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OBJECTIVES/GOALS: Maternal undernutrition, a form of malnutrition, can alter neonatal leptin signaling and result in metabolic dysfunction in adulthood. We developed a mild undernutrition model to relate more to societys nutritional challenges and to test the hypothesis that a shift in the neonatal leptin surge would result in sex-specific metabolic changes. METHODS/STUDY POPULATION: We studied pups from undernourished dams which were calorically restricted by 20% (CR20) from embryonic day 15 until postnatal day (PND) 21. We tested 216 offspring from 11 Fed dams and 13 undernourished dams (CR20), detecting a leptin surge in control fed progeny at PND11. At 3 months of age, offspring from 3 dams per maternal nutrient status were either exposed to a 45% high fat diet (HFD) or control diet (10% fat) for 16 weeks. Anterior pituitary hormones were analyzed in the pituitary and serum of neonates and adults. To determine the mechanism of the phenotype observed in male adult offspring on the HFD, single cell RNA sequencing was used to analyze the pituitary, fat and liver. RESULTS/ANTICIPATED RESULTS: Offspring of CR20 dams had an early leptin surge peaking at PND8 and GH levels at PND1 were higher in CR20 progeny. Weights of both male and female CR20 offspring were lower and body lengths were shorter than controls. As adults, Fed mice from both sexes had increased weight gain with HFD. However, although CR20 females gained weight on the HFD, male progeny from CR20 dams did not gain weight on the HFD and appeared protected from impact. We found sex-specific changes in pituitary Gh, Ghrhr, and Ghsr mRNA levels. Single cell RNA sequencing of pituitary, fat and liver of male offspring showed significant regulation of transcripts in fat of male offspring from Fed dams that was not found in CR20 males when compared to control fed mice. DISCUSSION/SIGNIFICANCE: Mild undernutrition causes a prematurely high leptin surge and sex-specific growth responses to a HFD, including resistance to a HFD in underfed males. Transcript analysis in fat of males resistant to HFD induced obesity may reveal mechanisms that provide protection against HFD induced weight gain.
Reasoning about probabilistic programs is hard because it compounds the difficulty of classic program analysis with sometimes subtle questions of probability theory. Having precise mathematical models, or semantics, describing their behaviour is therefore particularly important. In this chapter, we review two probabilistic semantics. First, an operational semantics which models the local, step-by-step, behaviour of programs, then a denotational semantics describing global behaviour as an operator transforming probability distributions over memory states.
What does a probabilistic program actually compute? How can one formally reason about such probabilistic programs? This valuable guide covers such elementary questions and more. It provides a state-of-the-art overview of the theoretical underpinnings of modern probabilistic programming and their applications in machine learning, security, and other domains, at a level suitable for graduate students and non-experts in the field. In addition, the book treats the connection between probabilistic programs and mathematical logic, security (what is the probability that software leaks confidential information?), and presents three programming languages for different applications: Excel tables, program testing, and approximate computing. This title is also available as Open Access on Cambridge Core.
Bovine babesiosis is the most important protozoan disease transmitted by ticks. In Plasmodium falciparum, another Apicomplexa protozoan, the interaction of rhoptry neck protein 2 (RON2) with apical membrane antigen-1 (AMA-1) has been described to have a key role in the invasion process. To date, RON2 has not been described in Babesia bigemina, the causal agent of bovine babesiosis in the Americas. In this work, we found a ron2 gene in the B. bigemina genome. RON2 encodes a protein that is 1351 amino acids long, has an identity of 64% (98% coverage) with RON2 of B. bovis and contains the CLAG domain, a conserved domain in Apicomplexa. B. bigemina ron2 is a single copy gene and it is transcribed and expressed in blood stages as determined by RT-PCR, Western blot, and confocal microscopy. Serum samples from B. bigemina-infected bovines were screened for the presence of RON2-specific antibodies, showing the recognition of conserved B-cell epitopes. Importantly, in vitro neutralization assays showed an inhibitory effect of RON2-specific antibodies on the red blood cell invasion by B. bigemina. Therefore, RON2 is a novel antigen in B. bigemina and contains conserved B-cell epitopes, which induce antibodies that inhibit merozoite invasion.
Successful organic farming requires crop varieties that are resilient to environmental variability. Assessing variety performance across the range of conditions represented on working farms is vital to developing such varieties; however, data collected from on-farm, participatory trials can be difficult to both collect and interpret. To assess the utility of data arising from participatory trialing efforts, we examined the performance of butternut squash (Cucurbita moschata L.), broccoli (Brassica oleracea L.) and carrot (Daucus carota L.) varieties grown in diverse organic production environments in participatory trials in Oregon, Washington, Wisconsin and New York using adaptability analysis (regression of variety means on environmental index). Patterns of adaptation varied across varieties, with some demonstrating broad adaptation and others showing specific adaptation to low- or high-yielding environments. Selection of varieties with broad vs specific adaptation should be guided by farmers’ risk tolerance and on-farm environmental variation. Adaptability analysis was appropriate for continuous variables (e.g., yield traits), but less so for ordinal variables and quality traits such as flavor and appearance, which can be vitally important in organic vegetable crop variety selection. The relative advantages of adaptability analysis and additive main effects and multiplicative interactions are also discussed in relation to on-farm trial networks. This work demonstrated the unique challenges presented by extensive participatory vegetable trialing efforts, which, as compared to grain crops, require novel approaches to facilitating farmer participation as well as data collection and analysis. Efficient, precise and reliable methods for evaluating quality related traits in these crops would allow researchers to assess stability and adaptation across a wider range of traits, providing advantages for effective plant breeding and trialing activities within the organic sector.
During the excavation of Rego da Murta Dolmen I, a structure belonging to a megalithic cluster in central Portugal, a number of small sub-quadrangular quartzite stones were found embedded within a layer below that of the deepest orthostat. In this paper, we report on these findings and highlight three key features of these small stones, namely their location relative to the dolmen’s plan, the distances between them, and their orientations. We suggest the quartzite stones could have been markers used in the planning of this megalithic structure. In addition, we analyse the orientations of the two main structures of the cluster (Dolmen I & Dolmen II), which are reflected by the orientation of the quartzite stones. We tentatively suggest potential landscape and skyscape alignments for their orientations, including three hypotheses for the observed differences in orientation between the two.
Background: The mechanisms and triggers of the attentional bias in social anxiety are not yet fully determined, and the modulating role of personality traits is being increasingly acknowledged. Aims: Our main purpose was to test whether social anxiety is associated with mechanisms of hypervigilance, avoidance (static biases), vigilance-avoidance or the maintenance of attention (dynamic biases). Our secondary goal was to explore the role of personality structure in shaping the attention bias. Method: Participants with high vs low social anxiety and different personality structures viewed pairs of faces (free-viewing eye-tracking task) representing different emotions (anger, happiness and neutrality). Their eye movements were registered and analysed for both whole-trial (static) and time-dependent (dynamic) measures. Results: Comparisons between participants with high and low social anxiety levels did not yield evidence of differences in eye-tracking measures for the whole trial (latency of first fixation, first fixation direction, total dwell time), but the two groups differed in the time course of overt attention during the trial (dwell time across three successive time segments): participants with high social anxiety were slower in disengaging their attention from happy faces. Similar results were obtained using a full-sample, regression-based analysis. Conclusion: Our results speak in favour of a maintenance bias in social anxiety. Preliminary results indicated that personality structure may not affect the maintenance (dynamic) bias of socially anxious individuals, although depressive personality structures may favour manifestations of a (static) hypervigilance bias.
This study aimed to contribute to the validation of the Portuguese version of the Prolonged Grief Disorder Questionnaire–Predeath (PG–12), examining its psychometric properties, including factorial, discriminant, and predictive validity. The prevalence of predeath prolonged grief disorder (PGD) and its psychosocial correlates were also analyzed.
The PG–12 was assessed in a sample of family caregivers (FCs) of oncological patients in palliative care. The factorial and discriminant validity of the PG–12 were evaluated by confirmatory factor analysis. The prevalence of predeath PGD was calculated and correlated with sociodemographic characteristics, perception of illness, intensity of care, coping, and caregiver burden. Prospective data were used to assess predictive validity.
The sample was composed of 94 FCs, mostly female (78.8%) and daughters (61.3%), with a mean age of 52.02 (SD = 12.87). The PG–12 has been shown to be reliable, to have high internal consistency, to be monofactorial in structure, and to be independent from depression, anxiety, and burden, although predeath grief influences these symptoms. In our sample, 33% met the criteria for predeath PGD. The circumstances and coping mechanisms are also correlated with predeath grief. The PG–12 has also been shown to be predictive of postdeath outcome.
Significance of results:
The PG–12 can be a useful screening tool for early identification of risk for maladjustment to loss among family caregivers.
We evaluated the effect of maternal vitamin E supplementation on the α-tocopherol concentrations of colostrum, transitional milk and mature milk of women who had given birth prematurely. This longitudinal randomised-controlled trial divided eighty-nine women into two groups: a control group and a supplemented group. Blood and breast milk were collected from all the participants after delivery. Next, each woman in the supplemented group received 400 IU of RRR-α-tocopheryl acetate. Further breast milk samples were collected 24 h after the first collection, as well as 7 and 30 d after delivery. α-Tocopherol concentrations were determined by HPLC. The baseline α-tocopherol concentrations in the maternal serum of the two groups were similar: 1159·8 (sd 292·4) μg/dl (27·0 (SD 6·8) μmol/l) for the control group and 1128·3 (sd 407·2) μg/dl (26·2 (SD 9·5) μmol/l) for the supplemented group. None of the women was vitamin E deficient. Breast milk α-tocopherol concentrations increased by 60 % 24 h after supplementation in the intervention group and did not increase at all in the control group. α-Tocopherol concentration of the transitional milk in the supplemented group was 35 % higher compared with the control group. α-Tocopherol concentrations of the mature milk in both groups were similar. Maternal supplementation with 400 IU of RRR-α-tocopherol increased the vitamin E concentrations of the colostrum and transitional milk, but not of the mature milk. This study presents relevant information for the design of strategies to prevent and combat vitamin E deficiency in the risk group of preterm infants.
Induction is a well-established proof principle that is taught in most undergraduate programs in mathematics and computer science. In computer science, it is used primarily to reason about inductively defined datatypes such as finite lists, finite trees and the natural numbers. Coinduction is the dual principle that can be used to reason about coinductive datatypes such as infinite streams or trees, but it is not as widespread or as well understood. In this paper, we illustrate through several examples the use of coinduction in informal mathematical arguments. Our aim is to promote the principle as a useful tool for the working mathematician and to bring it to a level of familiarity on par with induction. We show that coinduction is not only about bisimilarity and equality of behaviors, but also applicable to a variety of functions and relations defined on coinductive datatypes.
Theoretical models of recursion schemes have been well studied under the names well-founded coalgebras, recursive coalgebras, corecursive algebras and Elgot algebras. Much of this work focuses on conditions ensuring unique or canonical solutions, e.g. when the coalgebra is well founded.
If the coalgebra is not well founded, then there can be multiple solutions. The standard semantics of recursive programs gives a particular solution, typically the least fixpoint of a certain monotone map on a domain whose least element is the totally undefined function; but this solution may not be the desired one. We have recently proposed programming language constructs to allow the specification of alternative solutions and methods to compute them. We have implemented these new constructs as an extension of OCaml.
In this paper, we prove some theoretical results characterizing well-founded coalgebras, along with several examples for which this extension is useful. We also give several examples that are not well founded but still have a desired solution. In each case, the function would diverge under the standard semantics of recursion, but can be specified and computed with the programming language constructs we have proposed.
We present a systematic study of bisimulation-up-to techniques for coalgebras. This enhances the bisimulation proof method for a large class of state based systems, including labelled transition systems but also stream systems and weighted automata. Our approach allows for compositional reasoning about the soundness of enhancements. Applications include the soundness of bisimulation up to bisimilarity, up to equivalence and up to congruence. All in all, this gives a powerful and modular framework for simplified coinductive proofs of equivalence.
Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.