Synthesis and Properties of Dipyridylcyclopentenes

A short and general route to the substituted dipyridylcyclopentenes was explored and several new compounds belonging to this new group of diarylethenes were synthesized. The study of their photochromic and thermochromic properties shows that the rate of the thermal ring opening is strongly dependent on the polarity of the solvent.

Thermal transport in thin films measured by time-resolved, grazing incidence x-ray diffraction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98715/1/JApplPhys_110_102203.pd

Application of the LEPS technique for Quantitative Precipitation Forecasting (QPF) in Southern Italy: a preliminary study

International audienceThis paper reports preliminary results for a Limited area model Ensemble Prediction System (LEPS), based on RAMS (Regional Atmospheric Modelling System), for eight case studies of moderate-intense precipitation over Calabria, the southernmost tip of the Italian peninsula. LEPS aims to transfer the benefits of a probabilistic forecast from global to regional scales in countries where local orographic forcing is a key factor to force convection. To accomplish this task and to limit computational time in an operational implementation of LEPS, we perform a cluster analysis of ECMWF-EPS runs. Starting from the 51 members that form the ECMWF-EPS we generate five clusters. For each cluster a representative member is selected and used to provide initial and dynamic boundary conditions to RAMS, whose integrations generate LEPS. RAMS runs have 12-km horizontal resolution. To analyze the impact of enhanced horizontal resolution on quantitative precipitation forecasts, LEPS forecasts are compared to a full Brute Force (BF) ensemble. This ensemble is based on RAMS, has 36 km horizontal resolution and is generated by 51 members, nested in each ECMWF-EPS member. LEPS and BF results are compared subjectively and by objective scores. Subjective analysis is based on precipitation and probability maps of case studies whereas objective analysis is made by deterministic and probabilistic scores. Scores and maps are calculated by comparing ensemble precipitation forecasts against reports from the Calabria regional raingauge network. Results show that LEPS provided better rainfall predictions than BF for all case studies selected. This strongly suggests the importance of the enhanced horizontal resolution, compared to ensemble population, for Calabria for these cases. To further explore the impact of local physiographic features on QPF (Quantitative Precipitation Forecasting), LEPS results are also compared with a 6-km horizontal resolution deterministic forecast. Due to local and mesoscale forcing, the high resolution forecast (Hi-Res) has better performance compared to the ensemble mean for rainfall thresholds larger than 10mm but it tends to overestimate precipitation for lower amounts. This yields larger false alarms that have a detrimental effect on objective scores for lower thresholds. To exploit the advantages of a probabilistic forecast compared to a deterministic one, the relation between the ECMWF-EPS 700 hPa geopotential height spread and LEPS performance is analyzed. Results are promising even if additional studies are required

Structural optimization of reversible dibromomaleimide peptide stapling

Methods to constrain peptides in a bioactive α‐helical conformation for inhibition of protein‐protein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible “stapling” methodology was described which exploits native cysteine or homocysteine residues spaced at the i and i + 4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X1 = L‐Cys and X5 = L‐hCys in the context of the model peptide Ac‐X1AAAX5‐NH2, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes

Maleimide constrained BAD BH3 domain peptides as BCL-xL Inhibitors: A Versatile Approach to Rapidly Identify Sites Compatible with Peptide Constraining

Development of protein–protein interaction (PPI) inhibitors remains a major challenge. A significant number of PPIs are mediated by helical recognition epitopes; although peptides derived from such epitopes are attractive templates for inhibitor design, they may not readily adopt a bioactive conformation, are susceptible to proteolysis and rarely elicit optimal cell uptake properties. Constraining peptides has therefore emerged as a useful method to mitigate against these liabilities in the development of PPI inhibitors. Building on our recently reported method for constraining peptides by reaction of dibromomaleimide derivatives with two cysteines positioned in an i and i + 4 relationship, in this study, we showcase the power of the method for rapid identification of ideal constraining positions using a maleimide-staple scan based on a 19-mer sequence derived from the BAD BH3 domain. We found that the maleimide constraint had little or a detrimental impact on helicity and potency in most sequences, but successfully identified i, i + 4 positions where the maleimide constraint was tolerated. Analyses using modelling and molecular dynamics (MD) simulations revealed that the inactive constrained peptides likely lose interactions with the protein as a result of introducing the constraint

Diffractometer‐Control Software For Bragg‐Rod Measurements

We present Generalized Diffractometer Control (gdc), a diffractometer‐control software package developed specifically for high‐precision measurements of Bragg rods; we discuss its features and analyze its performance in data collection. gdc, implemented at several APS beamlines, controls a six‐circle diffractometer in either Eulerian or kappa geometry, yet does not assume a mechanically ideal diffractometer; instead, the measured directions of the diffractometer axes (and the direction of the incident beam) are input parameters. The Labview‐based program features a graphical interface, making it straightforward to find all the commands and operations. Other features include optimized scans along Bragg rods, straightforward background subtraction, and extensive sets of pseudomotors. © 2004 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87660/2/1221_1.pd

Experience with a fluorescence‐based beam position monitor at the APS

We have recently redesigned the first crystal mount of our cryogenically cooled monochromator to reduce its sensitivity to pressure fluctuations in the cryogenic lines feeding the Si (111) crystal. With the use of a fluorescence‐based X‐ray beam position monitor (BPM) placed 19 m away from the monochromator, much operational experience has been gained on the sensitivity of the beam position and intensity to small changes in the cooling system. In this presentation, we will describe our X‐ray BPM design and performance and will provide examples of changes that have made the beam position more stable on our beamline. One such change for example has been the top‐up operation of the Advanced Photon Source (APS), which has reduced the thermal drifts associated with the ring current decay. © 2004 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87659/2/679_1.pd

Order and phase nucleation in nonequilibrium nanocomposite Fe-Pt thin films with perpendicular magnetic anisotropy

We report on the time evolution of mass transport upon annealing nonequilibrium Fe-Pt nanocomposite films, leading to nucleation of L1(0) chemically ordered phase. The nonequilibrium nanocomposite films were fabricated by applying Fe(+) ion implantation to epitaxial Pt films grown on (001) MgO substrates, yielding Fe nanoclusters embedded in a Pt matrix at a tailored penetration depth. Time-resolved x-ray diffraction studies were carried out using synchrotron radiation, allowing determination of the activation energy for nucleation of the FePt L1(0) phase within the segregated nanoclusters during annealing. The growth of the segregated L1(0) ordered phase was modeled using ideal grain-size law and found to be dominated by strain-driven surface nucleation. The activation energies were found to correlate with the nanocluster size. Magnetic characterization of selected annealed samples indicates perpendicular magnetic anisotropy with high coercive field coincident with high value of the chemical order parameter of the ordered phase within the magnetic nanoclusters