Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. Methods Using a case–control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method. Results Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype. Conclusions We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours

Estimation of badger abundance using faecal DNA typing

1.Wildlife management and conservation programmes often require accurate information on population density, but this can be difficult to obtain, particularly when the species in question is nocturnal or cryptic. Badger populations in Britain are of intense management interest because they are a wildlife reservoir host of bovine tuberculosis (TB). Attempts to manage this infection in badgers, whether by population control or vaccination, require reliable methods of estimating population size. In addition, such estimates are also required to support research into badger ecology and TB epidemiology. Currently, the most accurate estimates of local badger population size are obtained from labour-intensive and time-consuming mark–recapture studies. 2. In recent years, DNA has been successfully extracted from the faeces of certain mammals, and used to generate a genetic profile of the defecating individual. Here we report on an application of this technology to estimate badger abundance.3.Faecal samples were collected on 10 consecutive days from every freshly deposited dropping at latrine sites close to occupied setts in three badger social groups. Badger DNA was extracted from 89% of samples, and 20 different individuals were reliably identified. The genotypes derived from the faecal samples were compared with those obtained from blood or samples from badgers live trapped at the same setts.4.The faecal genotypes from badgers with known trap histories revealed that latrines were used equally by males and females, and by badgers ranging in age from cubs(< 1 year old) to 9 years old. Individual badgers used the latrines on between one and six different nights. Rarefaction analysis produced abundance estimates that closely matched those obtained from live trapping. 5.Synthesis and applications. Systematic sampling and genetic typing of fresh faeces from badger latrines can provide data that can be used to estimate abundance accurately.This approach requires considerably less human resources than repeated live trapping and mark–recapture. The technique may be valuable for future badger research and management in relation to bovine TB, where accurate estimates of abundance at a local scale are required

A developmental cascade model for early adolescent onset substance use: The role of early childhood stress

Contains fulltext : 199688.pdf (publisher's version ) (Open Access)Backgrounds and aims: Despite the link between stress and addictive behavior in adulthood, little is known about how early life stress in families predicts the early emergence of substance use in adolescence. This study tested a developmental cascade model, proposing that early stressful life events and negative parent-child interaction covary, and both disrupt the refinement of inhibitory control, which evolves into problem behavior in middle/late childhood and subsequent substance use exploration in early adolescence. Methods: Data came from the Early Steps Multisite study, a community sample of at-risk families in the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon), and Charlottesville (Virginia) with children aged 2 at the start of the study and 14 at the last measurement (N = 364). Structural equation modeling was used to test the proposed model. Results: Early stressful life events and negative parent-child interaction assessed at ages 2 to 5 were negatively related to inhibitory control at ages 7 and 8. Low levels of inhibitory control were prognostic of childhood problem behavior at ages 9 and 10. Finally, late childhood problem behavior was associated with substance use at age 14. Parental drug use was directly related to substance use at age 14. Conclusions: Early life stress may disrupt child inhibitory control, which can cascade into behavioral and peer problem behavior in childhood and, in turn, heighten the risk for early adolescent substance use.9 p

A Shack-Hartmann wavefront sensor projected on to the sky with reduced focal anisoplanatism

A method for producing a laser guide star wavefront sensor for adaptive optics with reduced focal anisoplanatism is presented. A theoretical analysis and numerical simulations have been carried out and the results are presented. The technique, named Sky-Projected Laser Array Shack–Hartmann (SPLASH), is shown to suffer considerably less from focal anisoplanatism than a conventional laser guide star system. The method is potentially suitable for large telescope apertures (8 m), and possibly for extremely large telescopes

Scaffolding layered control architectures through constraint closure : insights into brain evolution and development

The functional organization of the mammalian brain can be considered to form a layered control architecture, but how this complex system has emerged through evolution and is constructed during development remains a puzzle. Here we consider brain organization through the framework of constraint closure, viewed as a general characteristic of living systems, that they are composed of multiple sub-systems that constrain each other at different timescales. We do so by developing a new formalism for constraint closure, inspired by a previous model showing how within-lifetime dynamics can constrain between-lifetime dynamics, and we demonstrate how this interaction can be generalized to multi-layered systems. Through this model, we consider brain organization in the context of two major examples of constraint closure—physiological regulation and visual orienting. Our analysis draws attention to the capacity of layered brain architectures to scaffold themselves across multiple timescales, including the ability of cortical processes to constrain the evolution of sub-cortical processes, and of the latter to constrain the space in which cortical systems self-organize and refine themselves

Understanding brain functional architecture through robotics

Robotics is increasingly seen as a useful test bed for computational models of the brain functional architecture underlying animal behavior. We provide an overview of past and current work, focusing on probabilistic and dynamical models, including approaches premised on the free energy principle, situating this endeavor in relation to evidence that the brain constitutes a layered control system. We argue that future neurorobotic models should integrate multiple neurobiological constraints and be hybrid in nature

Increasing the circle of light on professional development: the case of the next generation of science exemplar facilitator learning

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Stereo-SCIDAR: optical turbulence profiling with high sensitivity using a modified SCIDAR instrument

The next generation of adaptive optics systems will require tomographic reconstruction techniques to map the optical refractive index fluctuations, generated by the atmospheric turbulence, along the line of sight to the astronomical target. These systems can be enhanced with data from an external atmospheric profiler. This is important for Extremely Large Telescope scale tomography. Here we propose a new instrument which utilizes the generalized Scintillation Detection And Ranging (SCIDAR) technique to allow high sensitivity vertical profiles of the atmospheric optical turbulence and wind velocity profile above astronomical observatories. The new approach, which we refer to as ‘stereo-SCIDAR’, uses a stereoscopic system with the scintillation pattern from each star of a double-star target incident on a separate detector. Separating the pupil images for each star has several advantages including increased magnitude difference tolerance for the target stars; negating the need for re-calibration due to the normalization errors usually associated with SCIDAR; an increase of at least a factor of 2 in the signal-to-noise ratio of the cross-covariance function and hence the profile for equal magnitude target stars and up to a factor of 16 improvement for targets of 3 mag difference and easier real-time reconstruction of the wind-velocity profile. Theoretical response functions are calculated for the instrument, and the performance is investigated using a Monte Carlo simulation. The technique is demonstrated using data recorded at the 2.5-m Nordic Optical Telescope and the 1.0-m Jacobus Kapteyn Telescope, both on La Palma

Electronic Clocks for Timing Irrigation Advance

One of the basic parameters affecting surface irrigation performance is the rate of water advance in a furrow, basin or border. Rate-of-advance varies with the soil infiltration rate which, in turn, varies both within a given field and with time throughout the irrigation season. Mathematical models can predict rate-of-advance; however, they depend upon a knowledge of the actual field soil infiltration rate which is difficult to accurately measure or predict. Thus, rate-of-advance field data are needed to supplement model predictions and to calibrate the models. Recently, many rate-of-advance studies have been conducted to determine the effect of surge flow on the soil's intake rate and the water advance rate. Water applied intermittently advances to the end of the furrow in less application time for most soils than when applied in continuous streams