In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The 18F-radiolabeled polyamides were prepared by oxime ligation between 4-[18F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies

High porosity metallic glass foam: A powder metallurgy route

A powder metallurgy route to the fabrication of metallic glass foam is introduced. The method involves consolidating metallic glass powder blended with blowing agent particulates to produce expandable precursors, capable of yielding foams with porosities as high as 86%. The foams are found to inherit the strength of the parent metallic glass and to be able to deform heavily toward full densification absorbing high amounts of energy

Approaches to Aggregation and Decision Making - A Health Economics Approach : An ISPOR Special Task Force Report [5]

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted lifeyears. For example, we describe a recently developed extended costeffectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features—measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach—augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing “hedonic” value frameworks, and conclude with some recommendations in this area

On the form of growing strings

Patterns and forms adopted by Nature, such as the shape of living cells, the geometry of shells and the branched structure of plants, are often the result of simple dynamical paradigms. Here we show that a growing self-interacting string attached to a tracking origin, modeled to resemble nascent polypeptides in vivo, develops helical structures which are more pronounced at the growing end. We also show that the dynamic growth ensemble shares several features of an equilibrium ensemble in which the growing end of the polymer is under an effective stretching force. A statistical analysis of native states of proteins shows that the signature of this non-equilibrium phenomenon has been fixed by evolution at the C-terminus, the growing end of a nascent protein. These findings suggest that a generic non-equilibrium growth process might have provided an additional evolutionary advantage for nascent proteins by favoring the preferential selection of helical structures.Comment: 4 pages, 3 figures. Accepted for publication in Phys. Rev. Let

The cytoplasm of living cells: A functional mixture of thousands of components

Inside every living cell is the cytoplasm: a fluid mixture of thousands of different macromolecules, predominantly proteins. This mixture is where most of the biochemistry occurs that enables living cells to function, and it is perhaps the most complex liquid on earth. Here we take an inventory of what is actually in this mixture. Recent genome-sequencing work has given us for the first time at least some information on all of these thousands of components. Having done so we consider two physical phenomena in the cytoplasm: diffusion and possible phase separation. Diffusion is slower in the highly crowded cytoplasm than in dilute solution. Reasonable estimates of this slowdown can be obtained and their consequences explored, for example, monomer-dimer equilibria are established approximately twenty times slower than in a dilute solution. Phase separation in all except exceptional cells appears not to be a problem, despite the high density and so strong protein-protein interactions present. We suggest that this may be partially a byproduct of the evolution of other properties, and partially a result of the huge number of components present.Comment: 11 pages, 1 figure, 1 tabl

Microwave Gaseous Discharges

Contains reports on two research projects

Plasma Spectroscopy of Titanium Monoxide for Characterization of Laser Ablation

Ablation of titanium wafers in air is accomplished with 60 µs pulsed, 2.94 µm laser radiation. Titanium monoxide spectra are measured in the wavelength range of 500 nm to 750 nm, and molecular signatures include bands of the C3 Δ → X3 Δ α, B3 Π → X3 Δ γ\u27, and A3 Φ → X3 Δ γ transitions. The spatially and temporally averaged spectra appear to be in qualitative agreement with previous temporally resolved studies that employed shorter wavelengths and shorter pulse durations than utilized in this work. The background signals in the current study are possibly due to particulate content in the plume. A chemical kinetic model of the plume is being developed that will be coupled to a diatomic emission model in order to extract a molecular temperature from the observed spectra