Environmental chemical exposures and breast cancer

As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies

Molecular biology II: protein function

DNA may be viewed as the blueprint for the body, with mRNA/protein the component parts made from this blueprint. However, it is only when proteins are allowed to interact with each other and their surroundings that true biological complexity is achieved. Thus, while it is informative to study transcriptional control and mRNA transcript levels, it is equally important to assess the impact of the encoded proteins on the total cellular environment. For example, expression of a ligand-activated receptor such as the epidermal growth factor (EGF) receptor is of no biological consequence if no EGF is present in the system. It is thus important to be able to study protein interactions and modification, enabling a comprehensive understanding of the biological mechanisms that underlie any particular phenotype. This article will outline the basic technologies to both visualize protein localization and interaction between co-localized proteins. In addition, the manipulation of protein levels, both in vitro and in vivo, will be described, as this provides an important tool for the further examination of protein functionality within biological system

Pressures measured in flight on the aft fuselage and external nozzle of a twin-jet fighter

Fuselage, boundary layer, and nozzle pressures were measured in flight for a twin jet fighter over a Mach number range from 0.60 to 2.00 at test altitudes of 6100, 10,700, and 13,700 meters for angles of attack ranging from 0 deg to 7 deg. Test data were analyzed to find the effects of the propulsion system geometry. The flight variables, and flow interference. The aft fuselage flow field was complex and showed the influence of the vertical tail, nacelle contour, and the wing. Changes in the boattail angle of either engine affected upper fuselage and lower fuselage pressure coefficients upstream of the nozzle. Boundary layer profiles at the forward and aft locations on the upper nacelles were relatively insensitive to Mach number and altitude. Boundary layer thickness decreased at both stations as angle of attack increased above 4 deg. Nozzle pressure coefficient was influenced by the vertical tail, horizontal tail boom, and nozzle interfairing; the last two tended to separate flow over the top of the nozzle from flow over the bottom of the nozzle. The left nozzle axial force coefficient was most affected by Mach number and left nozzle boattail angle. At Mach 0.90, the nozzle axial force coefficient was 0.0013

Results of an aqueous source term model for a radiological risk assessment of the Drigg LLW Site, U.K.

A radionuclide source term model has been developed which simulates the biogeochemical evolution of the Drigg low level waste (LLW) disposal site. The DRINK (DRIgg Near field Kinetic) model provides data regarding radionuclide concentrations in groundwater over a period of 100,000 years, which are used as input to assessment calculations for a groundwater pathway. The DRINK model also provides input to human intrusion and gaseous assessment calculations through simulation of the solid radionuclide inventory. These calculations are being used to support the Drigg post closure safety case. The DRINK model considers the coupled interaction of the effects of fluid flow, microbiology, corrosion, chemical reaction, sorption and radioactive decay. It represents the first direct use of a mechanistic reaction-transport model in risk assessment calculations

Studying the Solar system with the International Pulsar Timing Array

Pulsar-timing analyses are sensitive to errors in the Solar-system ephemerides (SSEs) that timing models utilize to estimate the location of the Solar-system barycentre, the quasi-inertial reference frame to which all recorded pulse times-of-arrival are referred. Any error in the SSE will affect all pulsars, therefore pulsar timing arrays (PTAs) are a suitable tool to search for such errors and impose independent constraints on relevant physical parameters. We employ the first data release of the International Pulsar Timing Array to constrain the masses of the planet–moons systems and to search for possible unmodelled objects (UMOs) in the Solar system. We employ 10 SSEs from two independent research groups, derive and compare mass constraints of planetary systems, and derive the first PTA mass constraints on asteroid-belt objects. Constraints on planetary-system masses have been improved by factors of up to 20 from the previous relevant study using the same assumptions, with the mass of the Jovian system measured at 9.5479189(3) × 10^(−4) M⊙. The mass of the dwarf planet Ceres is measured at 4.7(4) × 10^(−10) M⊙. We also present the first sensitivity curves using real data that place generic limits on the masses of UMOs, which can also be used as upper limits on the mass of putative exotic objects. For example, upper limits on dark-matter clumps are comparable to published limits using independent methods. While the constraints on planetary masses derived with all employed SSEs are consistent, we note and discuss differences in the associated timing residuals and UMO sensitivity curves

Bounded analysis of constrained dynamical systems: a case study in nuclear arms control

We introduce a simple dynamical system that describes key features of a bilateral nuclear arms control regime. The evolution of each party's beliefs and declarations under the regime are represented, and the e ects of inspection processes are captured. Bounded analysis of this model allows us to explore { within a nite horizon { the consequences of changes to the rules of the arms control process and to the strategies of each party, bounded scope invariants for variables of interest, and dynamics for initial states containing strict uncertainty. Together these would potentially enable a decision support system to consider cases of interest irrespective of unknowns. We realize such abilities by building a Python package that draws on the capabilities of a Satis ability Modulo Theory (SMT) solver to explore particular scenarios and to optimize measures of interest { such as the belief of one nation in the statements made by another, or the timing of an unscheduled inspection such that it has maximum value. We show that these capabilities can in principle support the design or assessment of future bilateral arms control instruments by applying them to a set of representative and relevant test scenarios with realistic nite horizons

Hyperacute Corticosteroid Treatment of Optic Neuritis at the Onset of Pain May Prevent Visual Loss: A Case Series

Aim. To show that high-dose corticosteroids may prevent visual loss in patients with optic neuritis (ON) treated at the prodromal, hyperacute, phase of retrobulbar pain. Method. Prospective case series: patients were recruited with a history of ON associated with pain. The patients were advised to report immediately to the investigators should the pain recur in either eye. Where possible, orbital magnetic resonance imaging (MRI) was performed to confirm a recurrence of ON and treatment with high-dose corticosteroids was commenced. Visual function and the patient's subjective account were monitored. Results. Eight patients (including cases of MS, CRION and NMO) presented in the hyperacute phase. MRI confirmed optic nerve inflammation in 5/5. Treatment was commenced immediately, and, in all cases, no visual loss ensued. Conclusion. MRI can be used to confirm acute optic neuritis prior to visual loss in the hyperacute phase. We suggest that treatment with high-dose corticosteroids may abort the attack and prevent loss of vision in patients with ON who are treated at the onset of pain. This has potential implications for the management of acute ON and also for our understanding of the pathogenesis and potential therapeutic targets in the neuroinflammatory conditions associated with ON