Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions

Marginal states of the resistive tearing mode with flow in cylindrical geometry

The linear stability of tearing modes in a cylindrical plasma subject to a sub-Alfvénic equilibrium shear flow along the equilibrium magnetic field is considered. The equations in the resistive boundary layer at the rational surface are solved numerically using a Fourier transform combined with a finite-element approach. The behaviour of the growth rate as a function of the flow and the various parameters (including a perpendicular fluid viscosity) is obtained. Marginal stability curves showing the dependence of the familiar matching parameter Δ' with flow and shear are also given

Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits.

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation

Simple Vortex States in Films of Type-I Ginzburg-Landau Superconductor

Sufficiently thin films of type-I superconductor in a perpendicular magnetic field exhibit a triangular vortex lattice, while thick films develop an intermediate state. To elucidate what happens between these two regimes, precise numerical calculations have been made within Ginzburg-Landau theory at $\kappa=0.5$ and 0.25 for a variety of vortex lattice structures with one flux quantum per unit cell. The phase diagram in the space of mean induction and film thickness includes a narrow wedge in which a square lattice is stable, surrounded by the domain of stability of the triangular lattice at thinner films/lower fields and, on the other side, rectangular lattices with continuously varying aspect ratio. The vortex lattice has an anomalously small shear modulus within and close to the square lattice phase.Comment: 21 pages, 6 figure

Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis

Cardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cytometry to demonstrate that adiponectin prevented H/R-induced DNA fragmentation. The anti-apoptotic effect of adiponectin was also verified via attenuation of H/R-induced phosphatidylserine exposure using annexin V binding. H/R-induced apoptosis via the mitochondrial-mediated intrinsic pathway of apoptosis as assessed by cytochrome c release into cytosol and caspase-3 activation, both of which were attenuated by adiponectin. Mechanistically, we demonstrated that adiponectin enhanced anti-oxidative potential in these cells which led to attenuation of the increase in intracellular reactive oxygen species (ROS) caused by H/R. To further address the mechanism of adiponctins anti-apoptotic effects we used siRNA to efficiently knockdown adiponectin receptor (AdipoR1) expression and found that this attenuated the protective effects of adiponectin on ROS production and caspase 3 activity. Knockdown of APPL1, an important intracellular binding partner for AdipoR, also significantly reduced the ability of adiponectin to prevent H/R-induced ROS generation and caspase 3 activity. In summary, H/R-induced ROS generation and activation of the intrinsic apoptotic pathway was prevented by adiponectin via AdipoR1/APPL1 signaling and increased anti-oxidant potential. © 2011 Park et al.published_or_final_versio

Security Evaluation of Support Vector Machines in Adversarial Environments

Support Vector Machines (SVMs) are among the most popular classification techniques adopted in security applications like malware detection, intrusion detection, and spam filtering. However, if SVMs are to be incorporated in real-world security systems, they must be able to cope with attack patterns that can either mislead the learning algorithm (poisoning), evade detection (evasion), or gain information about their internal parameters (privacy breaches). The main contributions of this chapter are twofold. First, we introduce a formal general framework for the empirical evaluation of the security of machine-learning systems. Second, according to our framework, we demonstrate the feasibility of evasion, poisoning and privacy attacks against SVMs in real-world security problems. For each attack technique, we evaluate its impact and discuss whether (and how) it can be countered through an adversary-aware design of SVMs. Our experiments are easily reproducible thanks to open-source code that we have made available, together with all the employed datasets, on a public repository.Comment: 47 pages, 9 figures; chapter accepted into book 'Support Vector Machine Applications

Reduction in ionic permeability of a silicone hydrogel contact lenses after one month of daily wear

[EN] Purpose. To compare the ionic permeability using the ionoflux method of new and worn samples of a silicone hydrogel contact lens material. Methods. An ionoflux experimental setup was established to measure the ionic permeability (NaCl) of soft contact lenses. Samples of a silicone hydrogel lens (Comfilcon A, Coopervision, Pleasanton, CA) with optical powers of -1.00, -1.50 and -4.75 diopters (D) were used in this study. Three samples of each power were measured after being worn for one month on a daily wear basis. Lenses were cleaned and disinfected every night using multipurpose disinfecting solutions. Three samples of new lenses from the same batch and the same optical power were also measured to evaluate the effect of lens wear on the ionic permeability of the lens material. Before measurement, the lenses were equilibrated with a 1 M NaCl solution during one week before of each measurement. Results. Lens power had minimal effect on the ionic permeability of a modern silicone hydrogel contact lens with the -1.00 lens having a 15% lower permeability compared to the other two lenses. After one month of lens wear the apparent ionic permeability for lenses with -1.50 D decreased by 15%. In the case of -1.00 and -4.75 D lenses there was a decrease of 26%. Conclusions. The ionic permeability of silicone hydrogel lenses of different optical powers was not significantly different. Worn lenses present a significant reduction of the ionic permeability after a month of wear. The potential effect this reduction on lens movement and discomfort associated to lens wear should be further evaluated.The authors have no proprietary interest in any of the materials mentioned in this article. This work was funded in part by FEDER through the COMPTETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of projects PTDC/SAU-BEB/098391/2008, PTDC/SAU-BEB/098392/2008 and the Strategic Project PEST-C/FIS/UI607/2011.Ferreira Da Silva, AR.; Compañ Moreno, V.; Gonzalez-Meijome, JM. (2015). Reduction in ionic permeability of a silicone hydrogel contact lenses after one month of daily wear. Materials Research Express. 2(6). https://doi.org/10.1088/2053-1591/2/6/065007S26Yoon, S. C., & Jhon, M. S. (1982). The transport phenomena of some model solutes through postcrosslinked poly(2-hydroxyethyl methacrylate) membranes with different tactic precursors. Journal of Applied Polymer Science, 27(8), 3133-3149. doi:10.1002/app.1982.070270834Yasuda, H., Lamaze, C. E., & Ikenberry, L. D. (1968). Die Makromolekulare Chemie, 118(1), 19-35. doi:10.1002/macp.1968.021180102MURPHY, S., HAMILTON, C., & TIGHE, B. (1988). Synthetic hydrogels: 5. Transport processes in 2-hydroxyethyl methacrylate copolymers. Polymer, 29(10), 1887-1893. doi:10.1016/0032-3861(88)90407-7Nicolson, P. C., & Vogt, J. (2001). Soft contact lens polymers: an evolution. Biomaterials, 22(24), 3273-3283. doi:10.1016/s0142-9612(01)00165-xMonticelli, M. V., Chauhan, A., & Radke, C. J. (2005). The Effect of Water Hydraulic Permeability on the Settling of a Soft Contact Lens on the Eye. Current Eye Research, 30(5), 329-336. doi:10.1080/02713680590934085Guan, L., Jiménez, M. E. G., Walowski, C., Boushehri, A., Prausnitz, J. M., & Radke, C. J. (2011). Permeability and partition coefficient of aqueous sodium chloride in soft contact lenses. Journal of Applied Polymer Science, 122(3), 1457-1471. doi:10.1002/app.33336Cheng, M.-L., & Sun, Y.-M. (2005). Observation of the solute transport in the permeation through hydrogel membranes by using FTIR-microscopy. Journal of Membrane Science, 253(1-2), 191-198. doi:10.1016/j.memsci.2005.01.017CHHABRA, M., PRAUSNITZ, J., & RADKE, C. (2007). A single-lens polarographic measurement of oxygen permeability (Dk) for hypertransmissible soft contact lenses. Biomaterials, 28(30), 4331-4342. doi:10.1016/j.biomaterials.2007.06.024González-Méijome, J. M., López-Alemany, A., Almeida, J. B., & Parafita, M. A. (2009). Surface AFM microscopy of unworn and worn samples of silicone hydrogel contact lenses. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 88B(1), 75-82. doi:10.1002/jbm.b.31153González-Méijome, J. M., López-Alemany, A., Almeida, J. B., & Parafita, M. A. (2008). Dynamic in vitro dehydration patterns of unworn and worn silicone hydrogel contact lenses. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 90B(1), 250-258. doi:10.1002/jbm.b.31279Pozuelo, J., Compañ, V., González-Méijome, J. M., González, M., & Mollá, S. (2014). Oxygen and ionic transport in hydrogel and silicone-hydrogel contact lens materials: An experimental and theoretical study. Journal of Membrane Science, 452, 62-72. doi:10.1016/j.memsci.2013.10.010Wolffsohn, J. S., Hunt, O. A., & Basra, A. K. (2009). Simplified recording of soft contact lens fit. Contact Lens and Anterior Eye, 32(1), 37-42. doi:10.1016/j.clae.2008.12.00

The nonlinear time-dependent response of isotactic polypropylene

Tensile creep tests, tensile relaxation tests and a tensile test with a constant rate of strain are performed on injection-molded isotactic polypropylene at room temperature in the vicinity of the yield point. A constitutive model is derived for the time-dependent behavior of semi-crystalline polymers. A polymer is treated as an equivalent network of chains bridged by permanent junctions. The network is modelled as an ensemble of passive meso-regions (with affine nodes) and active meso-domains (where junctions slip with respect to their positions in the bulk medium with various rates). The distribution of activation energies for sliding in active meso-regions is described by a random energy model. Adjustable parameters in the stress--strain relations are found by fitting experimental data. It is demonstrated that the concentration of active meso-domains monotonically grows with strain, whereas the average potential energy for sliding of junctions and the standard deviation of activation energies suffer substantial drops at the yield point. With reference to the concept of dual population of crystalline lamellae, these changes in material parameters are attributed to transition from breakage of subsidiary (thin) lamellae in the sub-yield region to fragmentation of primary (thick) lamellae in the post-yield region of deformation.Comment: 29 pages, 12 figure