Characterization of depleted uranium oxides fabricated using different processing methods

Identifying both physical and chemical characteristics of Special Nuclear Material (SNM) production processes is the corner stone of nuclear forensics. Typically, processing markers are based on measuring an interdicted sample’s bulk chemical properties, such as the elemental or isotopic composition, or focusing on the chemical and physical morphology of only a few particles. Therefore, it is imperative that known SNM processes be fully characterized from bulk to trace level for each particle size range. This report outlines a series of particle size measurements and fractionation techniques that can be applied to a bulk SNM powders, categorizing both chemical and physical properties in discrete particle size fractions. This will be demonstrated by characterizing the process signatures of a series of different depleted uranium oxides prepared at increasing firing temperatures (350–1100 °C). Results will demonstrate how each oxides’ material density, particle size distribution, and morphology varies.     

Metal-mediated self-assembly of protein superstructures: influence of secondary interactions on protein oligomerization and aggregation

We have previously demonstrated that non-self-associating protein building blocks can oligomerize to form discrete supramolecular assemblies under the control of metal coordination. We show here that secondary interactions (salt bridges and hydrogen bonds) can be critical in guiding the metal-induced self-assembly of proteins. Crystallographic and hydrodynamic measurements on appropriately engineered cytochrome cb562 variants pinpoint the importance of a single salt-bridging arginine side chain in determining whether the protein monomers form a discrete Zn-induced tetrameric complex or heterogeneous aggregates. The combined ability to direct PPIs through metal coordination and secondary interactions should provide the specificity required for the construction of complex protein superstructures and the selective control of cellular processes that involve protein-protein association reactions.     

Quantifying the fraction of glycine and alanine in beta-sheet and helical conformations in spider dragline silk using solid-state NMR

Solid-state two-dimensional refocused INADEQUATE MAS NMR experiments resolve distinct helical and beta-sheet conformational environments for both alanine and glycine in Nephila clavipes dragline silk fibers; the fraction of alanine and glycine in beta-sheet structures is determined to be 82% +/- 4% and 28% +/- 5%, respectively.     

Phorbasins G-K: new cytotoxic diterpenes from a southern Australian marine sponge, Phorbas sp

Fractionation of a cytotoxic extract obtained from a southern Australian marine sponge, Phorbas sp., yielded the known diterpenes phorbasins B-F () together with five new members of the phorbasin family, phorbasins G-K (). Structures were assigned to the new phorbasins based on detailed spectroscopic analysis. A preliminary structure activity relationship (SAR) evaluation based on the co-metabolites phorbasins B-K () revealed aspects of the phorbasin pharmacophore.     

Finite groups with an irreducible character of large degree

Let G be a finite group and d the degree of a complex irreducible character of G, then write |G| = d(d + e) where e is a nonnegative integer. We prove that |G| ≤ e⁴?e³ whenever e > 1. This bound is best possible and improves on several earlier related results.     

Separating degenerate (1)H transitions in methyl group probes for single-quantum (1)H-CPMG relaxation dispersion NMR spectroscopy

A relaxation dispersion pulse scheme is presented for quantifying chemical exchange processes in proteins that exploits 1H chemical shifts as probes of changes in conformation. The experiment selects 1H single-quantum magnetization from the I = 1/2 manifolds of the methyl group, which behave like AX spin systems, while suppressing coherences that derive from the 3/2 manifold that are extremely sensitive to pulse imperfections and that would otherwise severely compromise the accuracy of the experiment. The utility of the sequence is first demonstrated with an application to a protein system that is known not to undergo chemical exchange and flat dispersion profiles are obtained. Subsequently, the methodology is applied to study the folding of a G48M mutant of the Fyn SH3 domain that has been shown previously to undergo exchange between folded and unfolded states on the millisecond time scale.     

Covalent reactions of wortmannin under physiological conditions

Wortmannin (Wm), a steroid-like molecule of 428.4 Da, appears to be unstable in biological fluids (apparent chemical instability), yet it exhibits an antiproliferative activity in assays employing a 48 hr incubation period (prolonged bioactivity), a situation we refer to as the "wortmannin paradox." Under physiological conditions, Wm covalently reacts with nucleophiles such as the side chains of cysteine, N-methyl hexanoic acid, lysine, or proline at the C20 position on the furan ring. Like Wm, WmC20 amino acid derivatives had significant antiproliferative activities. Three Wm derivatives, WmC20-proline, WmC20-cysteine, and a WmC20-N-methyl hexanoic acid, generated Wm that then reacted with lysine in an exchange-type reaction. This unusual, reversible, covalent reaction of Wm with nucleophiles under physiological conditions provides an explanation for the wortmannin paradox.     

Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling

In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.