Collisional fragmentation of Ar@C60

The fragmentation patterns resulting from collisions between (Ar@C₆₀)⁺ or (Ar@C₆₀)⁻ ions and H₂, He, CH₄, Ne, Ar and Kr target gases have been measured. The ion-source material Ar@C₆₀ was synthesized by heating C₆₀ under 3000 atm of argon gas, leading to a 10⁻³ concentration of endohedral fullerenes. The fragmentation spectra (charged molecules only) are dominated by positive ions both when positive or negative endohedrals break up. Endohedral fragment ions Ar@C_n⁺ (48n60) as well as all carbon fragments are observed. For collisions involving (Ar@C₆₀)⁻, ejection of the Ar atom together with two electrons, without permanently damaging the fullerene cage, is a prominent reaction channel, indicating that a ‘window' or a deformation in the form of e.g. a large hole, through which the argon atoms can exit, is opened during the collision.     

LeadScope: software for exploring large sets of screening data

Modern approaches to drug discovery have dramatically increased the speed and quantity of compounds that are made and tested for potential potency. The task of collecting, organizing, and assimilating this information is a major bottleneck in the discovery of new drugs. We have developed LeadScope a novel, interactive computer program for visualizing, browsing, and interpreting chemical and biological screening data that can assist pharmaceutical scientists in finding promising drug candidates. The software organizes the chemical data by structural features familiar to medicinal chemists. Graphs are used to summarize the data, and structural classes are highlighted that are statistically correlated with biological activity.     

Insight into the complex and dynamic process of activation of matrix metalloproteinases.

Matrix metalloproteinases (MMPs) are important hydrolytic enzymes with profound physiological and pathological functions in living organisms. MMPs are produced in their inactive zymogenic forms, which are subsequently proteolytically activated in an elaborate set of events. The propeptide in the zymogen blocks the active site, with a cysteine side-chain thiolate from this propeptide achieving coordination with the catalytically important zinc ion in the active site. Molecular dynamics simulations, ab initio calculations, and wet chemistry experiments presented herein argue for the critical importance of a protonation event at the coordinated thiolate as a prerequisite for the departure of the propeptide from the active site. Furthermore, a catalytically important glutamate is shown to coordinate transiently to the active-site zinc ion to "mask" the positive potential of the zinc ion and lower the energy barrier for dissociation of the protonated cysteine side chain from the zinc ion. In addition, a subtle conformational change by the propeptide is needed in the course of zymogen activation. These elaborate processes take place in concert in the activation process of MMPs, and the insight into these processes presented herein sheds light on a highly regulated physiological process with profound consequences for eukaryotic organisms.     

The active site of a zinc-dependent metalloproteinase influences the computed pK(a) of ligands coordinated to the catalytic zinc ion

TNF-alpha converting enzyme (TACE) is a multidomain, membrane-anchored protein that includes a Zn-dependent protease domain. It releases the soluble form of cytokine tumor necrosis factor-alpha (TNF-alpha) from its membrane-bound precursor. TACE is a metalloprotease containing a catalytic glutamic acid, Glu-406, and a Zn(2+) ion ligated to three imidazoles. The protonation states of the active site glutamic acid and inhibitors are important factors in understanding the potency of inhibitors with acidic zinc-ligating groups such as hydroxamic and carboxylic acids. Density functional methods were utilized to compute pK(a) values using a model of the catalytic site of TACE and to predict a concomitant mechanism of binding, consistent with lowering the pK(a) of the bound ligand and raising the pK(a) of the active site Glu-406. Weak acids, such as hydroxamic acids, bind in their neutral form and then transfer an acidic proton to Glu-406. Stronger acids, such as carboxylic acids, bind in their anionic form and require preprotonation of Glu-406. Similar binding events would be expected for other zinc-dependent proteases.     

The molecular structure of selenonyl fluoride,SeO2F2, and sulfuryl fluoride,SO2F2, as determined by gas-phase electron diffraction

The molecular structure of selenonyl fluoride (SeO₂F₂) and sulfuryl fluoride (SO₂F₂) has been studied by gas-phase electron diffraction. The geometries of both molecules are consistent with predictions of VSEPR (valence-shell electron-pair repulsion) theory. The results for the more important distance (r_a), bond angle, and r.m.s. amplitude (l) parameters with estimated uncertainties estimated at 2σ are for SeO₂F₂r(Se = 0) = 1.575 Å (0.002), r(Se-F) = 1.685 Å (0.002), ∠OSeO = 126.2° (0.5), ∠FSeF = 94.1° (0.5), l(Se = 0) = 0.0440 Å (0.0046), l(Se-F) = 0.0472 Å (0.0042), and for SO₂F₂r(S = 0) = 1.397 Å (0.002), r(S-F) = 1.530 Å (0.002), ∠OSO = 122.6° (1.2), ∠FSF = 96.7° (1.1), l(S = 0) = 0.0331 Å (0.0015), l(S-F) = 0.0393 Å (0.0018).     

High-efficiency wideband gyro-TWTs and gyro-BWOs with helically corrugated waveguides

We review the studies of gyrotron-type microwave devices whose electrodynamic system has the form of an oversized metal waveguide with a helically corrugated internal surface. For certain parameters, such a corrugation changes radically the waveguide dispersion ensuring an almost constant group velocity of the eigenmode for a small (close to zero) longitudinal wave number in a wide frequency band. The use of “helical” waveguides along with electron optical systems which form near-axis electron beams makes it possible to create high-efficiency amplifiers based on gyro-traveling-wave tubes (gyro-TWTs) with a wide instantaneous frequency band of amplification and gyro-backward-wave oscillators (gyro-BWOs) with continuous wideband tuning of the oscillation frequency. The studied devices are superior to the well-studied microwave sources of this type (gyroklystrons and gyrotrons) in frequency band, by more than an order of magnitude, and are not inferior to them in efficiency even for a wide spread of electron velocities. __________ Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Radiofizika, Vol. 50, No. 2, pp. 104–117, February 2007.     

Multidimensional NMR cross-correlation relaxation study of carrot phloem and xylem. Part I: Peak assignment

We report, for the first time, a detailed analysis of the complicated two-dimensional (2-D) nuclear magnetic resonance relaxation spectra of the xylem and phloem of carrots. By combining chemical extraction with different 2-D pulse sequences attempts are made to assign relaxation peaks to cell components, including compartmentalized water, pectins, starch, proteins and hemicelluloses. In a separate report, we use these assignments to interpret the effects of thermal and high-pressure processing (M. E. Furfaro, N. Marigheto, G. K. Moates, K. Cross, M. L. Parker, K. W. Waldron, B. P. Hills: Appl. Magn. Reson. 35, 537–547, 2009).     

Computational modelling of variably saturated flow in porous media with complex three‐dimensional geometries

A computational procedure is presented for solving complex variably saturated flows in porous media, that may easily be implemented into existing conventional finite‐volume‐based computational fluid dynamics codes, so that their functionality might be geared upon to readily enable the modelling of a complex suite of interacting fluid, thermal and chemical reaction process physics. This procedure has been integrated within a multi‐physics finite volume unstructured mesh framework, allowing arbitrarily complex three‐dimensional geometries to be modelled. The model is particularly targeted at ore heap‐leaching processes, which encounter complex flow problems, such as infiltration into dry soil, drainage, perched water tables and flow through heterogeneous materials, but is equally applicable to any process involving flow through porous media, such as in environmental recovery processes. The computational procedure is based on the mixed form of the classical Richards equation, employing an adaptive transformed mixed algorithm that is numerically robust and significantly reduces compute (or CPU) time. The computational procedure is accurate (compares well with other methods and analytical data), comprehensive (representing any kind of porous flow model), and is computationally efficient. As such, this procedure provides a suitable basis for the implementation of large‐scale industrial heap‐leach models. Copyright © 2005 John Wiley & Sons, Ltd.     

On the propagation mechanism of a detonation wave in a round tube with orifice plates

This study deals with the investigation of the detonation propagation mechanism in a circular tube with orifice plates. Experiments were performed with hydrogen air in a 10-cm-inner-diameter tube with the second half of the tube filled with equally spaced orifice plates. A self-sustained Chapman–Jouguet (CJ) detonation wave was initiated in the smooth first half of the tube and transmitted into the orifice-plate-laden second half of the tube. The details of the propagation were obtained using the soot-foil technique. Two types of foils were used between obstacles, a wall-foil placed on the tube wall, and a flat-foil (sooted on both sides) placed horizontally across the diameter of the tube. When placed after the first orifice plate, the flat foil shows symmetric detonation wave diffraction and failure, while the wall foil shows re-initiation via multiple local hot spots created when the decoupled shock wave interacts with the tube wall. At the end of the tube, where the detonation propagated at an average velocity much lower than the theoretical CJ value, the detonation propagation is much more asymmetric with only a few hot spots on the tube wall leading to local detonation initiation. Consecutive foils also show that the detonation structure changes after each obstacle interaction. For a mixture near the detonation propagation limit, detonation re-initiation occurs at a single wall hot spot producing a patch of small detonation cells. The local overdriven detonation wave is short lived, but is sufficient to keep the global explosion front propagating. Results associated with the effect of orifice plate blockage and spacing on the detonation propagation mechanism are also presented.