Rapamycin induces transactivation of the EGFR and increases cell survival.

The mammalian target of rapamycin (mTOR) signaling network regulates cell growth, proliferation and cell survival. Deregulated activation of this pathway is a common event in diverse human diseases such as cancers, cardiac hypertrophy, vascular restenosis and nephrotic hypertrophy. Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Thus, we studied the mechanism(s) by which cells may confer resistance to rapamycin. Our data show that in a variety of cell types the mTOR inhibitor rapamycin activates extracellularly regulated kinases (Erk1/2) signaling. Rapamycin-mediated activation of the Erk1/2 signaling requires (a) the epidermal growth factor receptor (EGFR), (b) its tyrosine kinase activity and (c) intact autophosphorylation sites on the receptor. Rapamycin treatment increases tyrosine phosphorylation of EGFR without the addition of growth factor and this transactivation of receptor involves activation of c-Src. We also show that rapamycin treatment triggers activation of cell survival signaling pathway by activating the prosurvival kinases Erk1/2 and p90RSK. These studies provide a novel paradigm by which cells escape the apoptotic actions of rapamycin and its derivatives that inhibit the mTOR pathway

Non-Gaussianity from Lifshitz Scalar

A Lifshitz scalar with the dynamical critical exponent z = 3 obtains scale-invariant, super-horizon field fluctuations without the need of an inflationary era. Since this mechanism is due to the special scaling of the Lifshitz scalar and persists in the presence of unsuppressed self-couplings, the resulting fluctuation spectrum can deviate from a Gaussian distribution. We study the non-Gaussian nature of the Lifshitz scalar's intrinsic field fluctuations, and show that primordial curvature perturbations sourced from such field fluctuations can have large non-Gaussianity of order f_NL = O(100), which will be detected by upcoming CMB observations. We compute the bispectrum and trispectrum of the fluctuations, and discuss their configurations in momentum space. In particular, the bispectrum is found to take various shapes, including the local, equilateral, and orthogonal shapes. Intriguingly, all integrals in the in-in formalism can be performed analytically.Comment: 17 pages, 15 figures, v2: published in JCA

Optimization of cool roof and night ventilation in office buildings: A case study in Xiamen, China

Increasing roof albedo (using a “cool” roof) and night ventilation are passive cooling technologies that can reduce the cooling loads in buildings, but existing studies have not comprehensively explored the potential benefits of integrating these two technologies. This study combines an experiment in the summer and transition seasons with an annual simulation so as to evaluate the thermal performance, energy savings and thermal comfort improvement that could be obtained by coupling a cool roof with night ventilation. A holistic approach integrating sensitivity analysis and multi-objective optimization is developed to explore key design parameters (roof albedo, night ventilation air change rate, roof insulation level and internal thermal mass level) and optimal design options for the combined application of the cool roof and night ventilation. The proposed approach is validated and demonstrated through studies on a six-storey office building in Xiamen, a cooling-dominated city in southeast China. Simulations show that combining a cool roof with night ventilation can significantly decrease the annual cooling energy consumption by 27% compared to using a black roof without night ventilation and by 13% compared to using a cool roof without night ventilation. Roof albedo is the most influential parameter for both building energy performance and indoor thermal comfort. Optimal use of the cool roof and night ventilation can reduce the annual cooling energy use by 28% during occupied hours when air-conditioners are on and reduce the uncomfortable time slightly during occupied hours when air-conditioners are off

A methodology to facilitate knowledge sharing in the new product development process

This paper describes the findings of an exploratory case study to investigate knowledge sharing problems in the new product development (NPD) process of a multi-national manufacturing company, and classifies the problems into three categories, i.e. (a) the lack of an explicit definition and prioritization of information about the knowledge used in the NPD process, (b) the challenges raised by, and lack of tools to support, knowledge sharing in a multilingual, multidisciplinary environment, and (c) the dissemination of information about the task and process knowledge to process users. An ontology-based methodology has been proposed, and a pilot study has been carried out to solve these problems. The pilot study includes the selection of suitable candidate tasks (or sub-processes) for the study, the elicitation of information about the selected task knowledge, the development of task knowledge ontology, and a mechanism to visualize and disseminate the ontology to process users. Early implementation and tests have shown that the proposed methodology may be used to facilitate knowledge sharing in the new product development process. The project was sponsored by a leading heating system manufacturer and further tests will be carried out with real industrial problems

Trispectrum from Ghost Inflation

Ghost inflation predicts almost scale-invariant primordial cosmological perturbations with relatively large non-Gaussianity. The bispectrum is known to have a large contribution at the wavenumbers forming an equilateral triangle and the corresponding nonlinear parameter $f_{NL}^{equil}$ is typically of order $O(10^2)$. In this paper we calculate trispectrum from ghost inflation and show that the corresponding nonlinear parameter $\tau_{NL}$ is typically of order $O(10^4)$. We investigate the shape dependence of the trispectrum and see that it has some features different from DBI inflation. Therefore, our result may be useful as a template to distinguish ghost inflation from other models of inflation by future experiments.Comment: 25 pages, 10 figure

Influence of heavy modes on perturbations in multiple field inflation

We investigate linear cosmological perturbations in multiple field inflationary models where some of the directions are light while others are heavy (with respect to the Hubble parameter). By integrating out the massive degrees of freedom, we determine the multi-dimensional effective theory for the light degrees of freedom and give explicitly the propagation matrix that replaces the effective sound speed of the one-dimensional case. We then examine in detail the consequences of a sudden turn along the inflationary trajectory, in particular the possible breakdown of the low energy effective theory in case the heavy modes are excited. Resorting to a new basis in field space, instead of the usual adiabatic/entropic basis, we study the evolution of the perturbations during the turn. In particular, we compute the power spectrum and compare with the result obtained from the low energy effective theory.Comment: 24 pages, 13 figures; v2 substantial changes in sec.V; v3 matching the published version on JCA

Effects of natural soiling and weathering on cool roof energy savings for dormitory buildings in Chinese cities with hot summers

Roofs with high-reflectance (solar reflectance) coating, commonly known as cool roofs, can stay cool in the sun, thereby reducing building energy consumption and mitigating the urban heat island. However, chemical-physical degradation and biological growth can decrease their solar reflectance and the ability to save energy. In this study, the solar spectral reflectance of 12 different roofing products with an initial albedo of 0.56–0.90 was measured before exposure and once every three months over 32 months. Specimens were exposed on the roofs of dormitory buildings in Xiamen and Chengdu, each major urban areas with hot summers. The albedos of high and medium-lightness coatings stabilized in the ranges 0.45–0.62 and 0.36–0.59 in both cities, respectively. This study yielded albedo loss exceeded those reported in the latest Chinese standard by 0.08–0.15. Finally, DesignBuilder (EnergyPlus) simulations estimate that a new cool roof with albedo 0.78 on a six-story dormitory building will yield annual site energy savings (heating and cooling) for the top floor, which are 8.01 kWh/m2 (24.2%) and 9.12 kWh/m2 (26.3%) per unit floor area in Xiamen and Chengdu, respectively; while an aged cool roof with albedo 0.45 and 0.56 will yield the annual savings by 5.12 kWh/m2 (15.4%) and 2.47 kWh/m2 (10.5%) in these two cities