Effect of cations on the structure of bilayers formed by lipopolysaccharides isolated from Pseudomonas aeruginosa PAO1

The asymmetric outer membrane of Gram-negative bacteria contains lipopolysaccharides (LPSs) which contribute significantly to the bacterium's surface properties and play a crucial role in regulating membrane permeability. We report on neutron diffraction studies performed on aligned, self-assembled bilayers of Na-, Ca-, and Mg-salt forms of LPS isolated from Pseudomonas aeruginosa PAO1. From the one-dimensional neutron scattering length density profiles we find that water penetrates Ca2+-LPS bilayers to a lesser extent than either Na+- or Mg2+-LPS bilayers. This differential water penetration could have implications as to how small molecules permeate the outer membrane of Gram-negative bacteria and, possibly, how nonlamellar phases are formed.     

Hot spot analysis for driving the development of hits into leads in fragment-based drug discovery

Fragment-based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high-affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency. The method places small molecular probes, the size of organic solvents, on a dense grid around the protein and identifies the hot spots as consensus clusters formed by clusters of several probes. The hot spots are ranked based on the number of probe clusters, which predicts the binding propensity of the subsites and hence their importance for drug design. Accordingly, with a single exception the main hot spot identified by FTMap binds the core compound found by fragment screening. The most useful information is provided by the neighboring secondary hot spots, indicating the regions where the core can be extended to increase its affinity. To quantify this information, we calculate the density of probes from mapping, which describes the binding propensity at each point, and show that the change in the correlation between a ligand position and the probe density upon extending or repositioning the core moiety predicts the expected change in ligand efficiency.     

Changes in the anti-inflammatory activity of soy isoflavonoidgenistein versus genistein incorporated in two types of cyclodextrin derivatives

ABSTRACT: BACKGROUND: The isoflavonoid genistein represents the major active compound from soybean, the vegetalproduct from Glycine max (Fabaceae). The aim of this study is to prove that genistein wasincorporated in two semisynthetic cyclodextrins, beta-cyclodextrin derivatives:hydroxypropyl-beta-cyclodextrin and randomly-methylated-beta-cyclodextrin as well as to compare the anti-inflammatory activity of genistein with that of genistein incorporated inthese two types of semisynthetic cyclodextrins. RESULTS: The animal studies were conducted on 8-week old C57BL/6 J female mice. Inflammation wasinduced in both ears of each mouse by topical application of 10 micrograms 12-Otetradecanoylphorbol-3-acetate dissolved in 0.1 ml solvent (acetone : dimethylsulfoxide in amolar ratio 9:1). Thirty minutes later treatment was applied. The inflammatory reaction wascorrelated with increased values in ear thickness. Treatment with genistein and genisteinincorporated in the two cyclodextrins led to decreased values for ear thickness. Better antiinflammatoryaction was found for the complexes of genistein. Both haematoxylin-eosinanalysis and CD45 marker expression are in agreement with these findings. CONCLUSIONS: Results allow concluding that genistein is an active anti-inflammatory phytocompound andits complexation with hydrophilic beta-cyclodextrin derivatives leads to a stronger antiinflammatoryactivity.     

Nuclear polarization and signs of quadrupole moments of high-spin Gd isomers

Time-differential perturbed-angular-distribution (TDPAD) experiments have been performed on polarized intermediate- and high-spin isomers ${}^{144}\text{Gd}\text{(10}{}^{\mathrm{+}}\text{)}\text{and}{}^{147}\text{Gd}\text{(}\text{13}\text{2}{}^{\mathrm{+}}\text{,}\text{27}\text{2}{}^{\mathrm{?}}\text{,}\text{49}\text{2}{}^{\mathrm{+}}\text{)}$. Excited Gd nuclei populated by $\text{(}{}^{28}\text{Si}\text{, x}\text{n}\text{)}$ reactions were polarized by the tilted-multifoil technique and implanted in a Gd single-crystal host. Observation of the subsequent electric quadrupole interaction with the known electric field gradient yielded negative values of the sign of the deformation for all isomers studied. The magnitude of the induced nuclear polarization P_I was also determined from the TDPAD data and compared to model calculations in order to deduce the average atomic angular momentum and polarization of Gd ions at v/c ～ 0.018.     

Bimetallic Ag‐Pt Sub‐nanometer Supported Clusters as Highly Efficient and Robust Oxidation Catalysts

A combined experimental and theoretical investigation of Ag‐Pt sub‐nanometer clusters as heterogeneous catalysts in the CO→CO₂ reaction (COox) is presented. Ag₉Pt₂ and Ag₉Pt₃ clusters are size‐selected in the gas phase, deposited on an ultrathin amorphous alumina support, and tested as catalysts experimentally under realistic conditions and by first‐principles simulations at realistic coverage. In situ GISAXS/TPRx demonstrates that the clusters do not sinter or deactivate even after prolonged exposure to reactants at high temperature, and present comparable, extremely high COox catalytic efficiency. Such high activity and stability are ascribed to a synergic role of Ag and Pt in ultranano‐aggregates, in which Pt anchors the clusters to the support and binds and activates two CO molecules, while Ag binds and activates O₂, and Ag/Pt surface proximity disfavors poisoning by CO or oxidized species.     

Ultrafast nuclear dynamics induced by photodetachment of Ag2- and Ag2O2-: oxygen desorption from a molecular silver surface

Femtosecond nuclear dynamics of mass-selected neutral Ag2 and Ag2O2 clusters are investigated with the 'negative ion-to neutral-to positive ion'(NeNePo) technique. For the bare silver dimer, wave packet dynamics occurring in the neutral electronic ground state and in the first excited triplet state are observed after photodetachment from the anion with 3.05 eV photon energy. While the dynamics in the ground state lead to an oscillatory structure in the NeNePo-pump-probe spectra with a vibrational constant of 185 cm-1, the dynamics in the triplet state are assigned to a bound-free transition leading to dissociation. Photodetachment from the Ag2O2- complex results in the desorption of O2. The experimental data clearly show the influence of the desorbing oxygen ligand on the nuclear dynamics of the silver dimer inducing a red shift in the vibrational frequency and an intensity enhancement of the oscillatory signal.     

Preparation of zirconium phosphate on support material and its application for the sorption of some radioions

Several sorbents were prepared by precipitating zirconium phosphate on activated carbon support material. The main parameters of the chemical procedure were optimized in order to obtain the highest decontamination factors which can be achieved in the case of Cs⁺, Sr²⁺ and I⁻ ions. For the characterization of the sorbents, sorption isotherms and capacity data were determined. The reproducibility of the preparation is about 10%.     

Mathematical Aspects of Manpower Planning

In this paper, concepts of linear programming-in particular the Simplex algorithm and the Dual Simplex algorithm-are used within a discrete renewal model for the development of a graded population, when the transfer rates between the various grades are given, and "wastage" is replaced by suitable recruiting.The following questions are dealt with:

1. 1)
   Which population structures (i.e. partitions into grades) can be attained from a given structure, after one or more steps?
    
2. 2)
   From which structures can a given structure be attained in one or more steps?
    
3. 3)
   If the present structure as well as a desired future structure are given, can the latter be attained from the former in one or more steps? If so, how?
    
4. 4)
   The last problem is of special interest if the starting structure is identical with that to be attained and is called re-attaining after more than one step, or strictly maintaining after one step.
    

Examples are given to illustrate the procedure, and some attention is given to the possibility of alternative routes in cases (3) and (4). It is observed that if a structure is attainable (or re-attainable) after n steps, then it is not necessarily attainable (or re-attainable) after n + 1 steps.