Insights into PBDE uptake, body burden, and elimination gained from Australian age–Concentration trends observed shortly after peak exposure

Background Population pharmacokinetic models combined with multiple sets of age– concentration biomonitoring data facilitate back-calculation of chemical uptake rates from biomonitoring data. Objectives We back-calculated uptake rates of PBDEs for the Australian population from multiple biomonitoring surveys (top-down) and compared them with uptake rates calculated from dietary intake estimates of PBDEs and PBDE concentrations in dust (bottom-up). Methods Using three sets of PBDE elimination half-lives, we applied a population pharmacokinetic model to the PBDE biomonitoring data measured between 2002–2003 and 2010–2011 to derive the top-down uptake rates of four key PBDE congeners and six age groups. For the bottom-up approach, we used PBDE concentrations measured around 2005. Results Top-down uptake rates of Σ4BDE (the sum of BDEs 47, 99, 100, and 153) varied from 7.9 to 19 ng/kg/day for toddlers and from 1.2 to 3.0 ng/kg/day for adults; in most cases, they were—for all age groups—higher than the bottom-up uptake rates. The discrepancy was largest for toddlers with factors up to 7–15 depending on the congener. Despite different elimination half-lives of the four congeners, the age–concentration trends showed no increase in concentration with age and were similar for all congeners. Conclusions In the bottom-up approach, PBDE uptake is underestimated; currently known pathways are not sufficient to explain measured PBDE concentrations, especially in young children. Although PBDE exposure of toddlers has declined in the past years, pre- and postnatal exposure to PBDEs has remained almost constant because the mothers’ PBDE body burden has not yet decreased substantially.

Magnetic Field Due to the Self-Gravity-Induced Electric Polarization of a Rotating Massive Body

he notion of the gravity-induced electric field has been applied to an entire self-gravitating massive body. The resulting electric polarization of the otherwise neutral body, when taken in conjunction with the latter's rotation, is shown to generate an axial-magnetic field of the right type and order of magnitude for certain astrophysical objects. In the present treatment the electric polarization is calculated in the ion-continuum Thomas-Fermi approximation while the electrodynamics of the continuous medium is treated in the nonrelativistic approximation.

Sleep and self-regulation from birth to 7 years: A retrospective study of children with and without ADHD at 8-9 years

Objective To examine mean level differences, and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without ADHD at 8-9 years. Method This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort (n = 4109 analyzed). Children with and without ADHD were identified at age 8-9 years via parent-report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0-1, 2-3, 4-5 and 6-7 years of age. ANOVA was used to compare mean level differences in sleep problems, emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Results Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2-3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation two years later from 2-3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Conclusion Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.

Israel Aviation Coin

Obverse: Design of the an aircraft in motion from the right to the left. The wings and body suggest a seven branched candelabra. Reverse: In the center, modified 10 Lirot, number 1 is designed like a rocket moving upwards.

Molecular Modelling of Estrogen-Producing Enzymes CYP450 Aromatase and 17beta-Hydroxysteroid Dehydrogenase Type 1

Breast cancer is the most common cancer in women in the western countries. Approximately two-thirds of breast cancer tumours are hormone dependent, requiring estrogens to grow. Estrogens are formed in the human body via a multistep route starting from cholesterol. The final steps in the biosynthesis include the CYP450 aromatase enzyme, converting the male hormones androgens (preferred substrate androstenedione ASD) into estrogens(estrone E1), and the 17beta-HSD1 enzyme, converting the biologically less active E1 into the active hormone 17beta-hydroxyestradiol E2. E2 is bound to the nuclear estrogen receptors causing a cascade of biochemical reactions leading to cell proliferation in normal tissue, and to tumour growth in cancer tissue. Aromatase and 17beta-HSD1 are expressed in or near the breast tumour, locally providing the tissue with estrogens. One approach in treating hormone dependent breast tumours is to block the local estrogen production by inhibiting these two enzymes. Aromatase inhibitors are already on the market in treating breast cancer, despite the lack of an experimentally solved structure. The structure of 17beta-HSD1, on the other hand, has been solved, but no commercial drugs have emerged from the drug discovery projects reported in the literature. Computer-assisted molecular modelling is an invaluable tool in modern drug design projects. Modelling techniques can be used to generate a model of the target protein and to design novel inhibitors for them even if the target protein structure is unknown. Molecular modelling has applications in predicting the activities of theoretical inhibitors and in finding possible active inhibitors from a compound database. Inhibitor binding at atomic level can also be studied with molecular modelling. To clarify the interactions between the aromatase enzyme and its substrate and inhibitors, we generated a homology model based on a mammalian CYP450 enzyme, rabbit progesterone 21-hydroxylase CYP2C5. The model was carefully validated using molecular dynamics simulations (MDS) with and without the natural substrate ASD. Binding orientation of the inhibitors was based on the hypothesis that the inhibitors coordinate to the heme iron, and were studied using MDS. The inhibitors were dietary phytoestrogens, which have been shown to reduce the risk for breast cancer. To further validate the model, the interactions of a commercial breast cancer drug were studied with MDS and ligand–protein docking. In the case of 17beta-HSD1, a 3D QSAR model was generated on the basis of MDS of an enzyme complex with active inhibitor and ligand–protein docking, employing a compound library synthesised in our laboratory. Furthermore, four pharmacophore hypotheses with and without a bound substrate or an inhibitor were developed and used in screening a commercial database of drug-like compounds. The homology model of aromatase showed stable behaviour in MDS and was capable of explaining most of the results from mutagenesis studies. We were able to identify the active site residues contributing to the inhibitor binding, and explain differences in coordination geometry corresponding to the inhibitory activity. Interactions between the inhibitors and aromatase were in agreement with the mutagenesis studies reported for aromatase. Simulations of 17beta-HSD1 with inhibitors revealed an inhibitor binding mode with hydrogen bond interactions previously not reported, and a hydrophobic pocket capable of accommodating a bulky side chain. Pharmacophore hypothesis generation, followed by virtual screening, was able to identify several compounds that can be used in lead compound generation. The visualisation of the interaction fields from the QSAR model and the pharmacophores provided us with novel ideas for inhibitor development in our drug discovery project.

The Genetic Architecture of Climatic Adaptation of Tropical Cattle

Adaptation of global food systems to climate change is essential to feed the world. Tropical cattle production, a mainstay of profitability for farmers in the developing world, is dominated by heat, lack of water, poor quality feedstuffs, parasites, and tropical diseases. In these systems European cattle suffer significant stock loss, and the cross breeding of taurine x indicine cattle is unpredictable due to the dilution of adaptation to heat and tropical diseases. We explored the genetic architecture of ten traits of tropical cattle production using genome wide association studies of 4,662 animals varying from 0% to 100% indicine. We show that nine of the ten have genetic architectures that include genes of major effect, and in one case, a single location that accounted for more than 71% of the genetic variation. One genetic region in particular had effects on parasite resistance, yearling weight, body condition score, coat colour and penile sheath score. This region, extending 20 Mb on BTA5, appeared to be under genetic selection possibly through maintenance of haplotypes by breeders. We found that the amount of genetic variation and the genetic correlations between traits did not depend upon the degree of indicine content in the animals. Climate change is expected to expand some conditions of the tropics to more temperate environments, which may impact negatively on global livestock health and production. Our results point to several important genes that have large effects on adaptation that could be introduced into more temperate cattle without detrimental effects on productivity.

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension band castrated with or without analgesia: 2. Responses related to stress, health and productivity

Tension banding castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the banders as a humane castration method. Two experiments were conducted, under tropical conditions using Bos indicus bulls comparing tension banding (Band) and surgical (Surgical) castration of weaner (7–10 months old) and mature (22–25 months old) bulls with and without pain management (NSAID (ketoprofen) or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a range of measures; this paper reports on some physiological, morbidity and productivity-related responses to augment the behavioural responses reported in an accompanying paper. Blood samples were taken on the day of castration (day 0) at the time of restraint (0 min) and 30 min (weaners) or 40 min (mature bulls), 2 h, and 7 h; and days 1, 2, 3, 7, 14, 21 and 28 post-castration. Plasmas from day 0 were assayed for cortisol, creatine kinase, total protein and packed cell volume. Plasmas from the other samples were assayed for cortisol and haptoglobin (plus the 0 min sample). Liveweights were recorded approximately weekly to 6 weeks and at 2 and 3 months post-castration. Castration sites were checked at these same times to 2 months post-castration to score the extent of healing and presence of sepsis. Cortisol concentrations (mean ± s.e. nmol/L) were significantly (P < 0.05) higher in the Band (67 ± 4.5) compared with Surgical weaners (42 ± 4.5) at 2 h post-castration, but at 24 h post-castration were greater in the Surgical (43 ± 3.2) compared with the Band weaners (30 ± 3.2). The main effect of ketoprofen was on the cortisol concentrations of the mature Surgical bulls; concentrations were significantly reduced at 40 min (47 ± 7.2 vs. 71 ± 7.2 nmol/L for saline) and 2 h post-castration (24 ± 7.2, vs. 87 ± 7.2 nmol/L for saline). Ketoprofen, however, had no effect on the Band mature bulls, with their cortisol concentrations averaging 54 ± 5.1 nmol/L at 40 min and 92 ± 5.1 nmol/L at 2 h. Cortisol concentrations were also significantly elevated in the Band (83 ± 3.0 nmol/L) compared with Surgical mature bulls (57 ± 3.0 nmol/L) at weeks 2–4 post-castration. The timing of this elevation coincided with significantly elevated haptoglobin concentrations (mg/mL) in the Band bulls (2.97 ± 0.102 for mature bulls and 1.71 ± 0.025 for weaners, vs. 2.10 ± 0.102 and 1.45 ± 0.025 respectively for the Surgical treatment) and evidence of slow wound healing and sepsis in both the weaner (0.81 ± 0.089 not healed at week 4 for Band, 0.13 ± 0.078 for Surgical) and mature bulls (0.81 ± 0.090 at week 4 for Band, 0.38 ± 0.104 for Surgical). Overall, liveweight gains of both age groups were not affected by castration method. The findings of acute pain, chronic inflammation and possibly chronic pain in the mature bulls at least, together with poor wound healing in the Band bulls support behavioural findings reported in the accompanying paper and demonstrate that tension banding produces inferior welfare outcomes for weaner and mature bulls compared with surgical castration.

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension band castrated with or without analgesia: 1. Behavioural responses

Tension-band castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the devices as a humane castration method. Furthermore, retailers encourage delaying castration to exploit the superior growth rates of bulls compared with steers. Two experiments were conducted, under tropical conditions, comparing tension banding and surgical castration of weaner (7–10 months old) and mature (22–25 months old) Bos indicus bulls with and without pain management (ketoprofen or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a wide range of measures; this paper reports on the behavioural responses of the bulls and an accompanying paper reports on other measures. Behavioural data were collected at intervals by direct observation and continuously via data loggers on the hind leg of the bulls to 4 weeks post-castration. Tension-banded bulls performed less movement in the crush/chute than the surgically castrated bulls during the procedures (weaner: 2.63 vs. 5.69, P < 0.001; mature: 1.00 vs. 5.94; P < 0.001 for tension-band and surgical castration, respectively), indicating that tension banding was less painful then surgical castration during conduct. To 1.5 h post-castration, tension-banded bulls performed significantly (all P < 0.05) more active behavioural responses indicative of pain compared with surgical castrates, e.g., percentage time walking forwards (weaner: 15.0% vs. 8.1%; mature: 22.3% vs. 15.1%), walking backwards (weaner: 4.3% vs. 1.4%; mature: 2.4% vs. 0.5%), numbers of tail movements (weaner: 21.9 vs. 1.4; mature: 51.5 vs. 39.4) and leg movements (weaner: 12.9 vs. 0.9; mature: 8.5 vs. 1.5), respectively. In contrast, surgically castrated bulls performed more immobile behaviours compared with tension-banded bulls (e.g., standing in mature bulls was 56.6% vs. 34.4%, respectively, P = 0.002). Ketoprofen administration appeared effective in moderating pain-related behaviours in the mature bulls from 1.5 to 3 h, e.g., reducing abnormal standing (0.0% vs. 7.7%, P = 0.009) and increasing feeding (12.7% vs. 0.0%, P = 0.048) in NSAID- and saline-treated bulls, respectively. There were few behavioural differences subsequent to 24 h post-castration, but some limited evidence of chronic pain (3–4 weeks post-castration) with both methods. Interpretation, however, was difficult from behaviours alone. Thus, tension banding is less painful than surgical castration during conduct of the procedures and pain-related behavioural responses differ with castration method (active restlessness in response to tension banding and minimisation of movement in response to surgical castration). Ketoprofen administered immediately prior to castration was somewhat effective in reducing pain, particularly in the mature bulls.

Effect of rabbit antiserum to ovine LH on reproductive organs in male hamsters and guinea-pigs

Administration of rabbit antiserum to ovine luteinizing hormone to immature hamsters and guinea-pigs resulted in a significant decrease in the weights of testes, seminal vesicle and ventral prostate. The author wishes to thank Prof. N.R. Moudgal for his interest and Family Planning Foundation for financial assistance.

Individuals on the Move : Body Condition Dependent Dispersal and Quasi-Local Competition in Metapopulations

Individual movement is very versatile and inevitable in ecology. In this thesis, I investigate two kinds of movement body condition dependent dispersal and small-range foraging movements resulting in quasi-local competition and their causes and consequences on the individual, population and metapopulation level. Body condition dependent dispersal is a widely evident but barely understood phenomenon. In nature, diverse relationships between body condition and dispersal are observed. I develop the first models that study the evolution of dispersal strategies that depend on individual body condition. In a patchy environment where patches differ in environmental conditions, individuals born in rich (e.g. nutritious) patches are on average stronger than their conspecifics that are born in poorer patches. Body condition (strength) determines competitive ability such that stronger individuals win competition with higher probability than weak individuals. Individuals compete for patches such that kin competition selects for dispersal. I determine the evolutionarily stable strategy (ESS) for different ecological scenarios. My models offer explanations for both dispersal of strong individuals and dispersal of weak individuals. Moreover, I find that within-family dispersal behaviour is not always reflected on the population level. This supports the fact that no consistent pattern is detected in data on body condition dependent dispersal. It also encourages the refining of empirical investigations. Quasi-local competition defines interactions between adjacent populations where one population negatively affects the growth of the other population. I model a metapopulation in a homogeneous environment where adults of different subpopulations compete for resources by spending part of their foraging time in the neighbouring patches, while their juveniles only feed on the resource in their natal patch. I show that spatial patterns (different population densities in the patches) are stable only if one age class depletes the resource very much but mainly the other age group depends on it.

Homoclinic Splitting without Trees

We study a Hamiltonian describing a pendulum coupled with several anisochronous oscillators, giving a simple construction of unstable KAM tori and their stable and unstable manifolds for analytic perturbations. When the coupling takes place through an even trigonometric polynomial in the angle variables, we extend analytically the solutions of the equations of motion, order by order in the perturbation parameter, to a large neighbourhood of the real line representing time. Subsequently, we devise an asymptotic expansion for the splitting (matrix) associated with a homoclinic point. This expansion consists of contributions that are manifestly exponentially small in the limit of vanishing gravity, by a shift-of-countour argument. Hence, we infer a similar upper bound for the splitting itself. In particular, the derivation of the result does not call for a tree expansion with explicit cancellation mechanisms.

Effect of electric arc discharge on hypersonic blunt body drag

Experimental results on the effect of energy deposition using an electric arc discharge, upstream of a 60° half angle blunt cone configuration in a hypersonic flow is reported.Investigations involving drag measurements and high speed schlieren flow visualization have been carried out in hypersonic shock tunnel using air and argon as the test gases; and an unsteady drag reduction of about 50% (maximum reduction) has been observed in the energy deposition experiments done in argon environment. These studies also show that the effect of discharge on the flow field is more pronounced in argon environment as compared to air, which confirms that thermal effects are mainly responsible for flow alteration in presence of the discharge.

Measurement of aerodynamic forces for missile shaped body in hypersonic shock tunnel using 6-component accelerometer based balance system

This paper reports the basic design of a new six component force balance system using miniature piezoelectric accelerometers to measure all aerodynamic forces and moments for a test model in hypersonic shock tunnel (HST2). Since the flow duration in a hypersonic shock tunnel is of the order of $1$ ms, the balance system [1] uses fast response accelerometers (PCB Piezotronics; frequency range of 1-10 kHz) for obtaining the aerodynamic data. The alance system has been used to measure the basic aerodynamic forces and moments on a missile shaped body at Mach $8$ in the IISc hypersonic shock tunnel. The experimentally measured values match well with theoretical predictions.