Analytical characterization of cell–asbestos fiber interactions in lung pathogenesis

Asbestos is a fiber causing lung diseases such as asbestosis and mesothelioma. Although the process involving these diseases remains to be elucidated for developing drugs and treatments, direct consequences of fiber exposure in humans have been clearly demonstrated. These diseases are first characterized by histological heterogeneity and combine chronic inflammation with fibrosis and cellular alterations. As a consequence, asbestosis is usually diagnosed at advanced stages of the disease and treatments are usually inefficient to cure the patients. Here, we review the links established between asbestos fiber chemistry and morphology with the occurrence of associated lung diseases. Cytological and histological aspects of diseases are described with respect to current analytical capabilities, notably for microscopy techniques.     

Fast search algorithms for computational protein design

One of the main challenges in computational protein design (CPD) is the huge size of the protein sequence and conformational space that has to be computationally explored. Recently, we showed that state‐of‐the‐art combinatorial optimization technologies based on Cost Function Network (CFN) processing allow speeding up provable rigid backbone protein design methods by several orders of magnitudes. Building up on this, we improved and injected CFN technology into the well‐established CPD package Osprey to allow all Osprey CPD algorithms to benefit from associated speedups. Because Osprey fundamentally relies on the ability of to produce conformations in increasing order of energy, we defined new strategies combining CFN lower bounds, with new side‐chain positioning‐based branching scheme. Beyond the speedups obtained in the new ‐CFN combination, this novel branching scheme enables a much faster enumeration of suboptimal sequences, far beyond what is reachable without it. Together with the immediate and important speedups provided by CFN technology, these developments directly benefit to all the algorithms that previously relied on the DEE/ combination inside Osprey* and make it possible to solve larger CPD problems with provable algorithms. © 2016 Wiley Periodicals, Inc.     

Intramolecular Path Determination of Active Electrons on Push-Pull Oligocarbazole Dyes-Sensitized Solar Cells

Several push-pull oligocarbazole dye-sensitizers have been studied using theoretical methods in order to better understand the relationship between structural electronic or optical properties and intramolecular path of active electrons during the ionization and injection processes. DFT/TD-DFT calculations were performed on a series of five dye sensitizers. They differ by the presence of electron donating group (EDG) by inductive effect (noted+I) or electron releasing group (ERG) by mesomeric effect (noted+M) or electron withdrawing group by inductive effect (noted-I) on the pushed part of the dyes studied. Our work focused on the internal distribution of electrons in the different parts of dye that are the push/pull moieties and the π -bridge. The study concerned the ground state, the electronic transition process and the excited state. In each situation, the fragment acting in the ionization or transition phenomena were identified. In the ground state, the electrons of the push part appear to be the least bound because they have the highest probabilities of ionization. In the excited state, the ionized atoms are essentially positioned in the pushing part and some neighboring atoms of the bridge. In the electronic transition, the active atoms are located in the π -conjugated part but only on the side adjacent to the acceptor group. To arrive to this conclusion, we optimized the structures of the five dyes in their ground and excited states. We calculated the atomic charges, the wavelengths and intensities of electronic transitions in the visible domain, the reorganization energies as well as the oxidation potential. It appears that +M donor ligands improve the performance of a dye because the great distribution of atoms to be ionized in the push parts.     

Geodesic diameter of sets defined by few quadratic equations and inequalities

We prove a bound for the geodesic diameter of a subset of the unit ball in ${\mathbb{R}^n}$ described by a fixed number of quadratic equations and inequalities, which is polynomial in n, whereas the known bound for general degree is exponential in n. Our proof uses methods borrowed from D’Acunto and Kurdyka (to deal with the geodesic diameter) and from Barvinok (to take advantage of the quadratic nature).     

Coherent recovery of the degree of polarization of light propagating in random anisotropy media

We report on the study of light polarization behavior in random anisotropy scattering media. It is shown that, in the case of low scattering events, the degree of polarization (DOP) demonstrates oscillatory behavior due to the coherent character of light scattering. A strong increase in the DOP is demonstrated by using electro-optic fine tuning of the refractive index modulation depth of the scattering media.     

The role of asbestos morphology on their cellular toxicity: an in vitro 3D Raman/Rayleigh imaging study

Amphiboles caused cohorts of deaths in exposed workers, leading to some of the largest class actions in the industry. Once inhaled, these inorganic fibers are thought to be both chemically and morphologically toxic, and their biopersistence in the lungs over decades lead to progressive pathologies, mesothelioma, and asbestosis. However, this exceptionally long chronicity for human pathologies suggests that chemical toxicity is certainly low, suggesting that morphological parameters could be more relevant in the pathology. Here, we developed a 3D Raman/optical imaging methodology in vitro to characterize both morphological and chemical parameters of cell/fiber interactions. We determined that lung cells could vesiculate amphiboles with length below 5 μm or could embed those not exceeding 15 μm in their fibrous extracellular matrix. Lung cells can thus develop defense strategies for handling the biopersistence of inorganic species, which may thus have major impact for biosafety issues related to nanomaterials.     

Use of synchrotron-radiation-based FTIR imaging for characterizing changes in cell contents

FTIR imaging of individual cells is still limited by the low signal-to-noise ratio obtained from analysis of such weakly absorbing organic matter when using a Globar IR source. In this study, we used FTIR imaging with a synchrotron radiation source and a focal plane array detector to determine changes in the cellular contents of cryofixed cells after culture for 48 h on Si(3)N(4) substrate. Several spectral differences were observed for cells deprived of glucose compared with control cells: a lower amide I-to-amide II ratio (P < 0.01); a different secondary structure profile of proteins (obtained from amide I spectral region curve fitting), with a significant increase in non-ordered structure components (P < 0.01); and a higher ν(C = C-H)/ν(as)(CH(3)) absorption ratio (P < 0.01), suggesting increased unsaturation of fatty acyl chains. Therefore, our study has shown that FTIR imaging with a synchrotron radiation source enables determination of several spectral changes of individual cells between two experimental conditions, which thus opens the way to cell biology studies with this vibrational spectroscopy technique.