Inelastic mean-free path and mean escape depth of 10-140 eV electrons in SiO2 nanoparticles determined by Si 2p photoelectron yields.

We report on photoelectron spectra of SiO2 nanoparticles (d = 157 ± 6 nm) above the Si 2p threshold in the photon energy range 118-248 eV with electron kinetic energy 10-140 eV and analyze the photoelectron yield as a function of photon energy. Comparison of the experimental results with Monte-Carlo simulations on electron transport allows us to quantify the inelastic mean-free path and mean escape depth of photoelectrons in the nanoparticle samples. The influence of the nanoparticle geometry and electron elastic scattering on photoelectron yields is highlighted. The results show that the previously proposed direct proportionality of the photoelectron signal to the inelastic mean-free path or the mean escape depth does not hold for photoelectron kinetic energies below 30 eV due to the strong influence of electron elastic scattering. The present results deviate for photoelectron kinetic energies below 30 eV from the previously proposed direct proportionality of the photoelectron signal to the inelastic mean-free path or the mean escape depth, which is the result of a strong influence of electron elastic scattering. The presented inelastic mean-free paths and mean escape depths appear to be useful for the quantitative interpretation of photoemission experiments on nanoparticles and for modeling of the experimental results.

Development and validation of a new cloud simulation experiment for lab-based aerosol-cloud studies.

The Aerosol Interaction and Dynamics in the Atmosphere (AIDA) cloud expansion chamber with a volume of 84 m3 was extended for the small cloud expansion chamber AIDA mini (AIDAm) with a volume of 20 L. AIDAm is located in the cold room of AIDA and can perform automated ice-nucleation measurements over longer time periods of hours to days. AIDAm samples from the AIDA chamber, which acts as a reservoir of atmospheric aerosol types, which can slowly be modified by physical or chemical processes similar to those occurring in the atmosphere. AIDAm was validated for accurate ice-nucleation temperature control by measuring homogeneous freezing of pure water droplets at temperatures around -34 °C and for immersion freezing induced by dust aerosol particles in the temperature range between -20 and -30 °C. Further validation experiments at cirrus cloud temperatures of -45 °C revealed that AIDAm can distinguish between heterogeneous ice formation on mineral dust aerosols and homogeneous freezing of sulfuric acid solution particles. The contribution of homogeneous and heterogeneous ice formation processes to the ice-nucleation activity of coated dust particles was investigated in a 7 h long experiment, where solid dust particles were slowly coated with sulfuric acid. The continuous AIDAm measurements with a time resolution of 6 min showed a substantial suppression of the heterogeneous freezing phenomenon and an increasing role of homogeneous freezing while the coating amount was slowly increased. This experiment proved the capability of AIDAm to sensitively detect small changes in the ice-nucleation ability of aerosols, which undergo slow processing like chemical surface coating.

Shape deformations of surface-charged microdroplets.

We present the deformation pathway of critically charged glycol and water droplets from the onset of the Rayleigh instability and compare it to numerical results, obtained for perfectly conducting inviscid droplets. In this simple model presented here, the time evolution of the droplet shape is given by the velocity potential equation. The Laplace equation for the velocity potential is solved by expanding the potential onto harmonic functions. For the part of the pathway dominated by electrostatic pressure, the calculations reproduce the experimental data nicely, obtained for both, glycol and water microdroplets. We find that the droplet shape and in particular the tips, just before charge emission, are well fitted by a lemon shape. We stress that the tip is tangent to a cone of 39 degrees and thus significantly narrower than a Taylor cone.

CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling.

CIB1 is a 22-kDa regulatory protein previously implicated in cell survival and proliferation. However, the mechanism by which CIB1 regulates these processes is poorly defined. Here, we report that CIB1 depletion in SK-N-SH neuroblastoma and MDA-MB-468 breast cancer cells promotes non-apoptotic, caspase-independent cell death that is not initiated by increased outer mitochondrial membrane permeability or translocation of apoptosis-inducing factor to the nucleus. Instead, cell death requires nuclear GAPDH accumulation. Furthermore, CIB1 depletion disrupts two commonly dysregulated, oncogenic pathways-PI3K/AKT and Ras/MEK/ERK, resulting in a synergistic mechanism of cell death, which was mimicked by simultaneous pharmacological inhibition of both pathways, but not either pathway alone. In defining each pathway's contributions, we found that AKT inhibition alone maximally induced GAPDH nuclear accumulation, whereas MEK/ERK inhibition alone had no effect on GAPDH localization. Concurrent GAPDH nuclear accumulation and ERK inhibition were required, however, to induce a significant DNA damage response, which was critical to subsequent cell death. Collectively, our results indicate that CIB1 is uniquely positioned to regulate PI3K/AKT and MEK/ERK signaling and that simultaneous disruption of these pathways synergistically induces a nuclear GAPDH-dependent cell death. The mechanistic insights into cell death induced by CIB1 interference suggest novel molecular targets for cancer therapy.

Elastic light scattering from free sub-micron particles in the soft X-ray regime.

We report the first experimental results on angle-resolved elastic light scattering in the soft X-ray regime, where free sub-micron particles in the size regime between 150 and 250 nm are studied in the gas phase by using a continuous particle beam. Two different types of studies are reported: (i) Angle-resolved elastic light scattering experiments provide specific information on the scattering patterns in the regime of element-selective inner-shell excitation near the Si 2p-edge (80-150 eV). In addition to intense forward scattering, we observe distinct features in the angle-resolved scattering patterns. These are modelled by using Mie theory as well as a model that includes contributions from diffuse and specular reflection. The results are primarily attributed to scattering from soft X-rays in the surface layer. (ii) Spectroscopic experiments are reported, where the photon detector is placed at a given scattering angle while scanning the photon energy near the Si 2p-absorption edge. These results are also analyzed by a Mie model, yielding accurate information of the size distribution.

Direct binding of the platelet integrin alphaIIbbeta3 (GPIIb-IIIa) to talin. Evidence that interaction is mediated through the cytoplasmic domains of both alphaIIb and beta3.

As a consequence of platelet activation and fibrinogen binding, glycoprotein (GP)IIb-IIIa (integrin alphaIIbbeta3) becomes associated with the cytoskeleton. Although talin has been suggested to act as a linkage protein mediating the attachment of GPIIb-IIIa to actin filaments, direct binding of GPIIb-IIIa to this cytoskeletal protein has not been demonstrated. In the present study, we examined the interaction of GPIIb-IIIa with purified talin using a solid-phase binding assay. Soluble GPIIb-IIIa bound in a time- and dose-dependent manner to microtiter wells coated with talin but not with BSA. Time course studies demonstrated that steady-state binding was achieved after 4-5 h incubation at 37 degrees C. Binding isotherms with varying concentrations of GPIIb-IIIa showed that half-saturation binding was achieved at approximately 15 nM GPIIb-IIIa. At saturation, there was 211 +/- 8 fmol of GPIIb-IIIa bound per well containing 117 +/- 10 fmol of immobilized talin. Besides binding to immobilized talin, GPIIb-IIIa also bound to talin captured by the anti-talin monoclonal antibody 8d4. Moreover, the interaction of GPIIb-IIIa to 8d4-captured talin was blocked by mAb10B2, a monoclonal antibody raised against a synthetic peptide encompassing the entire cytoplasmic sequence of GPIIb. The interaction of talin with the cytoplasmic domain of GPIIb-IIIa was further investigated using peptide-coated wells. Purified talin was found to bind to both synthetic peptides corresponding to the cytoplasmic sequences of GPIIb (P2b) and GPIIIa (P3a). As expected, the binding of talin to P2b-coated wells was specifically blocked by mAb10B2. Thus, these results demonstrate direct binding of GPIIb-IIIa to talin and suggest a role of the cytoplasmic sequences of both GPIIb and GPIIIa in mediating this interaction.

Shape oscillations and stability of charged microdroplets.

Classical Rayleigh theory predicts an instability of a surface charged liquid sphere, when the Coulomb energy E(C) exceeds twice the surface energy E(S). Previously, electrified liquid droplets have been found to disintegrate at a fissility X=E(C)/2E(S) well below one, however. We determine the stability of charged droplets in an electrodynamic levitator by observing the amplitude and phase of their quadrupolar shape oscillations as a function of the fissility. With this novel approach, which does not rely on an independent determination of the charge and surface tension of the droplets, we are able to confirm for the first time the Rayleigh limit of stability at X=1 for micrometer sized droplets of ethylene glycol.

Bidirectional transmembrane modulation of integrin alphaIIbbeta3 conformations.

Activation of blood platelets by physiological stimuli (e.g. thrombin, ADP) at sites of vascular injury induces inside-out signaling, resulting in a conformational change of the prototype integrin alphaIIbbeta3 from an inactive to an active state competent to bind soluble fibrinogen. Furthermore, ligand occupancy of alphaIIbbeta3 initiates outside-in signaling and additional conformational changes of the receptor, leading to the exposure of extracellular neoepitopes termed ligand-induced binding sites (LIBS), which are recognized by anti-LIBS monoclonal antibodies. To date, the mechanism of bidirectional transmembrane signaling of alphaIIbbeta3 has not been established. In this study, using our newly developed anti-LIBScyt1 monoclonal antibody, we showed that extracellular ligand binding to alphaIIbbeta3 on blood platelets induces a transmembrane conformational change in alphaIIbbeta3, thereby exposing the LIBScyt1 epitope in the alphaIIb cytoplasmic sequence between Lys994 and Asp1003. In addition, a point mutation at this site (P998A/P999A) renders alphaIIbbeta3 constitutively active to bind extracellular ligands, resulting in fibrinogen-dependent cell-cell aggregation. Taken collectively, these results demonstrated that the extracellular ligand-binding site and a cytoplasmic LIBS epitope in integrin alphaIIbbeta3 are conformationally and functionally coupled. Such bidirectional modulation of alphaIIbbeta3 conformation across the cell membrane may play a key role in inside-out and outside-in signaling via this integrin.