Acquired hypogammaglobulinemia in HIV ‐positive subjects after liver transplantation

Introduction As more solid organ transplantations are performed in patients infected with human immunodeficiency virus ( HIV ), post‐transplant complications in this population are becoming better defined. Methods Using serum samples from the Solid Organ Transplantation in HIV : Multi‐Site Study, we studied the epidemiology of acquired hypogammaglobulinemia ( HGG ) after liver transplantation ( LT ) in 79 HIV ‐infected individuals with a median CD 4 count at enrollment of 288 (interquartile range 200–423) cells/μL. Quantitative immunoglobulin G (IgG) levels before and after LT were measured, with moderate and severe HGG defined as IgG 350–500 mg/dL and <350 mg/dL, respectively. Incidence, risk factors, and associated outcomes of moderate or worse HGG were evaluated using K aplan– M eier estimator and proportional hazards ( PH ) models. Results The 1‐year cumulative incidence of moderate or worse HGG was 12% (95% confidence interval [ CI ]: 6–22%); no new cases were observed between years 1 and 2. In a multivariate PH model, higher pre‐transplant model for end‐stage liver disease score ( P  = 0.04) and treated acute rejection ( P  = 0.04) were both identified as significant predictors of moderate or worse HGG . There was a strong association of IgG levels <500 mg/dL with non‐opportunistic serious infection (hazard ratio [95% CI ]: 3.5 [1.1–10.6]; P  = 0.03) and mortality (3.2 [1.1–9.4]; P  = 0.04). These associations held after adjustment for important determinants of infection and survival among the entire cohort. Conclusion These results suggest that a proportion of HIV ‐positive LT recipients will develop clinically significant HGG after transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102205/1/tid12139.pd

Vapor Distribution above an Evaporating Sessile Drop

An experimental technique was developed that uses infrared tomography to measure the three-dimensional vapor distribution above an evaporating sessile drop. The technique was applied to measure the vapor distributions above evaporating drops of hexane and 3-methylpentane (3MP) at room temperature and pressure. The molecular masses of these two species are heavier than air and the vapor from the evaporating drop forms a flat, disk-shaped cloud. A Fourier transform infrared spectrometer (FTIR) was used to measure the spectral absorbance along a set of paths passing through the vapor cloud. From a set of path-averaged absorbance measurements, a two-dimensional spatial concentration distribution was determined using a computed tomography routine. A three-dimensional concentration distribution was obtained from multiple two-dimensional distributions obtained at different elevations above the drop. The vapor distributions for both hexane and 3MP differ significantly from the values predicted by the solutions for diffusion-limited evaporation and indicate the effect of buoyancy-induced convection of the vapor. These measurements are the first quantitative measurements of the vapor distribution above a sessile drop and are important for advancing the understanding of the vapor phase transport mechanisms, and thus sessile drop evaporation

Trace amounts of 8-oxo-dGTP in mitochondrial dNTP pools reduce DNA polymerase γ replication fidelity

Replication of the mitochondrial genome by DNA polymerase γ requires dNTP precursors that are subject to oxidation by reactive oxygen species generated by the mitochondrial respiratory chain. One such oxidation product is 8-oxo-dGTP, which can compete with dTTP for incorporation opposite template adenine to yield A-T to C-G transversions. Recent reports indicate that the ratio of undamaged dGTP to dTTP in mitochondrial dNTP pools from rodent tissues varies from ∼1:1 to >100:1. Within this wide range, we report here the proportion of 8-oxo-dGTP in the dNTP pool that would be needed to reduce the replication fidelity of human DNA polymerase γ. When various in vivo mitochondrial dNTP pools reported previously were used here in reactions performed in vitro, 8-oxo-dGTP was readily incorporated opposite template A and the resulting 8-oxo-G-A mismatch was not proofread efficiently by the intrinsic 3′ exonuclease activity of pol γ. At the dNTP ratios reported in rodent tissues, whether highly imbalanced or relatively balanced, the amount of 8-oxo-dGTP needed to reduce fidelity was <1% of dGTP. Moreover, direct measurements reveal that 8-oxo-dGTP is present at such concentrations in the mitochondrial dNTP pools of several rat tissues. The results suggest that oxidized dNTP precursors may contribute to mitochondrial mutagenesis in vivo, which could contribute to mitochondrial dysfunction and disease

Enhanced Oxygen Activation over Supported Bimetallic Au-Ni Catalysts

New bimetallic Ni-Au supported nanoparticle catalysts were prepared by using dendrimer templated nanoparticles. Amine-terminated generation 5 polyamidoamine (PAMAM) dendrimers were anchored to a commercial silica with a siloxane linked anhydride. The dendrimer was then alkylated and used to template Ni-Au nanoparticles, which were subsequently extracted into organic solution as thiol monolayer protected clusters (MPCs). Transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) indicated bimetallic nanoparticles of about 2 nm in size. Nanoparticles were deposited onto P-25 TiO2, and the capping thiol ligands were removed under flowing H2. DRIFTS infrared spectra of adsorbed CO showed only Au on the catalyst surface; no bands attributable to Ni or NiO were observed. Density functional theory (DFT) calculations showed that Au is substantially more stable than Ni on the surface of model slabs. DFT calculations also indicated that the incorporation of Ni into Au slabs results in stronger adsorption of O and CO on Au surfaces. Catalysts were evaluated with low-temperature CO oxidation. Kinetics studies indicated a substantial modification of Au catalysis through Ni incorporation. Apparent activation energies decreased by more than 50% and O2 reaction orders increased from 0.2 to 0.9. These results are placed in the context of the available literature regarding support effects for Au catalysts. The observed changes to Au chemistry in the current work are substantially larger than previous reports have attributed to support effects. A Michaelis-Menten (enzyme) treatment of the kinetics data indicated that the O2 reactivity constant increased by a factor of 40 for catalysts with high Ni content. This was in good qualitative agreement with the DFT calculations. At the same time, the introduction of Ni reduced the relative number of catalytically active sites

Kinetic Evaluation of Highly Active Supported Gold Catalysts Prepared from Monolayer-Protected Clusters: An Experimental Michaelis-Menten Approach for Determining the Oxygen Binding Constant during CO Oxidation Catalysis

Thiol monolayer-protected Au clusters (MPCs) were prepared using dendrimer templates, deposited onto a high-surface-area titania, and then the thiol stabilizers were removed under H2/N2. The resulting Au catalysts were characterized with transmission electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy of adsorbed CO. The Au catalysts prepared via this route displayed minimal particle agglomeration during the deposition and activation steps. Structural data obtained from the physical characterization of the Au catalysts were comparable to features exhibited from a traditionally prepared standard Au catalyst obtained from the World Gold Council (WGC). A differential kinetic study of CO oxidation catalysis by the MPC-prepared Au and the standard WGC catalyst showed that these two catalyst systems have essentially the same reaction order and Arrhenius apparent activation energies (28 kJ/mol). However, the MPC-prepared Au catalyst shows 50% greater activity for CO oxidation. Using a Michaelis-Menten approach, the oxygen binding constants for the two catalyst systems were determined and found to be essentially the same within experimental error. To our knowledge, this kinetic evaluation is the first experimental determination of oxygen binding by supported Au nanoparticle catalysts under working conditions. The values for the oxygen binding equilibrium constant obtained from the Michaelis-Menten treatment (ca. 29-39) are consistent with ultra-high-vacuum measurements on model catalyst systems and support density functional theory calculations for oxygen binding at corner or edge atoms on Au nanoparticles and clusters

An archaeal family-B DNA polymerase variant able to replicate past DNA damage: occurrence of replicative and translesion synthesis polymerases within the B family

A mutant of the high fidelity family-B DNA polymerase from the archaeon Thermococcus gorgonarius (Tgo-Pol), able to replicate past DNA lesions, is described. Gain of function requires replacement of the three amino acid loop region in the fingers domain of Tgo-Pol with a longer version, found naturally in eukaryotic Pol zeta (a family-B translesion synthesis polymerase). Inactivation of the 3'–5' proofreading exonuclease activity is also necessary. The resulting Tgo-Pol Z1 variant is proficient at initiating replication from base mismatches and can read through damaged bases, such as abasic sites and thymine photo-dimers. Tgo-Pol Z1 is also proficient at extending from primers that terminate opposite aberrant bases. The fidelity of Tgo-Pol Z1 is reduced, with amarked tendency tomake changes at G:C base pairs. Together, these results suggest that the loop region of the fingers domain may play a critical role in determining whether a family-B enzyme falls into the accurate genome-replicating category or is an errorprone translesion synthesis polymerase. Tgo-Pol Z1 may also be useful for amplification of damaged DNA

The high fidelity and unique error signature of human DNA polymerase ε

Bulk replicative DNA synthesis in eukaryotes is highly accurate and efficient, primarily because of two DNA polymerases (Pols): Pols δ and ε. The high fidelity of these enzymes is due to their intrinsic base selectivity and proofreading exonuclease activity which, when coupled with post-replication mismatch repair, helps to maintain human mutation rates at less than one mutation per genome duplication. Conditions that reduce polymerase fidelity result in increased mutagenesis and can lead to cancer in mice. Whereas yeast Pol ε has been well characterized, human Pol ε remains poorly understood. Here, we present the first report on the fidelity of human Pol ε. We find that human Pol ε carries out DNA synthesis with high fidelity, even in the absence of its 3′→5′ exonucleolytic proofreading and is significantly more accurate than yeast Pol ε. Though its spectrum of errors is similar to that of yeast Pol ε, there are several notable exceptions. These include a preference of the human enzyme for T→A over A→T transversions. As compared with other replicative DNA polymerases, human Pol ε is particularly accurate when copying homonucleotide runs of 4–5 bases. The base pair substitution specificity and high fidelity for frameshift errors observed for human Pol ε are distinct from the errors made by human Pol δ

Involvement of the genicular branches in cystic adventitial disease of the popliteal artery as a possible marker of unfavourable early clinical outcome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic adventitial disease of the popliteal artery is a rare cause of non-atheromatous claudication. It usually requires surgery to improve the distance walked by patients.</p> <p>Case presentation</p> <p>We report the case of a 44-year-old Caucasian man with unilateral symptomatic popliteal cysts extending to his genicular branches and associated with multilevel stenosis of his anterior tibial artery. A surgical evacuation of the cysts successfully restored his arterial patency and led to an objective haemodynamic improvement but was associated with early recurrence of symptoms.</p> <p>Conclusion</p> <p>We suggest that the involvement of the genicular branches in cystic adventitial disease of the popliteal artery is a possible indicator of extensive adventitial degeneration and unfavourable clinical prognosis.</p

CO Adsorption on Supported Gold Nanoparticle Catalysts: Application of the Temkin Model

The adsorption of CO on the supported gold nanoparticle catalysts Au/TiO2, Au/Fe2O3, and Au/ZrO2 was examined using infrared transmission spectroscopy to quantify the isobaric CO coverage as a function of temperature. The Temkin adsorbate interaction model was then applied to account for the adsorption behavior. To test the general applicability of the Temkin model, this treatment was also applied to three data sets from the literature. This included another real-world catalyst and two model catalysts. All data sets were accurately represented by the Temkin adsorbate interaction model. The resulting thermodynamic metrics are consistent with previous determinations and reflect a particle size-dependence. In particular, the intrinsic adsorption enthalpy at zero CO coverage varies almost linearly with Au particle size, and this trend appears to be correlated with the abundance of low-coordinate Au sites (cf., CN = 6 and 7 for corners and edges, respectively). For very small particles with mostly CN = 6 corner sites, the enthalpy reflects strong binding (cf., −ΔH0 ≈ 78 kJ/mol), while for large particles with mostly CN = 7 edge sites, the enthalpy reflects weaker binding (cf., −ΔH0 ≈ 63 kJ/mol). The results also suggest that these sites are coupled. This study demonstrates that the Temkin adsorbate interaction model accurately represents adsorption data, yields meaningful metrics that are useful for characterizing nanoparticle catalysts, and should be applicable to other adsorption data sets

Controlling Activity and Selectivity Using Water in the Au-Catalysed Preferential Oxidation of CO in H\u3csub\u3e2\u3c/sub\u3e

Industrial hydrogen production through methane steam reforming exceeds 50 million tons annually and accounts for 2–5% of global energy consumption. The hydrogen product, even after processing by the water–gas shift, still typically contains ∼1% CO, which must be removed for many applications. Methanation (CO + 3H2 → CH4 + H2O) is an effective solution to this problem, but consumes 5–15% of the generated hydrogen. The preferential oxidation (PROX) of CO with O2 in hydrogen represents a more-efficient solution. Supported gold nanoparticles, with their high CO-oxidation activity and notoriously low hydrogenation activity, have long been examined as PROX catalysts, but have shown disappointingly low activity and selectivity. Here we show that, under the proper conditions, a commercial Au/Al2O3 catalyst can remove CO to below 10 ppm and still maintain an O2-to-CO2 selectivity of 80–90%. The key to maximizing the catalyst activity and selectivity is to carefully control the feed-flow rate and maintain one to two monolayers of water (a key CO-oxidation co-catalyst) on the catalyst surface