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Achieving fine control over the dispersion of supported platinum nanoparticles (Pt) is a promising avenue to enhancing their catalytic activity and selectivity. Experimental observations suggest that exposing ceria-supported Pt nanoparticles to O2at 500 °C promotes their dispersion into smaller particles and eventually single atoms. The exact role of oxygen in this process is not yet well understood. Past density functional theory studies of ceria-supported Pt have typically narrowed their scope to single atoms and clusters of a few atoms. Herein, we combine several approaches and types of models in a consistent atomistic framework to evaluate the relative stability of ceria-supported Pt as a function of the degree of oxidation of Pt and of the particle size, ranging from single atoms to nanoparticles 1.5 nm of diameter. We find that the largest nanoparticles remain the thermodynamically most stable species on the lowest energy facet of ceria even under oxidizing conditions, suggesting that stronger adsorption sites are required to stabilize smaller clusters and single atoms and promote oxidative dispersion.

Density functional theory calculations are performed to develop atomistic surface models of ruthenium lithium amide catalytic interfaces. In preamble, the stability study of all the LiNH2(001) terminations demonstrates a preference for NH2-terminated surfaces with hydrogen pointing toward vacuum and a possibility to reconstruct metastable systems by rotating all the terminal NH2moieties. Then, the elaboration of interface models between Ru(0001) and LiNH2(001) surfaces is performed, which is strongly inspired from a preliminary study of isolated adsorption of lithium and NH2on Ru(0001). The competitive adsorption of these species leads to two possible contacts to interface Ru and LiNH2materials: either through lithium or NH2. Numerous interface models are optimized by considering the influences of LiNH2(100) thickness, its stoichiometry, and its polarity, including spin polarization and van der Waals interactions. The most stable interfaces are composed of NH2planes chemisorbed on Ru(0001). The contact via Li atoms leads to a family of highly metastable interfaces. Surprisingly, the five most competitive interfaces are all non-stoichiometric. The interface stability is then correlated to Bader charge transfer analysis. This study questions the specific catalytic role of lithium in the context of hydrogen storage and the reaction mechanism of ammonia decomposition on ruthenium lithium amide catalysts.

Monometallic platinum and nickel nanoparticles and platinum–nickel nanoalloys are examined in the range 13–976 atoms from density functional theory calculations. A large set of competitive symmetries and morphologies are considered including the usual Mackay icosahedral, Marks decahedral, and truncated octahedral forms. A comparative analysis of relative stability order is addressed on the basis of four stability descriptors all predicted at the ab initiolevel from spin-polarized calculations including van der Waals interactions. For platinum nanoparticles, they unanimously conclude on the preference of truncated octahedral morphology in the range of 147–201 atoms. For nickel and platinum–nickel nanoclusters, three descriptors (cohesion energy, nanoparticle surface energy, and vibrational band center) also support such octahedral symmetry (with a skin–heart chemical ordering for nanoalloys), whereas the excess energy rather favors the icosahedral morphology (with multishell and core–shell arrangement). Such discrepancies feed the debate related to the impact of normalization on the predictive power of these descriptors and recall the high importance of validating theoretical models from a quantitative standpoint. This work invites the experimentalists to synthesize, characterize, and measure surface energetics of PtNi nanolloys in highly controlled operating conditions.

Silver nanoparticles have been modeled by density functional theory calculations and ab initiomolecular dynamics simulations to explore their stability in air at room temperature. The role of contaminants is considered by adsorbing monoshells of methanethiol molecules on silver nanoparticles of various morphologies (icosahedral, strongly irregular and regular truncated octahedral structures) in the range of 147–201 atoms (∅= 1.66–1.80 nm), under atmospheric nitrogen pressure. While ab initiomolecular dynamics simulations suggest that the icosahedral and all the face-centered cubic FCC clusters are stable at 300 K under vacuum, the ino-decahedral geometry progressively transforms into a complex structure composed of an irregularly icosahedral outershell and a decahedral core. Nanoparticle surface energies, computed at 0 K and 300 K, show a preference for FCC clusters in vacuum, as previously reported experimentally. In the presence of air at 300 K, the icosahedral cluster presents the largest exothermicity in terms of adsorption surface energy of contaminant monoshells. This energetic gain is understood on the basis of a larger surface silver atomic density for the icosahedral structure, which better accommodates dense contaminant monoshells than FCC clusters. The methanethiol adlayers are composed of a complex phase of chemisorbed molecules bound to silver and in interaction with physisorbed contaminants through hydrogen bonds. This theoretical study agrees with measurements of silver nanoparticles exposed to air after synthesis in vacuum and also investigated in solution, and demonstrates that the air environment tunes the relative stability of morphologies in competition. This work paves the way for the understanding of nanoparticle ageing in environmental conditions at the atomic scale.

Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Functionalizing nickel nanoparticles with ligands, such as phosphines, can enhance their catalytic performance. However, the ligand effects are poorly known at the molecular level. In this work, the adsorption properties of trimethylphosphine (PMe3) on Ni nanoparticles (NPs) and extended surfaces were investigated via spin-polarized dispersion-corrected density functional theory calculations. The coverage effect of phosphine was explored by considering monoadsorption and monoshells on NPs and various adlayers from low coverage to saturation on surfaces. Icosahedral, ino-decahedral, cuboctahedral, truncated octahedral, and Marks-decahedral Ni nanoclusters at a size of 146–147 atoms were compared to the Ni(111), (100), and (110) surfaces. PMe3strongly adsorbs on Ni surfaces and NPs, with a clear preference for the icosahedron. The chemisorption on extended surfaces is globally stronger than the adsorption on NPs, demonstrating the necessity of describing NPs by explicit models. The topological analysis shows the formation of a Ni–P covalent dative bond with a net electronic donation from phosphorus to nickel. The presence of strongly chemisorbed PMe3weakens the total Ni magnetization by specifically quenching the spin polarization at Ni atoms bound to ligands. Our results invite the scientific community to explore the stability and reactivity of other phosphine ligands on metallic nanoparticles.

Statistical mechanics and transition-state theory have been used to investigate the diffusion kinetics of gold and copper atoms on pristine and various reduced surfaces of rutile TiO2(110). A DFT+Uapproach has been employed to calculate potential energy maps and to evaluate the required diffusion activation barriers. The role of the support reducibility has been examined on the adsorption properties (optimal structures, energetics, and spin polarization) and diffusion kinetics, especially for the reduced support presenting a single subsurface oxygen vacancy. This approach has allowed us to demonstrate key discrepancies between Au and Cu atoms and to sketch out a comparative scenario for the early-stage nucleation of Au and Cu nanoparticles on the various surface states of TiO2(110).

The role of the support anatase TiO2(100) and rutile TiO2(110) on the energetics, the shape, and the charge transfer of deposited CuAu nanoclusters (∼1 nm) has been examined by using density functional theory (DFT) calculations including Hubbard correction (DFT + U). Regular truncated octahedron clusters, Cu(1–x)Au(x)(xbeing in the range 0.15–0.36), representing different alloy types (core@shell, regular alloy, skin–heart), have been considered. From a thermodynamic standpoint, the core–shell-deposited nanoclusters present the strongest adsorption strength on both rutile and anatase supports, although they are the least stable homotops in vacuum. Interestingly, for skin–heart and regular alloy CuAu clusters, the stability on these supports decreases with the Au content. CuAu nanoclusters present larger adsorption energies on rutile than on the anatase support. This result has been explained by a Bader analysis of charge transfers and an energy decomposition analysis model, which shows a larger binding energy between the metal and the rutile support than that on anatase, in part compensated by the stronger deformation of the structure of rutile. At the size of 38 atoms, the bimetallic cluster exhibits a significant propensity to distort its structure and adapt it to the geometry of the oxide surface to maximize the stability of the formed metal–oxide chemical bonds. Such an interesting property is expected to decay with the increasing size of the metallic nanocluster. This work provides an original discussion related to the support effect, which is rarely evoked in the literature of DFT studies of such supported alloy clusters at the nanoscale.

Electrocatalysts are mainly characterized by their intrinsic adsorption properties. However, the observed electrocatalytic activity ultimately results from the interplay between such properties and various additional interactions within the electrified solid–liquid interface. One of such phenomena is solvation, which can substantially affect the stability of adsorbates. The incorporation of solvation in computational electrocatalysis models can be fully implicit (inaccurate for H-bonded adsorbates), fully explicit (challenging computation of free energies), or embedded. Here, we show that without any need for explicit or implicit media, a microsolvation approach with just three water molecules captures the contribution of co-adsorbed water to the adsorption energies of *OH and *OOH (two important adsorbates for oxygen reduction) on platinum nanoparticles of various sizes. The approach enables an accurate yet inexpensive explicit modeling of solvent–adsorbate interactions in nanoparticles and the calculation of solvation corrections, estimated as −0.59 ± 0.14 and −0.47 ± 0.13 eV for *OH and *OOH adsorption on Pt, respectively.

Presents the short story "The Silver Medalist," by Beth Loffreda.

In this study, density functional theory (DFT) calculations are presented for molecular and atomic oxygen adsorption on the Pt(111) surface at low coverage. The final goal is the atomistic description of oxygen dissociation kinetics in order to feed a multiscale kinetic model which simulates the Polymer Electrolyte Membrane Fuel Cell (PEMFC) electrochemical behavior. For molecular oxygen, the most favorable adsorption structure is top-top and shows an adsorption energy of -0.80 eV in agreement with previous studies. For atomic adsorption, only the threefold fcc and hcp hollow sites are stable at this coverage (-1.22 eV and -0.85 eV, respectively), in contrast with previous results.

Recently we presented high-resolution electron energy loss spectroscopy (HREELS) and temperature-programmed desorption (TPD) studies on the adsorption of prenal (3-methyl-2-butenal) and crotonaldehyde (2-butenal) on Pt(111) and on ultrathin Pt3Sn/Pt(111) and Pt2Sn/Pt(111) surface alloys. Vibrational studies employing HREELS have been analyzed with the help of extensive density functional theory (DFT) calculations of the energetic, structural, and vibrational properties of a large set of stable adsorption configurations. We were able to identify various adsorbate structures ranging from low hapticity η1-top and η2-diσ(CC) to flat η4types present in mixed phases below room temperature on these substrates. Completing this study, we now analyze common features and differences between the two molecules on the three surfaces. The key finding is that the adsorption energy turns out to be an unsatisfying measure of the interaction strength of such complex molecules on surfaces. For several identified structures lower desorption temperatures and smaller adsorption energies from DFT corroborated a weaker adsorption strength; however, vibrational and geometric properties obtained consistently from experiments and theory pointed to similarly strong molecule−surface bonding. We will show here that this phenomenon can only be rationalized by clearly differentiating between adsorption energy and interaction energy. Since the adsorption process includes significant relaxations of surface metal atoms and adsorbed molecules to optimize their covalent interactions, there is a deviation between the adsorption strength, measured by the interaction energy, and the final adsorption energy where the endothermic energetic costs of both relaxation processes have to be taken into account. Calculating these properties from DFT, we can show that adsorption energies may indeed decrease while the overall interaction energy of a molecule with a surface can, nonetheless, increase. The adsorption energy is hence not a good, unambiguous measure of molecule−surface interactions.

The seven oil lamps come from the antiquity dealers of Jerusalem and belong to the Museum of the Studium Biblicum Franciscanum or to some professors of the same Institute.Their Greek inscriptions are either very rare or completely new. The bibliography will help the reader to follow the increasing variety of types and subtypes discovered since the publication of LS1987.

By employing high-resolution electron energy loss spectroscopy (HREELS), temperature-programmed desorption (TPD), and low-energy electron diffraction (LEED), we have studied the adsorption and thermal decomposition of crotonaldehyde (2-butenal) on Pt(111) as well as Pt3Sn/Pt(111) and Pt2Sn/Pt(111) surface alloys. In order to understand the adsorption structures and the vibrational properties, an extensive theoretical study of the possible adsorption geometries and vibrational spectra on the three considered surfaces has been carried out using density functional theory (DFT). A careful analysis of the variety of possible adsorption configurations of crotonaldehyde allowed structural identification by correlating their vibrational fingerprints with the measured HREELS peaks. The mixed phases of crotonaldehyde formed on the model catalysts turned out to be even more complex than those we found in previous studies for prenal. The set of stable configurations identified by combination of HREELS with DFT consists of η2, η3, and η4flat adsorption structures, which exhibit adsorption energies from −69 to −80 kJ/mol. Nonetheless, the thermal decomposition measured with TPD and the general adsorption behavior show similarities to prenal and acrolein. Starting from a strongly adsorbed state on Pt(111) at low temperatures, crotonaldehyde decomposes at temperatures close to 300 K. On the surface alloys, a high-coverage phase with structures of low hapticity such as η2-diσ(CC) is measured at low temperatures (∼160 K), and a low-coverage situation of high hapticity η2, η3, and η4configurations is formed at higher temperatures (∼200 K). On Pt3Sn/Pt(111), two energetically competitive η1-top-E-(s)-trans-OSn forms cannot be excluded at low temperatures.

Amine ligands are expected to drive the organization of metallic centers as well as the chemical reactivity of silver clusters early growing during the very first steps of the synthesis of silver nanoparticles viaan organometallic route. Density functional theory (DFT) computational studies have been performed to characterize the structure, the atomic charge distribution, and the planar two-dimensional (2D)/three-dimensional (3D) relative stability of small-size silver clusters (Agn, 2 ≤ n≤ 7), with or without an ethylamine (EA) ligand coordinated to the Ag clusters. The transition from 2D to 3D structures is shifted from n= 7 to 6 in the presence of one EA coordinating ligand, and it is explained from the analysis of the Ag–N and Ag–Ag bond energies. For fully EA saturated silver clusters (Agn–EAn), the effect on the 2D/3D transition is even more pronounced with a shift between n= 4 and 5. Subsequent electron localization function (ELF) and quantum theory of atoms in molecules (QTAIM) topological analyses allow for the fine characterization of the dative Ag–N and metallic Ag–Ag bonds, both in nature and in strength. Electron transfer from ethylamine to the coordinated silver atoms induces an increase of the polarization of the metallic core.

The adsorption of CO on the two terminations, p(2 × 2) and (√3 × √3) R30°, of the bulk Pt 3Sn(111) alloy is studied by high pressure polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). The influence of O 2is also investigated. While no differences are observed when CO is chemisorbed alone, the behavior of the two terminations clearly differs in presence of O 2. The presence of oxygen induces modifications on the (√3 × √3)R30° surface. Finally we study how the interaction between O 2and the surface modifies the reactivity. Hence we show that the p(2 × 2) termination is more efficient than the (√3 × √3) R30° for CO oxidation. However this termination remains more efficient than pure platinum.

The adsorption and thermal decomposition of the ,-unsaturated aldehyde prenal (3-methyl-2-butenal) have been studied on Pt(111), the Pt3Sn/Pt(111) and Pt2Sn/Pt(111) surface alloys, and the corresponding terminations of the Pt3Sn(111) bulk alloy by means of high-resolution electron energy loss spectroscopy (HREELS), temperature-programmed desorption (TPD), and low-energy electron diffraction (LEED). By comparing the experimental results with extensive theoretical calculations of the multitude of possible adsorption configurations of prenal using density functional theory (DFT), the adsorption configurations actually present on all model catalysts have been identified. This approach, thus, reveals a new way to identify complex, multifunctional molecules adsorbed on model catalyst surfaces. On Pt(111), prenal is strongly adsorbed and decomposes at approximately 300 K. By the aid of density functional theory (DFT), five flat-lying adsorption structures of 2, 3, and 4hapticity, which exhibit similar adsorption energies Eadsbetween −47 and −59 kJ/mol, have been identified on the surface. The adsorption energy of prenal on the considered Pt−Sn alloys is significantly weaker. On the Pt3Sn and the Pt2Sn/Pt(111) surface alloys, the HREEL spectra recorded at 170 K are essentially assigned to two vertical 1-top-(s)-trans configurations (Eads−39.1 and −30.8 kJ/mol on Pt3Sn and −33.4 kJ/mol on Pt2Sn) adsorbed atop the protruding Sn atoms. Due to the weak adsorption of these structures, the vibrational frequencies are only slightly perturbed as compared to their corresponding gas-phase values. The primary role of tin is a general weakening of the adsorption of prenal on the alloy surfaces. While on Pt(111), flat adsorption configurations are preferred, alloying with tin induces a drastic change in the adsorption geometries to vertical 1-top forms. On the alloy surfaces, generally an oxygen−tin interaction is required to form competitive adsorption structures at all, whereas a coordination from the aldehydic function to a Pt is hardly stable.

Periodic density functional calculations are reported for NO dissociation on the Rh(221) and RhCu(221) surfaces. The analysis of the reaction pathways indicates that the presence of steps results not only in new adsorption sites for NO adsorption but also on the appearance of a completely new reaction pathway with activation energies which are smaller than those found previously for the regular Rh(111) surfaces. At low NO surface coverage and a small Cu density, the presence of Cu on Rh(221) does not change the reactivity of rhodium stepped surfaces toward NO dissociation, since the effective activation energy barrier is higher (1.32 eV for RhCu(221) versus 1.17 eV for Rh(221)). The essential reason is the increased metastability of the step sites. However, for stronger NO coverage or a higher Cu density, the stepped RhCu(221) surface is expected to exhibit an enhanced activity:  either by increasing the occupancy of these metastable sites along the RhCu steps or by removing the possibility of highly stable pure Rh bridge step sites.

Vibrational insights into the CO adsorption states on the (2 × 2) surface of the Pt3Sn(111) bulk alloy are reported for the first time by a systematic comparison between high-resolution electron energy loss spectroscopy (HREELS) measurements and density functional theory (DFT) anharmonic frequency calculations. CO adsorbs preferentially in top configuration on Pt atoms. In contrast with Pt(111), CO multifold sites are observed only at low coverage. This difference is interpreted on the basis of the relative stability between top and threefold hollow sites on Pt3Sn(111) compared to Pt(111). The evolution of the CO vibrational bands as a function of temperature shows that CO adsorption is weakened by the presence of tin; this result is confirmed by DFT calculations.

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A new method has been recently developed for the hydrodesulfurization of gasoils based on the formation of charge transfer complexes. This method is highly selective towards the removal of alkyldibenzothiophenes from other aromatic compounds present in gasoils. Total energy calculations based on density-functional theory have been performed to study the complexation phenomenon and clarify its high selectivity. DFT calculations improve the understanding of the process and they are also useful for the design of more efficient acceptor derivatives for the desulfurization process. Five charge transfer complexes between a given acceptor and five representative donor compounds present in gasoils have been studied. Three main criteria have been used to characterize the optimized complexes: their complexation energy, their geometry and their electronic structure. The decomposition of total energy showed that the main contribution to the complexation energy comes from the Pauli repulsion and the electrostatic interactions. Hence the charge transfer complexes are not only ruled by charge transfer but also by electrostatic contributions. However, the selectivity of the complexation phenomenon is controlled by the orbital interactions.

In the present work different adsorption modes of trichloroethene on the PdCu alloy have been investigated systematically. With application of ab initio periodic density functional theory, some insights about these adsorption modes have been revealed. The two different (110) terminations of the Cu3Pd alloy have been employed as models for the surface region of the Cu50Pd50 alloy because of Cu segregation. They are based on the regular phase of the face-centered cubic (fcc) structure. The first model shows a mixed (Pd/Cu =1) top layer, whereas the other one is Cu-terminated. The analysis of the position of the center of the d-band projected on the Pd and Cu atoms of both surfaces indicated that the Pd atom in the alloy has similar reactivity to the pure metal surface, whereas the opposite trend has been found for the Cu atoms. This has also been confirmed by the adsorption energy, calculated for the distinct modes. Trichlorethene prefers to interact with the Pd atoms on the mixed PdCu surface. Both di-σ and π modes are the most stable configurations among all studied. On the other hand, the adsorption via the chlorine atoms is the preferred on the Cu-terminated surface. The interaction of the C&dbd;C bond of trichloroethene on the Pd atoms is similar to the one of the ethene molecule. The main difference between the adsorption of these two molecules is due to the extra chlorine interactions with the Cu atoms. This allows one to suggest that the di-σ configurations are the precursors of the dissociation reaction on the mixed surface.

Chronic hepatitis C virus (HCV) infection has been associated with development of mixed cryoglobulinemia type 2 (MC2), a lymphoproliferative disorder characterized by B cell monoclonal expansion and immunoglobulin M/k cryoprecipitable immunoglobulin production. A short sequence (codons 384-410) of the HCV E2 protein, which has the potential to promote B cell proliferation, was investigated in 21 patients with HCV-related MC2 and in a control group of 20 HCV carriers without MC2. In 6 of the 21 (29%) patients with MC2, all the clones isolated from plasma, peripheral blood mononuclear cells, and liver showed sequence length variation compared with the hypervariable region 1 (HVR1) consensus sequence; 5 patients had an insertion at codon 385, and 1 patient had a deletion at codon 384. Inserted residues at position 385 were different within and between patients. No such mutations were observed in any of the HVR1 clones from control patients without MC2, and the difference between the 2 groups was statistically significant (P = .02). Analysis of 1345 HVR1 sequences obtained from GenBank strongly supported the conclusion that the observed insertions and deletion represent a rare event in HCV-infected patients, suggesting that they are significantly associated with MC2. The physical and chemical profiles of the 385 inserted residues detected in the MC2 patients were consistent with the possibility that these mutations, which occurred in a region containing immunodominant epitopes for neutralizing antibodies and binding sites for B lymphocytes, may be selected by functional constraints for interaction with host cells.

Chronic hepatitis C virus (HCV) infection has been associated with development of mixed cryoglobulinemia type 2 (MC2), a lymphoproliferative disorder characterized by B cell monoclonal expansion and immunoglobulin M/k cryoprecipitable immunoglobulin production. A short sequence (codons 384-410) of the HCV E2 protein, which has the potential to promote B cell proliferation, was investigated in 21 patients with HCV-related MC2 and in a control group of 20 HCV carriers without MC2. In 6 of the 21 (29%) patients with MC2, all the clones isolated from plasma, peripheral blood mononuclear cells, and liver showed sequence length variation compared with the hypervariable region 1 (HVR1) consensus sequence; 5 patients had an insertion at codon 385, and 1 patient had a deletion at codon 384. Inserted residues at position 385 were different within and between patients. No such mutations were observed in any of the HVR1 clones from control patients without MC2, and the difference between the 2 groups was statistically significant (P= .02). Analysis of 1345 HVR1 sequences obtained from GenBank strongly supported the conclusion that the observed insertions and deletion represent a rare event in HCV-infected patients, suggesting that they are significantly associated with MC2. The physical and chemical profiles of the 385 inserted residues detected in the MC2 patients were consistent with the possibility that these mutations, which occurred in a region containing immunodominant epitopes for neutralizing antibodies and binding sites for B lymphocytes, may be selected by functional constraints for interaction with host cells.

We present total energy and N−O stretching frequency calculations for the low-coverage adsorption of NO on palladium−manganese Pd3Mn (100) and (111) surfaces, on the basis of density-functional theory periodic calculations. A complete description of all the different adsorption sites and corresponding N−O vibrations is given and a theoretical interpretation of the experimental IR spectra is proposed. On both Pd3Mn (100) and (111) surfaces, the highly coordinated vertical adsorption sites are always energetically favored. The atop adsorption on the surface manganese atom is also a stable site. On Pd3Mn (100), a new horizontal dibridge site is reported. The adsorption on these palladium−manganese alloy surfaces is weaker than the adsorption on the pure corresponding palladium surfaces. The anharmonic N−O stretching frequencies on the Pd3Mn surfaces are shifted by 60−100 cm^-1 toward the lower frequencies by comparison with the pure palladium surfaces. The weakening of the adsorption strength and the global shift for the N−O frequencies has been correlated with the presence of the surface manganese atoms, which play a predominant role for the electronic interactions between the magnetic NO molecule and the alloy periodic surface. An interpretation of the alloying effect on the strength of the N−O bond and the NO adsorption is proposed on the basis of a qualitative Mulliken population analysis. The empty states on the surface manganese atoms are responsible for an increased electron-transfer toward NO, and hence of the smaller vibrational frequency on the alloy compared to pure Pd. Indeed these empty states interact with the π*NO and push it below the Fermi level, resulting in a transfer from the “surface electron reservoir” toward the π*NO molecular orbital.

To explain the beneficial effect of Mn addition to Pd catalysts in CO–NO conversion, a detailed study of the surface structure and composition of the catalytic sites was undertaken. The combination of analytical microscopy and EXAFS confirms the presence of bimetallic particles in which manganese is partly alloyed to palladium, as described in Part 1 (A. J. Renouprez, J. F. Trillat, B. Moraweck, J. Massardier, and G. Bergeret, J. Catal.179, 390 (1998)). Monte-Carlo modeling coupled with a simple energetic model and low-energy ion scattering (LEIS) shows that Mn has a larger concentration at the surface of the particles than the mean value measured by chemical analysis. This is attributed to a segregation of this element at the surface. To establish a correlation between the structure of these particles and their reactivity, infrared experiments of CO, NO adsorptions and coadsorption were carried out at both 300 and 573 K. The measured frequencies were interpreted on the basis of density functional theory (DFT) quantum chemical calculations. At 300 K, on pure Pd, CO and NO are located on the same sites and are displaced by each other. On the alloys, both molecules remain partly on the surface on adsorption of the other. DFT calculations show that the Mn atom at the surface induces a significant shift of the NO stretch frequency to lower values, especially if a Mn atom is present in the surface site. On mixed Pd–Mn sites, the chemisorbed NO molecule is found in a geometry quasi-parallel to the surface, with a long N–O bond and a low stretch frequency. This structure is stable on Pd3Mn, but not on pure Pd. This lying down geometry is a precursor for the dissociation. A dual-functional mechanism for the NO reduction, involving Mn oxides with oxygen vacancies and this form of adsorbed NO, is proposed.

The pharmacokinetics of cefodizime, a new expanded-spectrum cephalosporin for parenteral use, was studied in 45 subjects with various degrees of renal failure. Patients were divided into five groups according to the following creatinine clearances: group I >80 ml/min; group II <80–30 ml/min; group III <30–15 ml/min; group IV <15–5 ml/min and group V <5 ml/min. Cefodizime was administered as a 1 g i.v. bolus. Plasma and urinary concentrations of cefodizime were determined by high-performance liquid chromatography, using for detection UV absorbance. The following pharmacokinetic parameters were calculated: maximum plasma concentration (C5 min), area under the plasma concentration-time curve (AUC), terminal half-life (T1/2), terminal rate constant (λ-z), total clearance (Clt), volume of distribution (Vd), mean residence time (MRT), urine data-derived terminal half-life (T1/2 r), renal clearance (Clr). The results of this study showed that renal failure induced changes in cefodizime pharmacokinetics. Our data demonstrated a close correlation between degree of renal impairment and pharmacokinetic changes. The maximum plasma concentration (C5 min) was higher in patients with renal failure; T1/2 was increased; AUC also increased from 470.40 ± 17.80 mg·h/l in the control group to 1,562.30 ± 170.8 mg·h/l in group V. Moreover, no side effect was observed after treatment with 1 g i.v. of cefodizime. Although renal failure induces significant changes of cefodizime pharmacokinetics, the drug was well tolerated and only in patients with severe renal insufficiency we advise to monitor the interval dose of cefodizime or adjust doses to renal function.

SummaryThe study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally.The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design.The pharmacokinetic parameters AUC0-∞(ng h/ml), Tmax(h) and Cmax(ng/ml) were calculated for the two formulations after a single dose, while AUC t1-12( AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses.The bioequivalence assessment was the shortest 90 confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80–1.20).The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90 confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80–1.20(80–120).

B7 is a cell clone derived from rat brain microvessels. Expression of an amiloride-sensitive cationic channel has been recently established in these cells. In this study, the polymerase chain reaction (PCR) was used to amplify definite segments of mineralocorticoid and glucocorticoid receptor mRNA in B7 cells. Aldosterone binding was also characterized. Two classes of sites were detected. Aldosterone exhibited a high affinity for type I sites [dissociation constant (Kd) approximately 0.3 nM] and a lower one for type II sites (Kd approximately 20 nM). RU 28362, a highly specific glucocorticoid agonist, did not compete for type I sites. RU 28362 and dexamethasone were better competitors for type II sites than aldosterone. The sedimentation coefficients of aldosterone type I and type II complexes were approximately 9S. These characteristics are close to the one exhibited by aldosterone type I and type II receptors in rat kidney and other target tissues. In intact B7 cells, aldosterone binding expressed as number of acceptor sites per cell was higher (approximately 41,000 for type II and 8,800 for type I) than in the soluble cellular extract (approximately 18,000 for type II and 1,000 for type I).