Protein Structure Prediction: The Next Generation

Over the last 10-15 years a general understanding of the chemical reaction of protein folding has emerged from statistical mechanics. The lessons learned from protein folding kinetics based on energy landscape ideas have benefited protein structure prediction, in particular the development of coarse grained models. We survey results from blind structure prediction. We explore how second generation prediction energy functions can be developed by introducing information from an ensemble of previously simulated structures. This procedure relies on the assumption of a funnelled energy landscape keeping with the principle of minimal frustration. First generation simulated structures provide an improved input for associative memory energy functions in comparison to the experimental protein structures chosen on the basis of sequence alignment

Western australian pregnancy cohort (raine) study: Generation 1

Purpose: The purpose of the Raine Study is to improve human health and well-being by studying the life-course of a cohort of Western Australians, based on a life-course conceptual framework that considers interactions between genetics, phenotypes, behaviours, the environment and developmental and social outcomes. Participants: Between May 1989 and November 1991, 2900 pregnant women were enrolled in the Raine Study in Perth, Western Australia. In total, 2730 women gave birth to 2868 children (Generation 2) between August 1989 and April 1992. The mothers and fathers of Generation 2 are referred to as Generation 1 of the Raine Study. In the most recent Generation 1 follow-up, 636 mothers and 462 fathers participated. Findings to date: Until the 26-year follow-up of Generation 1 the focus of research within the Raine Study was on outcomes in Generation 2, with information on the parents mainly being used to examine its influence on their children's outcomes. For example, recent findings showed that several characteristics of mothers, such as obesity, early mid-gestational weight gain and socioeconomic status were associated with non-Alcoholic fatty liver disease, adiposity and cardiometabolic characteristics in offspring. Other findings showed that parents with back pain were more likely to have offspring who experienced back pain. Also, non-linear and dynamic relationships were found between maternal working hours and offspring overweight or obesity. Future plans: The Raine Study will continue to provide access to its dense longitudinal genetic, phenotypic, behavioural, environmental, developmental and social data to undertake studies with the ultimate goal of improving human health and well-being. Analyses of data from the recent Generation 1 year 26 follow-up are underway. Trial registration number ACTRN1261700159936

The Physical Properties and Effective Temperature Scale of O-type Stars as a Function of Metallicity. III. More Results from the Magellanic Clouds

In order to better determine the physical properties of hot, massive stars as a function of metallicity, we obtained very high SNR optical spectra of 26 O and early B stars in the Magellanic Clouds. These allow accurate modeling even in cases where the He I 4471 line has an equivalent width of only a few tens of mA. The spectra were modeled with FASTWIND, with good fits obtained for 18 stars; the remainder show signatures of being binaries. We include stars in common to recent studies to investigate possible systematic differences. The "automatic" FASTWIND modeling method of Mokiem and collaborators produced temperatures 1100 K hotter on the average, presumably due to the different emphasis given to various temperature-sensitive lines. More significant, however, is that the automatic method always produced some "best" answer, even for stars we identify as composite (binaries). The temperatures found by the TLUSTY/CMFGEN modeling of Bouret, Heap, and collaborators yielded temperatures 1000 K cooler than ours, on average. Significant outliers were due either to real differences in the data (some of the Bouret/Heap data were contaminated by moonlight continua) or the fact we could detect the HeI line needed to better constrain the temperature. Our new data agrees well with the effective temperature scale we presented previously. We confirm that the "Of" emission-lines do not track luminosity classes in the exact same manner as in Milky Way stars. We revisit the the issue of the "mass discrepancy", finding that some of the stars in our sample do have spectroscopic masses that are significantly smaller than those derived from stellar evolutionary models. We do not find that the size of the mass discrepancy is simply related to either effective temperature or surface gravity.Comment: ApJ, in pres

Homology groups of the curvature sets of S1S^1

For $n \geq 2$, the $n$-th curvature set of a metric space $X$ is the set of $n$-by-$n$ distance matrices of points coming from $X$. We give a geometric and topological study of the curvature sets of the unit circle equipped with the geodesic metric. We show that the $n$-th curvature set is a quotient of the $(n-1)$-torus by the action of the reflection on each factor. We also characterize the homotopy type of several notable subsets of the curvature set, allowing us to compute its homology using the Mayer-Vietoris sequence. We also construct an abstract simplicial complex, which we call the state complex, that can be constructed using relative positions of points rather than their distances. We prove that this simplicial complex is homeomorphic to the $n$-th curvature set of the circle. We also discuss a connection between elliptopes (a well known notion from semidefinite optimization) and curvature sets of spheres of increasing dimension

Information Resource Needs and Preference of Queensland General Practitioners on Complementary Medicines: Result of a Needs Assessment

Objectives. To explore in a cohort of Queensland (Qld) GPs' their attitudes to; knowledge about; and practice behaviour regarding complementary medicines (CMs), and to identify their perceptions of need for information resources on CMs. Design. A faxed self-administered survey to a random sample of 800 GPs in Qld. Participants. 463 completed surveys were returned, representing a 58% response rate. Results. The majority of GPs had a positive attitude about incorporating CMs in their clinical practice; however, only 12% perceived they had adequate knowledge to be able to advise patients about CMs. GPs most preferred evidence-based resources for receiving information on CMs (fact sheets, booklets, and journals) that contain clinical, pharmacological, and toxicological information. Most GPs perceived a need for an information resource on herbal medicines, vitamins, minerals, and trace elements, and nutritional supplements. Conclusion. GPs are open to integrating CMs into their clinical practice. They identify a current lack of knowledge coupled with a substantive level of interest to learn more. GPs perceive a high level of need for information resources on CMs. These resources should be developed and readily available to GPs to increase their knowledge about CMs and better equip them in communicating with patients about CMs use

Acoustic scattering by benthic and planktonic shelled animals

Author Posting. © Acoustical Society of America, 2000. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 108 (2000): 535-550, doi:10.1121/1.429584.Acoustic backscattering measurements and associated scattering modeling were recently conducted on a type of benthic shelled animal that has a spiral form of shell (Littorina littorea). Benthic and planktonic shelled animals with this shape occur on the seafloor and in the water column, respectively, and can be a significant source of acoustic scattering in the ocean. Modeling of the scattering properties allows reverberation predictions to be made for sonar performance predictions as well as for detection and classification of animals for biological and ecological applications. The studies involved measurements over the frequency range 24 kHz to 1 MHz and all angles of orientation in as small as 1° increments. This substantial data set is quite revealing of the physics of the acoustic scattering by these complex shelled bodies and served as a basis for the modeling. Specifically, the resonance structure of the scattering was strongly dependent upon angle of orientation and could be traced to various types of rays (e.g., subsonic Lamb waves and rays entering the opercular opening). The data are analyzed in both the frequency and time domain (compressed pulse processing) so that dominant scattering mechanisms could be identified. Given the complexity of the animal body (irregular elastic shell with discontinuities), approximate scattering models are used with only the dominant scattering properties retained. Two models are applied to the data, both approximating the body as a deformed sphere: (1) an averaged form of the exact modal-series-based solution for the spherical shell, which is used to estimate the backscattering by a deformed shell averaged over all angles of orientation, and produces reasonably accurate predictions over all k1aesr (k1 is the acoustic wave number of the surrounding water and aesr is the equivalent spherical radius of the body), and (2) a ray-based formula which is used to estimate the scattering at fixed angle of orientation, but only for high k1aesr. The ray-based model is an extension of a model recently developed for the shelled zooplankton Limacina retroversa that has a shape similar to that of the Littorina littorea but swims through the water [Stanton et al., J. Acoust. Soc. Am. 103, 236–253 (1998b)]. Applications of remote detection and classification of the seafloor and water column in the presence of shelled animals are discussed.This work was supported by the U.S. Office of Naval Research Grant Nos. N00014-95-1- 0287 and N00014-96-1-0878, and the MIT/WHOI Joint Graduate Education Program

Correlates of physical activity and sedentary time in young adults: The Western Australian Pregnancy Cohort (Raine) Study

Background: The socioecological model proposes a wide array of factors that influence behaviours. There is a need to understand salient correlates of these activity behaviours in a specific population. However, few studies identified socio-demographic, behavioural, physical, and psychological correlates of objectively-assessed physical activity and sedentary time in young adults. Methods: This was a cross-sectional analysis of participants in the Raine Study (a pregnancy cohort started in 1989). Australian young adults (mean 22.1 years ± SD 0.6) wore Actigraph GT3X+ accelerometers on the hip 24 h/day for seven days to assess moderate-to-vigorous physical activity (MVPA) and sedentary time (n = 256 women, n = 219 men). Potential correlates were assessed via clinical assessment and questionnaire and included socio-demographic variables (ethnicity, relationship status, work/study status, education, mothers education), health behaviours (food intake, alcohol consumption, smoking status, sleep quality), and physical and psychological health aspects (anthropometrics, diagnosed disorders, mental health, cognitive performance). Backwards elimination (p < 0.2 for retention) with mixed model regressions were used and the gender-stratified analyses were adjusted for demographic variables, waking wear time and number of valid days. Results: Increased time spent in MVPA was associated with: being single (IRR 1.44 vs in a relationship living together, 95%CI: 1.17, 1.77, p =.001) in women; and better sleep quality in men (lower scores better IRR 0.97, 95%CI: 0.93, 1.00). Less time spent sedentary was associated with: lower mother's education (- 32.1 min/day, 95%CI -52.9, 11.3, p = 0.002 for having mother with no university degree vs at least a baccalaureate degree) and smoking (- 44.3 min/day, 95%CI: - 72.8, - 15.9, p =.0002) for women; lower education status (- 32.1 min/day, 95%CI: -59.5, - 4.8, p = 0.021 for having no university degree vs at least a baccalaureate degree) and lower depression scores in men (- 2.0, 95%CI: - 3.5, - 0.4, p = 0.014); more alcoholic drinks per week for women (- 1.9 min/day, 95%CI: -3.1, - 0.6, p = 0.003) and men (- 1.0, 95%CI: -1.8, - 0.3, p = 0.007). Conclusions: Less desirable correlates were associated with positive levels of activity in young Australian adult women and men. Interventions to increase MVPA and decrease sedentary activity in young adults need to specifically consider the life stage of young adults

Sleep health of young adults in Western Australia and associations with physical and mental health: A population-level cross-sectional study

OBJECTIVES: This article aims to report on the sleep health characteristics of a population-level sample of young Australian adults and examine associations with measures of physical and mental health. METHODS: A cross-sectional study using data from the Raine Study. Data from participants (n = 1234) born into the study (Generation 2) at the 22-year follow-up were used, including data from a self-report questionnaire and polysomnography. RESULTS: The highest prevalence of suboptimal sleep health was seen on measures of sleep duration (30%), onset latency (18%), satisfaction (25%) and regularity (60%). Dissatisfaction with sleep (physical health: =0.08; mental health: =0.34) and impaired daytime alertness (physical health: =0.09; mental health: =0.08) were significantly associated with poorer physical and mental health and inadequate polysomnography-measured sleep duration was associated poorer mental health ( =0.07) (all ps \u3c 0.05). CONCLUSIONS: Satisfaction with sleep and daytime alertness, both of which are assessed via self-report, are essential aspects of sleep health for young adults. IMPLICATIONS FOR PUBLIC HEALTH: Findings could inform public health interventions, including screening guidelines, to improve the sleep health and, in turn, the physical and mental health of young adults in Australia

Immune function during early adolescence positively predicts adult facial sexual dimorphism in both men and women

Evolutionary theories suggest that humans prefer sexual dimorphism in faces because masculinity in men and femininity in women may be an indicator of immune function during development. In particular, the immunocompetence handicap hypothesis proposes that sexual dimorphism indicates good immune function during development because the sex hormones, particularly testosterone in men, required for the development of sexually dimorphic facial features also taxes the immune system. Therefore, only healthy males can afford the high level of testosterone for the development of sexually dimorphic traits without compromising their survival. Researchers have suggested that a similar mechanism via the effects of oestrogen might also explain male preferences for female femininity. Despite the prominence of the immunocompetence handicap hypothesis, no studies have tested whether immune function during development predicts adult facial sexual dimorphism. Here, using data from a longitudinal public health dataset, the Western Australian Pregnancy Cohort (Raine) Study (Generation 2), we show that some aspects of immune function during early adolescence (14 years) positively predict sexually dimorphic 3D face shape in both men and women. Our results support a fundamental assumption that facial sexual dimorphism is an indicator of immune function during the development of facial sexual dimorphism.PostprintPeer reviewe