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We present a new, fully generative model for constructing astronomical catalogs from optical telescope image sets. Each pixel intensity is treated as a random variable with parameters that depend on the latent properties of stars and galaxies. These latent properties are themselves modeled as random. We compare two procedures for posterior inference. One procedure is based on Markov chain Monte Carlo (MCMC) while the other is based on variational inference (VI). The MCMC procedure excels at quantifying uncertainty, while the VI procedure is 1000 times faster. On a supercomputer, the VI procedure efficiently uses 665,000 CPU cores to construct an astronomical catalog from 50 terabytes of images in 14.6 minutes, demonstrating the scaling characteristics necessary to construct catalogs for upcoming astronomical surveys.

Humans can learn complex functional relationships between variables from small amounts of data. In doing so, they draw on prior expectations about the form of these relationships. In three experiments, we show that people learn to adjust these expectations through experience, learning about the likely forms of the functions they will encounter. Previous work has used Gaussian processes-a statistical framework that extends Bayesian nonparametric approaches to regression-to model human function learning. We build on this work, modeling the process of learning to learn functions as a form of hierarchical Bayesian inference about the Gaussian process hyperparameters., (© 2023 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)

Reaction optimization is fundamental to synthetic chemistry, from optimizing the yield of industrial processes to selecting conditions for the preparation of medicinal candidates 1 . Likewise, parameter optimization is omnipresent in artificial intelligence, from tuning virtual personal assistants to training social media and product recommendation systems 2 . Owing to the high cost associated with carrying out experiments, scientists in both areas set numerous (hyper)parameter values by evaluating only a small subset of the possible configurations. Bayesian optimization, an iterative response surface-based global optimization algorithm, has demonstrated exceptional performance in the tuning of machine learning models 3 . Bayesian optimization has also been recently applied in chemistry 4-9 ; however, its application and assessment for reaction optimization in synthetic chemistry has not been investigated. Here we report the development of a framework for Bayesian reaction optimization and an open-source software tool that allows chemists to easily integrate state-of-the-art optimization algorithms into their everyday laboratory practices. We collect a large benchmark dataset for a palladium-catalysed direct arylation reaction, perform a systematic study of Bayesian optimization compared to human decision-making in reaction optimization, and apply Bayesian optimization to two real-world optimization efforts (Mitsunobu and deoxyfluorination reactions). Benchmarking is accomplished via an online game that links the decisions made by expert chemists and engineers to real experiments run in the laboratory. Our findings demonstrate that Bayesian optimization outperforms human decisionmaking in both average optimization efficiency (number of experiments) and consistency (variance of outcome against initially available data). Overall, our studies suggest that adopting Bayesian optimization methods into everyday laboratory practices could facilitate more efficient synthesis of functional chemicals by enabling better-informed, data-driven decisions about which experiments to run.

Background: Gene flow and polyploidy have been found to be important in Juniperus evolution. However, little evidence has been published elucidating the association of both phenomena in juniper taxa in the wild. Two main areas were studied in Spain (Eastern Iberian Range and Sierra de Baza) with both diploid and tetraploid taxa present in sympatry. Gene flow and ploidy level were assessed for these taxa and the resulted offspring., Results: Twenty-two allo-triploid hybrids between J. sabina var. sabina and J. thurifera were found in the Eastern Iberian Range population. However, in the Sierra de Baza population no triploids were found. Instead, 18 allo-tetraploid hybrids between two tetraploid taxa: J. sabina var. balkanensis and J. thurifera were discovered. High genetic diversity was exhibited among the tetraploid hybrids at Sierra de Baza, in contrast to the genetically identical triploid hybrids at the Eastern Iberian Range; this suggests meiotic difficulties within the triploid hybrids. In addition, unidirectional gene flow was observed in both studied areas., Conclusion: Polyploidy and hybridization can be complementary partners in the evolution of Juniperus taxa in sympatric occurrences. Juniperus was shown to be an ideal coniferous model to study these two phenomena, independently or in concert.

Hundreds of plant mitogenomes have been sequenced from angiosperms, but relatively few mitogenomes are available from its sister lineage, gymnosperms. To examine mitogenomic diversity among extant gymnosperms, we generated draft mitogenomes from 11 diverse species and compared them with four previously published mitogenomes. Examined mitogenomes from Pinaceae and cycads retained all 41 protein genes and 26 introns present in the common ancestor of seed plants, whereas gnetophyte and cupressophyte mitogenomes experienced extensive gene and intron loss. In Pinaceae and cupressophyte mitogenomes, an unprecedented number of exons are distantly dispersed, requiring trans-splicing of 50-70% of mitochondrial introns to generate mature transcripts. RNAseq data confirm trans-splicing of these dispersed exons in Pinus. The prevalence of trans-splicing in vascular plant lineages with recombinogenic mitogenomes suggests that genomic rearrangement is the primary cause of shifts from cis- to trans-splicing in plant mitochondria., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent research suggests that the frequency of polyploidy may have been underestimated in gymnosperms. One notable example is in the conifer genus Juniperus , where there are already a few reports of polyploids although data are still missing for most species. In this study, we evaluated the extent of polyploidy in Juniperus by conducting the first comprehensive screen across nearly all of the genus. Genome size data from fresh material, together with chromosome counts, were used to demonstrate that genome sizes estimated from dried material could be used as reliable proxies to uncover the extent of ploidy diversity across the genus. Our analysis revealed that 16 Juniperus taxa were polyploid, with tetraploids and one hexaploid being reported. Furthermore, by analyzing the genome size and chromosome data within a phylogenetic framework we provide the first evidence of possible lineage-specific polyploidizations within the genus. Genome downsizing following polyploidization is moderate, suggesting limited genome restructuring. This study highlights the importance of polyploidy in Juniperus , making it the first conifer genus and only the second genus in gymnosperms where polyploidy is frequent. In this sense, Juniperus represents an interesting model for investigating the genomic and ecological consequences of polyploidy in conifers.

When confronted with a substance of unknown identity, researchers often perform mass spectrometry on the sample and compare the observed spectrum to a library of previously collected spectra to identify the molecule. While popular, this approach will fail to identify molecules that are not in the existing library. In response, we propose to improve the library's coverage by augmenting it with synthetic spectra that are predicted from candidate molecules using machine learning. We contribute a lightweight neural network model that quickly predicts mass spectra for small molecules, averaging 5 ms per molecule with a recall-at-10 accuracy of 91.8%. Achieving high-accuracy predictions requires a novel neural network architecture that is designed to capture typical fragmentation patterns from electron ionization. We analyze the effects of our modeling innovations on library matching performance and compare our models to prior machine-learning-based work on spectrum prediction., Competing Interests: The authors declare no competing financial interest.

Background: Phylogenetic relationships among Eastern Hemisphere cypresses, Western Hemisphere cypresses, junipers, and their closest relatives are controversial, and generic delimitations have been in flux for the past decade. To address relationships and attempt to produce a more robust classification, we sequenced 11 new plastid genomes (plastomes) from the five variously described genera in this complex (Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis) and compared them with additional plastomes from diverse members of Cupressaceae., Results: Phylogenetic analysis of protein-coding genes recovered a topology in which Juniperus is sister to Cupressus, whereas a tree based on whole plastomes indicated that the Callitropsis-Hesperocyparis-Xanthocyparis (CaHX) clade is sister to Cupressus. A sliding window analysis of site-specific phylogenetic support identified a ~ 15 kb region, spanning the genes ycf1 and ycf2, which harbored an anomalous signal relative to the rest of the genome. After excluding these genes, trees based on the remainder of the genes and genome consistently recovered a topology grouping the CaHX clade and Cupressus with strong bootstrap support. In contrast, trees based on the ycf1 and ycf2 region strongly supported a sister relationship between Cupressus and Juniperus., Conclusions: These results demonstrate that standard phylogenomic analyses can result in strongly supported but conflicting trees. We suggest that the conflicting plastomic signals result from an ancient introgression event involving ycf1 and ycf2 that occurred in an ancestor of this species complex. The introgression event was facilitated by plastomic recombination in an ancestral heteroplasmic individual carrying distinct plastid haplotypes, offering further evidence that recombination occurs between plastomes. Finally, we provide strong support for previous proposals to recognize five genera in this species complex: Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis.

We report a method to convert discrete representations of molecules to and from a multidimensional continuous representation. This model allows us to generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds. A deep neural network was trained on hundreds of thousands of existing chemical structures to construct three coupled functions: an encoder, a decoder, and a predictor. The encoder converts the discrete representation of a molecule into a real-valued continuous vector, and the decoder converts these continuous vectors back to discrete molecular representations. The predictor estimates chemical properties from the latent continuous vector representation of the molecule. Continuous representations of molecules allow us to automatically generate novel chemical structures by performing simple operations in the latent space, such as decoding random vectors, perturbing known chemical structures, or interpolating between molecules. Continuous representations also allow the use of powerful gradient-based optimization to efficiently guide the search for optimized functional compounds. We demonstrate our method in the domain of drug-like molecules and also in a set of molecules with fewer that nine heavy atoms., Competing Interests: The authors declare no competing financial interest.

The objective of this research was to evaluate effects of replacing sorghum × Sudangrass hay with ground juniper in gestating ewe supplements on pre- and postpartum growth performance, serum metabolites and hormonal concentrations, milk fatty acid composition, and progeny preweaning performance. In a completely randomized design, commercial Rambouillet ewes (age = 3 to 5 yr; initial BW = 65.2 ± 1.6 kg) on a base diet of long-stem sorghum × Sudangrass hay were assigned to 1 of 4 dietary supplements in which ground juniper replaced 0% (CNTL), 33% (18JUN), 66% (36JUN), or 100% (54JUN) of the ground sorghum × Sudangrass hay in a pelleted supplement with ground juniper from d 38 ± 4 of gestation to 2 d postpartum. Treatment DM diet intake overall (g/kg BW) in ewes receiving no juniper was similar ( ≥ 0.38) to that of those receiving increasing concentrations of juniper. Changes in ewe BW and BCS were similar ( ≥ 0.24) in ewes throughout gestation. All serum metabolites and hormones were within normal clinical ranges; however, serum IGF-1 decreased linearly ( = 0.003), alanine increased (linear; = 0.003), and serum Na decreased (linear; = 0.049) as the percentage of juniper increased in the diet. Ewe milk fatty acid composition was similar ( > 0.05) for the majority of fatty acids across treatment groups, with the exception of arachidonic acid (C20:4n6) being greater ( < 0.02) in 54JUN vs. CNTL ewe milk. Lamb birth weights were similar ( = 0.13), whereas lamb ADG tended to differ (quadratic; = 0.06) from d 0 to 14, with 18JUN being the least. At weaning, BW tended ( = 0.09) to linearly decrease in lambs born to ewes consuming greater concentrations of juniper but were not different ( = 0.26) between CNTL and 18JUN, 36JUN, and 54JUN. Results indicated that feeding increasing levels of ground juniper in supplements did not negatively alter ewe performance or serum metabolites and hormones measured pre- and postpartum. Lamb birth weight and preweaning performance appeared unaffected by maternal consumption of ground juniper containing supplements. Results also provide novel information regarding the effects of plant secondary compound consumption throughout pregnancy on ewe and progeny performance and health.

Complex animal behaviors are likely built from simpler modules, but their systematic identification in mammals remains a significant challenge. Here we use depth imaging to show that 3D mouse pose dynamics are structured at the sub-second timescale. Computational modeling of these fast dynamics effectively describes mouse behavior as a series of reused and stereotyped modules with defined transition probabilities. We demonstrate this combined 3D imaging and machine learning method can be used to unmask potential strategies employed by the brain to adapt to the environment, to capture both predicted and previously hidden phenotypes caused by genetic or neural manipulations, and to systematically expose the global structure of behavior within an experiment. This work reveals that mouse body language is built from identifiable components and is organized in a predictable fashion; deciphering this language establishes an objective framework for characterizing the influence of environmental cues, genes and neural activity on behavior., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Palbociclib, an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6, was recently approved by the U.S. Food and Drug Administration in combination with letrozole for postmenopausal women with advanced hormone receptor-positive, her2-negative breast cancer. Patients with loss of CDKN2A (p16), an inherent negative regulator of cyclin-dependent kinases 4 and 6, were not separately studied because of the significant response of the patients selected based only on receptor status. Here, we report a patient with metastatic estrogen receptor- positive, her2-negative breast cancer with CDKN2A loss who experienced a clinical response to palbociclib.

Objective: To pilot and feasibility-test supervised final year undergraduate pharmacy student-led medication reviews for patients with diabetes to enable definitive trial design., Method: Third year pharmacy students were recruited from one UK School of Pharmacy and trained to review patient's medical records and provide face-to-face consultations under supervision while situated within the patient's medical practice. Patients with type 2 diabetes were recruited by postal invitation letter from their medical practice and randomised via automated system to intervention or usual care. Diabetes-related clinical data, quality of life, patient reported beliefs, adherence and satisfaction with medicines information were collected with validated tools at baseline and 6 months postintervention. The process for collecting resource utilisation data was tested. Stakeholder meetings were held before and after intervention to develop study design and learn from its implementation. Recruitment and attrition rates were determined plus the quality of the outcome data. Power calculations for a definitive trial were performed on the different outcome measures to identify the most appropriate primary outcome measure., Results: 792 patients were identified as eligible from five medical practices. 133 (16.8%) were recruited and randomised to control (n=66) or usual care (n=67). 32 students provided the complete intervention to 58 patients. Initial data analysis showed potential for impact in the right direction for some outcomes measured including glycated haemoglobin, quality of life and patient satisfaction with information about medicines. The intervention was found to be feasible and acceptable to patients. The pilot and feasibility study enabled the design of a future full randomised controlled trial., Conclusions: Student and patient recruitment are possible. The intervention was well received and demonstrated some potential benefits. While the intervention was relatively inexpensive and provided an experiential learning opportunity for pharmacy students, its cost-effectiveness remains to be determined., Trial Registration Number: ISRCTN26445805; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

All Qinghai-Tibetan Plateau (QTP) endemic species are assumed to have originated recently, although very rare species most likely diverged early. These ancient species provide an excellent model to examine the origin and evolution of QTP endemic plants in response to the QTP uplifts and the climate changes that followed in this high altitude region. In this study, we examined these hypotheses by employing sequence variation from multiple nuclear and chloroplast DNA of 239 individuals of Juniperus microsperma and its five congeners. Both phylogenetic and population genetic analyses revealed that J. microsperma diverged from its sister clade comprising two species with long isolation around the Early Miocene, which corresponds to early QTP uplift. Demographic modeling and coalescent tests suggest that J. microsperma experienced an obvious bottleneck event during the Quaternary when the global climate greatly oscillated. The results presented here support the hypotheses that the QTP uplifts and Quaternary climate changes played important roles in shaping the evolutionary history of this rare juniper.

Understanding the extent and distribution of genetic diversity is crucial for the conservation and management of endangered species. Cupressus chengiana, C. duclouxiana, C. gigantea, and C. funebris are four ecologically and economically important species in China. We investigated their genetic diversity, population structure, and extant effective population size (35 populations, 484 individuals) employing six pairs of nuclear microsatellite markers (selected from 53). Their genetic diversity is moderate among conifers, and genetic differentiation among populations is much lower in C. gigantea than in the other three species; the estimated effective population size was largest for C. chengiana, at 1.70, 2.91, and 3.91 times the estimates for C. duclouxiana, C. funebris, and C. gigantea, respectively. According to Bayesian clustering analysis, the most plausible population subdivision scheme within species is two groups in C. chengiana, three groups in C. duclouxiana, and a single group for both C. funebris and C. gigantea. We propose a conservation strategy for these cypress species.

Most land plant plastomes contain two copies of a large inverted repeat (IR) that promote high-frequency homologous recombination to generate isomeric genomic forms. Among conifer plastomes, this canonical IR is highly reduced in Pinaceae and completely lost from cupressophytes. However, both lineages have acquired short, novel IRs, some of which also exhibit recombinational activity to generate genomic structural diversity. This diversity has been shown to exist between, and occasionally within, cupressophyte species, but it is not known whether multiple genomic forms coexist within individual plants. To examine the recombinational potential of the novel cupressophyte IRs within individuals and between species, we sequenced the plastomes of four closely related species of Juniperus. The four plastomes have identical gene content and genome organization except for a large 36 kb inversion between approximately 250 bp IR containing trnQ-UUG. Southern blotting showed that different isomeric versions of the plastome predominate among individual junipers, whereas polymerase chain reaction and high-throughput read-pair mapping revealed the substoichiometric presence of the alternative isomeric form within each individual plant. Furthermore, our comparative genomic studies demonstrate that the predominant and substoichiometric arrangements of this IR have changed several times in other cupressophytes as well. These results provide compelling evidence for substoichiometric shifting of plastomic forms during cupressophyte evolution and suggest that substoichiometric shifting activity in plastid genomes may be adaptive.

• A central aim of biogeography is to understand when and how modern patterns of species diversity and distribution developed. Many plant groups have disjunct distributions within the Northern Hemisphere, but among these very few have been studied that prefer warm semi-arid habitats. • Here we examine the biogeography and diversification history of Juniperus, which occurs in semi-arid habitats through much of the Northern Hemisphere. A phylogeny was generated based on > 10,000 bp of cpDNA for 51 Juniperus species plus many outgroups. Phylogenies based on fewer species were also constructed based on nuclear internal transcribed spacer (nrITS) and combined nrITS/cpDNA data sets to check for congruence. Divergence time-scales and ancestral distributions were further inferred. • Both long dispersal and migration across land bridges probably contributed to the modern range of Juniperus, while long-term climatic changes and the uplift of the Qinghai-Tibetan plateau probably drove its diversification. Diversification apparently slowed down during climate-stable period of the Oligocene, and then speeded up from the Miocene onwards. • Juniperus probably originated in Eurasia, and was a part of the south Eurasian Tethyan vegetation of the Eocene to Oligocene. It reached America once at this time, once in the Miocene and once more recently.

cDNA cloning of a monoterpene synthase from Perilla frutescens whose steam-distilled oil contains 92.9% perillaketone, was performed by the PCR method using primers designed based on limonene synthase. The full-length nucleotide sequence of this cDNA consisted of 1978 bp including a 1827-bp translational region encoding a deduced protein of 608 amino acids, which was similar to that of limonene synthase from P. frutescens (85% identity). Functional expression of this clone in Escherichia coli yielded an active monoterpene synthase enzyme, which converted geranyl diphosphate into 53.8% myrcene, 20.9% sabinene, 19.8% linalool and 5.5% limonene. As for the extraction of reaction products, we performed SPME (solid phase micro extraction) as well as conventional solvent extraction, and compared these two extraction methods.

A new species of conifer was recently discovered in northern Vietnam. In a preliminary phylogenetic analysis of morphological data a possible sister species, Chamaecyparis nootkatensis (D. Don) Spach, was identified; however, because of the presumed phylogenetic remoteness of these two species to the remainder of the Cupressaceae, a new genus-Xanthocyparis-was described to accommodate both species. Here an analysis of ITS (nrDNA), matK, and rbcL sequence data in combination with 58 informative morphological characters was aimed at testing the monophyly of the remainder of Chamaecyparis and evaluating the placement and monophyly of Xanthocyparis. Chamaecyparis, minus C. nootkatensis, was resolved as a monophyletic group, remote from Cupressus and Xanthocyparis. Cupressus, Juniperus, and Xanthocyparis formed a very highly supported monophyletic group. However, Cupressus was not monophyletic. Instead the Old World species sampled were resolved sister to a clade containing a monophyletic Juniperus, a monophyletic Xanthocyparis, and a clade of New World Cupressus species. If both species of Xanthocyparis are to be treated as members of the same genus, then due to the principal of priority they will have to be recognized in the genus Callitropsis. Research is continuing to resolve the status of New World and Old World Cupressus.

Three plant species, spinach, juniper and broccoli, were stored in different alcohol solutions, and the DNAs were examined to determine changes in the quality and quantity of DNA over time. The smallest changes in the genomic DNA were found in the samples stored in the lower mol wt alcohols (100% methanol and 100% and 95% ethanol) and when proteinase (Pronase E) was used in the extraction procedure. After 11 months of storage in ethanol, excellent yields of high mol wt DNA were obtained, but only when the procedure utilized Pronase E. The use of proteinase was found to be essential to obtain DNA from preserved specimens of spinach and broccoli. This appears to explain the previous reports of failures to obtain DNA from alcohol-preserved specimens. Vacuum infiltration of ethanol resulted in better DNA preservation than passive infiltration of ethanol.

Twenty-four populations of Juniperus ashei were sampled throughout the range of this taxon and the terpenoids of the foliage were analyzed by gas/liquid chromatography. Population differentiation was investigated by analysis of variance and numerical taxonomy. Three south Texas and one Mexican population clustered together with the rest of the taxon appearing fairly uniform. No evidence was found of hybridization or introgression with other taxa. Disjunct populations in Oklahoma and the Ozarks, which have been genetically isolated from the central population for thousands of years, showed no signs of differentiation nor genetic drift. The present pattern of distribution probably dates from the Pleistocene. The south Texas and Mexican populations appear to be the primitive elements of the species. Populational differences have apparently been maintained in adjacent populations in spite of seemingly large gene flow and conversely, chemical uniformity is being maintained in many disjunct populations where there is little or no gene flow.