Using Rytov's fluctuational electrodynamics framework, Polder and Van Hove predicted that radiative heat transfer between planar surfaces separated by a vacuum gap smaller than the thermal wavelength ...exceeds the blackbody limit due to tunnelling of evanescent modes. This finding has led to the conceptualization of systems capitalizing on evanescent modes such as thermophotovoltaic converters and thermal rectifiers. Their development is, however, limited by the lack of devices enabling radiative transfer between macroscale planar surfaces separated by a nanosize vacuum gap. Here we measure radiative heat transfer for large temperature differences (∼120 K) using a custom-fabricated device in which the gap separating two 5 × 5 mm
intrinsic silicon planar surfaces is modulated from 3,500 to 150 nm. A substantial enhancement over the blackbody limit by a factor of 8.4 is reported for a 150-nm-thick gap. Our device paves the way for the establishment of novel evanescent wave-based systems.
Changes in mitochondrial morphology that occur during cell cycle, differentiation, and death are tightly regulated by the balance between fusion and fission processes. Excessive fragmentation can be ...caused by inhibition of the fusion machinery and is a common consequence of dysfunction of the organelle. Here, we show a role for calcineurin-dependent translocation of the profission dynamin related protein 1 (Drp1) to mitochondria in dysfunction-induced fragmentation. When mitochondrial depolarization is associated with sustained cytosolic Ca²⁺ rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. Thus, fragmentation of depolarized mitochondria depends on a loop involving sustained Ca²⁺ rise, activation of calcineurin, and dephosphorylation of Drp1 and its translocation to the organelle.
Ischemia and post-ischemic reperfusion cause a wide array of functional and structural alterations of mitochondria. Although mitochondrial impairment is recognized as pivotal in determining loss of ...viability, the causal relationships among the various processes involved is ill defined. Nevertheless, a wide consensus exists in attributing a crucial role to opening of the mitochondrial permeability transition pore (PTP). Strong support for this concept has recently been provided by the reduced infarct size observed in mice lacking cyclophilin D. This protein located within the mitochondrial matrix favours PTP opening by increasing its sensitivity to Ca2+ in a process that is antagonized by cyclosporin A. Genetic approaches have also been used to demonstrate that adenine nucleotide translocase is not an essential component of the PTP. Here, we discuss our current understanding of the structure and function of PTP in the context of heart injury caused by ischemia and reperfusion.
The impacts of radiative, electrical and thermal losses on the performances of nanoscale-gap thermophotovoltaic (nano-TPV) power generators consisting of a gallium antimonide cell paired with a ...broadband tungsten and a radiatively-optimized Drude radiator are analyzed. Results reveal that surface mode mediated nano-TPV power generation with the Drude radiator outperforms the tungsten radiator, dominated by frustrated modes, only for a vacuum gap thickness of 10 nm and if both electrical and thermal losses are neglected. The key limiting factors for the Drude- and tungsten-based devices are respectively the recombination of electron-hole pairs at the cell surface and thermalization of radiation with energy larger than the cell absorption bandgap. A design guideline is also proposed where a high energy cutoff above which radiation has a net negative effect on nano-TPV power output due to thermal losses is determined. It is shown that the power output of a tungsten-based device increases by 6.5% while the cell temperature decreases by 30 K when applying a high energy cutoff at 1.45 eV. This work demonstrates that design and optimization of nano-TPV devices must account for radiative, electrical and thermal losses.
Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy (BM), and Congenital Myosclerosis are diseases caused by mutations in the genes encoding the extracellular matrix protein collagen VI. A ...dystrophic mouse model, where collagen VI synthesis was prevented by targeted inactivation of the Col6a1 gene, allowed the investigation of pathogenesis, which revealed the existence of a Ca(2+)-mediated dysfunction of mitochondria and sarcoplasmic reticulum, and of defective autophagy. Key events are dysregulation of the mitochondrial permeability transition pore, an inner membrane high-conductance channel that for prolonged open times causes mitochondrial dysfunction, and inadequate removal of defective mitochondria, which amplifies the damage. Consistently, the Col6a1(-/-) myopathic mice could be cured through inhibition of cyclophilin D, a matrix protein that sensitizes the pore to opening, and through stimulation of autophagy. Similar defects contribute to disease pathogenesis in patients irrespective of the genetic lesion causing the collagen VI defect. These studies indicate that permeability transition pore opening and defective autophagy represent key elements for skeletal muscle fiber death, and provide a rationale for the use of cyclosporin A and its nonimmunosuppressive derivatives in patients affected by collagen VI myopathies, a strategy that holds great promise for treatment.
•Thermophotovoltaic conversion efficiency and output power density are maximized.•Optimal radiator emission spectra are obtained using a genetic algorithm.•Radiative, electrical and thermal losses in ...the cell are taken into account.•TPV performances with optimal emission spectra largely exceed those with blackbody and tungsten radiators.
Optimal radiator thermal emission spectra maximizing thermophotovoltaic (TPV) conversion efficiency and output power density are determined when thermal effects in the cell are considered. For this purpose, a framework is designed in which a TPV model that accounts for radiative, electrical and thermal losses is coupled with a genetic algorithm. The TPV device under study involves a spectrally selective radiator at a temperature of 2000K, a gallium antimonide cell, and a cell thermal management system characterized by a fluid temperature and a heat transfer coefficient of 293K and 600Wm−2K−1. It is shown that a maximum conversion efficiency of 38.8% is achievable with an emission spectrum that has emissivity of unity between 0.719eV and 0.763eV and zero elsewhere. This optimal spectrum is less than half of the width of the spectra obtained when thermal losses in the cell are neglected. A maximum output power density of 41,708Wm−2 is achievable with a radiator spectrum having emissivity values of unity between 0.684eV and 1.082eV and zero elsewhere when thermal losses are accounted for. These emission spectra are shown to greatly outperform blackbody and tungsten radiators, and could be obtained using artificial structures such as metamaterials or photonic crystals.
To develop and validate a practical, in vitro, cell-based model to assess human hepatotoxicity potential of drugs, we used the new technology of high content screening (HCS) and a novel combination ...of critical model features, including (1) use of live, human hepatocytes with drug metabolism capability, (2) preincubation of cells for 3 days with drugs at a range of concentrations up to at least 30 times the efficacious concentration or 100 microM, (3) measurement of multiple parameters that were (4) morphological and biochemical, (5) indicative of prelethal cytotoxic effects, (6) representative of different mechanisms of toxicity, (7) at the single cell level and (8) amenable to rapid throughput. HCS is based on automated epifluorescence microscopy and image analysis of cells in a microtiter plate format. The assay was applied to HepG2 human hepatocytes cultured in 96-well plates and loaded with four fluorescent dyes for: calcium (Fluo-4 AM), mitochondrial membrane potential (TMRM), DNA content (Hoechst 33,342) to determine nuclear area and cell number and plasma membrane permeability (TOTO-3). Assay results were compared with those from 7 conventional, in vitro cytotoxicity assays that were applied to 611 compounds and shown to have low sensitivity (<25%), although high specificity ( approximately 90%) for detection of toxic drugs. For 243 drugs with varying degrees of toxicity, the HCS, sublethal, cytotoxicity assay had a sensitivity of 93% and specificity of 98%. Drugs testing positive that did not cause hepatotoxicity produced other serious, human organ toxicities. For 201 positive assay results, 86% drugs affected cell number, 70% affected nuclear area and mitochondrial membrane potential and 45% affected membrane permeability and 41% intracellular calcium concentration. Cell number was the first parameter affected for 56% of these drugs, nuclear area for 34% and mitochondrial membrane potential for 29% and membrane permeability for 7% and intracellular calcium for 10%. Hormesis occurred for 48% of all drugs with positive response, for 26% of mitochondrial and 34% nuclear area changes and 12% of cell number changes. Pattern of change was dependent on the class of drug and mechanism of toxicity. The ratio of concentrations for in vitro cytotoxicity to maximal efficaciousness in humans was not different across groups (12+/-22). Human toxicity potential was detected with 80% sensitivity and 90% specificity at a concentration of 30x the maximal efficacious concentration or 100 microM when efficaciousness was not considered. We conclude that human hepatotoxicity is highly concordant with in vitro cytotoxicity in this novel model and as detected by HCS.
The paper presents the results of flexural and shear tests up to failure on full-scale hollow-core slabs (HCS) having a depth of 500 mm. A detailed non-linear 2D finite element model is also ...developed to predict the stress distribution and crack pattern within the slabs, providing a well match with experimental results. Experimental and numerical results are compared with analytical calculations provided by Product Standard EN 1168, highlighting the inaccuracy of technical regulations in predicting shear behavior. The proposed numerical procedure is instead viable and sound for the design and the strength assessment of HCS, and can be extended easily to the analysis of whole floor systems.
The microbial precipitation of CaCO3 is an emerging strategy for the consolidation of decayed limestone. Strains of Bacillus sp. and Micrococcus sp. isolated from black crusts were selected by ...polycyclic aromatic hydrocarbon enrichment culture and tested for their ability to precipitate CaCO3 by induced mineralization. Among the isolates, Bacillus sp. A2, B1, B5 and Micrococcus sp. A10 produced the largest quantities of biogenic calcite. Stone bio-consolidation was then tested using Carbogel as a carrier. The most efficient bio-cementation on limestone slabs was achieved by Bacillus sp. A2 and B1 and Micrococcus sp. A10. Bio-consolidation treatments were also applied to fragmented stones from the Church of Santa Maria dei Miracoli by inoculating the three bacterial strains individually or as a mixture. Bacillus sp. A2, Micrococcus sp. A10 and the mixture achieved the most efficient consolidation. Our data showed that Carbogel provides an appropriate substitute for natural biofilm formation in bio-consolidation protocols. Scanning electron microscopy and energy-dispersive X-ray spectroscopy revealed calcified bacterial cells filling the pores of stone specimens, increasing the calcium content by 100% more than a non-inoculated control treatment under the same conditions. Our new bio-consolidation protocol therefore provides an effective strategy to prevent the further deterioration of stone monuments.
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•PAH-acclimated Bacillus sp. and Micrococcus sp. can precipitate calcite.•Calcite formation involves an induced mineralization mechanism.•Biofilm formation can contribute to the bio-consolidation process.•Carbogel can substitute for biofilm formation in bio-consolidation protocols.•Carbogel is therefore a suitable carrier for bio-consolidation applications.
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