Facile kinetic induction of a dihydropyridide to pyrrolide ring contraction

A sterically demanding N-aryl carbodiimide reacts with magnesium 1,4-dihydropyridides to initiate heterocyclic ring contraction and pyrrolide formation under unprecedentedly mild conditions.</p

The Ultraviolet Imaging Telescope: Instrument and Data Characteristics

The Ultraviolet Imaging Telescope (UIT) was flown as part of the Astro observatory on the Space Shuttle Columbia in December 1990 and again on the Space Shuttle Endeavor in March 1995. Ultraviolet (1200-3300 Angstroms) images of a variety of astronomical objects, with a 40 arcmin field of view and a resolution of about 3 arcsec, were recorded on photographic film. The data recorded during the first flight are available to the astronomical community through the National Space Science Data Center (NSSDC); the data recorded during the second flight will soon be available as well. This paper discusses in detail the design, operation, data reduction, and calibration of UIT, providing the user of the data with information for understanding and using the data. It also provides guidelines for analyzing other astronomical imagery made with image intensifiers and photographic film.Comment: 44 pages, LaTeX, AAS preprint style and EPSF macros, accepted by PAS

Development of Query Strategies to Identify a Histologic Lymphoma Subtype in a Large Linked Database System

Background: Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specifi city of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specifi c cancer patient population.Methods: Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy.Results: Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verifi ed and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specifi city (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%).Conclusions: Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.Abbreviations: LLDB: Large Linked Database; SEER: Surveillance Epidemiology and End Results; EMR: Electronic Medical Record; ICD-9: International Classifi cation of Diseases (9th revision); ICD-O: International Classifi cation of Diseases for Oncology; AP: Anatomical Pathology; WHO: World Health Organization

Development of multiple strain competitive index assays for Listeria monocytogenes using pIMC; a new site-specific integrative vector

The foodborne, gram-positive pathogen, Listeria monocytogenes, is capable of causing lethal infections in compromised individuals. In the post genomic era of L. monocytogenes research, techniques are required to identify and validate genes involved in the pathogenicity and environmental biology of the organism. The aim here was to develop a widely applicable method to tag L. monocytogenes strains, with a particular emphasis on the development of multiple strain competitive index assays

Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures

Abstract Aims Sildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects. Methods A population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance. Results The analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9) −1.33 L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus &lt;10 mmHg (median area under the curve=533 versus 792 µg*h/L). Discussion Elevated hepatic pressure delays clearance of the sildenafil metabolite – des-methyl-sildenafil – and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism

Minimal length scales for the existence of local temperature

We review a recent approach to determine the minimal spatial length scales on which local temperature exists. After mentioning an experiment where such considerations are of relevance, we first discuss the precise definition of the existence of local temperature and its physical relevance. The approach to calculate the length scales in question considers homogenous chains of particles with nearest neighbor interactions. The entire chain is assumed to be in a thermal equilibrium state and it is analyzed when such an equilibrium state at the same time exists for a local part of it. The result yields estimates for real materials, the liability of which is discussed in the sequel. We finally consider a possibility to detect the existence or non-existence of a local thermal state in experiment.Comment: review, 13 pages, 11 figure

A Search for Time Variation of the Fine Structure Constant

A method offering an order of magnitude sensitivity gain is described for using quasar spectra to investigate possible time or space variation in the fine structure constant, alpha. Applying the technique to a sample of 30 absorption systems, spanning redshifts 0.5 < z< 1.6, obtained with the Keck I telescope, we derive limits on variations in alpha over a wide range of epochs. For the whole sample Delta(alpha)/alpha = -1.1 +/- 0.4 x 10^{-5}. This deviation is dominated by measurements at z > 1, where Delta(alpha)/alpha = -1.9 +/- 0.5 x 10^{-5}. For z < 1, Delta(alpha)/alpha = -0.2 +/- 0.4 x 10^{-5}, consistent with other known constraints. Whilst these results are consistent with a time-varying alpha, further work is required to explore possible systematic errors in the data, although careful searches have so far not revealed any.Comment: 4 pages, 1 figure, accepted for publication in Physical Review Letter

Finite Element Simulation Combination to Predict the Distortion of Thin Walled Milled Aluminum Workpieces as a Result of Machining Induced Residual Stresses

Machining induced residual stresses (MIRS) are a main driver for distortion of monolithic thin walled aluminum workpieces. A typical machining process for manufacturing such geometries for the aerospace industry is milling. In order to avoid high costs due to remanufacturing or part rejection, a simulation combination, consisting of two different finite element method (FEM) models, is developed to predict the part distortion due to MIRS. First, a 3D FEM cutting simulation is developed to predict the residual stresses due to machining. This simulation avoids cost intensive residual stress measurements. The milling process of the aluminum alloy AA7050-T7451 with a regular end mill is simulated. The simulation output, MIRS, forces and temperatures, is validated by face milling experiments on aluminum. The model takes mechanical dynamic effects, thermomechanical coupling, material properties and a damage law into account. Second, a subsequent finite element simulation, characterized by a static, linear elastic model, where the simulated MIRS from the cutting model are used as an input and the distortion of the workpiece is calculated, is presented. The predicted distortion is compared to an additional experiment, where a 1 mm thick wafer was removed at the milled surface of the aluminum workpiece. Furthermore, a thin walled component that represents a down scaled version of an aerospace component is manufactured and its distortion is analyzed. The results show that MIRS could be forecasted with moderate accuracy, which leads to the conclusion that the FEM cutting model needs to be improved in order to use the MIRS for a correct prediction of the distortion with the help of the linear elastic FEM model. The linear elastic model on the other hand is able to predict the part distortion with higher accuracy when using measured data instead of MIRS from the cutting simulation

Using remote substituents to control solution structure and anion binding in lanthanide complexes.

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers