Kinetic and Structural Analysis of the Mg2+ -binding Site of the Guanine Nucleotide-binding Protein p21 H-ras.

The coordination and binding of the Mg2+ ion in the nucleotide−binding site of p21 have been investigated using site−directed mutagenesis, kinetic methods, and phosphorous NMR. Mg2+ in the p21.nucleotide.Mg2+ complex appears to be in fast equilibrium with the solvent. The dissociation constant between Mg2+ and the p21.GDP complex was determined to be 2.8 microM. It decreases 30− or 16−fold on substituting Ser−17 or Asp−57 with alanine, respectively, whereas the T35A mutation has no effect. All three mutations influence the dissociation constants and the association and dissociation rate constants of the interaction between guanine nucleotides and p21, but to a different degree. We conclude that Thr−35 is only complexed to Mg2+ in the GTP conformation and both Asp−57 and Ser−17 appear to be critical for both GDP and GTP binding. 31P NMR spectra of the GDP and Gpp(NH)p (guanosine−5'−(beta,gamma−imido)triphosphate) complexes of mutated p21 show a remarkable perturbation of the guanine nucleotide− binding site compared to wild−type protein. The mutant proteins show reduced GTPase rates, which are not stimulated by the GTPase−activating protein GAP. p21(S17A) has been reported to function just as p21(S17N) as a dominant negative inhibitor of normal p21. We find that it inhibits oncogenic p21−induced survival of primary neuron

Determination of the basic timescale in kinetic Monte Carlo simulations by comparison with cyclic-voltammetry experiments

While kinetic Monte Carlo simulations can provide long-time simulations of the dynamics of physical and chemical systems, it is not yet possible in general to identify the inverse Monte Carlo attempt frequency with a physical timescale. Here we demonstrate such an identification by comparing simulations with experimental data. Using a dynamic lattice-gas model for the electrosorption of Br on Ag(100), we measure the scan-rate dependence of the separation between positive-and negative-going peaks in cyclic-voltammetry (CV) and compare simulated and experimental peak separations. By adjusting the Monte Carlo attempt frequency, good agreement between simulated and experimental peak separations is achieved. It is also found that the uniqueness of such a determination is dependent on the relative values of the adsorption/desorption and diffusion free-energy barriers.Comment: Accepted for publication in Surface Science Letters,8 pages, 4 figure

Review of 'The End of Desertification? Disputing Environmental Change in the Drylands' by Roy H. Behnke and Michael Mortimore

Tales of desertification across the world’s drylands are a recurrent theme in policy discourse. This book takes issue with many of the assumptions around desertification, with cases ranging from Central Asia to West Africa to the Mediterranean to the American West. It is edited by Roy Behnke, an anthropologist with deep knowledge of pastoral areas in North and Southern Africa, West Asia and more, and Michael Mortimore, sadly now late, a development geographer, who knew a huge amount about the drylands of Africa, and particularly northern Nigeria

Simulation studies of CZT Detectors as Gamma-Ray Calorimeter

We describe the results of detailed 3-D Monte Carlo simulations of a "CZT calorimeter" that can be used to detect photons in the keV to several MeV range. Several astrophysics applications require the detection of photons in the energy range of keV up to several MeV with good position and energy resolution. For certain applications Cadmium Zinc Telluride (CZT) detectors might be the detector option of choice. Up to now, CZT detectors have mainly been used in the energy range between a few keV to ~1 MeV, we describe the results of detailed 3-D Monte Carlo simulations of a "CZT calorimeter" that can be used to detect photons in the keV to several MeV range. The main objective of these studies is to evaluate the feasibility of CZT calorimeters, to study their performance and detect and understand performance limiting factors. Such a calorimeter consists of many layers of closely packed pixellated CZT detector units. Our simulations of single detector units reproduce experimental results, indicating that our simulations capture the main factors that limit the performance of a detector unit. Overall the conclusion of our simulation study is that between 1 cm and 1.5 cm thick detector units can be used to build a calorimeter with good performance over the energy range from ~20 keV to ~10 MeV.Comment: Accepted for publication in Astroparticle Physics, 20 pages, 14 figure

Longitudinal Atomic Beam Spin Echo Experiments: A possible way to study Parity Violation in Hydrogen

We discuss the propagation of hydrogen atoms in static electric and magnetic fields in a longitudinal atomic beam spin echo (lABSE) apparatus. Depending on the choice of the external fields the atoms may acquire both dynamical and geometrical quantum mechanical phases. As an example of the former, we show first in-beam spin rotation measurements on atomic hydrogen, which are in excellent agreement with theory. Additional calculations of the behaviour of the metastable 2S states of hydrogen reveal that the geometrical phases may exhibit the signature of parity-(P-)violation. This invites for possible future lABSE experiments, focusing on P-violating geometrical phases in the lightest of all atoms.Comment: 6 pages, 4 figure

Pediatric pacemaker infections: Twenty years of experience

AbstractObjective: We sought to evaluate possible predictors of early and late pacemaker infections in children. Methods: A review was performed of all pacemakers implanted in children at The Children's Hospital of Philadelphia between 1982 and 2001. Infections were classified as superficial cellulitus, deep pacemaker pocket infection necessitating removal, or positive blood culture without an identifiable source. Results: A total of 385 pacemakers (224 epicardial and 161 endocardial) were implanted in 267 patients at 8.4 ± 6.2 years. All 2141 outpatient visits were reviewed (median follow-up, 29.4 months; range, 2-232 months). There were 30 (7.8%) pacemaker infections: 19 (4.9%) superficial infections; 9 (2.3%) pocket infections; and 2 (0.5%) isolated positive blood cultures. All superficial infections resolved with intravenous antibiotics. The median time from implantation to infection was 16 days (range, 2 days-5 years). Only 1 deep infection occurred after primary pacemaker implantation. Six patients with deep infections were pacemaker dependent and were successfully managed with intravenous antibiotics, followed by lead-generator removal and implantation of a new pacemaker in a remote location. In univariate analyses trisomy 21 (relative risk, 3.9; P <.01), pacemaker revisions (relative risk, 2.5; P <.01), and single-chamber devices (relative risk, 2.4; P <.05) were identified as predictors of infection. However, in multivariate analyses only trisomy 21 and pacemaker revisions were predictors. Conclusions: The incidences of superficial and deep pacemaker infections were 4.9% and 2.3%, respectively. Trisomy 21 and pacemaker revisions were significant risk factors in the development of infection after pacemaker implantation. For primary pacemaker implantation, the risk of infection requiring system removal is low (0.3%).J Thorac Cardiovasc Surg 2002;124:821-

Micron-scale intrashell oxygen isotope variation in cultured planktic foraminifers

In this study, we show that the rate of shell precipitation in the extant planktic foraminifer Orbulina universa is sufficiently rapid that 12 h calcification periods in 18O-labeled seawater can be resolved and accurately measured using secondary ion mass spectrometry (SIMS) for in situ δ18O analyses. Calcifying O. universa held at constant temperature (22 °C) were transferred every 12 h between ambient seawater (δ18Ow = −0.4‰ VSMOW) and seawater with enriched barium and δ18Ow = +18.6‰ VSMOW, to produce geochemically distinct layers of calcite, separated by calcite precipitated with an ambient geochemical signature. We quantify the position of the Ba-labeled calcite in the shell wall of O. universa via laser ablation ICP-MS depth profiling of trace element ratios, and then measure intrashell δ18Ocalcite in the same shells using SIMS with a 3 μm spot and an average precision of 0.6‰ (±2 SD). Measured δ18Ocalcite values in O. universa shell layers are within ±1.1‰ of predicted δ18Ocalcite values. Elemental and oxygen isotope data show that LA-ICP-MS and SIMS measurements can be cross-correlated within the spatial resolution of the two analytical techniques, and that δ18Ocalcite and elemental tracers appear to be precipitated synchronously with no measurable spatial offsets. These results demonstrate the capability of SIMS to resolve daily growth increments in foraminifer shells, and highlight its potential for paleoceanographic and biomineralization applications on microfossils