Biocompatible and bioactivable terpolymer-lipid-MnO2 Nanoparticle-based MRI contrast agent for improving tumor detection and delineation.

Early and precise detection of solid tumor cancers is critical for improving therapeutic outcomes. In this regard, magnetic resonance imaging (MRI) has become a useful tool for tumor diagnosis and image-guided therapy. However, its effectiveness is limited by the shortcomings of clinically available gadolinium-based contrast agents (GBCAs), i.e. poor tumor penetration and retention, and safety concerns. Thus, we have developed a novel nanoparticulate contrast agent using a biocompatible terpolymer and lipids to encapsulate manganese dioxide nanoparticles (TPL-MDNP). The TPL-MDNP accumulated in tumor tissue and produced paramagnetic Mn2+ ions, enhancing T1-weight MRI contrast via the reaction with H2O2 rich in the acidic tumor microenvironment. Compared to the clinically used GBCA, Gadovist®1.0, TPL-MDNP generated stronger T1-weighted MR signals by over 2.0-fold at 30 % less of the recommended clinical dose with well-defined tumor delineation in preclinical orthotopic tumor models of brain, breast, prostate, and pancreas. Importantly, the MRI signals were retained for 60 min by TPL-MDNP, much longer than Gadovist®1.0. Biocompatibility of TPL-MDNP was evaluated and found to be safe up to 4-fold of the dose used for MRI. A robust large-scale manufacturing process was developed with batch-to-batch consistency. A lyophilization formulation was designed to maintain the nanostructure and storage stability of the new contrast agent.

Two-dimensional optokinetic nystagmus induced by moving plaids and texture boundaries. Evidence for multiple visual pathways.

Horizontal and vertical components of optokinetic nystagmus (OKN) were measured using the magnetic search coil technique in normal human adults during presentation of simple and complex moving patterns. Simple patterns were gratings moving horizontally and obliquely. Complex moving patterns consisted of plaids formed by superimposed oblique motion of two sets of gratings or of illusory contours formed by offset discontinuities in gratings. Slow-phase OKN gains (eye velocity divided by stimulus velocity) induced by high-contrast type I and type II plaids were comparable with those generated by one-dimensional moving gratings. The axis of OKN for high-contrast plaids was along the resultant direction determined by the intersection-of-constraints rule and not along any component. With low-contrast presentations, OKN induced by type I patterns remained in the resultant direction, but the OKN direction induced by type II patterns was biased toward the components' directions. The OKN generated by texture boundaries embedded in real pattern motion was measured for motion of illusory contours having systematically varying directions. The gain of OKN induced by real motion was independent of the direction of illusory contour motion, but the gain to illusory contour motion decreased with increasing contour angles. All these results suggest that input signals for driving the optokinetic system come from visual areas extracting higher order two-dimensional motion information.

Peripheral temporal frequency channels code frequency and speed inaccurately but allow accurate discrimination.

Perceived temporal frequency is vastly underestimated in the peripheral visual field, as all temporal frequencies above 10 Hz are perceived as flickering at 10 Hz even after scaling for acuity. Varying the contrast and spatial frequency of the peripheral pattern four-fold have negligible effects on the perceived flicker rate. Speed and auditory matching experiments also support this finding. Despite the saturation of perceived temporal frequency, frequency discrimination beyond 10 Hz was as accurate as in the fovea. By using a temporal masking paradigm, we obtained threshold elevation data that could be accounted for by three overlapping, broadly tuned temporal channels peaking at 5.5, 12 and 22 Hz. Based on these temporal frequency channels, we proposed that the visual system uses a line-element scheme for mediating temporal frequency discrimination, but adopts a weighted-average method for determining perceived temporal frequency. In the peripheral visual field, the weight assigned to the highest temporal channel is much larger than those assigned to the lower frequency channels.

Moving two-dimensional patterns can capture the perceived directions of lower or higher spatial frequency gratings.

Coherent plaid motion is produced by superimposing two one-dimensional gratings of the same spatial frequency moving +/- 60 degrees from the intersection-of-constraints (IOC) resultant direction. These moving plaids were found to change the perceived direction of a third one-dimensional grating, either 6-fold lower or higher in spatial frequency, from traveling in one of the plaid's component direction to the IOC resultant direction. We describe this phenomenon as coherence capture. Coherence capture was found to be effective between plaids with 0.5, 1.0, and 1.5 c/deg components and gratings of 3.0, 6.0 and 9.0 c/deg respectively. It was also found to be effective between plaids with 3.0 c/deg components and gratings of 0.5 c/deg. However, coherence capture between higher spatial frequency plaids and lower spatial frequency gratings became less effective when the component spatial frequencies of the plaid increased.

Perceived direction of moving two-dimensional patterns depends on duration, contrast and eccentricity.

Type II two-dimensional motion is produced by superimposing two one-dimensional drifting cosine gratings with velocity vectors lying on the same side of the intersection-of-constraints (IOC) resultant. When type II patterns were constructed with components having the same spatial frequency and contrast, perceived direction was found to be biased toward the vector sum direction at short durations and approached the direction predicted by IOC only after some time lag. This time lag was contrast dependent. At 5% contrast, the perceived direction after 1 sec of presentation remained biased by more than 20 degrees. Direction perception was also measured at 15 degrees eccentricity. At this eccentricity the perceived direction of type II patterns was grossly biased away from the IOC prediction in the direction of the component vectors by an average of 25 degrees.

Human albinos can discriminate spatial frequency and phase as accurately as normal subjects.

Previous experiments testing grating and vernier acuities in albino central vision are consistent with the hypothesis that the deficit in their monocular spatial processing is mainly due to the increased spacing of their foveal cones. This was tested by measuring albino spatial frequency discrimination over the range 0.25-4.0 cpd. The same experiments were performed on three normal subjects both in the fovea and at a peripheral locus at which their grating acuity was identical to that of the albino subjects. Spatial frequency discrimination thresholds averaged 3.71% for albinos, 5.18% for the normal fovea, and 8.81% for the normal periphery, the latter being over 2.3 times greater than albino thresholds. A comparable pattern of results was observed in phase discrimination experiments. These data reject the possibility that albino central vision is similar to normal peripheral vision, but the results are predictable on the hypothesis that the central retina of albinos is a spatially magnified (underdeveloped) version of the normal fovea.

Surgical outcomes of photorefractive keratectomy and laser in situ keratomileusis by inexperienced surgeons.

PURPOSE: To investigate the results of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) procedures performed by novice ophthalmologists and compare the results with those of experienced refractive surgeons. SETTING: Doheny Eye Institute, University of Southern California, Los Angeles, and Department of Ophthalmology, University of California, Irvine, California, USA. METHODS: In this retrospective case series, data were examined from the first PRK procedures by 33 consecutive ophthalmologists and the first LASIK procedures by 19 consecutive ophthalmologists. Preoperative and postoperative uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), as well as intraoperative and early postoperative complications, were recorded. RESULTS: In the PRK group, 33.3% of eyes achieved a UCVA of 20/20 and 87.8%, 20/40 or better; 54.5% were within +/-0.5 diopter (D) of emmetropia and 87.8%, within +/-1.0 D. Two eyes with a preoperative spherical equivalent of greater than -11.0 D lost 2 lines of BSCVA. If eyes with low myopia (

Synapse elimination by fiber type and maturational state in rabbit soleus muscle.

We have compared the development of fast and slow motor innervation in the neonatal rabbit soleus, a muscle which contains two distinct motor unit types during the early period of polyneuronal innervation. The innervation state of individual muscle fibers was ascertained using an intracellular electrode; a fluorescent dye was then injected into particular fibers to permit subsequent identification of histochemical type. We found no significant difference in the time course of synapse elimination for fast and slow motor units as judged by the percentage of fibers remaining polyneuronally innervated at two ages: 7-8 days, when most fibers are multiply innervated, and 10-11 days, when the level of polyinnervation is low. In a second experiment, we examined a phenomenon in which compound end-plate potentials were occasionally seen in muscle fibers at an age (17-23 days) well past the major episode of synapse elimination. We present evidence that this apparent polyinnervation in fact derives from an electrode-induced electrical coupling artifact and that genuinely polyinnervated fibers are very rare at this stage, if present at all.

A psychophysically motivated model for two-dimensional motion perception.

A quantitative model is developed to predict the perceived direction of moving two-dimensional patterns. The model incorporates both a simple motion energy pathway and a "texture boundary motion" pathway that incorporates response squaring before the extraction of motion energy. These pathways correspond to Fourier and non-Fourier motion pathways and are hypothesized to reflect processing in the V1-MT and V1-V2-MT pathway, respectively. A cosine-weighted sum of these pathways followed by competitive feedback inhibition accurately predicts the perceived direction for patterns composed of two cosine gratings at different orientations ("plaids"). The model also predicts direction discrimination, differences between foveal and peripheral viewing, changes in perceived direction with exposure duration, motion masking, and motion transparency.