Mass spectrometric contributions to problems related to the chemistry of atmospheres

Recent mass spectrometric studies of species and processes relevant to the chemistry of atmospheres are reported. New species have been detected, including HO(3); a stratospheric reservoir of OH radicals; the [H(2)O(+)O(2)(-)] charge transfer complex, central to the atmospheric photonucleation theory; and the OSOSO oxide and its cation, likely present in the Io's atmosphere. As to ionic processes, a new route to tropospheric N(2)O in air ionized by lightning and coronas is reported, as well as the complex chemistry promoted by ionization of ozone/freon and ozone/carbonyl sulfide mixtures and the formation of O(5)(+), relevant to the problem of (18)O excess in stratospheric ozone.     

Dynamics and fragmentation of thick-shelled microbubbles

Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 /spl mu/m in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 /spl mu/m in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.     

Nondestructive subharmonic imaging

Ultrasound contrast agent microbubbles are intravascular agents that can be used to estimate blood perfusion. Blood perfusion may be estimated by destroying the bubbles in a vascular bed and observing the refresh of contrast agents back into the vascular bed. Contrast agents can be readily destroyed by traditional imaging techniques. The design of a nondestructive imaging technique is necessary for the accurate quantification of contrast agent refresh. In this work, subharmonic imaging is investigated as a method for nondestructive imaging with the contrast agent microbubble MP1950 (Mallinckrodt, Inc., St. Louis, MO). Optical observation during insonation, in conjunction with a modified Rayleigh-Plesset (R-P) analysis, provides insight into the mechanisms of and parameters required for subharmonic frequency generation. Subharmonic imaging with a transmission frequency that is the same as the resonant frequency of the bubble is shown to require a minimum pressure of insonation that is greater than the experimentally-observed bubble destruction threshold. Subharmonic imaging with a transmission frequency that is twice the resonant frequency of the bubble produces a subharmonic frequency response while minimizing bubble instability. Optimization is performed using optical experimental analysis and R-P analysis     

Is accurate recording of the ECG surface Laplacian feasible?

Experimental and model studies were performed to measure the electrocardiographic surface Laplacian using a rectangular finite difference approximation. The experimental approach used ten normal subjects with two sites on the torso. Electrode spacing was 2 cm. The surface Laplacian is theoretically independent of rotation of the electrode array. The data showed considerable variation with rotation. Model studies employed a realistic 23-dipole source. A spherical volume conductor showed invariance with rotation, as anticipated theoretically. A realistic torso, however, showed variation with rotation, although not as severe as that measured. A separate experimental study considered the signal-to-noise ratio (SNR) for the surface Laplacian. The average SNR was 3.3 and 2.5 at the two sites. These results raise serious questions about the practical ability to measure the surface Laplacian on the torso.     

IL-13 increases the cPLA2 gene and protein expression and the mobilization of arachidonic acid during an inflammatory process in mouse peritoneal macrophages

Pretreatment of mouse peritoneal macrophages with interleukin-13 (IL-13) potentiates the mobilization of arachidonic acid (AA) and the production of HETEs but does not affect the production of cyclooxygenase metabolites triggered by the suboptimal concentration of an inflammatory agonist (opsonized-zymosan). Cycloheximide suppresses these effects of IL-13 suggesting that de novo protein synthesis is involved. Indeed, IL-13 induces a time-dependent increase in the levels of cytosolic PLA2 (cPLA2) protein and mRNA. This study demonstrates a new pathway for IL-13 to modulate the inflammatory process in macrophages via modifications of cPLA2 expression and subsequent AA mobilization.     

Peak procedure performance in young adult and aged rats: acquisition and adaptation to a changing temporal criterion

Twenty-four-month-old and 4-month-old rats were trained on a peak-interval procedure, where the time of reinforcement was varied twice between 20 and 40 sec. Peak times from the old rats were consistently longer than the reinforcement time, whereas those from younger animals tracked the 20- and 40-sec durations more closely. Different measures of performance suggested that the old rats were either (1) systematically misremembering the time of reinforcement or (2) using an internal clock with a substantially greater latency to start and stop timing than the younger animals. Old rats also adjusted more slowly to the first transition from 20 to 40 sec than did the younger ones, but not to later transitions. Correlations between measures derived from within-trial patterns of responding conformed in general to detailed predictions derived from scalar expectancy theory. However, some correlation values more closely resembled those derived from a study of peak-interval performance in humans and a theoretical model developed by Cheng and Westwood (1993), than those obtained in previous work with animals, for reasons that are at present unclear.     

A method for radiation-force localized drug delivery using gas-filled lipospheres

We have developed a method using ultrasound and acoustically active lipospheres (AALs) that might be used to deliver bioactive substances to the vascular endothelium. The AALs consist of a small gas bubble surrounded by a thick oil shell and enclosed by an outermost lipid layer. The AALs are similar to ultrasound contrast agents: they can be nondestructively deflected using ultrasound radiation force, and fragmented with high-intensity ultrasound pulses. The lipid-oil complex might be used to carry bioactive substances at high concentrations. An optimized sequence of ultrasound pulses can deflect the AALs toward a vessel wall then disrupt them, painting their contents across the vascular endothelium. This paper presents results from a series of in vitro and ex vivo experiments demonstrating localization of a fluorescent model drug. In experiments using a human melanoma cell (A2085) monolayer, a specific radiation force-fragmentation ultrasound pulse sequence increased cell fluorescence more than 10-fold over no ultrasound or fragmentation pulses alone, and by 50% over radiation force pulses alone. We observe that dye transfer is limited to cells that are in the region of ultrasonic focus, indicating that the application of radiation force pulses to bring the delivery vehicle into proximity with the cell is required for successful adhesion of the vehicle fragments to the cell membrane. We also demonstrate dye transfer from flowing AALs, both in a mimetic vessel and in excised rat cecum. We believe that this method could be successfully used for drug delivery in vivo.     

Ultradispersity of diamond at the nanoscale

Nanometre-sized diamond has been found in meteorites, protoplanetary nebulae and interstellar dusts, as well as in residues of detonation and in diamond films. Remarkably, the size distribution of diamond nanoparticles seems to be peaked around 2-5 nm, and to be largely independent of preparation conditions. We have carried out ab initio calculations of the stability of nanodiamond as a function of surface hydrogen coverage and of size. We have found that at about 3 nm, and for a broad range of pressures and temperatures, particles with bare, reconstructed surfaces become thermodynamically more stable than those with hydrogenated surfaces, thus preventing the formation of larger grains. Our findings provide an explanation of the size distribution of extraterrestrial and of terrestrial nanodiamond found in ultradispersed and ultracrystalline diamond films. They also provide an atomistic structural model of these films, based on the topology and structure of 2-3-nm dimond clusters consisting of a diamond core surrounded by a fullerene-like carbon network.     

Shell waves and acoustic scattering from ultrasound contrast agents

Ultrasound contrast agents are encapsulated microbubbles, filled either with air or a higher weight molecular gas, ranging in size from 1 to 10 μm in diameter. The agents are modeled as air-filled spherical elastic shells of variable thickness and material properties. The scattered acoustic field is computed from a modal series solution, and reflectivity and angular scattering are then determined from the computed fields for agents of various properties. We show that contrast agents also support shell resonance responses in addition to the monopole response, which has been the focus of previous contrast agent studies. Lamb waves appear to be the source of these additional responses. A shell or curvature Lamb wave generates dipole peaks in the 1- to 40-MHz range for 2.5 to 3.5 μm radius agents with elastic properties approximating those of albumin protein. The inclusion of damping affects the lower frequency dipole peaks but is less important for responses occurring above approximately 30 MHz. Moreover, these responses hold untapped potential for clinical ultrasound applications such as tissue perfusion studies and high frequency contrast agent imaging     

“Collapsible” lightweight aggregate concrete. Part II: characterization under static and dynamic loadings

In this work a granular cementitious composite has been developed, tailoring its performance to a low compressive strength and high deformation and energy dissipation capacity, which can be required to the material when employed in post-installed screeds for protection of structures and infrastructures against accidental actions such as impact and blast. The required level of performance can be achieved by uniform grain size distribution, paste content as low as minimum theoretical void ratio and low paste strength: it is believed that the synergy between the aforementioned three requirements can allow for energy dissipation capacity after paste cracking due to both rearrangement of grain meso-structure and, in case, grain crushing. After the mix design concept and optimization of the material composition, illustrated in the first part of this companion paper study, the mechanical performance of the composite under static and impact compressive loadings has been thoroughly characterized, as affected by mix-design variables, such as paste volume fraction, water to cement ratio and aggregate size. The reliability will thus be thoroughly checked, of the employed material concept, and the influence will also be investigated, if any, of specimen shape, size and boundary conditions.