MALDI-TOF/TOF CID experiments were conducted on a variety of hydroxylated polystyrene precursor ions (m/z 1249.6 (n ) 10), 1769.9 (n ) 15), 2290.2 (n ) 20), 2810.5 (n ) 25), and 3330.8 (n ) 30)) to examine the influence of molecular weight and collision kinetic energy on the degradation mechanisms. Our study indicates that polystyrene free radicals are formed initially through multiple chain breaks and subsequently undergo a variety of secondary depolymerization reactions to yield predominantly monomer, dimer, and trimer species; the intensity of each species depends on the kinetic energy selected for the CID process. Long-chain "unzipping" is not a major pathway for any of the experimental conditions. Each depolymerization mechanism is presented in detail with experimental and computational data to justify/rationalize its process and kinetic energy dependence. These processes show the complex interrelationships between the various pathways along with preferred production of secondary radicals (which suppresses the appearance of primary radicals). Additionally, Py-GC/MS experimental data are presented, for comparison of the multimolecular free radical reactions in pyrolysis with the unimolecular fragmentation reactions of MS/MS.

The exciton dynamics of CdSe nanocrystals are intimately linked to the surface morphology. Photo-oxidation of the selenium surfaces of the nanocrystal leads to an increase in radiative decay efficiency from both the band edge and deep trap emission states. The addition of the primary amine hexadecylamine curtails nonradiative excitonic decay attributed to the dangling surface selenium orbitals by passivation of those trap sites by the methylene protons on the amine, leading to enhanced band edge emission and the absence of deep trap emission. Furthermore, CdSeZnSe core/shell nanocrystals are not immune from contributions from surface states because of the alignment of the band structures of the core and shell materials.

Fluorescence upconversion spectroscopy has been performed on high-quality, low size dispersion CdSe nanocrystals synthesized using the CdO precursor with tri-n-octylphosphine oxide and hexadecylamine cosurfactants. These measurements reveal that an increase in nanocrystal diameter, from 25 to 60 Å, is accompanied by an increase in both the short-lived (τ 1 ) and long-lived (τ 2 ) components of the fluorescence lifetime at the band edge. The increase in τ 1 is explained by the decrease in accessible trap sites through a reduction in surface-to-volume ratio. The addition of hexadecylamine as a cosolvent, through interaction with dangling selenium bonds on the nanocrystal surface, is shown to increase τ 1 as compared to nanocrystals synthesized only in tri-n-octylphosphine oxide. These results indicate that carrier dynamics are preparation dependent.

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Quantum dot (QD) imaging is a powerful tool for studying signaling pathways as they occur. Here we employ this tool to study adhesion molecule expression with lung inflammation in vivo. A key event in pulmonary inflammation is the regulation of vascular endothelial cell adhesion molecule-1 (VCAM), which drives activated immune cell adherence. The induction of VCAM expression is known to be associated with reactive oxygen species (ROS) production, but the exact mechanism or the cellular source of ROS that regulates VCAM in inflamed lungs is not known. NADPH oxidase 2 (NOX2) has been reported to be a major source of ROS with pulmonary inflammation. NOX2 is expressed by both endothelial and immune cells. Here we use VCAM-targeted QDs in a mouse model to show that NOX2, specifically endothelial NOX2, induces VCAM expression with lung inflammation in vivo.

High affinity peptide neurotoxins are effective agents for integrating technological advances with biological inquiries. Both chlorotoxin (CTX) and dendrotoxin-1 (DTX-1) are peptide neurotoxins demonstrated to bind targets expressed by glioma cancer cells and are suitable ligands for quantum dot (QD) live cell investigations. Here, we present dual labeling of endogenously expressed cellular proteins within living cells utilizing high affinity peptide neurotoxins conjugated to QDs. Multiplexing experiments reveal quantifiable evidence that CTX and DTX-1 conjugated QDs may potentially be used as a live assessment of markers toward identification of cancer cell presence.

Nicotinic receptors (nAchRs) are responsible for fast excitatory signaling by the neurotransmitter acetylcholine (Ach). They are present on the postsynaptic membrane at neuromuscular junctions (NMJs) and also at brain synapses. Alpha-bungarotoxin (alpha-BTX), a high-affinity nAchR antagonist, inhibits Ach binding and neurotransmission. Here we demonstrate biotinylated alpha-BTX, bound to native mouse diaphragm nAchRs, can be quantified and visualized ex vivo using streptavidin-conjugated quantum dots. This approach provides a novel methodology for the direct assessment of the presence and mobility of neurotransmitter receptors in native tissue.

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses. Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) studies and their extensions. Methods: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course. Results: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses. Conclusion: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown.