A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy

Background  

Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection.     

Characterization of cell lysis events on a microfluidic device for high-throughput single cell analysis

A microfluidic device capable of rapidly analyzing cells in a high-throughput manner using electrical cell lysis is further characterized. In the experiments performed, cell lysis events were studied using an electron multiplying charge coupled device camera with high frame rate (>100 fps) data collection. It was found that, with this microfluidic design, the path that a cell follows through the electric field affects the amount of lysate injected into the analysis channel. Elimination of variable flow paths through the electric field was achieved by coating the analysis channel with a polyamine compound to reverse the electroosmotic flow (EOF). EOF reversal forced the cells to take the same path through the electric field. The improved control of the cell trajectory will reduce device-imposed bias on the analysis and maximizes the amount of lysate injected into the analysis channel for each cell, resulting in improved analyte detection capabilities.     

Unlocking the binding and reaction mechanism of hydroxyurea substrates as biological nitric oxide donors

Hydroxyurea is the only FDA approved treatment of sickle cell disease. It is believed that the primary mechanism of action is associated with the pharmacological elevation of nitric oxide in the blood; however, the exact details of this are still unclear. In the current work, we investigate the atomic level details of this process using a combination of flexible-ligand/flexible-receptor virtual screening coupled with energetic analysis that decomposes interaction energies. Utilizing these methods, we were able to elucidate the previously unknown substrate binding modes of a series of hydroxyurea analogs to hemoglobin and the concomitant structural changes of the enzyme. We identify a backbone carbonyl that forms a hydrogen bond with bound substrates. Our results are consistent with kinetic and electron paramagnetic resonance (EPR) measurements of hydroxyurea-hemoglobin reactions, and a full mechanism is proposed that offers new insights into possibly improving substrate binding and/or reactivity.     

Atomic fluorescence spectrometry of thallium with a frequency-doubled dye laser and vitreous carbon atomizer

A vitreous carbon atomizer is described for use in laser-excited atomic fluorescence spectrometry and is applied to the determination of thallium in aqueous solution. When a frequency-doubled N₂ laser-pumped dye laser is used to excite the atomic thallium at 276.8 nm and the combined direct-line fluorescence and stepwise-line fluorescence are detected at 352.9 and 351.9 nm, respectively, the limit of detection is 2.5 × 10^-14 g in a 0.5-pg ml^-1 sample solution. The calibration curve for thallium has a linear range extending over six orders of magnitude.     

TRPM5-expressing microvillous cells in the main olfactory epithelium

Background  

The main olfactory epithelium (MOE) in the nasal cavity detects a variety of air borne molecules that provide information regarding the presence of food, predators and other relevant social and environmental factors. Within the epithelium are ciliated sensory neurons, supporting cells, basal cells and microvillous cells, each of which is distinct in morphology and function. Arguably, the least understood, are the microvillous cells, a population of cells that are small in number and whose function is not known. We previously found that in a mouse strain in which the TRPM5 promoter drives expression of the green fluorescent protein (GFP), a population of ciliated olfactory sensory neurons (OSNs), as well as a population of cells displaying microvilli-like structures is labeled. Here we examined the morphology and immunocytochemical properties of these microvillous-like cells using immunocytochemical methods.     

Femtosecond vibrational dynamics of self-trapping in a quasi-one-dimensional system

We have directly time resolved the lattice motions associated with the formation of the self-trapped exciton in the quasi-one-dimensional system [Pt(en)(2)] [Pt(en)2Br2];(PF6)(4) ( en = ethylene-diamine, C2H8N2), using femtosecond impulsive excitation techniques. A strongly damped, low-frequency wave packet modulation at approximately 110 cm(-1) accompanies the formation of the self-trapped exciton on a approximately 200 fs time scale following excitation of the intervalence charge-transfer transition. Coherent oscillations at the ground state vibrational frequency and its harmonics are also detected.