Biomedical subjects

P Hu

Publications and source records attributed to P Hu.

At least 19 recordsLinked to original sources

PubMed2006

Importance of electronegativity differences and surface structure in molecular dissociation reactions at transition metal surfaces.

The dissociative adsorption of N2 has been studied at both monatomic steps and flat regions on the surfaces of the 4d transition metals from Zr to Pd. Using density functional theory (DFT) calculations, we have determined and analyzed the trends in both straight reactivity and structure sensitivity across the periodic table. With regards to reactivity, we find that the trend in activation energy (Ea) is determined mainly by a charge transfer from the surface metal atoms to the N atoms during transition state formation, namely, the degree of ionicity of the N-surface bond at the transition state. Indeed, we find that the strength of the metal-N bond at the transition state (and therefore the trend in Ea) can be predicted by the difference in Mulliken electronegativity between the metal and N. Structure sensitivity is analyzed in terms of geometric and electronic effects. We find that the lowering of Ea due to steps is more pronounced on the right-hand side of the periodic table. It is found that for the early transition metals the geometric and electronic effects work in opposition when going from terrace to step active site. In the case of the late 4d metals, however, these effects work in combination, producing a more marked reduction in Ea.

Journal Article↗

PubMed2006

Insight into the solvent effect: a density functional theory study of cisplatin hydrolysis.

The solvent effect on reactions in solutions is crucial for many systems. In this study, the reaction barrier with respect to the number of solvent molecules included in the system is systematically studied using density function theory calculations. Our results show that the barriers rapidly converge with respect to the number of solvent molecules. The solvent effect is investigated by calculating cisplatin hydrolysis in several types of solvents. The results are analyzed and a linear relationship between the reaction barrier and the interaction strength of solvent-reactants is found. Insight into the general solvent effect is obtained.

Journal Article↗

PubMed2006

Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma.

Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant, which can stimulate T cells bearing certain T-cell receptor beta-chain variable regions, when bound to major histocompatibility complex II molecules. In vivo administration of intact superantigen in sufficient therapeutic amounts risks unwanted cytotoxicity against normal cells. In this study, we used SEA fused with CD80 transmembrane region (named as SEAtm) driven by alpha-fetoprotein (AFP) enhancer/promoter to reduce toxicity and to improve safety and efficiency in the application of SEA. We demonstrated that SEAtm by adenovirus from the AFP enhancer/promoter (AdAFPSEA) could be expressed on the surface of AFP-producing cell line Hepa1-6 instead of non-AFP-producing cell lines. Hepa1-6 infected by recombinant adenovirus stimulated proliferation of splenocytes and activated CD4(+) and CD8(+) T cells in vitro. After AdAFPSEA was injected into the subcutaneously established hepatoma in vivo, the expression of SEA was detected in tumor tissues, which subsequently induced tumor-specific cytotoxic T cells in spleen. Moreover, hepatocellular carcinoma (HCC) xenografts were suppressed by treatment with AdAFPSEA and the survival time of treated mice was prolonged. These findings suggest that membrane-expressed SEA by adenovirus from AdAFPSEA can generate stronger local and systemic antitumor responses against HCC.

Adenoviridae↗

PubMed2006

Identifying an O2 supply pathway in CO oxidation on Au/TiO2(110): a density functional theory study on the intrinsic role of water.

Au catalysis has been one of the hottest topics in chemistry in the last 10 years or so. How O2 is supplied and what role water plays in CO oxidation are the two challenging issues in the field at the moment. In this study, using density functional theory we show that these two issues are in fact related to each other. The following observations are revealed: (i) water that can dissociate readily into OH groups can facilitate O2 adsorption on TiO2; (ii) the effect of OH group on the O2 adsorption is surprisingly long-ranged; and (iii) O2 can also diffuse along the channel of Ti (5c) atoms on TiO2(110), and this may well be the rate-limiting step for the CO oxidation. We provide direct evidence that O2 is supplied by O2 adsorption on TiO2 in the presence of OH and can diffuse to the interface of Au/TiO2 to participate in CO oxidation. Furthermore, the physical origin of the water effects on Au catalysis has been identified by electronic structure analyses: There is a charge transfer from TiO2 in the presence of OH to O2, and the O2 adsorption energy depends linearly on the O2 charge. These results are of importance to understand water effects in general in heterogeneous catalysis.

Journal Article↗

PubMed2006

Reactivity of the 4d transition metals toward N hydrogenation and NH dissociation: a DFT-based HSAB analysis.

The density functional theory (DFT) based hard-soft acid-base (HSAB) reactivity indices, including the electrophilicity index, have been successfully applied to many areas of molecular chemistry. In this work we test the applicability of such an approach to fundamental surface chemistry. We have considered, as prototypical surface reactions, both the hydrogenation of atomic nitrogen and the dissociative adsorption of the NH molecular radical. By use of a DFT methodology, the minimum energy reaction pathways, and corresponding reaction barriers, of the above reactions over Zr(001), Nb(110), Mo(110), Tc(001), Ru(001), Rh(111), and Pd(111) have been determined. By consideration of the chemical potential and chemical hardness of the surface metal atoms, and the principle of electronegativity equalization, it is found that the charge transferred to the NH radical during the process of dissociative adsorption correlates very well with that determined by Mulliken population analysis. Furthermore, it is found that the stability of the NH/surface transition state complex relates directly to this charge transfer and that the trend in transition state stability predicted by a HSAB treatment correlates very strongly with that determined by DFT calculations. With regards to N hydrogenation, we find that during the course of the reaction, H loses cohesion to the surface, as it must migrate from a 3-fold hollow site to either a bridge or top site, to react with N. Partial density of states (PDOS) and Mulliken population analysis reveal that this loss of bonding is accompanied by charge transfer from H to the surface metal atoms. Moreover, by simple modeling, we show that the reaction barriers are directly proportional to this mandatory charge transfer. Indeed, it is found that the reaction barriers correlate very well with the electrophilicity index of the metal atoms.

Journal Article↗

PubMed2006

The importance of hydrogen's potential-energy surface and the strength of the forming R-H bond in surface hydrogenation reactions.

An understanding of surface hydrogenation reactivity is a prevailing issue in chemistry and vital to the rational design of future catalysts. In this density-functional theory study, we address hydrogenation reactivity by examining the reaction pathways for N+H-->NH and NH+H-->NH(2) over the close-packed surfaces of the 4d transition metals from Zr-Pd. It is found that the minimum-energy reaction pathway is dictated by the ease with which H can relocate between hollow-site and top-site adsorption geometries. A transition state where H is close to a top site reduces the instability associated with bond sharing of metal atoms by H and N (NH) (bonding competition). However, if the energy difference between hollow-site and top-site adsorption energies (DeltaE(H)) is large this type of transition state is unfavorable. Thus we have determined that hydrogenation reactivity is primarily controlled by the potential-energy surface of H on the metal, which is approximated by DeltaE(H), and that the strength of N (NH) chemisorption energy is of less importance. DeltaE(H) has also enabled us to make predictions regarding the structure sensitivity of these reactions. Furthermore, we have found that the degree of bonding competition at the transition state is responsible for the trend in reaction barriers (E(a)) across the transition series. When this effect is quantified a very good linear correlation is found with E(a). In addition, we find that when considering a particular type of reaction pathway, a good linear correlation is found between the destabilizing effects of bonding competition at the transition state and the strength of the forming N-H (HN-H) bond.

Journal Article↗

PubMed2006

Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB.

A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria.

Archaea↗

PubMed2006

Morphologies of fibroblast cells cultured on surfaces of PHB films implanted by hydroxyl ions.

Polyhydroxybutyrate (PHB) films were implanted with 40 keV hydroxyl ions with fluences ranging from 1 x 10(12) to 1 x 10(15) ions/cm2, respectively. The as-implanted PHB films were characterized by scanning electron microscopy (SEM), electron spectroscopy for chemical analysis (ESCA) and water contact angle measurements. The surface structures and properties of the as-implanted PHB films were closely related with hydroxyl ion fluence. They were further investigated by inoculating 3T6 fibroblasts cells on their surfaces. Morphologies of the 3T6 fibroblast cells cultured on surfaces of the as-implanted PHB films were observed by SEM. Characterization of the cultural 3T6 cells was analyzed qualitatively. The preliminary experimental results reveal that the bioactivity of the PHB films modified by hydroxyl ion implantation was improved at different levels, and the fluence of 1 x 10(13) ions/cm2 is optimal for PHB film.

Animals↗

PubMed2006

Bioprofiling over grid for eHealthcare.

A trend in modern medicine is towards individualization of healthcare and, potentially, grid computing can play an important role in this by allowing sharing of resources and expertise to improve the quality of care. In this paper, we present a new test bed, the BIOPATTERN Grid, which aims to fulfil this role in the long term. The main objectives in this paper are 1) to report the development of the BIOPATTERN Grid, for biopattern analysis and bioprofiling in support of individualization of healthcare. The BIOPATTERN Grid is designed to facilitate secure and seamless sharing of geographically distributed bioprofile databases and to support the analysis of bioprofiles to combat major diseases such as brain diseases and cancer within a major EU project, BIOPATTERN (www.biopattern.org); 2) to illustrate how the BIOPATTERN Grid could be used for biopattern analysis and bioprofiling for early detection of dementia and for brain injury assessment on an individual basis. We highlight important issues that would arise from the mobility of citizens in the EU, such as those associated with access to medical data, ethical and security; and 3) to describe two grid services which aim to integrate BIOPATTERN Grid with existing grid projects on crawling service and remote data acquisition which is necessary to underpin the use of the test bed for biopattern analysis and bioprofiling.

Computational Biology↗

PubMed2005

DFT and in situ EXAFS investigation of gold/ceria-zirconia low-temperature water gas shift catalysts: identification of the nature of the active form of gold.

A combined experimental and theoretical investigation of the nature of the active form of gold in oxide-supported gold catalysts for the water gas shift reaction has been performed. In situ extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) experiments have shown that in the fresh catalysts the gold is in the form of highly dispersed gold ions. However, under water gas shift reaction conditions, even at temperatures as low as 100 degrees C, the evidence from EXAFS and XANES is only consistent with rapid, and essentially complete, reduction of the gold to form metallic clusters containing about 50 atoms. The presence of Au-Ce distances in the EXAFS spectra, and the fact that about 15% of the gold atoms can be reoxidized after exposure to air at 150 degrees C, is indicative of a close interaction between a fraction (ca. 15%) of the gold atoms and the oxide support. Density functional theory (DFT) calculations are entirely consistent with this model and suggest that an important aspect of the active and stable form of gold under water gas shift reaction conditions is the location of a partially oxidized gold (Audelta+) species at a cerium cation vacancy in the surface of the oxide support. It is found that even with a low loading gold catalysts (0.2%) the fraction of ionic gold under water gas shift conditions is below the limit of detection by XANES (<5%). It is concluded that under water gas shift reaction conditions the active form of gold comprises small metallic gold clusters in intimate contact with the oxide support.

Journal Article↗

PubMed2005

A density functional theory study of sulfur poisoning.

Density functional theory calculations have been used to investigate the chemisorption of H, S, SH, and H(2)S as well as the hydrogenation reactions S+H and SH+H on a Rh surface with steps, Rh(211), aiming to explain sulfur poisoning effect. In the S hydrogenation from S to H(2)S, the transition state of the first step S+H-->SH is reached when the S moves to the step-bridge and H is on the off-top site. In the second step, SH+H-->H(2)S, the transition state is reached when SH moves to the top site and H is close to another top site nearby. Our results show that it is difficult to hydrogenate S and they poison defects such as steps. In order to address why S is poisoning, hydrogenation of C, N, and O on Rh(211) has also been calculated and has been found that the reverse and forward reactions possess similar barriers in contrast to the S hydrogenation. The physical origin of these differences has been analyzed and discussed.

Journal Article↗

PubMed2005

CHx hydrogenation on Co(0001): a density functional theory study.

Hydrogenation is an important process in the Fischer-Tropsch synthesis. In this work, all the elementary steps of the hydrogenation from C to CH4 are studied on both flat and stepped Co(0001) using density functional theory (DFT). We found that (i) CH3 hydrogenation (CH3+H-->CH4) is the most difficult one among all the elementary reactions on both surfaces, possessing barriers of around 1.0 eV; (ii) the other elementary reactions have the barriers below 0.9 eV on the flat and stepped surfaces; (iii) CH2 is the least stable species among all the CHx(x=1-3) species on both surfaces; and (iv) surface restructuring may have little effect on the CHx(x=0-3) hydrogenation. The barriers of each elementary step on both flat and stepped surfaces are similar and energy profiles are also similar. The reason as to why CHx hydrogenation is not structure-sensitive is also discussed.

Journal Article↗

PubMed2004

General insight into CO oxidation: a density functional theory study of the reaction mechanism on platinum oxides.

CO oxidation on PtO2(110) has been studied using density functional theory calculations. Four possible reaction mechanisms were investigated and the most feasible one is the following: (i) the O at the bridge site of PtO2(110) reacts with CO on the coordinatively unsaturated site (CUS) with a negligible barrier; (ii) O2 adsorbs on the bridge site and then interacts with CO on the CUS to form an OO-CO complex; (iii) the bond of O-OCO breaks to produce CO2 with a small barrier (0.01 eV). The CO oxidation mechanisms on metals and metal oxides are rationalized by a simple model: The O-surface bonding determines the reactivity on surfaces; it also determines whether the atomic or molecular mechanism is preferred. The reactivity on metal oxides is further found to be related to the 3rd ionization energy of the metal atom.

Journal Article↗

PubMed2004

The mechanism of N2O formation via the (NO)2 dimer: a density functional theory study.

Catalytic formation of N(2)O via a (NO)(2) intermediate was studied employing density functional theory with generalized gradient approximations. Dimer formation was not favored on Pt(111), in agreement with previous reports. On Pt(211) a variety of dimer structures were studied, including trans-(NO)(2) and cis-(NO)(2) configurations. A possible pathway involving (NO)(2) formation at the terrace near to a Pt step is identified as the possible mechanism for low-temperature N(2)O formation. The dimer is stabilized by bond formation between one O atom of the dimer and two Pt step atoms. The overall mechanism has a low barrier of approximately 0.32 eV. The mechanism is also put into the context of the overall NO + H(2) reaction. A consideration of the step-wise hydrogenation of O(ads) from the step is also presented. Removal of O(ads) from the step is significantly different from O(ads) hydrogenation on Pt(111). The energetically favored structure at the transition state for OH(ads) formation has an activation energy of 0.63 eV. Further hydrogenation of OH(ads) has an activation energy of 0.80 eV.

Journal Article↗

PubMed2004

The unexpected preference for the fac-isomer with the tris(5-ester-substituted-2,2'-bipyridine) complexes of ruthenium(II).

The synthesis of a number of new 2,2'-bipyridine ligands, functionalized with bulky ester side groups, is reported (L2-L8). Their reaction with [Ru(DMSO)(4)Cl(2)] gives rise to tris-chelate ruthenium(II) metal complexes which show an unusually high proportion of the fac-isomer, as judged by (1)H NMR following conversion to the ruthenium(II) complex of 2,2'-bipyridine-5-carboxylic acid methyl ester (L1). The initial reaction appears to have thermodynamic control with the steric bulk of the ligands causing the third ligand to be labile under the reaction conditions used, giving rise to disappointing yields and allowing rearrangement to the more stable facial form. DFT studies indicate that this does not appear to be as a consequence of a metal centered electronic effect. The two isomers of [Ru(L1)(3)](PF(6))(2) were separated into the two individual forms using silica preparative plate chromatographic procedures, and the photophysical characteristics of the two forms compared. The results appear to indicate that there is no significant difference in both their room temperature electronic absorption and emission spectra or their excited state lifetimes at 77 K.

Journal Article↗

PubMed2004

A systematic study of CO oxidation on metals and metal oxides: density functional theory calculations.

CO oxidation on Ru(0001), Rh(111), Pd(111), Os(0001), Ir(111), Pt(111), and their corresponding metal oxides is studied using density functional theory. It is found that (i) the reactivity of metal oxide is generally higher than that of the corresponding metal, and (ii) on both metals and metal oxides, the higher the chemisorption energy is in the initial state, the larger the reaction barrier. The barriers are further analyzed by decomposing them into electronic and geometric effects, and the higher reactivity of metal oxides is attributed mainly to the surface geometric effect. Moreover, the electronic effect on both metals and metal oxides follows the same pattern: the shorter the OC-O bond distance in the TS, the higher the barrier.

Journal Article↗

PubMed2004

Cloning and characterization of an inversion breakpoint at 6q23.3 suggests a role for Map7 in sacral dysgenesis.

Here we report on a male patient with sacral dysgenesis (SD) and constitutional pericentric inversion of chromosome 6 (p11.2;q23.3). SD is a heterogeneous group of congenital anomalies with complex genetic etiology. Previously, a patient with sacral abnormalities and an interstitial deletion of 6q23-->q25 region has been described. We speculated that a susceptibility gene for SD lies in 6q23.3 region (disrupted in both patients), and therefore, cloning of the breakpoint in our patient would lead to the identification of the disrupted gene. We performed FISH analysis followed by Southern blot analysis and inverse PCR to clone the breakpoint. The 6p11.2 breakpoint mapped very close to the centromere, and the 6q23.3 breakpoint localized in the ninth intron of the MAP7 gene. We then evaluated the involvement of MAP7 in SD by further screening of the gene in several patients with a similar phenotype. Two nucleotide changes causing Ile257Asn and Glu571Ala substitutions in the protein, both affecting amino acid residues conserved in the mouse homolog, were identified in two patients. Both changes are either very rare polymorphisms or true mutations, since they were not detected in 167 normal individuals nor found in the SNP database. Therefore, our study suggests MAP7 as a candidate gene for SD. However, we were unable to detect any sacral defects in the MAP7 knockout mice.

Abnormalities, Multiple↗

PubMed2003

Catalytic role of metal oxides in gold-based catalysts: a first principles study of CO oxidation on TiO2 supported Au.

CO oxidation on TiO2 supported Au has been studied using density functional theory calculations. Important catalytic roles of the oxide have been identified: (i) CO oxidation occurs at the interface between Au and the oxide with a very small barrier; and (ii) O2 adsorption at the interface is the key step in the reaction. The physical origin of the oxide promotion effect has been further investigated: The oxide enhances electron transfer from the Au to the antibonding states of O2, giving rise to (i) strong ionic bonding between the adsorbed O2, Au, and the Ti cation; and (ii) a significant activation of O2 towards CO oxidation.

Journal Article↗