Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells).

Epidemiological evidence suggests that cadmium (Cd) exposure causes pulmonary damage such as emphysema and lung cancer. However, relatively little is known about the mechanisms involved in Cd pulmonary toxicity. In the present study, the effects of Cd exposure on human fetal lung fibroblasts (MRC-5 cells) were evaluated by determination of lipid peroxidation, intra-cellular production of reactive oxygen species (ROS), and changes of mitochondrial membrane potential. A time- and dose-dependent increase of both lactate dehydrogenase leakage and malondialdehyde formation was observed in Cd-treated cells. A close correlation between these two events suggests that lipid peroxidation may be one of the main pathways causing its cytotoxicity. It was also noted that Cd-induced cell injury and lipid peroxidation were inhibited by catalase and superoxide dismutase, two antioxidant enzymes. By using the fluorescent probe 2',7'-dichlorofluorescin diacetate, a significant increase of ROS production in Cd-treated MRC-5 cells was detected. The inhibition of dichlorofluorescein fluorescence by catalase, not superoxide dismutase, suggests that hydrogen peroxide is the main ROS involved. Moreover, the significant dose-dependent changes of mitochondrial membrane potential in Cd-treated MRC-5 cells, demonstrated by increased fluorescence of rhodamine 123 examined using a laser-scanning confocal microscope, also indicate the involvement of mitochondrial damage in Cd cytotoxicity. These findings provide in vitro evidence that Cd causes oxidative cellular damage in human fetal lung fibroblasts, which may be closely associated with the pulmonary toxicity of Cd

Generative adversarial network-based semi-supervised learning for pathological speech classification

A challenge in applying machine learning algorithms to pathological speech classification is the labelled data shortage problem. Labelled data acquisition often requires significant human effort and time-consuming experimental design. Further, for medical applications, privacy and ethical issues must be addressed where patient data is collected. While labelled data are expensive and scarce, unlabelled data are typically inexpensive and plentiful. In this paper, we propose a semi-supervised learning approach that employs a generative adversarial network to incorporate both labelled and unlabelled data into training. We observe a promising accuracy gain with this approach compared to a baseline convolutional neural network trained only on labelled pathological speech data

Power quality improvements of arc welding power supplies by modified bridgeless SEPIC PFC converter

This paper proposes an efficient bridgeless power factor corrected (PFC) modified single ended primary inductor converter (SEPIC) for arc welding power supplies (AWPS). The overall configuration is composed of two converters: (1) a modified bridgeless SEPIC PFC converter, which is controlled by a PI controller to achieve a high power factor and fast response; and (2) a full bridge buck converter with high-frequency transformer for high-frequency isolation to ensure arc welding stability. The proposed system is simulated under different operating conditions of an AWPS. It is also tested in real time by a hardware-in-the-loop system based on a dSPACE DS1103 control board. The system performances are evaluated based on power quality indices such as power factor, total harmonic distortions of the AC grid current, and voltage regulation. The obtained results show that the proposed controller enhances the weld bead quality by keeping a constant current at the output and a stable arc, meet the international power quality standards and robustness for voltage regulation

An Exact Fluctuating 1/2-BPS Configuration

This work explores the role of thermodynamic fluctuations in the two parameter giant and superstar configurations characterized by an ensemble of arbitrary liquid droplets or irregular shaped fuzzballs. Our analysis illustrates that the chemical and state-space geometric descriptions exhibit an intriguing set of exact pair correction functions and the global correlation lengths. The first principle of statistical mechanics shows that the possible canonical fluctuations may precisely be ascertained without any approximation. Interestingly, our intrinsic geometric study exemplifies that there exist exact fluctuating 1/2-BPS statistical configurations which involve an ensemble of microstates describing the liquid droplets or fuzzballs. The Gaussian fluctuations over an equilibrium chemical and state-space configurations accomplish a well-defined, non-degenerate, curved and regular intrinsic Riemannian manifolds for all physically admissible domains of black hole parameters. An explicit computation demonstrates that the underlying chemical correlations involve ordinary summations, whilst the state-space correlations may simply be depicted by standard polygamma functions. Our construction ascribes definite stability character to the canonical energy fluctuations and to the counting entropy associated with an arbitrary choice of excited boxes from an ensemble of ample boxes constituting a variety of Young tableaux.Comment: Minor changes, added references, 30 pages, 4 figures, PACS numbers: 04.70.-s: Physics of black holes; 04.70.-Bw: Classical black holes; 04.50.Gh Higher-dimensional black holes, black strings, and related objects; 04.60.Cf Gravitational aspects of string theory, accepted for publication in JHE

On the Temperature Dependence of the Shear Viscosity and Holography

We examine the structure of the shear viscosity to entropy density ratio eta/s in holographic theories of gravity coupled to a scalar field, in the presence of higher derivative corrections. Thanks to a non-trivial scalar field profile, eta/s in this setup generically runs as a function of temperature. In particular, its temperature behavior is dictated by the shape of the scalar potential and of the scalar couplings to the higher derivative terms. We consider a number of dilatonic setups, but focus mostly on phenomenological models that are QCD-like. We determine the geometric conditions needed to identify local and global minima for eta/s as a function of temperature, which translate to restrictions on the signs and ranges of the higher derivative couplings. Finally, such restrictions lead to an holographic argument for the existence of a global minimum for eta/s in these models, at or above the deconfinement transition.Comment: references adde

A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Gated Diffusion-controlled Reactions

The binding and active sites of proteins are often dynamically occluded by motion of the nearby polypeptide. A variety of theoretical and computational methods have been developed to predict rates of ligand binding and reactivity in such cases. Two general approaches exist, "protein centric" approaches that explicitly treat only the protein target, and more detailed dynamical simulation approaches in which target and ligand are both treated explicitly. This mini-review describes recent work in this area and some of the biological implications