitter release. In this study, we determined whether and to what extent 4AP could enhance muscle force production in HCSMA. Systemic 4AP (1–2 mg/kg) increased nerve-evoked whole muscle twitch force and electromyograms (EMG) to a greater extent in older homozygous animals than in similarly aged, symptomless HCSMA animals or in one younger homozygous animal. The possibility that this difference was caused by the presence of failing motor units in the muscles from homozygotes was tested directly by administering 4AP while recording force produced by failing motor units. The results showed that the twitch force and EMG of failing motor units could be significantly increased by 4AP, whereas no effect was observed in a nonfailing motor unit from a symptomless, aged-matched HCSMA animal. The ability of 4AP to increase force in failing units may be related to the extent of failure. Although 4AP increased peak forces during unit tetanic activation, tetanic force failure was not eliminated. These results demonstrate that the force outputs of failing motor units in HCSMA homozygotes can be increased by 4AP. Possible sites of 4AP action are considered