Overcoming the Circular Problem for \gamma-ray Bursts in Cosmological Global Fitting Analysis

Due to the lack of low redshift long Gamma-Ray Bursts (GRBs), the circular problem has been a severe obstacle for using GRBs as cosmological candles. In this paper, we present a new method to deal with such a problem in MCMC global fitting analysis. Assuming that a certain type of correlations between different observables exists in a subsample of GRBs, for the parameters involved in the correlation relation, we treat them as free parameters and determine them simultaneously with cosmological parameters through MCMC analysis on GRB data together with other observational data. Then the circular problem is naturally eliminated in this procedure. We take the Ghirlanda relation as an example while keeping in mind the debate about its physical validity. Together with SNe Ia, WMAP and SDSS data, we include 27 GRBs with the reported Ghirlanda relation in our study, and perform MCMC global fitting. We consider the $\Lambda$CDM model and dynamical dark energy models. In each case, in addition to the constraints on the relevant cosmological parameters, we obtain the best fit values as well as the distributions of the correlation parameters $A$ and $C$. We find that the observational data sets other than GRBs can affect $A$ and $C$ considerably through their degeneracies with the cosmological parameters. The results on $A$ and $C$ for different cosmological models are in well agreement within $1\sigma$ range. The best fit value of $A$ in all models being analyzed is $A\sim 1.53$ with $\sigma \sim 0.08$. For $C$, we have the best value in the range of $0.94-0.98$ with $\sigma\sim 0.1$. It is also noted that the distributions of $A$ and $C$ are generally broader than the priors used in many studies in literature. (Abriged)Comment: 9 pages, 2 figures, 2 tables, Accepted for publication in Ap

Involvement of TRPC Channels in Lung Cancer Cell Differentiation and the Correlation Analysis in Human Non-Small Cell Lung Cancer

The canonical transient receptor potential (TRPC) channels are Ca2+-permeable cationic channels controlling the Ca2+ influx evoked by G protein-coupled receptor activation and/or by Ca2+ store depletion. Here we investigate the involvement of TRPCs in the cell differentiation of lung cancer. The expression of TRPCs and the correlation to cancer differentiation grade in non-small cell lung cancer (NSCLC) were analyzed by real-time PCR and immunostaining using tissue microarrays from 28 patient lung cancer samples. The association of TRPCs with cell differentiation was also investigated in the lung cancer cell line A549 by PCR and Western blotting. The channel activity was monitored by Ca2+ imaging and patch recording after treatment with all-trans-retinoic acid (ATRA). The expression of TRPC1, 3, 4 and 6 was correlated to the differentiation grade of NSCLC in patients, but there was no correlation to age, sex, smoking history and lung cancer cell type. ATRA upregulated TRPC3, TRPC4 and TRPC6 expression and enhanced Ca2+ influx in A549 cells, however, ATRA showed no direct effect on TRPC channels. Inhibition of TRPC channels by pore-blocking antibodies decreased the cell mitosis, which was counteracted by chronic treatment with ATRA. Blockade of TRPC channels inhibited A549 cell proliferation, while overexpression of TRPCs increased the proliferation. We conclude that TRPC expression correlates to lung cancer differentiation. TRPCs mediate the pharmacological effect of ATRA and play important roles in regulating lung cancer cell differentiation and proliferation, which gives a new understanding of lung cancer biology and potential anti-cancer therapy. © 2013 Jiang et al

Manifold Path Guiding for Importance Sampling Specular Chains

Complex visual effects such as caustics are often produced by light paths containing multiple consecutive specular vertices (dubbed specular chains), which pose a challenge to unbiased estimation in Monte Carlo rendering. In this work, we study the light transport behavior within a sub-path that is comprised of a specular chain and two non-specular separators. We show that the specular manifolds formed by all the sub-paths could be exploited to provide coherence among sub-paths. By reconstructing continuous energy distributions from historical and coherent sub-paths, seed chains can be generated in the context of importance sampling and converge to admissible chains through manifold walks. We verify that importance sampling the seed chain in the continuous space reaches the goal of importance sampling the discrete admissible specular chain. Based on these observations and theoretical analyses, a progressive pipeline, manifold path guiding, is designed and implemented to importance sample challenging paths featuring long specular chains. To our best knowledge, this is the first general framework for importance sampling discrete specular chains in regular Monte Carlo rendering. Extensive experiments demonstrate that our method outperforms state-of-the-art unbiased solutions with up to 40x variance reduction, especially in typical scenes containing long specular chains and complex visibility.Comment: 14 pages, 19 figure

Deletion of heat shock protein 60 in adult mouse cardiomyocytes perturbs mitochondrial protein homeostasis and causes heart failure.

To maintain healthy mitochondrial enzyme content and function, mitochondria possess a complex protein quality control system, which is composed of different endogenous sets of chaperones and proteases. Heat shock protein 60 (HSP60) is one of these mitochondrial molecular chaperones and has been proposed to play a pivotal role in the regulation of protein folding and the prevention of protein aggregation. However, the physiological function of HSP60 in mammalian tissues is not fully understood. Here we generated an inducible cardiac-specific HSP60 knockout mouse model, and demonstrated that HSP60 deletion in adult mouse hearts altered mitochondrial complex activity, mitochondrial membrane potential, and ROS production, and eventually led to dilated cardiomyopathy, heart failure, and lethality. Proteomic analysis was performed in purified control and mutant mitochondria before mutant hearts developed obvious cardiac abnormalities, and revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria. We also utilized an in vitro system to assess the effects of HSP60 deletion on mitochondrial protein import and protein stability after import, and found that both HSP60-dependent and HSP60-independent mitochondrial proteins could be normally imported in mutant mitochondria. However, the former underwent degradation in mutant mitochondria after import, suggesting that the protein exhibited low stability in mutant mitochondria. Interestingly, the degradation could be almost fully rescued by a non-specific LONP1 and proteasome inhibitor, MG132, in mutant mitochondria. Therefore, our results demonstrated that HSP60 plays an essential role in maintaining normal cardiac morphology and function by regulating mitochondrial protein homeostasis and mitochondrial function

Molecular simulation and spectroscopic studies on the interaction between perfluorohexadecanoic acid and human serum albumin

185-192In the present study, the interaction between Perfluorohexadecanoic acid (PFHxDA) and human serum albumin (HAS) was studied by fluorescence spectroscopy, molecular docking, dynamic simulation and circular dichroism (CD). The interaction character and the effect on human serum albumin conformation were measured by simulating the physiological condition (pH= 7.4). Experiments and simulation results revealed that PFHxDA molecules and HSA have regular fluorescence quenching, and the quenching mechanism is static quenching and non-radiative energy transfer. Thermodynamic analysis revealed the binding behavior was mainly governed by hydrophobic forces. Specific binding site experiments showed that the binding site of PFHxDA was a site I of HSA. The results from the CD spectrum demonstrated that PFHxDA changed the molecular conformation of HSA, which is consistent with the results obtained by molecular docking and dynamic simulation