The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

Heat transfer analysis of viscous incompressible fluid by combined natural convection and radiation in an open cavity

The effect of radiation on natural convection of Newtonian fluid contained in an open cavity is investigated in this study. The governing partial differential equations are solved numerically using the Alternate Direct Implicit method together with the Successive Over Relaxation method. The study is focused on studying the flow pattern and the convective and radiative heat transfer rates are studied for different values of radiation parameters namely, the optical thickness of the fluid, scattering albedo, and the Planck number. It was found that in the optically thin limit, an increase in the optical thickness of the fluid raises the temperature and radiation heat transfer of the fluid. However, a further increase in the optical thickness decreases the radiative heat transfer rate due to increase in the energy level of the fluid, which ultimately reduces the total heat transfer rate within the fluid.

Diagnostics and two-dimensional simulation of low-frequency inductively coupled plasmas with neutral gas heating and electron heat fluxes

This article presents the results on the diagnostics and numerical modeling of low-frequency (∼460 KHz) inductively coupled plasmas generated in a cylindrical metal chamber by an external flat spiral coil. Experimental data on the electron number densities and temperatures, electron energy distribution functions, and optical emission intensities of the abundant plasma species in low/intermediate pressure argon discharges are included. The spatial profiles of the plasma density, electron temperature, and excited argon species are computed, for different rf powers and working gas pressures, using the two-dimensional fluid approach. The model allows one to achieve a reasonable agreement between the computed and experimental data. The effect of the neutral gas temperature on the plasma parameters is also investigated. It is shown that neutral gas heating (at rf powers≥0.55kW) is one of the key factors that control the electron number density and temperature. The dependence of the average rf power loss, per electron-ion pair created, on the working gas pressure shows that the electron heat flux to the walls appears to be a critical factor in the total power loss in the discharge.

Electron-conduction mechanism and specific heat above transition temperature in LaFeAsO and BaFe2As2 superconductors

The ionization energy theory is used to calculate the evolution of the resistivity and specific heat curves with respect to different doping elements in the recently discovered superconducting pnictide materials. Electron-conduction mechanism in the pnictides above the structural transition temperature is explained unambiguously, which is also consistent with other strongly correlated materials, such as cuprates, manganites, titanates and magnetic semiconductors.

CFD simulations of flow and heat transfer through the porous interface of a metal foam heat exchanger

This paper offers numerical modelling of a waste heat recovery system. A thin layer of metal foam is attached to a cold plate to absorb heat from hot gases leaving the system. The heat transferred from the exhaust gas is then transferred to a cold liquid flowing in a secondary loop. Two different foam PPI (Pores Per Inch) values are examined over a range of fluid velocities. Numerical results are then compared to both experimental data and theoretical results available in the literature. Challenges in getting the simulation results to match those of the experiments are addressed and discussed in detail. In particular, interface boundary conditions specified between a porous layer and a fluid layer are investigated. While physically one expects much lower fluid velocity in the pores compared to that of free flow, capturing this sharp gradient at the interface can add to the difficulties of numerical simulation. The existing models in the literature are modified by considering the pressure gradient inside and outside the foam. Comparisons against the numerical modelling are presented. Finally, based on experimentally-validated numerical results, thermo-hydraulic performance of foam heat exchangers as waste heat recovery units is discussed with the main goal of reducing the excess pressure drop and maximising the amount of heat that can be recovered from the hot gas stream.

A review on solar assisted heat pump systems in Singapore

A solar assisted heat pump is used for different applications, such as, water heating, drying and air conditioning. The unglazed evaporator-collector enables to absorb both solar energy and ambient energy due to low operating temperature. Three different systems are described: solar assisted heat pump system for hot water using an unglazed evaporator collector; solar assisted heat pump for hot water and drying, where evaporator collector and air collector are used; an integrated solar heat pump system making use of solar and ambient energy, and air-con waste heat. Unlike conventional collector, evaporator collector was found to have higher efficiency, 80% to 90%, and the coefficient of performance attained a value as high as 8.0. The integrated system leads to a reduction of global warming, as it uses solar energy, ambient energy and air-con waste heat.

Desalination with a solar-assisted heat pump : an economic optimization

The solar-assisted heat pump (SAHP) desalination, based on the Rankin cycle, operates in low temperature and utilizes both solar and ambient energy. An experimental SAHP desalination system has been constructed at the National University of Singapore, Singapore. The system consisted of two main sections: an SAHP and a water distillation section. Experiments were carried out under the different meteorological condition of Singapore and results showed that the system had a performance ratio close to 1.3. The heat pump has a coefficient of performance of about 8, with solar collector efficiencies of 80% and 60% for evaporator and liquid collectors, respectively. Economic analysis showed that at a production rate of 900 L/day and an evaporator collector area of around 70m2 will have a payback period of about 3.5 years.

Desalination of seawater using solar, ambient energy and waste heat from air conditioning

Desalination is considered one of the most suitable areas for the utilization of solar energy, as there are many places in the world where abundant supply of solar energy is available and also there is a great demand for fresh water. An integrated solar heat pump desalination system has been developed at the National University of Singapore. The system also offers the opportunity of water heating and drying utilizing solar, ambient energy and waste heat from air conditioning system, which is conventionally dumped into the environment causing global warming. Desalination is carried out by making use of a single effect of Multi-Effect Distillation (MED) system. Within the desalination chamber, both fl ashing and evaporation of saline water take place. The maximum Coefficient of Performance (COP) of the heat pump system was around 5.8. In the integrated system, the maximum fresh water production rate was 9.6 l h−1 and a Performance Ratio (PR) of 1.2. For only desalination, the system has the potential to produce a maximum of 30 l h−1 of fresh water.

Water heating and dehumidification with heat pump utilizing solar, ambient and waste heat

The low temperature operation of a heat pump makes it an excellent match for the use of solar energy. At the National University of Singapore, a solar assisted heat pump system has been designed, fabricated and installed to provide water heating and drying. The system also utilizes the air con waste heat, which would normally be released to atmosphere adding to global warming. Experimental results show that the twophase unglazed solar evaporator-collector, instead of losing energy to the ambient, gained a significant amount due to low operating temperature of the collector. As a result, the collector efficiency attains a value greater than 1, when conventional collector equations are used. With this evaporator-collector, the system can be operated even in the absence of solar irradiation. The waste heat was collected from an air-con system, which maintained a room at 20-22 oC. In the condenser side, water at 60 oC was produced at a rate of 3 liter/minute and the drying capacity was 2.2kg/hour. Maximum COP of the system was found to be about 5.5.

Mathematical modelling and experimental validation of solar assisted heat pump system

Singapore is located at the equator, with abundant supply of solar radiation, relatively high ambient temperature and relative humidity throughout the year. The meteorological conditions of Singapore are favourable for efficient operation of solar energy based systems. Solar assisted heat pump systems are built on the roof-top of National University of Singapore’s Faculty of Engineering. The objectives of this study include the design and performance evaluation of a solar assisted heat-pump system for water desalination, water heating and drying of clothes. Using MATLAB programming language, a 2-dimensional simulation model has been developed to conduct parametric studies on the system. The system shows good prospect to be implemented in both industrial and residential applications and would give new opportunities in replacing conventional energy sources with green renewable energy.

Integrating the impact of climate into event based failure models for water pipes

This paper presents an event-based failure model to predict the number of failures that occur in water distribution assets. Often, such models have been based on analysis of historical failure data combined with pipe characteristics and environmental conditions. In this paper weather data have been added to the model to take into account the commonly observed seasonal variation of the failure rate. The theoretical basis of existing logistic regression models is briefly described in this paper, along with the refinements made to the model for inclusion of seasonal variation of weather. The performance of these refinements is tested using data from two Australian water authorities.

Seasonal factors influencing the failure of buried water reticulation pipes

While the use of environmental factors in the analysis and prediction of failures of buried reticulation pipes in cold environments has been the focus of extensive work, the same cannot be said for failures occurring on pipes in other (non-freezing) environments. A novel analysis of pipe failures in such an environment is the subject of this paper. An exploratory statistical analysis was undertaken, identifying a peak in failure rates during mid to late summer. This peak was found to correspond to a peak in the rate of circumferential failures, whilst the rate of longitudinal failures remained constant. Investigation into the effect of climate on failure rates revealed that the peak in failure rates occurs due to differential soil movement as the result of shrinkage in expansive soils.

Development of a Solar Assisted Heat Pump Desalination System

In view of the growing global demand for energy and concern expressed for environmental degradation, a clean and "free" energy source, such as solar energy, has been receiving greater attention in recent years for various applications using different techniques. The Direct Expansion Solar Assisted Heat Pump (DX-SAHP) principle is one of the most promising techniques as it makes use of both solar and ambient energy. As the system has capability to function at low temperatures, it has the potential to operate at night in the tropics. The system utilizes multi-effect distillation (MED) principle for the conversion of seawater to fresh water. An experimental setup of the DX-SAHP desalination system has been built at the Department of Mechanical Engineering, National University of Singapore (NUS). This system uses two types of flat-plate solar collectors. One is called evaporator-collector, where no glazing is used, and the efficiency varies between 80 and 90%. The other type of collector is single-glazed, where the maximum efficiency is about 60%, and it is used for feed water heating. For the heat pump cycle, refrigerant R134a is used. The present study provides a comprehensive analyses and performance evaluation of this system under different operating and meteorological conditions of Singapore. The Coefficient of Performance (COP) of the heat pump system reached a maximum value of 10. For a single effect of desalination, the system shows a Performance Ratio (PR) of around 1.3.

Heat-related morbidity in Brisbane, Australia : spatial variation and area-level predictors

Background: Extreme heat is a leading weather-related cause of illness and death in many locations across the globe, including subtropical Australia. The possibility of increasingly frequent and severe heat waves warrants continued efforts to reduce this health burden, which could be accomplished by targeting intervention measures toward the most vulnerable communities. Objectives: We sought to quantify spatial variability in heat-related morbidity in Brisbane, Australia, to highlight regions of the city with the greatest risk. We also aimed to find area-level social and environmental determinants of high risk within Brisbane. Methods: We used a series of hierarchical Bayesian models to examine city-wide and intracity associations between temperature and morbidity using a 2007–2011 time series of geographically referenced hospital admissions data. The models accounted for long-term time trends, seasonality, and day of week and holiday effects. Results: On average, a 10°C increase in daily maximum temperature during the summer was associated with a 7.2% increase in hospital admissions (95% CI: 4.7, 9.8%) on the following day. Positive statistically significant relationships between admissions and temperature were found for 16 of the city’s 158 areas; negative relationships were found for 5 areas. High-risk areas were associated with a lack of high income earners and higher population density. Conclusions: Geographically targeted public health strategies for extreme heat may be effective in Brisbane, because morbidity risk was found to be spatially variable. Emergency responders, health officials, and city planners could focus on short- and long-term intervention measures that reach communities in the city with lower incomes and higher population densities, including reduction of urban heat island effects.

Heat strain evaluation of overt and covert body armour in a hot and humid environment

The aim of this study was to elucidate the thermophysiological effects of wearing lightweight non-military overt and covert personal body armour (PBA) in a hot and humid environment. Eight healthy males walked on a treadmill for 120 min at 22% of their heart rate reserve in a climate chamber simulating 31 °C (60%RH) wearing either no armour (control), overt or covert PBA in addition to a security guard uniform, in a randomised controlled crossover design. No significant difference between conditions at the end of each trial was observed in core temperature, heart rate or skin temperature (P > 0.05). Covert PBA produced a significantly greater amount of body mass change (−1.81 ± 0.44%) compared to control (−1.07 ± 0.38%, P = 0.009) and overt conditions (−1.27 ± 0.44%, P = 0.025). Although a greater change in body mass was observed after the covert PBA trial; based on the physiological outcome measures recorded, the heat strain encountered while wearing lightweight, non-military overt or covert PBA was negligible compared to no PBA. Practitioner summary The wearing of bullet proof vests or body armour is a requirement of personnel engaged in a wide range of occupations including police, security, customs and even journalists in theatres of war. This randomised controlled crossover study is the first to examine the thermophysiological effects of wearing lightweight non-military overt and covert personal body armour (PBA) in a hot and humid environment. We conclude that the heat strain encountered while wearing both overt and covert lightweight, non-military PBA was negligible compared to no PBA.