Measurements of pollen grain dispersal in still air and stationary, near homogeneous, isotropic turbulence

The dispersal of ragweed, pine and corn pollen as well as polystyrene spheres in still air and stationary, near homogeneous, isotropic turbulence (HIT) was investigated using high-speed, digital inline holographic cinematography enabling Lagrangian tracking of the particles. Mean still air settling velocities were similar as reported literature values. Small discrepancies were most likely related to species/size differences and water content of the grains. Near-HIT was generated by loudspeakers mounted on the corners of a 40 cm³ chamber and the turbulent flow field at the center of the chamber was validated using stereoscopic Particle Image Velocimetry (PIV). Results showed near homogeneity and near isotropy with mean velocities 5–10 times smaller than the corresponding rms values of velocity fluctuations. The turbulent kinetic energy dissipation rate was determined from the PIV data sets and used to calculate the Kolmogorov scales and Taylor microscales. Experiments were carried out for two different loudspeaker amplifications corresponding to Taylor microscale Reynolds numbers, R_λ=144 and 162, respectively. The mean settling velocity in turbulent conditions was in all cases higher than the corresponding still air value, the difference becoming smaller as particle Stokes numbers increased. For the present conditions, the still air particle settling velocity was lower than the rms values of air fluctuating velocities. As a result, dispersion was dominated by inertia and for a given R_λ, particle fluctuating velocity autocorrelations fell more rapidly as the particle Stokes number decreased; corresponding particle diffusion coefficients also decreased. Transverse particle diffusion coefficients were lower than those in the direction of gravity in agreement with the continuity effect. Under the present range of experimental parameters, results showed that inertial particles (0.6<St<11) in highly turbulent conditions disperse more effectively than the air.     

Spacer effects on in vivo properties of DOTA-conjugated dimeric [Tyr3]octreotate peptides synthesized by a "Cu(I)-click" and "sulfo-click" ligation method

We report on the SSTR2-binding properties of a series of four dimeric [Tyr3]octreotate analogues with different spacer lengths (nine, 19, 41, and 57 atoms) between the peptides. Two analogues (9 and 57 atoms) were selected as precursors for the design, synthesis, and biological evaluation of DOTA-conjugated dimeric [Tyr3]octreotate analogues for tumor targeting. These compounds were synthesized by using a two-stage click ligation procedure: a Cu(I) -catalyzed 1,3-dipolar cycloaddition ("copper-click" reaction) and a thio acid/sulfonyl azide amidation ("sulfo-click" reaction). The IC(50) values of these DOTA-conjugated [Tyr3]octreotate analogues were comparable, and internalization studies showed that the nine-atom (111) In-DOTA-labeled [Tyr3]octreotate dimer had rapid and high receptor binding. Biodistribution studies with BALB/c nude mice bearing subcutaneous AR42J tumors showed that the (111) In-labeled [Tyr3]octreotate dimer (nine atoms) had a high tumor uptake at 1 h p.i. (38.8 ± 8.3 % ID g(-1) ), and excellent tumor retention at 4 h p.i. (40.9 ± 2.5 % ID g(-1) ). However, the introduction of the extended hydrophilic 57 atoms spacer led to rapid clearance from the circulation; this limited tumor accumulation of the radiotracer (21.4 ± 4.9 % ID g(-1) at 1 h p.i.). These findings provide important insight on dimerization and spacer effects on the in vivo properties of DOTA-conjugated [Tyr3]octreotate dimers.     

Design and synthesis of conformationally constrained cyclophilin inhibitors showing a cyclosporin-A phenotype in C. elegans

Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small-molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.     

A Highly Active and Selective Manganese Oxide Promoted Cobalt-on-Silica Fischer�CTropsch Catalyst

A highly active and selective manganese oxide-promoted silica-supported cobalt catalyst for the Fischer?CTropsch reaction is reported. Co/MnO/SiO₂ catalysts were prepared via impregnation of a cobalt nitrate and manganese nitrate precursor, followed by drying and calcination in an NO/He flow. The catalysts were studied with STEM?CEELS, infrared spectroscopy measurements of adsorbed CO and Steady-State Isotopic Transient Kinetic Analysis experiments. Based on those experiments, a relation between C₅₊-selectivity and surface-coverages of CH _x -intermediates on cobalt was found.     

Biomineralization in diatoms: the role of silacidins

Diatoms are eukaryotic, unicellular algae encased within siliceous cell walls (frustules), which are precisely reproduced generation by generation. The production of this nanostructured silica is under genetic control and the isolation of specific gene products (the proteins silaffins, silacidins) guiding the biomineralization processes, and which are necessary to produce the frustules, has already been described. Under silicon starvation, the amount of silacidins present in the cell walls of Thalassiosira pseudonana increases relative to other proteins. Natsilacidins, the native and highly phosphorylated silacidins are enormously effective in silica precipitation whereas silacidin A', the nonphosphorylated form, is not. This indicates an important role for natsilacidins in the survival of diatoms under silicic acid depleted conditions.     

Activity-based profiling of retaining β-glucosidases: a comparative study

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based profiling of glycosidases, on the other hand, has proven more difficult, and to date no broad-spectrum glycosidase activity-based probes (ABPs) have been reported. In a comparative study, we investigated both 2-deoxy-2-fluoroglycosides and cyclitol epoxides for their utility as a starting point towards retaining β-glucosidase ABP. We also investigated the merits of direct labeling and two-step bio-orthogonal labeling in reporting on glucosidase activity under various conditions. Our results demonstrate that 1) in general cyclitol epoxides are the superior glucosidase ABPs, 2) that direct labeling is the more efficient approach but it hinges on the ability of the glucosidase to be accommodated in the active site of the reporter (BODIPY) entity, and 3) that two-step bio-orthogonal labeling can be achieved on isolated enzymes but translating this protocol to cell extracts requires more investigation.     

The utility of coal molecular models

There are a large number (> 125) of molecular representations for coals that span the rank range over seven decades. However, their utility has mostly been in representing chemical structural features, rather than in probing physical structure or exploring the structure-behavior relationship. This paper examines the utility of coal models and reviews the existing and emerging opportunities for coal models to contribute to coals effective utilization via demystification of the structure-behavior relationship. Coal models have been used to explore the coalification pathway, including contraction with water removal. Physical evaluations have probed the density of models as a check on their accuracy. Pore size distribution and sorption have been explored in simple pores and more recent work with carbon dioxide, water and methane sorption within the porous structure of large-scale (< 20,000 atoms) model. Pair distribution frequency and small angle X-ray scattering simulations have also been compared with experimental observations and offer an additional check on the constitution of the model structure. Simulated HRTEM and simulated (calculated) NMR spectra also exist. Models have been disassembled in efforts to represent the pyrolysis process, char formation, and char reactivity (including the role of ion-exchangable ions). Similar to the pyrolysis models, direct liquefaction has been explored with a pyrolysis style approach. Coal-solvent swelling, and coal-solvent solubility have also been explored. While considerable progress has accompanied improvements in computational power and software advances, it is the generation of the model that is the most significant barrier to the meaningful utility of these models. The ability to generate large-scale models (incorporation of molecular weight diversity and structural diversity) with new automation approaches, coupled with new dynamic force-fields that can simulate reactive events in complicated materials like coals, offers a new hope for the utility of coal or char molecular models to probe our understanding and aid in the scientific method rather than our current informed trial and error approach.     

Substructure-based virtual screening for adenosine A2A receptor ligands

A virtual ligand-based screening approach was designed and evaluated for the discovery of new A(2A) adenosine receptor (AR) ligands. For comparison and evaluation, the procedures from a recently published virtual screening study that used the A(2A) AR X-ray crystal structure for the target-based discovery of new A(2A) ligands were largely followed. Several screening models were constructed by deriving the distinguishing structural features from selected sets of A(2A) AR antagonists, so-called frequent substructure mining. The best model in statistical terms was subsequently applied to large-scale virtual screens of a commercial vendor library. This resulted in the selection of 36 candidates for acquisition and testing. Of the selected candidates, eight compounds significantly inhibited radioligand binding at A(2A) AR (>30%) at 10 μM, corresponding to a "hit rate" of 22%. This hit rate is quite similar to that of the referenced target-based virtual screening study, while both approaches yield new, non-overlapping sets of ligands.     

Predicting and rationalizing the effect of surface charge distribution and orientation on nano-wire based FET bio-sensors

A single charge screening model of surface charge sensors in liquids (De Vico et al., Nanoscale, 2011, 3, 706-717) is extended to multiple charges to model the effect of the charge distributions of analyte proteins on FET sensor response. With this model we show that counter-intuitive signal changes (e.g. a positive signal change due to a net positive protein binding to a p-type conductor) can occur for certain combinations of charge distributions and Debye lengths. The new method is applied to interpret published experimental data on Streptavidin (Ishikawa et al., ACS Nano, 2009, 3, 3969-3976) and Nucleocapsid protein (Ishikawa et al., ACS Nano, 2009, 3, 1219-1224).