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.     

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.     

Spectral Asymptotics for Higher-Order Ordinary Differential Equations

This paper gives one-term componentwise asymptotics for theM and spectral matrices of a self-adjoint realisation of aneven-order ordinary differential expression. The underlyinginterval is assumed to have at least one regular endpoint, andthe boundary conditions are supposed to be separated. Furthermore,the weight function and the reciprocal of the highest-ordercoefficient are supposed to be of regular variation at the regularendpoint, in the sense of Bingham, Goldie and Teugels. 1991Mathematics Subject Classification: 34B24, 34E05.     

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.     

An absorbance-based micro-fluidic sensor for diffusion coefficient and molar mass determinations

The H-Sensor reported herein is a micro-fluidic device compatible with flow injection analysis (FIA) and high performance liquid chromatography (HPLC). The device detects analytes at two separate off-chip absorbance flow cells, providing two simultaneous absorbance measurements. The ratio of these two absorbance signals contains analyte diffusion coefficient information. A theoretical model for the sensing mechanism is presented. The model relates the signal Ratio to analyte diffusion coefficient. The model is qualitatively evaluated by comparing theoretical and experimental signal Ratio values. Experimental signal Ratios were collected via FIA for a variety of analytes, including sodium azide, benzoic acid, amino acids, peptides, and proteins. Measuring absorbance at multiple wavelengths provides higher order data allowing the analyte signals from mixtures to be deconvolved via classical least squares (CLS). As a result of the H-Sensor providing two simultaneous signals as a function of time for each sample injection, two simulated second-order HPLC chromatograms were generated using experimental H-Sensor data. The chemometric deconvolution method referred to as the generalized rank annihilation method (GRAM) was used to demonstrate chromatographic and spectroscopic deconvolution. GRAM also provides the signal Ratio value, therefore simultaneously obtaining the analyte diffusion coefficient information during deconvolution. The two chromatograms successfully serve as the standard and unknown for the GRAM deconvolution. GRAM was evaluated on chromatograms at various chromatographic resolutions. GRAM was found to function to a chromatographic resolution at and above 0.25 with a percent quantitative error of less then 10%.     

Microfabricated refractive index gradient based detector for reversed-phase liquid chromatography with mobile phase gradient elution

Typical refractive index (RI) detectors for liquid chromatography (LC) are not well suited to application with mobile phase gradient elution, due to the difficulty in correcting for the detected baseline shift during the gradient. We report a sensitive, highly reproducible, microfabricated refractive index gradient (micro-RIG) detector that performs well with mobile phase gradient elution LC. Since the micro-RIG signal remains on-scale throughout the mobile phase gradient, one can apply a baseline correction procedure. We demonstrate that by collecting two mobile phase gradient blanks and subtracting one of them from the other, a reproducible, flat baseline is achieved. Therefore, subtracting a blank from a separation provides a baseline corrected chromatogram with reasonably high signal-to-noise ratio for eluting analytes. The micro-RIG detector uses a collimated diode laser beam to optically probe a RIG formed perpendicular to the laminar flow direction within a microfabricated borosilicate glass chip. The chip-based design of the detector is suitable for either traditional bench-top or LC-on-a-chip technologies. We report reversed phase high performance liquid chromatography (RP-HPLC) separations of proteins and polymers, over mobile phase gradient conditions of 67% A:33% B to 3% A:97% B by volume, where A is 96% methanol:3.9% water:0.1% trifluoroacetic acid (TFA), and B is 3.9% methanol:96% water:0.1% TFA. The separations were performed on a Jupiter 5 mu C4 300 A 150 mm x 1.0 mm Phenomenex column at a flow rate of 20 microl/min. Viscosity changes during the mobile phase gradient separation are found to shift the on-chip merge position of the detected concentration gradient (i.e., RIG), in a reproducible fashion. However, this viscosity effect makes detection sensitivity vary throughout the mobile phase gradient, due to moving the optimized position of the probe beam in relation to the analyte concentration gradient being probed. None-the-less, consistent limits of detection (LODs) were achieved. The 3-sigma deflection angle LOD was 16 microrad for micro-RIG detection, corresponding to an injected concentration LOD of 7 ppm (mass/mass) for cytochrome c.     

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

Background  

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸ or 1 × 10⁹ genomic copies of AAV1-GFP and 1 × 10⁵ transducing units of LV-dsRed.