Purpose: To biochemically characterize the receptor for connective tissue growth factor (CTGF) of human corneal fibroblasts.Methods: Radiolabeled recombinant human CTGF was used to determine the specificity and time course of binding to low passage cultures of human corneal fibroblasts. The affinity and number of receptors present were calculated by Scatchard analysis. In vitro immunoprecipitation assays with radiolabeled CTGF and soluble mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II-R) alone, or with CTGF-related growth factors were conducted. Additionally, 125I-CTGF binding and CTGF-stimulated proliferation were measured in cultures of M6P/IGF-II-R knockout fibroblasts. Results: Binding of 125I-CTGF to fibroblast cultures was significantly displaced by CTGF, but not by related growth factors. Scatchard plot analysis indicated the presence of both a high-affinity, low-abundance binding site, and a low-affinity, high-abundance binding site. While, best-fit analysis suggests a single high-affinity, low-abundance binding site. A 280 kDa complex containing cross-linked 125I-CTGF was immunoprecipitated by antibodies to CTGF or M6P/IGF-II-R. M6P/IGF-II-R knockout cells have a reduced proliferative response to TGF-β and don't proliferate at all in response to CTGF.Conclusions: CTGF binds to the M6P/IGF-II-R with high affinity, and the M6P/IGF-II-R is required for CTGF-stimulated proliferation in fibroblasts. These observations suggest that the M6P/IGF-II-R may be a new anti-fibrotic target.

PURPOSE:This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1)-induced corneal fibrosis in vitro. METHODS:Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measured its efficacy. RESULTS:Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit eyes in vivo screened 4 weeks after PRK. Vorinostat reduced TGFβ1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation. CONCLUSIONS:Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia.

PURPOSE: Exposure creep is the gradual increase in x-ray exposures over time that results in increased radiation dose to the patient. It has been theorized as being a phenomenon that results from the wide-exposure latitude of computed radiography (CR) and direct/indirect digital radiography (DR). This project evaluates radiographic exposures over 43 months to determine if exposure creep exists and if measures can be applied to halt or reverse exposure creep trends. METHODS: Exposure indices were initially recorded over 29 months between August 2007 and December 2009 from the intensive and critical care unit (ICCU) and the emergency department (ED) departments where manual CR exposures were used. The data from this period were then assessed and the exposure indexes (EI) values from the radiographic images were compared to the radiology department criteria of EI values between 1400 to 1800 as being in the optimal exposure range. EI values below this were considered underexposed and over this as overexposed. An intervention was required to be used in ICCU and implemented in January 2010 to halt a noted trend of overexposure. The EI value for each chest x-ray (CXR) was recorded in the patients' ICCU records and was to be used by radiologic technologists/radiographers in determine exposure factors in subsequent CXR. After the intervention, EI values were recorded and evaluated for an additional 15 months between February 2010 and March 2011. RESULTS: Between August 2007 and December 2009, 17,678 ICCU CXR images and 69,327 ED x-ray examinations were evaluated for over- and underexposure. A trend was noted in ICCU that showed a significant increase (P =.023) in EI values from the beginning to the end of the evaluation. No such trend was seen in the ED EI values (P =.120). After the intervention in ICCU, the overexposure trend was halted. CONCLUSIONS: Exposure creep has been show to exist. It is surmised that this occurs where judgment in determine the correct radiographic exposure factors is need when taking into account a large range of patient sizes. It has also been shown that providing radiologic technologists/radiographers with previous EI values for the same x-ray examination can halt a trend of exposure creep.

• Premise of the study: For metapopulation and metacommunity studies,"suitable habitat" is an area within an otherwise inhospitable matrix in which a species can potentially or does occur. When examining aquatic habitats, for example, this habitat is much easier to define than in terrestrial regions. We tested the assumption that suitable habitat can be delimited in terrestrial ecosystems.• Methods: We surveyed vascular plant species found in 38 forest openings (open suitable habitats) within a matrix of dry forest (an inhospitable habitat) at three sites in southern Illinois over two growing seasons. We compared species composition and environmental variables between these two habitats at three sites using non-metric multidimensional scaling (NMDS) and analysis of similarity (ANOSIM).• Key results: Distinctions such as high canopy openness and high soil temperature were common to all forest openings compared with the forest matrix. Differences in canopy openness and soil temperature were correlated with significantly different vegetation between forest openings and forest matrix at each of the three sites. Among the three sites, 9.3-18.9% were forest opening specialists, consisting of 44 taxa, of which the majority were herbaceous forbs.• Conclusions: The distinction between suitable and unsuitable habitat for some plant species may depend on a few variables, which may not be consistent between sites. This distinction means that there are potentially more situations than previously thought that metapopulation and metacommunity theory may be capable of explaining, meaning that more systems can be studied using a metapopulation context than previously thought.

Rhythmic brain activity is thought to reflect, and to help organize, spike activity in populations of neurons during on-going behavior. We report that during learning, a major transition occurs in task-related oscillatory activity in the ventromedial striatum, a striatal region related to motivation-dependent learning. Early on as rats learned a T-maze task, bursts of 70- to 90-Hz high-γ activity were prominent during T-maze runs, but these gradually receded as bursts of 15- to 28-Hz β-band activity became pronounced. Populations of simultaneously recorded neurons synchronized their spike firing similarly during both the high-γ-band and β-band bursts. Thus, the structure of spike firing was reorganized during learning in relation to different rhythms. Spiking was concentrated around the troughs of the β-oscillations for fast-spiking interneurons and around the peaks for projection neurons, indicating alternating periods of firing at different frequencies as learning progressed. Spike-field synchrony was primarily local during high-γ-bursts but was widespread during β-bursts. The learning-related shift in the probability of high-γ and β-bursting thus could reflect a transition from a mainly focal rhythmic inhibition during early phases of learning to a more distributed mode of rhythmic inhibition as learning continues and behavior becomes habitual. These dynamics could underlie changing functions of the ventromedial striatum during habit formation. More generally, our findings suggest that coordinated changes in the spatiotemporal relationships of local field potential oscillations and spike activity could be hallmarks of the learning process.

OBJECTIVE To investigate the feasibility of a pragmatic lifestyle intervention in patients who had recently completed surgery and chemotherapy for colon cancer and to obtain preliminary data of its impact on important health outcomes. DESIGN A prospective, randomized, controlled pilot trial. SETTING University rehabilitation facility. PARTICIPANTS Eighteen (N=18) colon cancer survivors (mean age=69y; range, 52-80y), Dukes stage A to C. INTERVENTIONS Participants were randomized 6 to 24 months postoperatively to either a 12-week program of combined exercise and dietary advice or standard treatment. MAIN OUTCOME MEASURES Exercise and dietary behavior, fatigue, health-related quality of life (QOL), aerobic exercise tolerance, functional capacity, muscle strength, and anthropometery were assessed at baseline and immediately after the intervention. RESULTS Adherences to supervised and independent exercise during the intervention were 90% and 94%, respectively, and there was low attrition (6%). The lifestyle intervention elicited improvements in exercise behavior (P=.068), fatigue (P=.005), aerobic exercise tolerance (P=.010), chair sit-to-stand performance (P=.003), and waist-to-hip ratio (P=.002). A positive change in dietary fiber intake (P=.044) was also observed in the intervention group. No change in QOL was observed (P=.795). CONCLUSIONS These preliminary results suggest that a pragmatic lifestyle intervention implemented 6 to 24 months after primary treatment for colon cancer was feasible. We observed a significant impact on dietary behavior, fatigue, aerobic exercise tolerance, functional capacity, and waist-to-hip ratio. These findings need to be confirmed with a larger-scale definitive randomized controlled trial.

We demonstrate a compact hyperdispersion stretcher and compressor pair that permit chirped-pulse amplification in Nd:YAG. We generate 750 mJ, 0.2 nm FWHM, 10 Hz pulses recompressed to an 8 ps near-transform-limited duration. The dispersion-matched pulse compressor and stretcher impart a chirp of 7300 ps/nm, in a 3 m x 1 m footprint.

We demonstrate a nonlinear crystal-based short pulse recirculation cavity for trapping the second harmonic of an incident high-power laser pulse. This scheme aims to increase the efficiency and flux of Compton-scattering-based light sources. We demonstrate up to 40x average power enhancement of frequency-doubled submillijoule picosecond pulses, and 17x average power enhancement of 177 mJ, 10 ps, 10 Hz pulses.

We describe a modification to a transmission electron microscope (TEM) that allows it to briefly (using a pulsed-laser-driven photocathode) operate at currents in excess of 10 mA while keeping the effects of condenser lens aberrations to a minimum. This modification allows real-space imaging of material microstructure with a resolution of order 10 nm over regions several microm across with an exposure time of 15 ns. This is more than six orders of magnitude faster than typical video-rate TEM imaging. The key is the addition of a weak magnetic lens to couple the large-diameter high-current beam exiting the accelerator into the acceptance aperture of a conventional TEM condenser lens system. We show that the performance of the system is essentially consistent with models derived from ray tracing and finite element simulations. The instrument can also be operated as a conventional TEM by using the electron gun in a thermionic mode. The modification enables very high electron current densities in microm-sized areas and could also be used in a nonpulsed system for high-throughput imaging and analytical TEM.

What we believe to be the first demonstration of isotope-specific detection of a low-Z and low density object shielded by a high-Z and high-density material using monoenergetic gamma rays is reported. The isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of L7i at 478 keV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general, and the confidence level obtained is shown to be superior to that yielded by conventional x-ray and gamma-ray techniques in these situations.