Experimental and DFT Studies on Cp*Co(III)-Catalyzed Selective C8-Olefination and Oxyarylation of Quinoline N-Oxides with Terminal Alkynes

Herein we report Cp*Co(III)-catalysed site-selective (C8)-H olefination and oxyarylation of quinoline N-oxides with terminal alkynes. The selectivity for C8-olefination and oxyarylation is sterically and electronically controlled. In case of quinoline N-oxides (unsubstituted at C2-position), only olefination product is obtained irrespective of the nature of alkynes. In contrast, majorly oxyarylation is observed when 2-substituted quinoline N-oxides are reacted with bulkier alkynes such as 9-ethynyl phenanthrene. However, alkynes with electron-withdrawing groups provided only olefination products with 2-substituted quinoline N-oxides also. The developed strategy allowed a facile functionalization of naturally derived quinoline N-oxides and terminal alkynes to deliver corresponding olefinated and oxyarylated products. In the developed protocol, the 'N-O’ bond played a dual role i.e., as a traceless directing group and an oxygen atom source (in case of oxyarylation), which is confirmed by 18O-labeling and crossover experiments. In addition, control experiments, deuterium labeling experiments, KIE studies and DFT studies are performed to understand the mechanism and origin of selectivity for different substrates. DFT studies revealed that the alkyne addition into Co-C bond is the rate limiting step. The observed product selectivity is reproduced by DFT methods. Furthermore, the energy decomposition analysis is performed to understand the origin of selec-tivity.

Acute effects of hemp protein consumption on glycemic and satiety control: results of two randomized crossover trials

Research investigating hemp protein consumption on glycemic response is limited. The effects of hemp protein consumption on blood glucose (BG), insulin, and satiety compared to soybean protein and a carbohydrate control were examined. Two acute randomized repeated-measures crossover experiments were conducted. In both, participants consumed isocaloric treatments 40g of hemp protein (hemp40), 20g of hemp protein (hemp20), 40g of soybean protein (soy40), 20g of soybean protein (soy20), and a carbohydrate control. In experiments 1 (n=27) and 2 (n=16), appetite and BG were measured before (0-60 min, pre-pizza) and after a pizza meal (80-200 min, post-pizza). In experiment 1, food intake was measured at 60 min by ad libitum meal; in experiment 2 a fixed meal was provided (based on body weight) and insulin was measured pre-pizza and post-pizza. In both experiments, BG response was affected by treatment (p<0.01), time (p<0.001) and time-by-treatment (p<0.001) from 0-200 min. Protein treatments lowered 0-60 min BG overall mean, and area under the curve (AUC) compared to control (p<0.05) dose-dependently. In experiment 2, hemp40 and soy40 lowered (p<0.05) overall mean insulin concentrations compared to hemp20, soy20, and control pre-meal. Results suggest that hemp protein, like soybean, dose-dependently lowers post-prandial BG and insulin concentrations compared to a carbohydrate control. Clinical trial registry: NCT02366598 (Experiment 1) and NCT02458027 (Experiment 2) Novelty bullets: 1) Hemp protein concentrate dose-dependently leads to lower post-prandial BG response compare to a carbohydrate control. 2) No differences were seen between hemp and soy protein.

Between Temperament and Psychopathology: Examples from Neuropharmacological Challenge Tests in Healthy Humans

Background: This paper tries to demonstrate that the questionnaire-based continuum between temperament traits and psychopathology can also be shown on the biochemical level. A common feature is the incapacity to adapt to external demands, as demonstrated by examples of disturbed hormone cycles as well as neurotransmitter (TM) responses related to affective and impulse control disorders. Methods: Pharmacological challenge tests performed in placebo-controlled balanced crossover experiments with consecutive challenges by serotonin (5-HT), noradrenaline (NA), and dopamine (DA) agonistic drugs were applied to healthy subjects, and individual responsivities of each TM system assessed by respective cortisol and prolactin responses were related to questionnaire-based facets of depressiveness and impulsivity, respectively. Results: The depression-related traits “Fatigue” and “Physical Anhedonia” were characterized by low and late responses to DA stimulation as opposed to “Social Anhedonia,” which rather mirrored the pattern of schizophrenia. Reward-related and premature responding-related impulsivity represented by high scores on “Disinhibition” and “Motor Impulsivity,” respectively, as well as the questionnaire-based components of attention deficit hyperactivity disorder, “Cognitive” and “Motor Impulsivity,” could be discriminated by their patterns of DA/NA responses. 5-HT responses suggested that instead of the expected low availability of 5-HT claimed to be associated with impulse control disorders, low NA responses indicated lack of inhibition in impulsivity and high NA responses in depression-related “Anhedonia” indicated suppression of approach motivation. Conclusions: In spite of the flaws of pharmacological challenge tests, they may be suitable for demonstrating similarities in TM affinities between psychopathological disturbances and respective temperament traits and for separating sub-entities of larger disease spectra.

Predictors of postprandial glycaemia, insulinaemia and insulin resistance in adolescents

Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.

Linking synthesis and structure descriptors from a large collection of synthetic records of zeolite materials

Correlating synthesis conditions and their consequences is a significant challenge, particularly for materials formed as metastable phases via kinetically controlled pathways, such as zeolites, owing to a lack of descriptors that effectively illustrate the synthesis protocols and their corresponding results. This study analyzes the synthetic records of zeolites compiled from the literature using machine learning techniques to rationalize physicochemical, structural, and heuristic insights to their chemistry. The synthesis descriptors extracted from the machine learning models are used to identify structure descriptors with the appropriate importance. A similarity network of crystal structures based on the structure descriptors shows the formation of communities populated by synthetically similar materials, including those outside the dataset. Crossover experiments based on previously overlooked structural similarities reveal the synthesis similarity of zeolites, confirming the synthesis–structure relationship. This approach is applicable to any system to rationalize empirical knowledge, populate synthesis records, and discover novel materials.

Portion size normality and additional within-meal food intake: two crossover laboratory experiments

Reducing food portion size could reduce energy intake. However, it is unclear at what point consumers respond to reductions by increasing intake of other foods. We predicted that a change in served portion size would only result in significant additional eating within the same meal if the resulting portion size was no longer visually perceived as ‘normal’. Participants in two crossover experiments (Study 1: n 45; Study 2: n 37; adults, 51 % female) were served different-sized lunchtime portions on three occasions that were perceived by a previous sample of participants as ‘large-normal’, ‘small-normal’ and ‘smaller than normal’, respectively. Participants were able to serve themselves additional helpings of the same food (Study 1) or dessert items (Study 2). In Study 1 there was a small but significant increase in additional intake when participants were served the ‘smaller than normal’ compared with the ‘small-normal’ portion (m difference = 161 kJ, P = 0·002, d = 0·35), but there was no significant difference between the ‘small-normal’ and ‘large-normal’ conditions (m difference = 88 kJ, P = 0·08, d = 0·24). A similar pattern was observed in Study 2 (m difference = 149 kJ, P = 0·06, d = 0·18; m difference = 83 kJ, P = 0·26, d = 0·10). However, smaller portion sizes were each associated with a significant reduction in total meal intake. The findings provide preliminary evidence that reductions that result in portions appearing ‘normal’ in size may limit additional eating, but confirmatory research is needed.

How Crossover Speeds up Building Block Assembly in Genetic Algorithms

We reinvestigate a fundamental question: How effective is crossover in genetic algorithms in combining building blocks of good solutions? Although this has been discussed controversially for decades, we are still lacking a rigorous and intuitive answer. We provide such answers for royal road functions and OneMax, where every bit is a building block. For the latter, we show that using crossover makes every ([Formula: see text]+[Formula: see text]) genetic algorithm at least twice as fast as the fastest evolutionary algorithm using only standard bit mutation, up to small-order terms and for moderate [Formula: see text] and [Formula: see text]. Crossover is beneficial because it can capitalize on mutations that have both beneficial and disruptive effects on building blocks: crossover is able to repair the disruptive effects of mutation in later generations. Compared to mutation-based evolutionary algorithms, this makes multibit mutations more useful. Introducing crossover changes the optimal mutation rate on OneMax from [Formula: see text] to [Formula: see text]. This holds both for uniform crossover and k-point crossover. Experiments and statistical tests confirm that our findings apply to a broad class of building block functions.