Bilayer-mediated assembly of cationic nanoparticles adsorbed to lipid bilayers: Insights from molecular simulations

Understanding interactions between functionalized gold nanoparticles (NPs) and lipid bilayers is essential for biomedical applications. Experiments have shown that NPs that are stable in solution can assemble into clusters when adsorbed to a lipid bilayer, suggesting that bilayer-mediated interactions facilitate assembly. In this work, we use coarse-grained molecular dynamics simulations to study bilayer-mediated interactions between NPs adsorbed to single- and multicomponent lipid bilayers. We perform unbiased simulations and umbrella sampling calculations using an implicit solvent force field to determine the thermodynamic contributions to assembly. We show that bilayer-mediated interactions drive the assembly of NPs into linear aggregates on liquid-disordered bilayers, which we attribute to a reduction in bilayer curvature. Similar bilayer-mediated interactions induce the alignment of NP clusters with phase boundaries in phase-separated bilayers. Together, these simulation results provide new physical insight into the balance of forces that dictate the assembly of charged NPs at multicomponent lipid bilayer interfaces.     

Towards deterministic downscaling of SMOS soil moisture using MODIS derived soil evaporative efficiency

A deterministic approach for downscaling ～ 40 km resolution Soil Moisture and Ocean Salinity (SMOS) observations is developed from 1 km resolution MODerate resolution Imaging Spectroradiometer (MODIS) data. To account for the lower soil moisture sensitivity of MODIS surface temperature compared to that of L-band brightness temperature, the disaggregation scale is fixed to 10 times the spatial resolution of MODIS thermal data (10 km). Four different analytic downscaling relationships are derived from MODIS and physically-based model predictions of soil evaporative efficiency. The four downscaling algorithms differ with regards to i) the assumed relationship (linear or nonlinear) between soil evaporative efficiency and near-surface soil moisture, and ii) the scale at which soil parameters are available (40 km or 10 km). The 1 km resolution airborne L-band brightness temperature from the National Airborne Field Experiment 2006 (NAFE'06) are used to generate a time series of eleven clear sky 40 km by 60 km near-surface soil moisture observations to represent SMOS pixels across the three-week experiment. The overall root mean square difference between downscaled and observed soil moisture varies between 1.4% v/v and 1.8% v/v depending on the downscaling algorithm used, with soil moisture values ranging from 0 to 15% v/v. The accuracy and robustness of the downscaling algorithms are discussed in terms of their assumptions and applicability to SMOS.     

Florida DOT Project-Level Bridge Management Models

The Florida Department of Transportation (FDOT) is in the process of implementing Pontis, a Bridge Management System, to provide decision support to engineers in the headquarters and district offices as they make routine policy, programming, and budgeting decisions regarding the preservation and improvement of the state’s bridges. As part of this effort, an ongoing research program is underway to adapt the system to FDOT needs as well as to advance the state of the art in several areas important to the Department. Most of the research results are organized around a new project-level decision support framework that complements and builds on Pontis’ existing network-level analysis. Specific new models include accident risk and user cost due to roadway width and alignment deficiencies; user cost of load capacity and vertical clearance restrictions, and moveable bridge openings; project-level prediction models for bridge element condition and costs; and prediction of economics of scale and scoping possibilities. The new models are built into a highly graphical spreadsheet model for decision support use.     

The roles of conserved carboxylate residues in IMP dehydrogenase and identification of a transition state analog

IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD+; the enzyme is activated by K+. This reaction is the rate-limiting step in de novo guanine nucleotide biosynthesis. In order to identify functionally important residues in IMPDH, including those involved in substrate and K+ binding, we have mutated 11 conserved Asp and Glu residues to Ala in Escherichia coli IMPDH. The values of kcat, Km, and Ki for GMP, XMP, mizoribine 5'-monophosphate (MMP), and beta-methylene-tiazofurin adenine dinucleotide (TAD) were determined. Five of these mutations caused a significant change (>/=10-fold) in one of these parameters. The Asp248 --> Ala mutation caused 100-fold decrease in the value of kcat and a 25-fold increase in the value of Kii for TAD; these observations suggest that Asp248 is in the NAD+ binding site. The Asp338 --> Ala mutation caused a 600-fold decrease in the value of kcat, but only a 5-10-fold increase in the values of Km for IMP and Kis for IMP analogs, suggesting that Asp338 may be involved in acid-base catalysis as well as IMP binding. The remaining three residues, Asp13, Asp50, and Glu469, appear to be involved in K+ activation; these residues may be ligands at one or more K+ binding sites. Interestingly, changes in the values of Ki for MMP correlate with changes in kcat/KmKm of IMPDH, while no such correlation is observed for GMP, XMP, and TAD. This observation indicates that MMP is a transition state analog for the IMPDH reaction.     

Characterization and modeling of a noncollinearly phase-matchedfemtosecond optical parametric oscillator based on KTA and operating tobeyond 4 μm

We describe the design and operation of a critically phase-matched femtosecond optical parametric oscillator based on KTA. By employing a small pump-signal noncollinear angle, tuning of the idler to beyond 4 μm is achieved using a Ti:sapphire pump laser. A Gaussian-beam model is described which can be used to identify the optimal noncollinear phase-matching geometry. Idler and signal pulses are characterized fully both temporally and spectrally and interferometric autocorrelation data at 3.5 μm showing idler pulses of only eight optical cycles duration are presented     

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

The Tenckhoff catheter in acute renal failure

The results of a retrospective study of routine measurement of haemoglobin at the examination of one-year-old children at Gr?land mother and child clinic during 1989-91 showed that 37% of the children had anaemia. There was no difference between immigrants and the European population. There was no correlation between anaemia and sex in either of the population groups. This may imply that routine haemoglobin measurement should be generally introduced as part of the regular control of one-year-old children.     

Dissolved organic carbon of coal slurry transport water

The qualitative and quantitative occurrence and fate of dissolved organic carbon (DOC) leaching into coal slurry transport water was examined in laboratory-generated coal slurries and wastewaters from the Black Mesa coal slurry pipeline. Laboratory slurries were formulated for both western coals (Wyodak, Montana Rosebud and Black Mesa) and eastern coals (Illinois No. 6 and Pittsburgh No. 8). Sephadex G-25 elution profiles and ultrafiltration studies indicate that the majority of the organic compounds in western coal slurry wastewaters were lower (less than 1000) molecular weight species (62% for Wyodak and 74% for Montana Rosebud). Biochemical Oxygen Demand (BOD) for these particular wastewaters ranged from 50 to 150 mg l⁻¹ as determined through the use of an electrolytic respirometer. Also, there was a concomitant 51–74% reduction in the DOC levels in the wastewaters. This removal was primarily due to the removal of the lower (< 1000) molecular weight compounds by the seed inoculum. There was no evidence for the presence of mutagenic organics in the raw wastewater.