Exploration of Reaction Pathways and Chemical Transformation Networks

For the investigation of chemical reaction networks, the identification of all relevant intermediates and elementary reactions is mandatory. Many algorithmic approaches exist that perform explorations efficiently and automatedly. These approaches differ in their application range, the level of completeness of the exploration, as well as the amount of heuristics and human intervention required. Here, we describe and compare the different approaches based on these criteria. Future directions leveraging the strengths of chemical heuristics, human interaction, and physical rigor are discussed.Comment: 48 pages, 4 figure

Effects of index selection on the carcass composition of sheep given either ad libitum or controlled amounts of food

Sheep of a line (S) selected on an index to increase lean weight and decrease fatness at an age, and a control line (C), were given a high quality food at different levels including ad libitum. Live performance was measured from about 21 to 114 kg live weight, The carcasses of each line were analysed for lean, fat and bone at three widely varying weights in both males and females. Level of feeding did not affect the extent to which S was superior to C in either the level of fatness in the carcass (0·86 as much) or the ratio of lean tofat (1·28 as much). The lean to bone ratio was slightly greater in S (1·028 of the value of C; P \u3c 0,05) and was higher on the lowest level of feeding compared with the two higher levels used (P \u3c 0·05 in one experiment on females and P \u3c 0,001 in another on males). On ad libitum feeding the S line grew 1·19 times as fast and was 1·17 times as efficient compared with C. These advantages to S decreased as level of feeding decreased to become virtually zero at the lowest level of feeding used, which allowed C to grow at only 0·53 of the rate seen on ad libitum feeding. On ad libitum feeding growth was well described by a Gompertz growth function of the form W= (Z/B) exp(-exp (Go -8 t)). The maximum growth rate is (Z/e). Line S had a value of 2 that was 1·10 that of C averaged across the two sexes. A Spillman function W= Wo+ (A-WO) (l-exp (-k F)) was used to describe weight, W, in terms of cumulative intake, F. It worked well for ad libitum feeding andfor the two restricted regimes used. The value of the combined parameter (A k) varied across treatments in the same wayas efficiency did

Effects of index selection on the carcass composition of sheep given either ad libitum or controlled amounts of food

Sheep of a line (S) selected on an index to increase lean weight and decrease fatness at an age, and a control line (C), were given a high quality food at different levels including ad libitum. Live performance was measured from about 21 to 114 kg live weight, The carcasses of each line were analysed for lean, fat and bone at three widely varying weights in both males and females. Level of feeding did not affect the extent to which S was superior to C in either the level of fatness in the carcass (0·86 as much) or the ratio of lean tofat (1·28 as much). The lean to bone ratio was slightly greater in S (1·028 of the value of C; P \u3c 0,05) and was higher on the lowest level of feeding compared with the two higher levels used (P \u3c 0·05 in one experiment on females and P \u3c 0,001 in another on males). On ad libitum feeding the S line grew 1·19 times as fast and was 1·17 times as efficient compared with C. These advantages to S decreased as level of feeding decreased to become virtually zero at the lowest level of feeding used, which allowed C to grow at only 0·53 of the rate seen on ad libitum feeding. On ad libitum feeding growth was well described by a Gompertz growth function of the form W= (Z/B) exp(-exp (Go -8 t)). The maximum growth rate is (Z/e). Line S had a value of 2 that was 1·10 that of C averaged across the two sexes. A Spillman function W= Wo+ (A-WO) (l-exp (-k F)) was used to describe weight, W, in terms of cumulative intake, F. It worked well for ad libitum feeding andfor the two restricted regimes used. The value of the combined parameter (A k) varied across treatments in the same wayas efficiency did

The role of model complexity in assessing water supply system resilience

Assessing water supply system resilience is becoming increasingly important as system pressures, including climate change and population, increase. The resilience of water supply systems in the UK to droughts of differing intensity and duration is now assessed through the simulation of a range of extreme droughts using water resource models. This process can be time consuming, data intensive and in some cases, may not be proportionate to the system response. The drought response surface has become a useful tool in UK water resources planning to quickly visualise modelled outputs, and therefore resilience, to droughts of differing intensity and duration. Work undertaken as part of the NERC Historic Droughts project has sought to compare results within the drought response surface framework to different levels of modelling complexity. Models of increasing complexity were developed that are rapid, accommodate varying data quality and provenance, and can be applied worldwide. Droughts were characterised for a range of reservoir systems based on duration and system response in the historic record. Flexible linear and polynomial regression models were trained on historic storage data and increasingly complex inputs – firstly rainfall, then site-translated historic reconstructed streamflow, and finally site-specific historic reconstructed streamflow – to hindcast reservoir storage to 1891. System understanding was important in drought duration selection, which was dependent on the length and distribution of reservoir storage in the observed record. The models permit the input of fuzzy data points, accommodating anecdotal evidence related to drought intensity and duration. Extreme value analysis of storage allowed for water company levels of service to be considered, therefore providing a description of the system response of an event in terms of the customer experience. Drought response surfaces produced under increasingly complex inputs were compared with those produced through water resource modelling to demonstrate the implications of different levels of modelling complexity. While simple, statistical modelling approaches that do not incorporate physical parameters should not replace deterministic system modelling, they allow for identification of periods and systems of interest that can focus further, more detailed analysis using more complex models and may have particular applications in data and model poor regions

Flow Annealed Importance Sampling Bootstrap

Normalizing flows are tractable density models that can approximate complicated target distributions, e.g. Boltzmann distributions of physical systems. However, current methods for training flows either suffer from mode-seeking behavior, use samples from the target generated beforehand by expensive MCMC simulations, or use stochastic losses that have very high variance. To avoid these problems, we augment flows with annealed importance sampling (AIS) and minimize the mass covering $\alpha$-divergence with $\alpha=2$, which minimizes importance weight variance. Our method, Flow AIS Bootstrap (FAB), uses AIS to generate samples in regions where the flow is a poor approximation of the target, facilitating the discovery of new modes. We target with AIS the minimum variance distribution for the estimation of the $\alpha$-divergence via importance sampling. We also use a prioritized buffer to store and reuse AIS samples. These two features significantly improve FAB's performance. We apply FAB to complex multimodal targets and show that we can approximate them very accurately where previous methods fail. To the best of our knowledge, we are the first to learn the Boltzmann distribution of the alanine dipeptide molecule using only the unnormalized target density and without access to samples generated via Molecular Dynamics (MD) simulations: FAB produces better results than training via maximum likelihood on MD samples while using 100 times fewer target evaluations. After reweighting samples with importance weights, we obtain unbiased histograms of dihedral angles that are almost identical to the ground truth ones

Index Selection in Terminal Sires Improves Early Lamb Growth

The use of terminal sires (TS) for crossbreeding is integral to the UK sheep industry where approximately 71% of market lambs are sired by TS rams. Early growth of these crossbred lambs affects profitability. The objectives of this study were i) to evaluate the effectiveness of index selection among TS on BW and ADG of their crossbred offspring; and ii) to compare the efficacy of that selection within TS breeds. The most widely used TS breeds in the United Kingdom are Charollais, Suffolk, and Texel. These participated in sire referencing schemes in which they were evaluated on a lean growth index designed to increase carcass lean weight at a given age. From 1999 to 2002, approximately 15 high and 15 low lean growth index rams per breed (93 in total, differing in index on average by 4.6 SD) were selected from within their sire referencing schemes and mated to Welsh and Scottish Mule ewes. Their crossbred offspring were reared commercially on 3 experimental farms in England, Scotland, and Wales. A total of 6,515 lambs were born between 2000 and 2003. Lambs were weighed at birth (BWT), 5 wk (5WT), and 10 wk (10WT), and their ADG from birth to 10 wk was calculated. Lambs sired by high index rams were on average, across breeds, heavier at all ages (P \u3c 0.01) with 0.07 ± 0.03, 0.3 ± 0.1, and 0.4 ± 0.1 kg greater BWT, 5WT, and 10WT, respectively. Their ADG was 5.1 ± 1.9 g/d greater than low-index-sired lambs (P \u3c 0.01). Suffolk-sired lambs were on average heavier at all ages, with greater ADG, whereas Charollais-sired lambs were lightest with smallest ADG. Overall, there was no significant interaction between sire index and sire breed (P \u3e 0.10). Within Suffolk-sired lambs, there was little difference between high and low index sires for the traits studied (P \u3e 0.3). High and low index Charollais-sired lambs differed in BWT (0.09 ± 0.04 kg) and 5WT (0.3 ± 0.1 kg), and Texel-sired lambs differed in 5WT (0.5 ± 0.1 kg), 10WT (0.9 ± 0.2 kg), and ADG (10.2 ± 3.3 g/d; P \u3c 0.01). Lambs from Scottish Mule dams were heavier, with greater ADG, than lambs born to Welsh Mules (P \u3c 0.01). Lambs reared in Scotland were heavier at all ages (P \u3c 0.01). The results suggest that using index selection in TS can improve the growth of their commercial offspring reared on grass