a comparative experimental and numerical study of baroclinic wave dynamics

The differentially heated rotating annulus is a widely studied tabletop-size laboratory model of the general mid-latitude atmospheric circulation. The two most relevant factors of cyclogenesis, namely rotation and meridional temperature gradient are quite well captured in this simple arrangement. The radial temperature difference in the cylindrical tank and its rotation rate can be set so that the isothermal surfaces in the bulk tilt, leading to the formation of baroclinic waves. The signatures of these waves at the free water surface have been analyzed via infrared thermography in a wide range of rotation rates (keeping the radial temperature difference constant) and under different initial conditions. In parallel to the laboratory experiments, five groups of the MetStröm collaboration have conducted numerical simulations in the same parameter regime using different approaches and solvers, and applying different initial conditions and perturbations. The experimentally and numerically obtained baroclinic wave patterns have been evaluated and compared in terms of their dominant wave modes, spatio-temporal variance properties and drift rates. Thus certain “benchmarks” have been created that can later be used as test cases for atmospheric numerical model validation

Direct numerical simulation of a breaking inertia-gravity wave

We have performed fully resolved three-dimensional numerical simulations of a statically unstable monochromatic inertia–gravity wave using the Boussinesq equations on an f-plane with constant stratification. The chosen parameters represent a gravity wave with almost vertical direction of propagation and a wavelength of 3 km breaking in the middle atmosphere. We initialized the simulation with a statically unstable gravity wave perturbed by its leading transverse normal mode and the leading instability modes of the time-dependent wave breaking in a two-dimensional space. The wave was simulated for approximately 16 h, which is twice the wave period. After the first breaking triggered by the imposed perturbation, two secondary breaking events are observed. Similarities and differences between the three-dimensional and previous two-dimensional solutions of the problem and effects of domain size and initial perturbations are discussed

Fine tuning Nanocarriers Specifically toward Cargo A Competitive Study on Solubilizing Related Photosensitizers for Photodynamic Therapy

Tailor made drug solubilizers are studied based on peptide poly ethylene glycol conjugates, which exhibit peptide segments constituting binding motifs for the small molecule drugs of interest to render them water soluble. Suitable 7mer peptides are selected via combinatorial means by screening large one bead one compound OBOC peptide libraries. The capability of the screening method to read out structural detail of the drugs is investigated by comparing three related photosensitizers Chlorin E6 Ce6 , Pheophorbide A Pba and meta tetra hydroxyphenyl chlorin m THPC , which are applicable for photodynamic cancer therapy. The screening procedure delivers de novo solubilizers that show the best solubilization efficiency for the drug the screening is performed with. While molecular recognition events between peptide and drug are not expected to be found, significant binding capacity differences of, e.g., the Ce6 solubilizer for Pba are suggesting selectivity in drug binding, even among structurally closely related drugs. Cyro Electron microscopy revealed the formation of colloidal aggregates between drug moieties and peptide conjugates. Insights into relevant amino acids in the identified peptide sequences are gained by studying capacities of systematic point mutations alanine scans , enabling understanding of drug binding motifs. These reveal the importance of sequence positioning of appropriate H bonding between polar functional groups of the peptide and the drugs, which agrees well with computational binding studies performed on drug peptide model complexe

On the way to precision formulation additives: 2D-screening to select solubilizers with tailored host and release capabilities

A 2-dimensional high-throughput screening method is presented to select peptide sequences from large peptide libraries for precision formulation additives, having a high capacity to specifically host a drug of interest and provide tailored drug release properties. The identified sequences are conjugated with poly(ethylene glycol) (PEG) to obtain peptide-PEG conjugates that proved to be valuable as solubilizers for small organic molecule drugs to overcome limitations of poor water-solubility and low bio-availability. The 2D-screening method selects peptide sequences on both (i) high loading capacities and (ii) preferred drug-release capabilities as demonstrated on an experimental Tau-protein aggregation inhibitor/Tau- deaggregator with potentials for an anti-Alzheimer disease drug (BB17). To enable 2D-screening, a one-bead one-compound (OBOC) peptide library was immobilized on a glass slide, allocating individual beads to permanent positions. While the first screening step involved incubation of the supported OBOC library with BB17 to identify beads with high drug binding capacities by fluorescence scanner readouts, the second step reveals release properties of the high capacity binders by incubation with blood plasma protein model solutions. Efficiently peptides with high BB17 capacities and either keeper or medium or fast releaser properties can be identified by direct sequence readouts from the glass slide supported resin beads via matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. Four peptides are synthesized as peptide-PEG solubilizers representing strong, medium, weak releasers and non-binders. Loading capacities reached up to 1:3.4 (mol drug per mol carrier) and release kinetics (fast/medium/slow) are in agreement with the selection process as investigated by fluorescence anisotropy and fluorescence correlation spectroscopy. The ability of BB17/conjugate complexes to inhibit the aggregation of Tau4RDΔK (four repeat Tau ((M)Q244-E372 with deletion of K280), 129 residues) in N2a cells is studied by a Tau-pelleting assay showing the modulation of cellular Tau aggregation. Promising effects such as the reduction of 55% of total Tau load are observed for the strong releaser additive. Studies of in vitro Thioflavin S Tau-aggregation assays show half-maximal inhibitory activities (IC50 values) of BB17/conjugates in the low micro-molar range

Finite-volume models with implicit subgrid-scale parameterization for the differentially heated rotating annulus

The differentially heated rotating annulus is a classical experiment for the investigation of baroclinic flows and can be regarded as a strongly simplified laboratory model of the atmosphere in mid-latitudes. Data of this experiment, measured at the BTU Cottbus-Senftenberg, are used to validate two numerical finite-volume models (INCA and cylFloit) which differ basically in their grid structure. Both models employ an implicit parameterization of the subgrid-scale turbulence by the Adaptive Local Deconvolution Method (ALDM). One part of the laboratory procedure, which is commonly neglected in simulations, is the annulus spin-up. During this phase the annulus is accelerated from a state of rest to a desired angular velocity. We use a simple modelling approach of the spin-up to investigate whether it increases the agreement between experiment and simulation. The model validation compares the azimuthal mode numbers of the baroclinic waves and does a principal component analysis of time series of the temperature field. The Eady model of baroclinic instability provides a guideline for the qualitative understanding of the observations