Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

A discussion of the Pearl stanza as an approach to the poem

Pearl, written in the second half of the fourteenth century, remains today an intriguing combination of lyric and narrative poetry. Dramatic throughout, it at the same time has an emblematic quality which is developed through symbolic ornamentation. Both of these levels work toward a cyclic effect, and the end of the poem is a return to the beginning. Themes work against and/or with each other to create tensions, and even these tensions are at times elusive. Much scholarship on the Pearl has sought to find the key to disentangling the shifting themes which are so abundant in this psychological vision. In most cases, however, questions concerning the artistic nature and the structural form of Pearl are never raised. At the end of his interpretation, René Wellek called attention to the fact that Pearl scholarship is wanting in this type criticism. The actual study of the artistic value of the poem is still in its beginnings," he wrote. "Even the obvious approach through questions of meter and structure has not been much utilized hitherto.

Justice reasoning and responsibility reasoning in relation to commitment and happiness in long-term marriages

Marriage, as a microcosm of society, involves the moral dilemmas of conflicting rights, competing claims, and responsibility for decisions. This study focused on the moral development of the individual-in-relationship using commitment and happiness as the common ground. The purposes of this study were (a) to describe justice reasoning and responsibility reasoning of individuals in long-term marriages and (b) to assess the relationship of justice and responsibility reasoning to commitment and perceived happiness. Separate in-depth interviews were conducted with 30 individuals in 15 long-term marriages. Data collected were responses to three hypothetical dilemmas, four real-life dilemmas, and questions on commitment and happiness

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Instability of contingencies of self-worth: the role of approach-avoidance temperament

Self-esteem has multiple facets and individuals can derive their feelings of self-worth from specific domains in life (i.e., competition, approval of others, virtue; Crocker & Wolfe, 2001). Additionally, research on self-esteem suggests that it evolved as a social monitoring system, known as the sociometer (Leary, Tambor, Terdal, & Downs, 1995). The function of the sociometer is to alert individuals to changes in their relational value to others, which in turn influences their self-esteem, and ultimately their behavior (Leary, Tambor, Terdal, & Downs, 1995; Park & Crocker, 2008). A better understanding of the connection between self-evaluations and behavior can be gained by considering how individuals derive their feelings of self-worth. While people are motivated to succeed and avoid failure, this may particularly be true in the domains from which people derive their feelings of self-worth. Additionally, approach-avoidance motivation may further influence the relationship between evaluations in contingent domains, self-esteem, and behavioral outcomes. The present study expands this research by investigating how approach-avoidance motivation affects the relationship between contingencies of self-worth, self-esteem, and behavioral outcomes. Therefore, I hypothesized that individuals with low self-esteem and avoidance motivation would shift away from a domain that receives negative feedback. Those with high self-esteem and approach motivation, however, would increase the value placed on a domain after receiving negative feedback and positive feedback. Results suggest that avoidantly motivated individuals’ self-worth became increasingly contingent upon other’s approval no matter the feedback they received

Clustering cliques for graph-based summarization of the biomedical research literature

BACKGROUND: Graph-based notions are increasingly used in biomedical data mining and knowledge discovery tasks. In this paper, we present a clique-clustering method to automatically summarize graphs of semantic predications produced from PubMed citations (titles and abstracts). RESULTS: SemRep is used to extract semantic predications from the citations returned by a PubMed search. Cliques were identified from frequently occurring predications with highly connected arguments filtered by degree centrality. Themes contained in the summary were identified with a hierarchical clustering algorithm based on common arguments shared among cliques. The validity of the clusters in the summaries produced was compared to the Silhouette-generated baseline for cohesion, separation and overall validity. The theme labels were also compared to a reference standard produced with major MeSH headings. CONCLUSIONS: For 11 topics in the testing data set, the overall validity of clusters from the system summary was 10% better than the baseline (43% versus 33%). While compared to the reference standard from MeSH headings, the results for recall, precision and F-score were 0.64, 0.65, and 0.65 respectively

The Occurrence Of The Spiral Aftereffect In Children

No abstract available

Considering Black male consciousness within the context of genre : a framework for engaging and analyzing bodies of literature that center Black male bodies and their racialized experiences

Considering Black Male Consciousness within the Context of Genre: A Framework for Engaging and Analyzing Bodies of Literature that Center Black Male Bodies and their Racialized Experiences represents primarily the union of genre studies and Tommy J. Curry’s (2017) Man-Not—a theory that accounts for the historical/societal gendering of Black males, a practice that does not account for the various masculinities, or genres represented by Black manhood. The coupling of these concepts ultimately leads to the culmination of Black Male Consciousness (BMC) as genre and a related set of signposts for analysis to be used in the secondary English classroom. The historical underpinnings of Curry’s (2017) work with genre in relation to Black men and boys along with the conceptual frameworks presented by genre systems are rarely, if ever, met with a level of pedagogical nuance necessary for disrupting deficit models of being that are continuously used to construct and perpetuate caricatures associated with Black male bodies in both literature and in life. As such, the Black Male Consciousness (BMC) as genre framework aims to help readers (both teachers and students) make meaning from Black males’ lived experiences—as presented by Black males—while creating a space in which readers are urged to interrogate social constructs and internalized beliefs around Black manhood