Improved generation of anti-tumor immunity by antigen dose limitation

Background  

The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high.     

Statistical and receiver operating characteristic analysis of empirical spike-count distributions: quantifying the ability of cochlear nucleus units to signal intensity changes

Analytical methods from signal detection theory were applied in an effort to quantify the ability of cochlear nucleus (CN) units to signal changes in intensity. Of particular interest was the relation between this ability and the different patterns of discharge that characterize auditory neurons. Single-unit responses to best-frequency (BF) tone bursts were recorded from neurons in the gerbil cochlear nucleus, and empirical spike-count distributions were generated. The mean-to-variance ratios for regular units were generally larger than those of irregular units. Receiver operating characteristic (ROC) curves were generated from empirical spike-count distributions. The area under the ROC curve [P(A)] was computed and used to define the performance of an observer detecting whether or not a change in firing rate has occurred, thus signaling a change in intensity. For a given change in mean spike count, units characterized by regular interspike-interval (ISI) histograms typically gave larger P(A) values than did units characterized by irregular ISI histograms. In addition, onset units gave larger values of P(A) than did irregular units for a given change in mean spike count. These results suggest that regular and onset units are better able to signal intensity changes than are irregular units.     

Temporal representation of rippled noise in the anteroventral cochlear nucleus of the chinchilla.

This paper describes the temporal responses of anteroventral cochlear nucleus (AVCN) units in the chinchilla to rippled noises. Rippled noise is generated when a wideband noise is delayed and added (cos+ noise) or subtracted (cos- noise) to the undelayed noise. Renewal densities were constructed to evaluate synchronous discharges at the delay. In response to rippled noise, AVCN units which show phase locking to best frequency (BF) tones gave renewal densities having major peaks at the delay for cos+ noise, but nulls at the delay for cos- noise. Most AVCN units which did not show BF phase locking gave renewal densities that did not contain features related to the rippled noise delay; a few of these nonphase-locked units did show peaks in renewal densities for both cos+ and cos- noises. Synchrony at the rippled noise delay was also demonstrated with evoked potential recording. Autocorrelation functions of the neurophonic potential showed peaks at the rippled noise delay for both cos+ and cos- noises. In addition, peaks could be observed in the autocorrelation functions of neurophonic potentials for rippled noises with delays as short as 1 ms; peaks were never observed in renewal densities of single units for ripple delays as short as 1 ms. The results show that a temporal representation of rippled noise delay does exist in the AVCN and are consistent with current hypotheses regarding functions of AVCN subsystems. The temporal representation of the delay is a presumptive neural code for the pitches of rippled noises.     

Acryloyl-modified cellulose nanocrystals: effects of substitution on crystallinity and copolymerization with acrylic monomers

Cellulose nanocrystals (CNCs) are crystalline nano-rods that have high specific strength with hydroxyl surface chemistry. A wide range of chemical modifications have been performed on the surface of CNCs to increase their potential to be used in applications where compatibilization with other materials is required. Understanding the surface chemistry of CNCs and critically examining the functionalization technique are crucial to enable control over the extent of modification and the properties of CNCs. This work aims to optimize the surface modification of wood-derived CNCs with isocyanatoethyl methacrylate (IEM), a bifunctional molecule carrying both isocyanate and vinyl functional groups. We studied the effect of modification reaction time and temperature on the degree of substitution, crystallinity, and morphology of the CNCs. We found that the degree of modification is a strong and increasing function of reaction temperature over the range studied. However, the highest temperature (65 °C) and the longest time of reaction (6 h) resulted in shorter, thinner, and less crystalline CNCs. We obtained surface hydroxyl conversion of 60.1?±?6% and percent crystallinity of 84% by keeping the reaction shorter (30 min) at 65 ºC. Also, the copolymerization ability of modified CNCs was verified by polymerizing attached IEM groups with acrylic monomers via solution polymerization. The polymer-grafted CNCs (6% w/w) dispersed better in an acrylic polymer matrix compared to unmodified CNCs (umCNCs), resulting in approximately 100% improvement in the tensile strength and about 53% enhancement in the hardness of the acrylic, whereas addition of 6% w/w umCNCs did not influence the strength and hardness.

Graphic abstract

     

The correlation between ion beam/material interactions and practical FIB specimen preparation.

The focused ion beam (FIB) tool has been successfully used as both a stand alone analytical instrument and a means to prepare specimens for subsequent analysis by SEM, TEM, SIMS, XPS, and AUGER. In this work, special emphasis is given to TEM specimen preparation by the FIB lift-out technique. The fundamental ion/solid interactions that govern the FIB milling process are examined and discussed with respect to the preparation of electron transparent membranes. TRIM, a Monte Carlo simulation code, is used to physically model variables that influence FIB sputtering behavior. The results of such computer generated models are compared with empirical observations in a number of materials processed with an FEI 611 FIB workstation. The roles of incident ion attack angle, beam current, trench geometry, raster pattern, and target-material-dependent removal rates are considered. These interrelationships are used to explain observed phenomena and predict expected milling behaviors, thus increasing the potential for the FIB to be used more efficiently with reproducible results.     

Surface activity of lysozyme and dipalmitoyl phosphatidylcholine vesicles at compressed and supercritical fluid interfaces

The surface activities of lysozyme and dipalmitoyl phosphatidylcholine (DPPC) vesicles at aqueous/compressed fluid interfaces are examined via high-pressure interfacial tension measurements using the pendant drop technique. The density and interfacial tension in compressible fluid systems vary significantly with pressure, providing a versatile medium for elucidating interactions between biomolecules and fluid interfaces and a method to elicit pressure-dependent interfacial morphological responses. The effects of lysozyme concentration (0.0008, 0.01, and 1 mg/mL) and pressure (> or = 7 MPa) on the dynamic surface response in the presence of ethane, propane, N2, and CO2 at 298 K were examined. Interfacial lysozyme adsorption reduced the induction phase and quickly led to interfacial tensions consistent with protein conformational changes and monolayer saturation at the compressed fluid interfaces. Protein adsorption, as indicated by surface pressure, correlated with calculated Hamaker constants for the compressed gases, denoting the importance of dispersion interactions. For DPPC at aqueous/compressed or aqueous/supercritical CO2 interfaces (1.8-20.7 MPa, 308 K), 2-3-fold reductions in interfacial tension were observed relative to the pure binary fluid system. The resulting surface pressures infer pressure-dependent morphological changes within the DPPC monolayer.     

Listening experience with iterated rippled noise alters the perception of 'pitch' strength of complex sounds in the chinchilla

Behavioral responses obtained from chinchillas trained to discriminate a cosine-phase harmonic tone complex from wideband noise indicate that the perception of 'pitch' strength in chinchillas is largely influenced by periodicity information in the stimulus envelope. The perception of 'pitch' strength was examined in chinchillas in a stimulus generalization paradigm after animals had been retrained to discriminate infinitely iterated rippled noise from wideband noise. Retrained chinchillas gave larger behavioral responses to test stimuli having strong fine structure periodicity, but weak envelope periodicity. That is, chinchillas learn to use the information in the fine structure and consequently, their perception of 'pitch' strength is altered. Behavioral responses to rippled noises having similar periodicity strengths, but large spectral differences were also tested. Responses to these rippled noises were similar, suggesting a temporal analysis can be used to account for the behavior. Animals were then retested using the cosine-phase harmonic tone complex as the expected signal stimulus. Generalization gradients returned to those obtained originally in the na?ve condition, suggesting that chinchillas do not remain "fine structure listeners," but rather revert back to being "envelope listeners" when the periodicity strength in the envelope of the expected stimulus is high.