Electrochemical Oxidation of Ergolines

An electrochemical procedure for the preparation of D -3-alkoxy-halogen-2,3-dihydro-6-methyl-2-oxoergolines-I is described.     

Pressure-broadened iodine-laser-amplifier kinetics and a comparison of diluent effectiveness

An iodine laser kinetic model is used to investigate inversion parameters in highly pressure-broadened amplifier systems using i-C₃F₇I as the parent compound and CO₂, N₂, He, Ne, Ar, Kr, and Xe as the diluent gas. These data are used to calculate a diluent merit function for diluent pressures P_d = 1–100 atm. The most effective choices for buffer gases are as follows: P_d ? 1 atm, CO₂; 1 atm ? P_d ? 10 atm, Ar; and P_d ? 10 atm, Ne.     

Monte carlo simulation of a quantized universe

A Monte Carlo simulation method which yields groundstate wave functions for multielectron atoms is applied to quantized cosmological models. In quantum mechanics, the propagator for the Schrödinger equation reduces to the absolute value squared of the groundstate wave function in the limit of infinite Euclidean time. The wave function of the universe as the solution to the Wheeler-DeWitt equation may be regarded as the zero energy mode of a Schrödinger equation in coordinate time. The simulation evaluates the path integral formulation of the propagator by constructing a large number of paths and computing their contribution to the path integral using the Metropolis algorithm to drive the paths toward a global minimum in the path energy. The result agrees with a solution to the Wheeler-DeWitt equation which has the characteristics of a nodeless groundstate wave function. Oscillatory behavior cannot be reproduced although the simulation results may be physically reasonable. The primary advantage of the simulations is that they may easily be extended to cosmologies with many degrees of freedom. Examples with one, two, and three degrees of freedom (d.f.) are presented.This essay was awarded Honorable Mention by the Gravity Research Foundation.Part of this work was performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under contract number W-7405-ENG-48 and part was supported by National Science Foundation Grant PHY82-13411 to Oakland University.     

The synthesis of N-(tetrazol-5-yl)azetidin-2-ones

A series of N-(tetrazol-5-yl)azetidin-2-ones have been prepared from serine and threonine and evaluated as antibiotics against a range of bacteria.     

Flow Characterization Through a Network Cell Using Particle Image Velocimetry

Particle image velocimetry (PIV) with refractive index matching was developed to map pore-scale fluid flow through a clear, acrylic two-dimensional network flow cell. A microscope objective lens was incorporated in the PIV set up so that flow in micro-scale throats could be measured. The flow cell consists of 20 × 20, equal-size cylindrical pore bodies, 2.5mm in diameter and 1.0mm in height, connected on a diamond lattice by 2.5 mm long, square cross-section throats of widths that varied randomly among 0.2, 0.6, and 1.0 mm. Micro-PIV data was used to obtain the two-dimensional streamline pattern of fluid flow and the velocity field over the field of view (FOV) by periodically illuminating seed particles following the flow and cross correlating particle positions to determine displacements over time. Refractive index matching of the flow cell and test fluid minimizes extraneous scattering of light at solid--liquid interfaces improving image resolution. Experimentally determined velocity vectors for single-phase flow through three pore bodies and their adjoining throats as well as for the outlet of the flow cell were compared with numerical simulations of flow through the cell.     

Polymer Nanoparticle Hydrogels with Autonomous Affinity Switching for the Protection of Proteins from Thermal Stress

We report a new material design concept for synthetic, thermally responsive poly(N‐isopropylacrylamide)‐based copolymer nanoparticle (NP) hydrogels, which protect proteins from thermal stress. The NP hydrogels bind and protect a target enzyme from irreversible activity loss upon exposure to heat but “autonomously” release the enzyme upon subsequent cooling of the solution. Incorporation of the optimized amount of negatively charged and hydrophobic comonomers to the NP hydrogels was key to achieve these desired functions. As the NP hydrogels do not show a strong affinity for the enzyme at room temperature, they can remain in solution without adversely affecting enzymatic activity or they can be removed by filtration to leave the enzyme in solution. The results demonstrate the promise of this approach for improving the thermal tolerance of proteins.     

Multidimensional mass spectrometry-based shotgun lipidomics analysis of vinyl ether diglycerides

Diglycerides play a central role in lipid metabolism and signaling in mammalian cells. Although diacylglycerol molecular species comprise the majority of cellular diglycerides that are commonly measured using a variety of approaches, identification of extremely low abundance vinyl ether diglycerides has remained challenging. In this work, representative molecular species from the three diglyceride subclasses (diacyl, vinyl ether, and alkyl ether diglycerides; hereafter referred to as diradylglycerols) were interrogated by mass spectrometric analysis. Product ion mass spectra of the synthesized diradylglycerols with varied chain lengths and degrees of unsaturation demonstrated diagnostic fragmentation patterns indicative of each subclass. Multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) analysis of mouse brain and heart lipid extracts were performed using the identified informative signature product ions. Through an array of tandem mass spectrometric analyses utilizing the orthogonal characteristics of neutral loss scanning and precursor ion scanning, the differential fragmentation of each subclass was exploited for high-yield structural analyses. Although molecular ion mass spectra readily identified diacylglycerol molecular species directly from the hexane fractions of tissue extracts enriched in nonpolar lipids, molecular ion peaks corresponding to ether-linked diglycerides were not observable. The power of MDMS-SL utilizing the tandem mass spectrometric array analysis was demonstrated by identification and profiling of individual molecular species of vinyl ether diglycerides in mouse brain and heart from their undetectable molecular ion peaks during MS¹ analysis. Collectively, this technology enabled the identification and profiling of previously inaccessible vinyl ether diglyceride molecular species in mammalian tissues directly from extracts of biologic tissues.

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Graphical Abstract ?

     

Adapting Japanese Lesson Study to enhance the teaching and learning of geometry and spatial reasoning in early years classrooms: a case study

Increased efforts are needed to meet the demand for high quality mathematics in early years classrooms. Despite the foundational role of geometry and spatial reasoning for later mathematics success, the strand receives inadequate instructional time and is limited to concepts of static geometry. Moreover, early years teachers typically lack both content knowledge and confidence in teaching geometry and spatial reasoning. We describe our attempt to deal with these issues through a research initiative known as the Math for Young Children project. The project integrates effective features of both design research and Japanese Lesson Study and is designed to support teachers in developing content knowledge and new approaches for teaching geometry and spatial reasoning. Central to our Professional Development model is the integration of four adaptations to the Japanese Lesson Study model: (1) teachers engaging in the mathematics, (2) teachers designing and conducting task-based clinical interviews, (3) teachers and researchers co-designing and carrying out exploratory lessons and activities, and (4) the creation of resources for other educators. We present our methods and the results of our adaptations through a case study of one Professional Learning Team. Our results suggest that the adaptations were effective in: (1) supporting teachers’ content knowledge of and comfort level with geometry and spatial reasoning, (2) increasing teachers’ perceptions of young children’s mathematical competencies, (3) increasing teachers’ awareness and commitment for the inclusion of high quality geometry and spatial reasoning as a critical component of early years mathematics, and (4) the creation of innovative resources for other educators. We conclude with theoretical considerations and implications of our results.     

Drug design with a new transition state analog of the hydrated carbonyl: silicon-based inhibitors of the HIV protease

BACKGROUND: Silicon is the element most similar to carbon, and bioactive organosilanes have therefore been of longstanding interest. Design of bioactive organosilanes has often involved a systematic replacement of a bioactive molecule's stable carbon atoms with silicon. Silanediols, which are best known as unstable precursors of the robust and ubiquitous silicone polymers, have the potential to mimic an unstable carbon, the hydrated carbonyl. As a bioisostere of the tetrahedral intermediate of amide hydrolysis, a silanediol could act as a transition state analog inhibitor of protease enzymes. RESULTS: Silanediol analogs of a carbinol-based inhibitor of the HIV protease were prepared as single enantiomers, with up to six stereogenic centers. As inhibitors of this aspartic protease, the silanediols were nearly equivalent to both their carbinol analogs and indinavir, a current treatment for AIDS, with low nanomolar K(i) values. IC(90) data from a cell culture assay mirrored the K(i) data, demonstrating that the silanediols can also cross cell membranes and deliver their antiviral effects. CONCLUSIONS: In their first evaluation as inhibitors of an aspartic protease, silanediol peptidomimetics have been found to be nearly as potent as currently available pharmaceutical agents, in enzyme and cell protection assays. These neutral, cell-permeable transition state analogs therefore provide a novel foundation for the design of therapeutic agents.     

Discharge ignition phenomena in CO2 and N2O lasers with preliminary filling of the interelectrode gap by electrons

A comprehensive model is presented that describes preionization and discharge ignition processes in large-aperture molecular-gas lasers. By initially filling the interelectrode gap with electrons and establishing a space-charge screen at the cathode, electron avalanche begins adjacent to the anode. Cathode-directed ionization waves develop and ignite the discharge. Dynamic profiling of the electric-field distribution and Penning ionization of a readily ionizable additive combine to decrease both the ignition and quasi-steady-state voltages.