Resistive State of Superconductor-Ferromagnet-Superconductor Josephson Junctions in the Presence of Moving Domain Walls.

We describe resistive states of the system combining two types of orderings-a superconducting and a ferromagnetic one. It is shown that in the presence of magnetization dynamics such systems become inherently dissipative and in principle cannot sustain any amount of the superconducting current because of the voltage generated by the magnetization dynamics. We calculate generic current-voltage characteristics of a superconductor-ferromagnet-superconductor Josephson junction with an unpinned domain wall and find the low-current resistance associated with the domain wall motion. We suggest the finite slope of Shapiro steps as the characteristic feature of the regime with domain wall oscillations driven by the ac external current flowing through the junction.

DNA bending by an adenine--thymine tract and its role in gene regulation.

To gain insight into the structural basis of DNA bending by adenine-thymine tracts (A-tracts) and their role in DNA recognition by gene-regulatory proteins, we have determined the crystal structure of the high-affinity DNA target of the cancer-associated human papillomavirus E2 protein. The three independent B-DNA molecules of the crystal structure determined at 2.2-A resolution are examples of A-tract-containing helices where the global direction and magnitude of curvature are in accord with solution data, thereby providing insights, at the base pair level, into the mechanism of DNA bending by such sequence motifs. A comparative analysis of E2-DNA conformations with respect to other structural and biochemical studies demonstrates that (i) the A-tract structure of the core region, which is not contacted by the protein, is critical for the formation of the high-affinity sequence-specific protein-DNA complex, and (ii) differential binding affinity is regulated by the intrinsic structure and deformability encoded in the base sequence of the DNA target.

[Experience in using perftoran in combined treatment of placental insufficiency in severe gestosis]. / Opyt primeneniia perftorana v kompleksnom lechenii platsentarnoi nedostatochnosti pri tiazhelykh gestozakh.

Twenty-two women with severe gestosis were examined during weeks 27-38. They were divided into 2 groups with different intensive care protocols: 1) osmooncotherapy and 2) 3-4 infusions of perfluorane in a dose of 3-4 ml/kg every other day. Addition of perfluorane to combined therapy promoted a more rapid stabilization of hemodynamics, metabolism, and helped prolong the pregnancy to 37-38 weeks.

Syntheses and structures of methyltris(pyrazolyl)silane complexes of the group 6 metals.

The methyltris(3,5-dimethylpyrazolyl)silane ligand, TpsMe2, was readily prepared by the metathesis reaction of methyltrichlorosilane with 3 equiv of lithium 3,5-dimethylpyrazolate. The octahedral tricarbonyl complexes (TpsMe2)M(CO)3 were synthesized either by ligand exchange with the labile nitrile adducts M(CO)3(NCR)3 (M = Cr, Mo, R = Me; M = W, R = Et) or thermally by direct substitution on the hexacarbonyls M(CO)6 (M = Cr, Mo). The three new complexes were characterized by a combination of analytical and spectroscopic techniques, including electrospray ionization mass spectrometry and single-crystal X-ray diffraction. They are all isostructural and display in the solid state the expected distorted octahedral geometries with facially coordinated tris(pyrazolyl)silane ligands. Crystallographic data were used to calculate the ligand cone angles (251-264 degrees) in (TpsMe2)M(CO)3 and also to estimate a value of 1.59 A for the covalent radius of octahedral W(0).

Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets.

Transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein E2 to several sites in the viral genome. Crystal structures of bovine papillomavirus E2 DNA targets reveal a conformational variant of B-DNA characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. A comparison between the free and the protein-bound DNA demonstrates that the intrinsic structure of the DNA regions contacted directly by the protein and the deformability of the DNA region that is not contacted by the protein are critical for sequence-specific protein/DNA recognition and hence for gene-regulatory signals in the viral system. We show that the selection of dinucleotide or longer segments with appropriate conformational characteristics, when positioned at correct intervals along the DNA helix, can constitute a structural code for DNA recognition by regulatory proteins. This structural code facilitates the formation of a complementary protein-DNA interface that can be further specified by hydrogen bonds and nonpolar interactions between the protein amino acids and the DNA bases.

Molecular replacement: the revival of the molecular Fourier transform method.

The molecular Fourier transform method, perhaps the first application of the molecular-replacement approach, used in the 1950s for the two-dimensional structure determination of small molecules, has been modernised for the efficient solution of complex structures. In the modern application of the molecular Fourier transform (MFT), the three-dimensional transform of the molecular model is calculated and fitting is achieved by rotating the weighted reciprocal lattice with respect to the calculated transform. The fit between the transform and the weighted reciprocal lattice is gauged by three different criteria corresponding to R factor, correlation coefficient and product function. Since the procedure involves the rotation of indices and is, therefore, independent of the number of atoms, it is much faster than other methods which employ the rotation of the molecular model. This feature enabled the renovation of the rotation-translation search method ULTIMA, which utilizes low-order data and packing considerations for the efficient solution of large structures.

X-ray and solution studies of DNA oligomers and implications for the structural basis of A-tract-dependent curvature.

DNA containing short periodic stretches of adenine residues (known as A-tracts), which are aligned with the helical repeat, exhibit a pronounced macroscopic curvature. This property is thought to arise from the cumulative effects of a distinctive structure of the A-tract. It has also been observed by gel electrophoresis that macroscopic curvature is largely retained when inosine bases are introduced singly into A-tracts but decreases abruptly for pure I-tracts. The structural basis of this effect is unknown. Here we describe X-ray and gel electrophoretic analyses of several oligomers incorporating adenine or inosine bases or both. We find that macroscopic curvature is correlated with a distinctive base-stacking geometry characterized by propeller twisting of the base-pairs. Regions of alternating adenine and inosine bases display large propeller twisting comparable to that of pure A-tracts, whereas the values observed for pure I-tracts are significantly smaller. We also observe in the crystal structures that propeller twist leads to close cross-strand contacts between amino groups from adenine and cytosine bases, indicating an attractive NH-N interaction, which is analogous to the NH-O interaction proposed for A-tracts. This interaction also occurs between adenine bases across an A-T step and may explain in part the different behavior of A-T versus T-A steps in the context of A-tract-induced curvature. We also note that hydration patterns may contribute to propeller-twisted conformation. Based on the present data and other structural and biophysical studies, we propose that DNA macroscopic curvature is related to the structural invariance of A-tract and A-tract-like regions conferred by high propeller twist, cross-strand interactions and characteristic hydration. The implications of these findings to the mechanism of DNA bending are discussed.

Determinants of repressor/operator recognition from the structure of the trp operator binding site.

On the basis of the crystal structure of the trp repressor/operator complex, it has been proposed that the specificity of the interaction can be explained not only by direct hydrogen bonding and non-polar contacts between the protein and the bases of its target DNA, but also by indirect structural effects and water-mediated interactions. To understand the contribution of DNA structure and hydration in this context, the structure of the free DNA must be compared with its structure when complexed with the protein. Here we present the high-resolution crystal structure of the trp operator region that is most important in the recognition process. By comparing the free and bound states of the DNA regulatory sequence, we show that the structure and hydration of the DNA target are important elements in its recognition by the repressor protein.

Operator approach to electromagnetic coupled-wave calculations of lamellar gratings: infrared optical properties of intrinsic silicon gratings.

The system of coupled-wave equations for electromagnetic calculations of lamellar gratings is transformed to a new operator-vector form. The numerical procedure is based on truncation of the transformed system and proves to be stable, to be free of ill conditioning, and to preserve the power-conservation requirement for a lossless dielectric with high accuracy. To execute the procedure a very compact MATLAB-based program is developed, and numerical simulations for thick intrinsic silicon gratings are performed. Zero-reflectance phenomena at normal incidence for both TE and TM polarizations are studied. The ratios of the grating dimensions to be wavelengths at which these anomalies occur are found numerically. It is shown that by keeping the period- and slot-width-towavelength ratios constant and by increasing the slot depth one can repeat the anomalies. An antiblazing property at oblique incidence is also considered. The connection with recent directional polarized-emission experiments on intrinsic silicon g atings is discussed.

Three-dimensional structures of bulge-containing DNA fragments.

The three-dimensional structure of a DNA tridecamer d(CGCAGAATTCGCG)2 containing bulged adenine bases was determined by single crystal X-ray diffraction methods, at 120 K, to 2.6 A resolution. The structure is a B-DNA type double helix with a single duplex in the asymmetric unit. One of the bulged adenine bases loops out from the double helix, while the other stacks in to it. This is in contrast to our preliminary finding, which indicated that both adenine bases were looped out. This revised model was confirmed by the use of a covalently bound heavy-atom derivative. The conformation of the looped-out bulge hardly disrupts base stacking interactions of the bases flanking it. This is achieved by the backbone making a "loop-the-loop" curve with the extra adenine flipping over with respect to the other nucleotides in the strand. The looped-out base intercalates into the stacked-in bulge site of a symmetrically related duplex. The looped-out and stacked-in bases form an A.A reversed Hoogsteen base-pair that stacks between the surrounding base-pairs, thus stabilizing both bulges. The double helix is frayed at one end with the two "melted" bases participating in intermolecular interactions. A related structure, of the same tridecamer, after soaking the crystals with proflavin, was determined to 3.2 A resolution. The main features of this B-DNA duplex are basically similar to the native tridecamer but differ in detail especially in the conformation of the bulged-out base. Accommodation of a large perturbation such as that described here with minimal disruption of the double helix shows both the flexibility and resiliency of the DNA molecule.

Drug-induced DNA repair: X-ray structure of a DNA-ditercalinium complex.

Ditercalinium is a synthetic anticancer drug that binds to DNA by bis-intercalation and activates DNA repair processes. In prokaryotes, noncovalent DNA-ditercalinium complexes are incorrectly recognized by the uvrABC repair system as covalent lesions on DNA. In eukaryotes, mitochondrial DNA is degraded by excess and futile DNA repair. Using x-ray crystallography, we have determined, to 1.7 A resolution, the three-dimensional structure of a complex of ditercalinium bound to the double-stranded DNA fragment [d(CGCG)]2. The DNA in the complex with ditercalinium is kinked (by 15 degrees) and severely unwound (by 36 degrees) with exceptionally wide major and minor grooves. Recognition of the DNA-ditercalinium complex by uvrABC in prokaryotes, and by mitochondrial DNA repair systems in eukaryotes, might be related to drug-induced distortion of the DNA helix.

The structure and hydration of the A-DNA fragment d(GGGTACCC) at room temperature and low temperature.

The DNA fragment d(GGGTACCC) was crystallized as an A-DNA duplex in the hexagonal space group P6(1). The structure was analyzed at room temperature and low temperature (100K) at a resolution of 2.5 A. The helical conformations at the two temperatures are similar but the low-temperature structure is more economically hydrated than the room-temperature one. The structure of d(GGGTACCC) is compared to those of d(GGGTGCCC) and d(GGGCGCCC). This series of molecules, which consists of a mismatched duplex and its two Watson-Crick analogues, exhibits three conformational variants of the A-form of DNA, which are correlated with the specific intermolecular interactions observed in the various crystals. The largest differences in local conformation are displayed by the stacking geometries of the central pyrimidine-purine and the flanking purine-pyrimidine sites in each of the three duplexes. Stacking energy calculations performed on the crystal structures show that the mismatched duplex is destabilized with respect to each of the error-free duplexes, in accordance with helix-coil transition measurements.

The conformation of the DNA double helix in the crystal is dependent on its environment.

Studies of the crystal structures of more than 30 synthetic DNA fragments have provided structural information about three basic forms of the double helix: A-, B- and Z-form DNA. These studies have demonstrated that the DNA double helix adopts a highly variable structure which is related to its base sequence. The extent to which such observed structures are influenced by the crystalline environment can be found by studying the same molecule in different crystalline forms. We have recently crystallized one particular oligomer in various crystal forms. Here we report the results of structural analyses of the different crystal structures and demonstrate that the DNA double helix can adopt a range of conformations in the crystalline state depending on hydration, molecular packing and temperature. These results have implications on our understanding of the influence of the environment on DNA structure, and on the modes of DNA recognition by proteins.

Low-temperature study of the A-DNA fragment d(GGGCGCCC).

The structure of the A-type duplex d(GGGCGCCC) was determined from data measured at 115 K to 2.0 A resolution. The space group, P4(3)2(1)2, is the same as for the 293 K structure; cell dimensions are a = 42.74 (4), c = 24.57 (1) A; R = 0.21 for 1694 observed reflections. The conformation and hydration are similar at the two temperatures. The average displacement parameters (B) for bases, sugars and phosphates all decrease by about 9 A2 relative to those found at 293 K. The individual values of B1/2 are linearly related to the distance from the molecular center of mass.

The three-dimensional structure of a DNA duplex containing looped-out bases.

Unpaired bases in DNA have been assigned a possible role in the mechanism of frameshift mutagenesis in sequences with repeated base pairs. They also occur in quasipalindromic DNA sequences, which have been implicated in mutagenesis where there are no repeated base pairs, through the formation of single-stranded hairpin loops. The conformation of unpaired bases in DNA has been the subject of numerous thermodynamic as well as high resolution NMR (nuclear magnetic resonance) studies (reviewed in ref. 4). The NMR studies in solution have shown that the duplex of the tridecamer DNA fragment d(CGCAGAATTCGCG) remains intact, and that the unpaired adenosines are stacked into the duplex. Having crystallized this oligonucleotide and determined its structure, we find its conformation in the crystal is close to that of a B-DNA duplex, with the two additional adenosines looped out from the double helix and causing little disruption of the rest of the structure.

Structures of the mismatched duplex d(GGGTGCCC) and one of its Watson-Crick analogues d(GGGCGCCC).

The mismatched duplex d(GGGTGCCC) (I) and its two Watson-Crick analogues (dGGGCGCCC) (II) and d(GGGTACCC) (III) were synthesized. The X-ray crystal structures of (I) and (II) were determined at resolutions of 2.5 and 1.7 A (1 A = 0.1 nm) and refined to R factors of 15 and 16%, respectively. (I) and (II) crystallize as A-DNA doublehelical octamers in space groups P61 and P4(3)2(1)2, respectively, and are stable at room temperature. The central two G.T mispairs of (I) adopt the wobble geometry as observed in other G.T mismatches. The two structures differ significantly in their local conformational features at the central helical regions as well as in some global ones. In particular, T-G adopts a large helical twist (44 degrees) whereas C-G adopts a small one (24 degrees). This difference can be rationalized on the basis of simple geometrical considerations. Base-pair stacking energies which were calculated for the two duplexes indicate that (I) is destabilized with respect to (II). Helix-coil transition measurements were performed for each of the three oligomers by means of ultraviolet absorbance spectrophotometry. The results indicate that the stability of the duplexes and the co-operativity of the transition are in the following order: (I) less than (III) less than (II). Such studies may help in understanding why certain regions of DNA are more likely to undergo spontaneous mutations than others.

The structure of guanosine-thymidine mismatches in B-DNA at 2.5-A resolution.

The structure of the deoxyoligomer d(C-G-C-G-A-A-T-T-T-G-C-G) was determined at 2.5-A resolution by single crystal x-ray diffraction techniques. The final R factor is 18% with the location of 71 water molecules. The oligomer crystallizes in a B-DNA-type conformation, with two strands interacting to form a dodecamer duplex. The double helix consists of four A X T and six G X C Watson-Crick base pairs and two G X T mismatches. The G X T pairs adopt a "wobble" structure with the thymine projecting into the major groove and the guanine into the minor groove. The mispairs are accommodated in the normal double helix by small adjustments in the conformation of the sugar phosphate backbone. A comparison with the isomorphous parent compound containing only Watson-Crick base pairs shows that any changes in the structure induced by the presence of G X T mispairs are highly localized. The global conformation of the duplex is conserved. The G X T mismatch has already been studied by x-ray techniques in A and Z helices where similar results were found. The geometry of the mispair is essentially identical in all structures so far examined, irrespective of the DNA conformation. The hydration is also similar with solvent molecules bridging the functional groups of the bases via hydrogen bonds. Hydration may be an important factor in stabilizing G X T mismatches. A characteristic of Watson-Crick paired A X T and G X C bases is the pseudo 2-fold symmetry axis in the plane of the base pairs. The G X T wobble base pair is pronouncedly asymmetric. This asymmetry, coupled with the disposition of functional groups in the major and minor grooves, provides a number of features which may contribute to the recognition of the mismatch by repair enzymes.