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Electronic structure theory, which in recent years has been actively and effectively applied to the modeling of chemical reactions involving transition-metal complexes, is now also being applied to the modeling of biological processes involving metalloenzymes. In the first part of this paper, we review our recent electronic structure studies using relatively simple models of two metalloenzymes--methane monooxygenase and ribonucleotide reductase. In the second part of the paper, we review a new hybrid theoretical method we have developed for modeling the reactivities of large molecular systems. We describe the limitations of these models and indicate how they may be further improved to reliably model the reactivities of complicated metalloenzymes.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes.

Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions.

Le scanner, dans le bilan d’un cancer bronchique, guide la réalisation de la bronchoscopie et précise si le cancer bronchique non à petites cellules (CBNPC) est potentiellement accessible à un traitement local ou s’il s’agit d’un stade avancé. Si une lésion suspecte de métastase est objectivée, sa ponction première permet la confirmation histologique et le staging. La présentation initiale est polymorphe, fonction du stade et du type histologique : nodule ou masse isolés, atélectasie ou pneumonie obstructive, atteinte ganglionnaire ou épanchement pleural isolés, miliaire dans les formes avec mutation epithelial growth factor receptor(EGFR). Le statut T dépend de la taille tumorale, de la distance à la carène, de l’envahissement pariétal et aux organes du médiastin. Le TEP est plus performant que le scanner pour l’extension ganglionnaire, N2 si elle est médiastinale homolatérale, N3 si elle est controlatérale ou sus-claviculaire. La règle doit être de valider toute contre-indication chirurgicale par une preuve histologique, métastases cérébrales mises à part.

We demonstrate experimentally how to harness quasi-periodic dynamics in a semiconductor laser with dual optical feedback for measuring subwavelength changes in each arm of the cavity simultaneously. We exploit the multifrequency spectrum of quasi-periodic dynamics and show that independent frequency shifts are mapped uniquely to two-dimensional displacements of the arms in the external cavity. Considering a laser diode operating at telecommunication wavelength λ≈1550  nm, we achieve an average nanoscale resolution of approximately 9.8 nm (∼λ/160).

Semiconductor to metal and semiconductor to insulator phase transitions in the α”'- and $\alpha $'-(ET)2Br1.3I1.1Cl0.6single crystals were investigated by Raman spectroscopy. A charge ordered nature of the insulating state of the α'-phase was confirmed. For the metallic $\beta $”-phase (α”' above 185 K) the Raman spectrum shows more bands than expected from the number of the C=C stretching agmodes. Key words. Organic conductors, Raman spectroscopy, charge order.

Starting from the first organic spin ladder reported, a dithiophene‐tetrathiafulvalene salt ((DT‐TTF)2[Au(mnt)2]) (mnt = maleonitriledithiolate), two different approaches to enlarge the family of organic spin‐ladder systems are described. The first approach consists of a molecular variation of the donor; to that purpose, the new TTF derivative ethylenethiothiophene‐tetrathiafulvalene (ETT‐TTF, 3), is synthesized and structurally characterized. From this donor a new ladder‐like structure compound, (ETT‐TTF)2[Au(mnt)2] (4), isostructural with (DT‐TTF)2[Au(mnt)2], is obtained. However, the magnetic properties of 4do not follow the known spin‐ladder behavior owing to orientational disorder exhibited by the ETT‐TTF molecules in the crystal structure. In the second approach, the acceptor complex is changed, either in the nature of the ligand or in the metal. With the [Au(i‐mnt)2]–salt (i‐mnt = iso‐maleonitriledithiolate), the new ladder‐like compound (DT‐TTF)2[Au(i‐mnt)2] (5), isostructural with 4, is obtained, but only as a minority product. Two other compounds with a different anion generated in situ, bearing a Au(I) dimeric core, were also isolated; (DT‐TTF)9[Au2(i‐mnt)2]2(6) as the most abundant phase and (DT‐TTF)2[Au2(i‐mnt)2] (7) as another minority phase. Salt 7is characterized by X‐ray crystallography as a chiral compound, due to the torsion of the ligands around the central Au–Au bond. The magnetic properties of (DT‐TTF)2[Au(i‐mnt)2] (5) indicate that it follows a spin‐ladder behavior and the electron paramagnetic resonance (EPR) data is fitted to the Troyer and Barnes and Riera equations with the parameters Δ/kB= 71 K, J∥/kB= 86 K, and J⟂/kB= 142 K, indicating a J⟂/J∥ratio of 1.65. The change of the gold complex [Au(mnt)2] for its copper analogue, [Cu(mnt)2] also leads to a ladder‐like structure, (DT‐TTF)2[Cu(mnt)2] (8), which is isostructural with the gold analogue and with salts 4and 5.The fully ionic salt (DT‐TTF)[Cu(mnt)2] (9) is also obtained. The magnetic properties demonstrated that compound 8is the third organic spin‐ladder system of this family, and the values found by a fitting to the ladder equations were Δ/kB= 123 K, J∥/kB= 121 K, and J⟂/kB= 218 K, corresponding to a J⟂/J∥ratio of 1.75, similar to that of 5and close to that of an ideal spin ladder.

Abstract:: This article reports the investigation of a new low-dimensional organic salt, (TTDM-TTF)2 [Au(mnt)2], by single crystal X-ray diffraction, static magnetic susceptibility, EPR, thermopower, electrical resistivity measurements under pressure up to 25 kbar and band structure calculations. The crystal structure consists in a dimerized head to tail stacking of TTDM-TTF molecules separated by layers of orthogonal Au(mnt)2 anions. The absence of overlap between neighboring chains coming from this particular crystal structure leads to an extreme one-dimensionality (1-D) for which the carriers of the half-filled conduction band become strongly localized in a Mott-Hubbard insulating state. This material is the first 1-D conductor in which the Mott-Hubbard insulating character cannot be suppressed under pressure.

Electrocrystallization of the novel π-electron donor (ethylenethio)(ethylenedithio)tetrathiafulvalene (ETEDT-TTF) with trihalide anions has given rise to a new family of radical cation salts with insulating properties, [ETEDT-TTF]X, and conducting properties, ETEDT-TTF]X0.42, where X = I3^- or IyBr3-y^-. According to X-ray data, in the isostructural completely ionic [ETEDT-TTF]X salts, the donor radical cations are strongly dimerized, with an interplane distance of 3.310−3.317 Å, and the mixed-valence [ETEDT-TTF](I3)0.42 salt is formed by segregated radical cation and anion layers alternating along the b axis. The latter salt exhibits semiconductor behavior with a high room-temperature conductivity of 24 S·cm^-1. The large angle between the molecular planes of the donors in neighboring stacks precludes the possible metallic behavior of this salt. Interestingly, nanocrystals of the mixed-valence salts are the conducting component of new bilayer (BL) composite films that have been generated via the ETEDT-TTF + I2 and ETEDT-TTF + IBr chemical reactions. The structure and composition of the conducting layers of these new BL films were confirmed by X-ray, EPR, and Raman spectroscopies. Similarly to the single crystals, these composite materials exhibit semiconducting behavior with a room-temperature conductivity ranging from 0.25 to 2.5 S·cm^-1. SEM and NIR studies of the film samples were also carried out.

The mechanism of copolymerization of CO2 with cyclohexene oxide catalyzed by the Zn(II) organometallic compound (BDI)ZnOCH3 (BDI = N(2,6-ⁱPr2C6H3)C(Me)CHC(Me)N(2,6-ⁱPr2C6H3) chelating β-diimine ligand) has been studied with the hybrid molecular orbital (MO) method ONIOM, combining the density functional method B3LYP/LANL2DZ(d) with the semiempirical MO method PM3. In particular, the insertions of CO2 and cyclohexene oxide/ethylene oxide into zinc−alkoxyl and zinc−carbonate bonds have been investigated in detail. The insertion of CO2 into either a zinc−alkoxyl (epoxide + CO2 alternating insertion) or zinc−carbonate (consecutive CO2 insertion) bond has been found to be thermodynamically less favorable but is in general kinetically favored over the insertion of epoxide, due to a high barrier for the latter. This high barrier is associated with a rather asynchronous transition state where the ring opening has taken place and yet the C−O bond is not formed. However, only in the case of insertion of sterically strained cyclohexene oxide into the zinc−carbonate bond is the barrier low enough to compete with CO2 insertion, resulting in alternating copolymerization. This lowering is driven by the release of the extra strain energy in the three- and six-membered-ring bicyclic structure in cyclohexene oxide. The rate-determining step in copolymerization is epoxide insertion, which can be controlled by the catalyst and the epoxide.

New conducting bilayer films (BL-film) containing (BEDT-TTF)2(IxBr1-x)3 molecular metals as active components have been prepared. The effect of various parameters of the BL-film preparation on the conducting layer composition was systematically studied by X-ray, Raman, EPR, and SEM. It was shown that the conducting layer of new BL-films is formed by “c” oriented (BEDT-TTF)2(IxBr1-x)3 nanocrystals which contain a set of the IBr2^-, I2Br^-, and/or I3^- anions. It was found that the α‘ → β phase transition takes place in the (BEDT-TTF)2(IxBr1-x)3 nanocrystals under film annealing. Some of the new composite BL-films, being flexible and transparent, reveal a metal-like temperature dependence of resistance down to nitrogen temperature.

Mechanistic aspects of the biological activation of O2 catalyzed by methane monooxygenase (MMO) were investigated by using a hybrid density functional method. The reduced form of the metalloenzyme was modeled by cis-(H2O)(NH2)Fe(η²-HCOO)2Fe(NH2)(H2O), where the O2 molecule may coordinate the Fe centers from two different sides, the H2O-side and the NH2-side, leading to two different mechanisms, O-side and N-side pathways, respectively. Calculations show that both pathways proceed via similar intermediates. The energy profile for the reaction of O2 coming from the O-side, however, is more consistent with available experimental data than for the N-side. On the other hand, the N-side mechanism is thermodynamically more favorable. This study suggests that, if the protein backbone did not block the N-side, the O2 molecule would most likely approach the dinuclear iron center from this side rather than from the O-side. Several mixed-valence intermediates have been found during the reaction, including an Fe^II−Fe^III mixed-valence species, P*, prior to formation of intermediate P, and a species similar to intermediate X in the analogous mechanism of Ribonucleotide Reductase, as well as an Fe^III−Fe^IV mixed-valence species prior to formation of intermediate Q. Our theoretical findings give support to the idea that electrons do not need to be transferred by pairs in the studied diiron system. This is the first time that a structure for intermediate P* has been proposed in the literature.

A flexible low‐density metallic material, which is extremely transparent, was obtained using as active component the highly conducting molecular metal θ‐(BET‐TTF)2Br·3H2O, BET‐TTF = bis(ethylenethio)tetrathiafulvalene. This material is a bilayer (BL) film that was prepared by treating a polycarbonate film containing 2 wt.‐% of molecularly dispersed BET‐TTF with vapor of a Br2/CH2Cl2solution. Optimum conditions for the preparation of very transparent metallic materials were established. The X‐ray diffraction patterns indicate that the conducting layer of the BL films is formed by well a* oriented θ‐(BET‐TTF)2Br·3H2O nanocrystals, which are clearly observed in the SEM images. Conductivity measurements confirm that the nanocrystalline layers have the same transport properties as those of the single crystals, displaying metal‐like behavior down to He temperature and the highest room temperature conductivity (120 Ω–1cm–1) reported so far for this kind of film.

The structure and stabilities of various intermediates of the “water-assisted” O−O bond activation reaction on the MMOHred and R2red were studied using the B3LYP hybrid density functional method, and are compared with those for the “water-free” model studies. It was shown that the first step of the reaction is coordination of the O2 molecule to one of the Fe atoms of complex I_H2O (“water-assisted” model complex) leading to formation of the mixed-valence superoxo species, [Fe^II(O2)^-Fe^III], II_H2O. Then, the second electron transfer from the other Fe atom to the O2 moiety leads to formation of the peroxo complex [Fe^III(O2)^2-Fe^III], which is found to have four different isomers, III_H2O, IV_H2O, V_H2O, and VI_H2O, corresponding to the cis-μ-1,2, end-on μ-1,1, distorted trans-μ-1,2, and μ-η²-η² coordination modes of O2, respectively. The stability (relative to I_H2O + O2) of these isomers increases via III_H2O (34.5 kcal/mol) < VI_H2O (36.4 kcal/mol) < V_H2O (44.7 kcal/mol) < IV_H2O (57.4 kcal/mol). On the basis of the structural analysis and calculated O−O bond distances, we have predicted that isomers III_H2O, V_H2O, and VI_H2O are intermediates on the potential energy surface of the homolytic O−O activation process, while isomers III_H2O and IV_H2O are intermediates of the heterolytic O−O activation reaction. The homolytic O−O activation by MMOHred is predicted to occur via the following intermediates:  I_H2O + O2 → II_H2O (superoxo species) → III_H2O (cis-μ-1,2-peroxo) → V_H2O (distorted trans-μ-1,2-peroxo) → VI_H2O (μ-η²-η² peroxo) → VII_H2O (compound Q with water) → VIII (compound Q). Having an additional water molecule around the active site of MMOHred (and R2red) facilitates the superoxo → peroxo conversion process because of the opening of one of the “legs” of μ−1,2-bridged carboxylate leading to formation of Fe¹-HOH...OCHO-Fe² network.

Theoretical calculations of ¹⁷O and ¹⁴N nuclear quadrupole coupling (NQC) constants (χ) and asymmetry parameters (η) for small α-helix and β-sheet protein fragments have been carried out using the density functional theory. This computational study is intended to shed light on the differences between the two major structural elements found in the secondary structure of proteins. Specific NQDR spectra are computationally simulated for the ¹⁷O and ¹⁴N nuclei inherent in protein backbones. The separate signals resulting from α-helices and β-sheet models are predicted to be experimentally distinguishable for ¹⁷O but not for ¹⁴N. In particular, we predict that the differences in χ (in MHz) between α-helix and β-sheet proteins in solution are Δχ(¹⁷O) = 0.53(15) and Δχ(¹⁴N) = 0.14(16), with the standard deviations in parentheses. It is found that ¹⁷O NQC parameters of proteins are dependent on the particular conformation of the backbone, specifically on the hydrogen bond angle θ = ∠H−N···O and the backbone dihedral angle ψ = ∠NC−C(O)N. Due to this, ¹⁷O NQC parameters are observably different in α-helices and β-sheets. Conversely, ¹⁷O NQC parameters are not dependent on the length of the hydrogen bond RO···N, as had been previously thought, nor are they dependent on either the hydrogen bond dihedral angle ξ = ∠N−C&dbd;O···H or the backbone dihedral angle φ = ∠C(O)C−NC(O). We also conclude that, unlike ¹⁷O NQC parameters, ¹⁴N NQC parameters of proteins are within the uncertainties identical for both α-helices and β-sheets. Finally, differing residues on protein side chains do not significantly affect the NQC parameters of the backbone C&dbd;O and NH groups, and can be modeled computationally by using glycine.

The bleaching effect was simulated in pilot plant by measuring the influence of temperature (40, 50, 60, 70, 80, and 90°C), time (5, 10, 15, 20, 25, and 30 min), and concentration of solid adsorbent [1.5 and 8% (w/w) of Tonsil supreme NFF] on stigmasta-3,5-diene (STIG) obtained by dehydration of steroidal compounds. Conditions were chosen to simulate those used in industrial operations. The presence of refined oils in extra virgin olive oil can be detected by these newly formed steroid hydrocarbons. Experimental results indicated that STIG did not exceed an imposed limit of 0.15 mg/kg in extra virgin olive oil, when oils were bleached with 1.5% earth at temperatures =80°C for 30 min in admixed to oils sold as virgin. A large proportion of the adulterations were not detectable by the official methods. Color determinations (CIE-1931) chromatic coordinates) were replicated on a refined oil and in admixed extra virgin olive oil. Color of olive oil was not significantly affected by mixing with refined oil (=20%).

Available experimental data for the active sites of the hydroxylase component of methane monooxygenase (MMOH) and the R2 subunit of ribonucleotide reductase (R2) indicates high flexibility of the ligand environment of the iron centers in these two metalloproteins, suggesting that carboxylate ligands may play a special role for proper enzymatic functioning. By using quantum chemical methods, here we have investigated (1) the so-called 1,2-carboxylate shift (i.e., shift of a bridging carboxylate ligand from μ-1,1 to μ-1,2 between two metal centers), and (2) the monodentate ↔ bidentate rearrangement of terminal carboxylate ligands (bound to only one metal center), in the reduced forms of MMOH and R2. Our results show that (i) MMOH-like and R2-like structures, with a μ-1,1 and μ-1,2 bridged carboxylate ligand, respectively, are energetically very close; (ii) complexes with lower coordination numbers in the Fe² center are computed to be slightly more stable than those with higher coordination numbers, and (iii) the two studied carboxylate shifts are easy processes, not only thermodynamically but also kinetically, with activation barriers of only a few kcal/mol. Our conclusion that the carboxylate ligands of dinuclear complexes such as MMOHred and R2red are very flexible is in a good agreement with the available experimental data.

A theoretical study has been carried out for the mechanism of the reactions of allylammonium and -iminium substrates with Ni(0) complexes using the B3LYP density functional method. The main findings are as follows:  (1) The actual active catalyst in the oxidative addition of ammonium and iminium salts is the bisphosphine−nickel complex. (2) For allylammonium salts the reaction is found to proceed via an associative mechanism (rather than a dissociative path) which involves (i) coordination of the allylammonium cation to the active metal catalyst, (ii) oxidative addition of the C−N bond to the Ni(0) complex, (iii) coordination of NH3 to yield a pentacoordinated intermediate, and (iv) loss of a phosphine ligand. The analogous reaction involving allyliminium salts does not follow the same mechanistic pattern; once the allyliminium cation is coordinated to the metal, the reaction prefers to proceed in a dissociative fashion. This preference is likely to be enhanced in solution. (3) The main difference between allylammonium and -iminium reaction mechanisms lies in the relative barriers corresponding to the insertion of the catalyst into the C−N bond leading to the pentacoordinated intermediate. For allylammonium cations, such a step is calculated to be less energy demanding than phosphine loss, whereas for allyliminium, the situation is reversed. (4) Finally the observed preference of allyliminium substrates to undergo C−N cleavage rather than N−H cleavage has been also investigated. The reason that allyl salt does not yield hydrido complexes is the kinetic impairment found for the N−H bond cleavage as compared to C−N. Intramolecular N−H activation is not allowed because of the high barriers corresponding to the three-centered transition states involved in the reaction. The structural rearrangements required for the coordinated iminium to form an η²-NH complex make the process prohibitive.

Revision of the homogeneously Fe(CO)5-catalyzed water gas shift reaction in the gas phase has been performed by means of quantum chemical calculations using gradient-corrected density functional theory (B3LYP) and ab initio methods at the CCSD(T) level. The classically assumed reaction path has been scrutinized step by step, and enlarged with novel mechanistic proposals. Our calculations lend additional credit to some of the previously accepted steps in the catalytic cycle, such as the initial attack of OH^- to Fe(CO)5 and also to the recently accepted decarboxylation of (CO)4FeCOOH^- (via a concerted mechanism involving a four-centered transition state), as well as to the acidification of the metal hydride (CO)4FeH^- with water to yield the dihydride (CO)4FeH2. The present investigation also examines in terms of energies and activation barriers the existence/participation of new intermediates (in particular, a metalloformate species, a water−hydride adduct, and a dihydrogen complex), not mentioned in prior studies. Finally, a transition-metal-containing SN2-type reaction is explored for the last stages of this chemical process as a mechanistic alternative to regenerate the starting catalyst.

The ¹⁴N nuclear quadrupole coupling (NQC) constants (χ) and asymmetry parameters (η) for a series of small nitrogen-containing imidazole derivatives are investigated, by using density functional theory (DFT), in three clearly distinct environments:  as free molecules, in the solid state, and in solution. The spectroscopic characterization is also extended to coenzyme B12 and cob(II)alamin systems. The main findings can be summarized as follows:  (i) Deviations in the calculated χ for the two nitrogen sites in the free imidazole molecule are small enough to allow quantitatively accurate predictions for isolated molecules of substituted benzimidazole compounds. (ii) Asymmetry parameters, however, are difficult to reproduce with accuracy; only trends along a series of compounds can be taken as informative. (iii) Shifts of the NQC parameters on going from gas phase to solid state are reasonably well reproduced at a qualitative level by using a trimer model; to reach similar levels of accuracy in the case of η, both the continuum and the point-charge effects need to be included. (iv) Short-range effects play an important role in the ¹⁴N NQC parameters of imidazole in solution, although the NQC constants are also sensitive to solvent molecules beyond the first shell. (v) Long-range effects taken into account by an averaged continuum model alone are not enough to reproduce the effect of hydrogen bonding with water on the ¹⁴N NQC parameters of imidazole; whenever water molecules are present, these solvent molecules have to be included explicitly. (vi) Metal−ligand interactions are relevant only for the NQC parameters of the proximal N, more specifically for the η value of this atom; most of the environmental effects in the real coenzymes are handled correctly by employing a solvated nonmetallic model. (viii) We estimate that the χ and η for the proximal nitrogen atom in cob(II)alamin (which so far has escaped experimental observation) will be approximately 2.7 MHz and 0.8, respectively, as indicated by our calculations.

Experiments to establish the site of biosynthesis and the possible translocation into microsomes of glutelins-2 (28 kD G2) and low molecular weight zeins (10, 14, 15 kD Z2) have been carried out. Free and membrane-bound polyribosomes as well as microsomal membranes were isolated from immature endosperms of W64A Zea mays L. In vitro translation studies were carried out in the presence and in the absence of membranes using [35S]-methionine or [35S]-cysteine as precursors. Cell-free translation products were characterized by electrophoretic mobility, solubility and antigenic properties. The results obtained indicate that 28 kD G2 and low molecular weight zeins are primarily synthesized on membrane-bound polysomes. From experiments using proteinase K as a probe, we also conclude that these proteins are translocated into microsomes where they accumulate. The translocated and pre-28 kD G2 proteins do not present changes in the apparent molecular weight. However we show that there are differences in their isoelectric points, a fact that indicates the existence of 28 kD G2 processing.

Accumulation of the 28 KD protein of the glutelin-(G2) fraction was followed in developing maize endosperm, using sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and peak integration of scanned gels. 28 KD glutelin-2 could already be observed from 15 days after pollination and its accumulates reached a plateau during the second half of the development period. The process of biosynthesis of 28 KD glutelin-2 and zeins occurs in a parallel way. Subcellular fractions obtained from linear sucrose gradient centrifugation of developing maize endosperms were analyzed by SDS-PAGE and immunoblotting using a serum reacting against glutelin-2 and 14 KD Z2. Glutelin-2 was found to be present in the protein bodies when subcellular fractionation was carried out without dithiothreitol (DTT). The presence of a reducing agent causes the elution of glutelin-2 from protein bodies. Immunocytochemical labelling using the protein A-colloidal gold technique in protein bodies incubated with anti-G2 IgG revealed that G2 is located mainly in the periphery of protein bodies. These results are interpreted as indicating a structural role for glutelins in protein bodies.

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The postulated intermediates in the base-free and base-assisted addition of OsO4 to olefins have been optimized using density functional theory (DFT). Ammonia was chosen as the base and ethylene as the olefin. The corresponding transition states have been characterized fully. Further, the activation barriers have been computed at the nonlocal level, and special attention has been given to the two different mechanistic hypothesis proposed for this reaction. In particular, the hypothesis by Sharpless of a [2+2]-cycloaddition pathway involving the formation of a four-member ring as an intermediate has been ruled out since the corresponding activation barrier was calculated to be as high as 39 kcal mol^-1. The addition of a NH3 ligand to the osmium catalyst does not reduce significantly the [2+2] energy barrier. By contrast, it seems perfectly feasible that the dihydroxylation reaction proceeds through a [2+3] mechanism leading to the formation of a five-member ring intermediate as claimed by Corey. Such a process is found to be clearly exothermic and to involve a very small activation barrier of less than 2 kcal mol^-1. A detailed analysis of the sequence describing exactly how the cycloaddition proceeds along the reaction path has also been performed by means of intrinsic reaction coordinate (IRC) calculations for the two studied mechanisms.

A case-control study on diet and gastric cancer, carried out in selected areas of four regions of Spain (Aragon, Castile, Catalonia, and Galicia) in 1988 and 1989, included 354 cases of histologically confirmed gastric adenocarcinoma and 354 controls matched by age, sex, and area of residence. Cases and controls were selected from 15 hospitals, representing most of the hospital facilities in the study areas. Usual diet was estimated by means of a dietary history questionnaire administered by interview. An increased risk of gastric cancer was observed for high consumption of exogenous nitrosamines (odds ratio = 2.1 for the highest quartile of consumption versus the lowest; p for linear trend = 0.007), nitrites, fat, and cholesterol. However, in a multivariate regression model, the effect of fat and cholesterol disappeared. An inverse association with the risk for gastric cancer was seen for high intake of fiber, vitamin C, folate, carotene, and nitrates. High consumption of vitamin C seemed to neutralize the increased risk related to simultaneous consumption of nitrosamines. For histologic type, the authors found no meaningful differences in the effect of most of the nutrients between intestinal and diffuse cancers. Their findings are consistent with previously reported results about the protective effect of fruit and vegetables and the increased risk associated with foods that are important sources of nitrites and preformed nitrosamines.

We show that maize storage protein translocation across microsomal membranes is mediated by signal recognition particles (SRPs) similar to those described in animal systems (Dobberstein, B. (1978) Hoppe-Seyler's Z. Physiol. Chem. 252, 955-962; Walter, P., and Blobel, G. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 7112-7116). We have prepared a high salt extract from endosperm cell homogenates, from which a ribosome-free fraction was obtained. This fraction is enriched in an SRP-like factor which apparently corresponds to a ribonucleoprotein particle that sediments at about 12 S. The RNA moiety of this 12 S particle is complex, showing a three-band electrophoretic pattern and sedimenting at about 8 S. The fraction restores translocation competence of salt-washed maize microsomes as tested by using a pre-zein message. In contrast to canine SRPs, the maize SRP-like component does not cause a translation arrest of maize storage proteins (zein) in a wheat germ cell-free system.

A new type of boundary condition, named Möbius or antiperiodic boundary conditions, is proposed and tested, both analytically and within the context of numerical simulations. It is shown that these boundary conditions are very useful for twist grain boundary atomistic simulations. By contrast to the use of the ordinary Born von Kármán periodic boundary conditions, they allow only one grain boundary per box instead of two. The risk of migration and overinteraction of two grain boundaries at high temperature is thus avoided while more complex grain boundaries can also be tackled at the same computer price. Such examples are presented and discussed.

Density functional calculations are reported for the molecular structures, harmonic vibrational frequencies, UV/visible spectra, and oxo-transferability of MoO2X2 (X = F, Cl, Br, I). Available experimental data have been used to check the validity of the theoretical calculations. Given the good agreement between theory and gas-phase experiment, predictions have been issued for the less studied members of this family of compounds. Furthermore, electronic spectra of the full series have been computed for the first time. For all transitions studied, excitation energies decrease in the order F > Cl > Br > I. Finally, the labilization of Mo(SINGLE BOND)O bonds generated by the HOMO(SINGLE BOND)LUMO transition, which is related to the oxygen-atom transfer reaction in the active site of molybdenum oxidoreductases, was also investigated. For MoO2Cl2 and MoO2Br2 compounds, the HOMO-LUMO transition yields a considerable lengthening of the Mo(SINGLE BOND)O bond, yet not requiring a large excitation energy. © 1997 John Wiley & Sons, Inc.

Two different mechanistic proposals have been investigated theoretically for the initial steps of the chromium-assisted Dötz benzannulation reaction at the nonlocal density functional level of theory. The energy requirements needed for the reaction to start through the usually assumed CO-dissociative mechanism are calculated to be 144.7 kJ mol^-1 for (CO)5Cr&dbd;C(OH)(C2H3) (1). Under the mild thermal experimental conditions, the decarbonylation step may be sometimes a serious bottleneck for the reaction to proceed, even to the extent of completely blocking the formation of the subsequent tetracarbonyl compound (CO)4Cr&dbd;C(OH)(C2H3) (5), which is supposed to add an alkyne molecule in the second step. An alternative path is suggested, where the alkyne reacts directly with the saturated metal−carbene complex 1 instead of competing with a CO molecule for a position in the coordination sphere of the metal center in 5. Our calculations reveal that if alkyne addition takes place in 1 before CO loss, then the initial process becomes clearly exothermic (−163.4 kJ mol^-1). Moreover, this alternative path makes it easier for CO dissociation to occur as the second step because at this point the complex has more internal energy than 1 to expel a CO ligand. From a comparison of both mechanistic routes, it is concluded that the Dötz reaction better proceeds initially through an associative step.

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When we stimulated 3T6 fibroblasts, we observed a mobilization of arachidonic acid (AA) from phospholipids. The magnitude of this response decreased as the cells became confluent and the change coincided with a decrease in the percentage of cells in growth phases (G2+ M); this was not a consequence of the time in culture or a factor in the growth medium. Preconfluent fibroblasts incubated with the calcium ionophore A23187 (1 μM), 4β-phorbol-12-myristate acetate (PMA, 10 μM), bradykinin (10 μM) or fetal calf serum (20%) released 38.8%, 62.5%, 11.2% and 45.6% [3H]AA, respectively. Confluent cells stimulated under the same conditions released only 16.9%, 1.5%, 0.5% and 18.5% [3H]AA, respectively. This decreasing mobilization of AA was demonstrated using metabolic labelling and measurement of prostaglandin PGE2. The decrease was not due to a changing pool of AA. [3H]AA release from each phospholipid decreased with confluence. Conversion of confluent cells to the proliferative phenotype by mechanical wounding of the monolayer increased the release of [3H]AA. This effect is consistent with regulated, growth-dependent changes in the activity of phospholipase A2, a process regulated by changes in phosphorylation of the enzyme. The increased release of [3H]AA from preconfluent, actively dividing cells may have important physiological implications and may help elucidate mechanisms regulating release of AA.

The transient dynamics of a single-mode semiconductor laser subjected to both weak optical feedback and light injection is studied. Even at detuning values for which injection locking is not effective, turn-on jitter and frequency jitter can still be strongly reduced by adjusting either the length of the external cavity or the detuning.

We present a systematic comparison of several tight-binding total-energy modelisations of silicon. These modelisations include the tight-binding electronic cohesive energy and a phenomenological description of a repulsive term. We examine both the electronic band gap and various structural properties such as structural stability, bulk modulus, elastic constants, four typical vibrational modes and their Grüneisen constants. We then apply these models to the calculations of the minimised energies of some multivariant grain boundaries. We discuss the influence of the choice of cut radii.