High-throughput screening and optimization of photoembossed relief structures

A methodology for the rapid design, screening, and optimization of coating systems with surface relief structures, using a combination of statistical experimental design, high-throughput experimentation, data mining, and graphical and mathematical optimization routines was developed. The methodology was applied to photopolymers used in photoembossing applications. A library of 72 films was prepared by dispensing a given amount of sample onto a chemically patterned substrate consisting of hydrophilic areas separated by fluorinated hydrophobic barriers. Film composition and film processing conditions were determined using statistical experimental design. The surface topology of the films was characterized by automated AFM. Subsequently, models explaining the dependence of surface topologies on sample composition and processing parameters were developed and used for screening a virtual 4000-membered in silico library of photopolymer lacquers. Simple graphical optimization or Pareto algorithms were subsequently used to find an ensemble of formulations, which were optimal with respect to a predefined set of properties, such as aspect ratio and shape of the relief structures.     

Comments on ultra-high-energy photons and D-foam models

We revisit the constraints that the non-observation of ultra-high-energy photons due to the GZK cutoff can impose on models of Lorentz violation in photon propagation, following recent work by Maccione, Liberati and Sigl (2010) [arXiv:1003.5468] that carries further an earlier analysis by the present authors [J. Ellis et al., Phys. Rev. D 63 (2001) 12402, hep-th/0012216]. We argue that the GZK cutoff constraint is naturally evaded in the D-brane model of space–time foam presented recently by the present authors [J. Ellis et al., Phys. Lett. B 665 (2008) 412, arXiv:0804.3566], in which Lorentz-violating effects on photon propagation are independent of possible effects during interactions. We also note a novel absorption mechanism that could provide a GZK-like cutoff for photons in low-scale string models.     

Highly efficient synthesis and solid-state characterization of 1,2,4,5-tetrakis(alkyl- and arylamino)benzenes and cyclization to their respective benzobis(imidazolium) salts

[reaction: see text] New synthetic methodology to a variety of 1,2,4,5-tetraaminobenzenes and their corresponding benzobis(imidazolium) salts has been accomplished. Palladium-catalyzed coupling of various 1,2,4,5-tetrabromo- or 1,2,4,5-tetrachlorobenzenes with aryl- or tert-alkylamines afforded the respective tetrakis(N-substituted)aminobenzenes in excellent yields. This enabled comparative solid-state structural analyses of this elusive class of electron-rich arenes with their oxidized derivatives. The tetraamines were found to undergo formylative cyclization to the corresponding benzobis(imidazolium) salts in good to excellent yields.     

A Mössbauer spectral study of the Jilin meteorite

The iron57 Mössbauer spectra of three different samples of the Jilin meteorite have been measured at 78 and 295 K. Five iron containing major components are identified, two magnetic components, kamacite and troilite, and three nonmagnetic components, olivine, pyroxene, and an iron(III) component. The relative absorption areas of these five components show that sample A contains a larger fraction of magnetic components, ca. 50 percent, than samples B and C, which contain ca. 30 percent. This difference indicates a significant compositional inhomogeneity in the Jilin meteorite. The fit of the troilite component sextet is extensively discussed in the paper and requires the adjustment of not only the isomer shift and hyperfine field, but also of the quadrupole interaction, the asymmetry parameter of the electric field gradient tensor, and the orientation of the hyperfine field in the principal axes of the electric field gradient tensor. The smaller isomer shift and hyperfine field of the kamacite mineral in sample B indicate that this sample contains less nickel than the kamacite in samples A and C, in which the amount of nickel is estimated to be ca. 9 percent. On the basis of its hyperfine parameters, the iron(III) component is assigned to iron(III) substituted on the M1 site of pyroxene.     

CuII binding sites located at His-96 and His-111 of the human prion protein: thermodynamic and spectroscopic studies on model peptides

The prion protein (PrP) is a Cu(2+)-binding cell-surface glycoprotein. Using PrP peptide fragments, by means of potentiometric, spectroscopic and thermodynamic techniques, we have shown that Cu(2+) ions bind to the region comprising His-96, His-111 and the octarepeat domain within residues 60-91. Cu(2+) may bind in different modes, which strongly depend both on His position within the peptide sequence and on the adjacent residues. We have used a series of protected oligopeptides having His at the C- or the N-terminus, inducing different binding modes to amide nitrogens around the His residue, either towards the N- or C-terminus. His imidazole acts as an anchoring site for Cu(2+) and then binding to ionized amide nitrogens follows. When it is directed towards the C-terminus the formation of a less stable seven-membered chelate ring with a {N(im), N(-)} binding mode occurs. When coordination goes towards the N-terminus the thermodynamically more stable six-membered chelate ring is formed. NMR data suggest that both the coordination modes are possible for the model peptides; however, the thermodynamic measurements show that they only slightly differ in energy and the influence of the adjacent amino acid residues can address the coordination toward the C- or the N-terminus.     

Cell culture chip using low-shear mass transport

We have developed a flow cell that allows culturing adherent cells as well as suspended cells in a stable, homogeneous, and low-shear force environment. The device features continuous medium supply and waste exchange. In this paper, a simple and fast protocol for device design, fabrication, and assembly (sealing) based on a poly(dimethylsiloxane) (PMDS)/glass slide hybrid structure is described. The cell culture system performance was monitored, and the effective shear force inside the culture well was also determined. By manipulating the device dimensions and volumetric flow rate, shear stress was controlled during experiments. Cell adhesion, growth, proliferation, and death over long-term culture periods were observed by microscopy. The growth of both endothelial and suspension cells in this device exhibited comparable characteristics to those of traditional approaches. The low-shear culture device significantly reduced shear stress encountered in microfluidic systems, allowing both adherent and suspended cells to be grown in a simple device.     

Highly symmetric hypertopes

We study incidence geometries that are thin and residually connected. These geometries generalise abstract polytopes. In this generalised setting, guided by the ideas from the polytope theory, we introduce the concept of chirality, a property of orderly asymmetry occurring frequently in nature as a natural phenomenon. The main result in this paper is that automorphism groups of regular and chiral thin residually connected geometries need to be C-groups in the regular case and \({C^+}\)-groups in the chiral case.     

Structural isotopic effects in the smallest chiral amino acid: observation of a structural phase transition in fully deuterated alanine

A first study of possible changes instigated by deuteration in amino acids was carried out using neutron diffraction, inelastic neutron scattering, and Raman scattering in l-alanine, C2H4(NH2)COOH. Careful analysis of the structural parameters shows that deuteration of l-alanine engenders significant geometric changes as a function of temperature, which can be directly related to the observation of new lattice vibration modes in the Raman spectra. The combination of the experimental data suggests that C2D4(ND2)COOD undergoes a structural phase transition (or a structural rearrangement) at about 170 K. Considering that this particular amino acid is a hydrogen-bonded system with short hydrogen bonds (O...H approximately 1.8 A), we evoke the Ubbelohde effect to conclude that substitution of hydrogen for deuterium gives rise to changes in the hydrogen-bonding interactions. The structural differences suggest distinct relative stabilities for the hydrogenous and deuterated l-alanine.     

Reaction of Aplysia limacina metmyoglobin with hydrogen peroxide

Myoglobin (Mb) from gastropod mollusc Aplysia limacina shows only 20% sequence homology to the 'prototype' sperm whale Mb but exhibits a typical Mb fold and can reversibly bind oxygen. An intriguing feature of aplysia Mb is that it lacks the distal histidine and displays a ligand stabilisation based on an arginine. Here we report the reaction of aplysia metMb with hydrogen peroxide studied by optical and electron paramagnetic resonance (EPR) spectroscopies. Two electron oxidation of the protein by H2O2 results in formation of two intermediates typical for this class of reactions, the oxoferryl haem state and a globin-bound free radical. An unusual characteristic of the aplysia Mb reaction is formation, prior to haem oxidation, of an optically distinct compound with an EPR spectrum typical of the low spin Fe3+ haem state. This compound is interpreted as the complex between H2O2 and the ferric haem state (Compound), formed prior to cleavage of the dioxygen bond. We conclude that H2O2 is singly deprotonated in Compound which can thus be notated as [Fe3+--OOH]. A new low spin ferric haem state has been observed over the period of Compound decay, and hypotheses have been formulated as to its identity and role. The location of the protein bound radical observed in aplysia Mb is discussed in light of the fact that the protein does not have any tyrosine residues, the most common site of free radical formation in the haem protein/peroxide systems. All intermediates of the reaction are kinetically characterised.     

Dithiolane quartets: thiol-mediated uptake enables cytosolic delivery in deep tissue

The cytosolic delivery of various substrates in 3D multicellular spheroids by thiol-mediated uptake is reported. This is important because most orthodox systems, including polycationic cell-penetrating peptides, fail to deliver efficiently into deep tissue. The grand principles of supramolecular chemistry, that is the pH dependence of dynamic covalent disulfide exchange with known thiols on the transferrin receptor, are proposed to account for transcytosis into deep tissue, while the known but elusive exchange cascades along the same or other partners assure cytosolic delivery in kinetic competition. For quantitative detection in the cytosol, the 2D chloroalkane penetration assay (CAPA) is translated to 3D deep tissue. The targeted delivery of quantum dots, otherwise already troublesome in 2D culture, and the controlled release of mechanophores are realized to exemplify the power of thiol-mediated uptake into spheroids. As transporters, dithiolane quartets on streptavidin templates are introduced as modular motifs. Built from two amino acids only, the varied stereochemistry and peptide sequence are shown to cover maximal functional space with minimal structural change, i.e., constitutional isomers. Reviving a classic in peptide chemistry, this templated assembly of β quartets promises to expand streptavidin biotechnology in new directions, while the discovery of general cytosolic delivery in deep tissue as an intrinsic advantage further enhances the significance and usefulness of thiol-mediated uptake.

Cytosolic delivery in multicellular 3D spheroids is shown to be an intrinsic advantage of thiol-mediated uptake, which is compatible with proteins and QDs, achieving targeting and controlled release.