Ligand bridging of the DNA Holliday junction: molecular recognition of a stacked-X four-way junction by a small molecule

Planning a Holliday: A new mode of binding to a stacked-X, four-way Holliday junction is described in which a chromophore molecule binds across the center of the junction and two adenine residues are replaced by the acridine chromophores at either side of the crossover. This binding mode is specific for the Holliday junction and does not cause unwinding of the DNA helices.

Stabilisation of two Cu(I)-amino N bonds in presence of imino N's

Two structurally characterised examples of air stable Cu-1 (amino N)(2)(imino N)(2) chromophores having a Cu(II/I) potential of 0.01-0.19 V vs SCE in CH2Cl2 are provided using two tetradentate N-donor ligands.

Novel charge transfer supramolecular assemblies with Keggin anions and 2-amino-5-nitropyridine

Several novel compounds with the non-linear optical chromophore 2-amino-5-nitropyridine (2A5NP) and Keggin polyoxoanions (alpha-isomers), having the general formula (2A5NP)(m)H-n[XM12O40]center dot xH(2)O, M = Mo, W, were synthesised. Compounds were obtained with X = P, n = 3, m = 3 and 4 and X = Si, n = m = 4 ( x = 2 - 6). Thus, for each of the anions [PMo12O40](3-) and [PW12O40](3-) two different compounds were obtained, with the same anion and organic counterpart but with a different stoichiometric ratio. These presented different charge transfer properties and thermal stability. All compounds were characterised by spectroscopic and analytical techniques. The single crystal X-ray diffraction structure of (2A5NP)(4)H-3[PMo12O40]center dot 2.5H(2)O center dot 0.5C(2)H(5)OH showed that the water solvent molecules and the organic chromophores are assembled via infinite one-dimensional chains of hydrogen bonds with formation of open channels, which accommodate [ PMo12O40] 3- and ethanol solvent molecules.

Syntheses and crystal structures of two new coordination polymers of Cd(II) using organic spacer and inorganic-bridging ligands

Two new cadmium (II) complexes [Cd(hmt)(dca)(2)] (n) (1) and [Cd-3(hmt)(2)(SeCN)(6)(H2O)(2)] (n) (2) (hmt=hexamethylenetetramine, dca=dicyanamide) have been synthesized and characterized by X-ray single-crystal analysis. The complex 1 is a 2D rectangular grid of octahedral cadmium (II) with CdN6 chromophore where cadmium centers are doubly bridged by dicyanamide and hmt along a-axis, which are interlinked by dicyanamide running along c-axis. Whereas, complex 2 is a 1D chain of octahedral cadmium (II) with a three-leg ladder topology running along a-axis. The Cd(II) centers are doubly bridged through SeCN (infinite rail) along a-axis and singly bridged by hmt (two-step rung) along c-axis, having cadmium centers with CdSe2N3O and CdSe2N4 chromophores. The adjacent chains through H-bonding between coordinated water and hmt, and (SeSe)-Se-... interaction are extended to 2D supramolecular architecture.

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.

Photochemical, photophysical and redox properties of novel fulgimide derivatives with attached 2,2 '-bipyridine (bpy) and [M(bpy)(3)](2+) (M = Ru and Os) moieties

Fulgimides monosubstituted with [M(bpy)(3)](2+) (M = Ru, Os; bpy = 2,2'-bipyridine) chromophore units and with a single bpy group were synthesized and investigated as components of conceivable dinuclear photochromic switches of luminescence. The E-, Z- and closed-ring (C) photoisomer forms of the bpy-bound fulgimide were successfully separated by semi-preparative HPLC. The same procedure failed, however, in the case of the [M(bpy)(3)](2+)-substituted fulgimides. Energy transfer from the excited photochromic unit to the metal-bpy centre competes with the fulgimide cyclization, reducing the photocyclization quantum yields by approximately one order of magnitude compared to the non-complexed fulgimide-bpy ligand (phi(EC) = 0.17, phi(EZ) = 0.071, phi(ZE) = 0.15 at lambda(exc) = 334 nm). The cycloreversion of the fulgimide-bpy ligand is less efficient (phi(CE) = 0.047 at lambda(exc) = 520 nm). The intensity of the (MLCT)-M-3-based luminescence of the metal-bpy chromophore (in MeCN, phi(deaer) = 6.6 x 10(-2) and tau(deaer) = 1.09 mu s for Ru; phi(deaer) = 6.7 x 10(-3) and tau(deaer) = 62 ns for Os) is not affected by the fulgimide photoconversion. These results and supporting spectro-electrochemical data reveal that the lowest triplet excited states of the photochromic fulgimide moiety in all its E-, Z- and closed-ring forms lie above the lowest 3MLCT levels of the attached ruthenium and osmium chromophores. The actual components are therefore unlikely to form a triad acting as functional switch of energy transfer from [Ru(bpy)(3)](2+) to [Os(bpy)(3)](2+) through the photochromic fulgimide bridge.

Self-assembled biomimetic [2Fe2S]-hydrogenase-based photocatalyst for molecular hydrogen evolution

The large-scale production of clean energy is one of the major challenges society is currently facing. Molecular hydrogen is envisaged as a key green fuel for the future, but it becomes a sustainable alternative for classical fuels only if it is also produced in a clean fashion. Here, we report a supramolecular biomimetic approach to form a catalyst that produces molecular hydrogen using light as the energy source. It is composed of an assembly of chromophores to a bis(thiolate)-bridged diiron ([2Fe2S]) based hydrogenase catalyst. The supramolecular building block approach introduced in this article enabled the easy formation of a series of complexes, which are all thoroughly characterized, revealing that the photoactivity of the catalyst assembly strongly depends on its nature. The active species, formed from different complexes, appears to be the [Fe-2(mu-pdt)(CO)(4){PPh2(4-py)}(2)] (3) with 2 different types of porphyrins (5a and 5b) coordinated to it. The modular supramolecular approach was important in this study as with a limited number of building blocks several different complexes were generated.

Slicing of soft, flexible solids with industrial applications

Thin slices of soft flexible solids have negligible bending resistance and hence store negligible elastic strain energy; furthermore such offcuts are rarely permanently deformed after slicing. Cutting forces thus depend only on work of separation (toughness work) and friction. These simplifying assumptions are not as restrictive as it might seem, and the mechanics are found to apply to a wide variety of foodstuffs and biological materials. The fracture toughness of such materials may be determined from cutting experiments: the use of scissors instrumented for load and displacement is a popular method where toughness is obtained from the work areas beneath load–displacement plots. Surprisingly, there is no analysis for the variation of forces with scissor blade opening and this paper provides the theory. Comparison is made with experimental results in cutting with scissors. The analysis is generalised to cutting with blades of variable curvature and applied to a commercial food cutting device having a rotating spiral plan form blade. The strong influence of the ‘slice/push ratio’ (blade tangential speed to blade edge normal speed) on the cutting forces is revealed. Small cutting forces are important in food cutting machinery as damage to slices is minimised. How high slice/push ratios may be achieved by choice of blade profile is discussed.

Cutting, by 'pressing and slicing,' of thin floppy slices of materials illustrated by experiments on cheddar cheese and salami

Why it is easier to cut with even the sharpest knife when 'pressing down and sliding' than when merely 'pressing down alone' is explained. A variety of cases of cutting where the blade and workpiece have different relative motions is analysed and it is shown that the greater the 'slice/push ratio' xi given by ( blade speed parallel to the cutting edge/blade speed perpendicular to the cutting edge), the lower the cutting forces. However, friction limits the reductions attainable at the highest.. The analysis is applied to the geometry of a wheel cutting device (delicatessan slicer) and experiments with a cheddar cheese and a salami using such an instrumented device confirm the general predictions. (C) 2004 Kluwer Academic Publishers.

Mathematical modelling for the digital society

We argue the case for a new branch of mathematics and its applications: Mathematics for the Digital Society. There is a challenge for mathematics, a strong “pull” from new and emerging commercial and public activities; and a need to train and inspire a generation of quantitative scientists who will seek careers within the associated sectors. Although now going through an early phase of boiling up, prior to scholarly distillation, we discuss how data rich activities and applications may benefit from a wide range of continuous and discrete models, methods, analysis and inference. In ten years time such applications will be common place and associated courses may be embedded within the undergraduate curriculum.

Interaction of the coronavirus nucleoprotein with nucleolar antigens and the host cell

Coronavirus nucleoproteins (N proteins) localize to the cytoplasm and the nucleolus, a subnuclear structure, in both virus-infected primary cells and in cells transfected with plasmids that express N protein. The nucleolus is the site of ribosome biogenesis and sequesters cell cycle regulatory complexes. Two of the major components of the nucleolus are fibrillarin and nucleolin. These proteins are involved in nucleolar assembly and ribosome biogenesis and act as chaperones for the import of proteins into the nucleolus. We have found that fibrillarin is reorganized in primary cells infected with the avian coronavirus infectious bronchitis virus (IBV) and in continuous cell lines that express either IBV or mouse hepatitis virus N protein. Both N protein and a fibrillarin-green fluorescent protein fusion protein colocalized to the perinuclear region and the nucleolus. Pull-down assays demonstrated that IBV N protein interacted with nucleolin and therefore provided a possible explanation as to how coronavirus N proteins localize to the nucleolus. Nucleoli, and proteins that localize to the nucleolus, have been implicated in cell growth-cell cycle regulation. Comparison of cells expressing IBV N protein with controls indicated that cells expressing N protein had delayed cellular growth. This result could not to be attributed to apoptosis. Morphological analysis of these cells indicated that cytokinesis was disrupted, an observation subsequently found in primary cells infected with IBV. Coronaviruses might therefore delay the cell cycle in interphase, where maximum translation of viral mRNAs can occur.

Strong-segregation limit of the self-consistent field theory for diblock copolymer melts

The self-consistent field theory (SCFT) introduced by Helfand for diblock copolymer melts is expected to converge to the strong-segregation theory (SST) of Semenov in the asymptotic limit, $\chi N \rightarrow \infty$. However, past extrapolations of the lamellar/cylinder and cylinder/sphere phase boundaries, within the standard unit-cell approximation, have cast some doubts on whether or not this is actually true. Here we push the comparison further by extending the SCFT calculations to $\chi N = 512,000$, by accounting for exclusion zones in the coronae of the cylindrical and spherical unit cells, and by examining finite-segregation corrections to SST. In doing so, we provide the first compelling evidence that SCFT does indeed reduce to SST.

Modelling human dynamics in-situ for rehabilitation and therapy robots

This paper outlines some rehabilitation applications of manipulators and identifies that new approaches demand that the robot make an intimate contact with the user. Design of new generations of manipulators with programmable compliance along with higher level controllers that can set the compliance appropriately for the task, are both feasible propositions. We must thus gain a greater insight into the way in which a person interacts with a machine, particularly given that the interaction may be non-passive. We are primarily interested in the change in wrist and arm dynamics as the person co-contracts his/her muscles. It is observed that this leads to a change in stiffness that can push an actuated interface into a limit cycle. We use both experimental results gathered from a PHANToM haptic interface and a mathematical model to observe this effect. Results are relevant to the fields of rehabilitation and therapy robots, haptic interfaces, and telerobotics

Another Proof of the Preceding Theory

Another Proof of the Preceding Theory was produced as part of a residency run by Artists in Archeology in conjunction with the Stonehenge Riverside project. The film explores the relationship between science, work and ritual, imagining archaeology as a future cult. As two robed disciples stray off from the dig, they are drawn to the drone of the stones and proceed to play the henge like a gigantic Theremin. Just as a Theremin is played with the hand interfering in an electric circuit and producing sound without contact, so the stones respond to the choreographed bodily proximity. Finally, one of the two continues alone to the avenue at Avebury, where the magnetic pull of the stones reaches its climax. Shot on VHS, the film features a score by Zuzushi Monkey, with percussion and theremin sounds mirroring the action. The performers are mostly artists and archeologists from the art and archaeology teams. The archeologists were encouraged to perform their normal work in the robes, in an attempt to explore the meeting points of science and ritual and interrogate our relationship to an ultimately unknowable prehistoric past where activities we do not understand are relegated to the realm of religion. Stonehenge has unique acoustic properties, it’s large sarsen stones are finely worked on the inside, left rough on the outside, intensifying sound waves within the inner horseshoe, but since their real use, having been built over centuries, remains ambiguous, the film proposes that our attempts to decode them may themselves become encoded in their cumulative meaning for future researchers.

Caracterização de interações entre subunidades do complexo de iniciação da tradução EIF4F e homólogos da proteína de ligação ao poli-A (PABP) de Leishmania sp

Os tripanossomatídeos são caracterizados por processos moleculares diferenciados como a transcrição policistrônica e regulação pós-transcricional da expressão gênica. Em mamíferos, a tradução se inicia com a ligação do complexo eIF4F (formado pelos eIF4A, eIF4E e eIF4G) a extremidade 5' dos mRNAs, o que facilita seu reconhecimento pelo ribossomo. A atividade do eIF4F é reforçada pela proteína de ligação a cauda poli-A (PABP), na extremidade 3' dos mRNAs, que interage com o eIF4G. Dois complexos do tipo eIF4F foram identificados em tripanossomatídeos: o primeiro formado pelos EIF4G3, EIF4E4 e EIF4AI com a PABP1; e um outro baseado na interação do EIF4G4 com o EIF4E3 e o EIF4A1. Este trabalho buscou caracterizar as interações entre as subunidades destes complexos e sua associação com PABPs de Leishmania, avaliando o efeito de mutações em motivos específicos. Proteínas recombinantes foram geradas fusionadas a GST e avaliadas quanto a sua habilidade de interagir com parceiros marcados radioativamente em ensaios do tipo pull-down. Para o EIF4G3, mutações individuais em dois resíduos vizinhos (I8A e R9A), afetaram a interação com o EIF4E4 e a mutação de ambos os resíduos equivalentes do EIF4G4 (IL25-26AA) também impediu sua ligação ao EIF4E3, sugerindo um motivo comum para a ligação aos seus parceiros. As proteínas EIF4E3 e EIF4E4 foram avaliadas quanto à capacidade de interagir com a PABP2 e PABP1 respectivamente, e mutações em motivos conservados nas regiões N-terminais dos EIF4E (Boxes A, B e C) aboliram sua interação com os homólogos da PABP. Para identificar que regiões da PABP1 estão relacionadas às interações com o parceiro EIF4E4, foram obtidas proteínas PABP1 mutantes em motivos conservados e observou-se que a mutação no motivo TGM, C-terminal, aboliu sua interação com o EIF4E4. Com estas abordagens conseguiu-se avançar na definição das interações entre as referidas subunidades do eIF4F e PABP, identificando-se diferenças relevantes em relação a outros eucariotos