This work focuses on the development of a system to control the formation of bone to complement developments that have enabled potent regeneration of bony tissue. Scaffolds were fabricated with chemically modified RNA encoding for bone morphogenetic protein-9 (cmBMP9) and capped with salicylic acid (SA)-containing polymer (SAPAE). The goal was to determine if SAPAE could inhibit the formation of bone in a pilot animal study since cmBMP9 has been demonstrated to be highly effective in regenerating bone in a rat calvarial defect model. The results indicated that cmBMP9 increased bone formation (30% increase in area covered compared to control) and that SAPAE trended toward reducing the bone formation. These results suggest SAPAE could be useful as a chemical agent in reducing unwanted bone formation in implants loaded with cmBMP9.

OBJECTIVES/SPECIFIC AIMS: Our main objectives are to study sensory encoding in the adult cortex and quantify rodents’ ability to use intracortical microstimulation to guide behavior. METHODS/STUDY POPULATION: Three rats were implanted with unilateral bipolar stimulating electrodes. The electrodes were connected to a wireless neural stimulator housed in the rat’s backpack. The rat’s swim path was tracked by a video camera above the circular pool, and stimulation parameters were updated in real-time based on distance from the platform. Stimulation was delivered as the distance from the platform increased. Stimulation amplitude was determined through behavioral threshold testing, and parameters ranged from 15–75 μA with 100-Hz pulse trains and 0.2-ms pulses. Rats were first challenged with the 4-platform task in which the submerged platform was randomized across 4 possible locations. This dissociated visual cues from the platform location, as rats had knowledge of the 4 possible locations, but had to use stimulation to guide them efficiently. Next, rats were tasked with the more challenging random-platform task. Visual cues were completely dissociated from the platform location by randomizing the platform location across the entire pool. Performance using the neuroprosthetic device was assessed by comparing trials when the device was on (stimulation trial) Versus off (no-stim trial) for the 2 tasks. RESULTS/ANTICIPATED RESULTS: 4-platform task: Rats visited less potential platform locations when the neuroprosthetic was on Versus off. Rats were also more likely to visit the correct platform location on their first swim trajectory when brain stimulation was delivered. When artificial cues were not available, rats had a greater chance of visiting the platform location from the previous trial. This indicated that rats relied on visuospatial memory without the neuroprosthetic. Random platform task: Performance was measured by taking the ratio of the rat’s actual path length to the optimal path length. When the neuroprosthetic was on, rats demonstrated superior performance through a smaller path to length ratio compared with when the device was off. The platform locations of catch trials were matched to a random subset of stimulation trials, permitting a paired sample t-test. Both rats had significantly shorter path lengths when the device was on. DISCUSSION/SIGNIFICANCE OF IMPACT: Rodents have excellent navigation skills that have been well studied. They have been shown to rely on multimodal sensory information from visual, olfactory, auditory, and idiothetic cues to navigate through their environment. The importance of these cues depends on both their environmental presence and task relevance. In the original Morris water maze experiment, rats use vision to form a visuospatial map of the platform location for allocentric navigation. Here, we have shown that sensory augmented rats can pick up on novel sensory information delivered through ICMS to efficiently find a hidden platform when visual cues are made irrelevant.Our results have implications for the design of the bi-directional sensorimotor neuroprosthetic. We have demonstrated that mammals can interpret artificial sensory information to guide behavior. Future directions include investigating sensory encoding in other primary sensory areas and downstream targets along the somatosensory neuraxis.

To determine simazine movement and dissipation in a drip-irrigated Vitis vinifera vineyard under two irrigation schedules [ grower standard (GS) and current evaporation/transpiration (CET)], field experiments were conducted in a Hanford fine sandy loam, a soil type prone to leaching. In experiment 1, simazine was surface-applied in a 1.7-m swath down the vine row, and chloride was applied as a tracer. Total recovery of simazine was < 1.0% under the irrigation emitters 51 and 57 d after simazine application in 1997 and 1999, respectively. Simazine was not detected in the soil profile from 0 to 150 cm deep, 1.0 m from the emitters. A chloride tracer moved to a soil depth of 90 cm but not deeper. In experiment 2, simazine moved 75 cm under the emitters in 7 d but did not move deeper into the soil. Under the emitter, 28% of applied simazine was found 0 to 45 cm deep and 3% was > 45 cm deep. In experiment 3, which was conducted in the absence of irrigation, total recovery of simazine was 30% when sheltered from rain and 8% when exposed to rain. Rapid dissipation and proper irrigation management were key factors preventing deep percolation of simazine in these studies.

A symptom of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2–5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation. (JINS, 2015, 21, 455–467)

Impulse-control disorders have received relatively little attention from the mental health community. An increasing awareness of the prevalence and impact of these disorders is emerging. Among impulse control disorders, problematic Internet use has been considered and examined. Prevalence estimate studies indicate that problematic Internet use is experienced across geographic locations by many individuals of diverse backgrounds. This review examines problematic Internet use from epidemiological and clinical perspectives. Clinicians should be familiar with the extent of problematic Internet use and the data regarding the efficacies and tolerabilities of available treatments.

A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M – 15 % protein and 65 % carbohydrate; (2) 6M – 15 % protein and 65 % carbohydrate; (3) 6MHP – 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P< 0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6MHP regimen (glucose: 3569 (se 83) mmol/l × min (64·3 (se 1·5) g/dl × min), insulin: 1·577 (se 0·146) pmol/l (22·7 (se 2·1) μIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (se 78) mmol/l × min (70·5 (se 1·4) g/dl × min), insulin: 2·195 (se 0·146) pmol/l × min (31·6 (se 2·1) μIU/dl × min) for 12 h) or the 6M regimen (glucose: 3902 (se 83) mmol/l × min (70·3 (se 1·5) g/dl × min), insulin: 1·861 (se 0·174) pmol/l × min (26·8 (se 2·5) μIU/dl × min) for 12 h; P< 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

High-resolution radial distribution functions of as-implanted and thermally relaxed amorphous silicon created by ion implantation were measured using tilted-illumination selected area electron diffraction at room temperature. The diffracted intensities were measured out to a maximum scattering vector 2 sin(θ)/λ of 3.3–3.7 Å−1. The volume-averaged pair-correlation statistics of as-implanted and relaxed ion-implanted amorphous silicon are virtually indistinguishable with coordination numbers of 3.7 ± 0.3 and 3.9 ± 0.3 (for neighbors closer than 3 Å) and average bond angles of 109 ± 0.5° and 110 ± 0.6°, respectively. The atomic rearrangements in ion-implanted amorphous silicon due to a low temperature anneal are subtle.

While it is clear that self-reported racial/ethnic discrimination is related to illness, there are challenges in measuring self-reported discrimination or unfair treatment. In the present study, we evaluate the psychometric properties of a self-reported instrument across racial/ethnic groups in a population-based sample, and we test and interpret findings from applying two different widely-used approaches to asking about discrimination and unfair treatment. Even though we found that the subset of items we tested tap into a single underlying concept, we also found that different groups are more likely to report on different aspects of discrimination. Whether race is mentioned in the survey question affects both frequency and mean scores of reports of racial/ethnic discrimination. Our findings suggest caution to researchers when comparing studies that have used different approaches to measure racial/ethnic discrimination and allow us to suggest practical empirical guidelines for measuring and analyzing racial/ethnic discrimination. No less important, we have developed a self-reported measure of recent racial/ethnic discrimination that functions well in a range of different racial/ethnic groups and makes it possible to compare how racial/ethnic discrimination is associated with health disparities among multiple racial/ethnic groups.

Efforts to extract weak geomagnetic excursion signals from Chinese loess-paleosol 10Be have generally been unsuccessful due to the complexities of its accumulation, because the geomagnetic and climate (precipitation and dust) signals contained in loess-paleosol sequence are tightly overprinted. Here, we present a reconstruction of geomagnetic relative paleointensities for the past 130 kyr from 10Be records in 2 Chinese loess-paleosol sections using a correction based on the correlation of 10Be with magnetic susceptibility (SUS) to remove the climatic contamination. Both these records reveal the Laschamp and Blake events, which lie in the loess and paleosol (L1SS1 and S1SS3) horizons corresponding to mid-MIS 3 and 5e, respectively. The good agreement between our results and other geomagnetic intensities reconstructions from Atlantic and Pacific sediments indicates that our method is robust. Our study suggests the potential application of loess-paleosol 10Be for reconstructing geomagnetic intensity variations spanning the whole Quaternary.

The thermal structure in the boundary layer and its relation to the heat flux from the cooling and evaporating surface of a deep tank of water are investigated. When a deep layer of water in contact with still air above loses heat to the air, the cooled water in a region just under the surface converges along lines and then plunges down in sheets. These sheets of falling water dissipate as they move into the body of the water, which is in turbulent motion. The vertical profiles of the horizontally averaged temperature and its standard deviation agree fairly closely with theoretical profiles based on time averages of the solution to the heat diffusion equation. The differences between observed and thus predicted profile shapes are consistent with the expected effects of the falling cold thermals and the warm return flow, which are neglected in the theories. The profiles of the standard deviation have large values up to the interface and lie between predictions based on boundary conditions of constant surface temperature and constant heat flux, in keeping with the experimental conditions.

The relation between the net heat flux and the temperature difference across the boundary layer is given in non-dimensional form by N = 0[sdot ]156R0[sdot ]33, which is in good agreement with the asymptotic similarity prediction N [vprop ] R1/3 but lower than theoretical calculations of the upper bound of N vs. R.

We develop and apply bootstrap methods for diffusion models when fitted to the long run as characterized by the stationary distribution of the data. To obtain bootstrap refinements to statistical inference, we simulate candidate diffusion processes. We use these bootstrap methods to assess measurements of local mean reversion or “pull” to the center of the distribution for short-term interest rates. We also use them to evaluate the fit of the model to the empirical density.

Marine diatoms are a class of microalgae that possess cell walls composed of silica nanoparticles. These organisms actively assimilate silicic acid Si(OH)4 from seawater, polymerize silicic acid to silica nanoparticles by a protein-mediated precipitation process, then assemble the silica nanoparticles into intricate patterns that constitute the cell wall microarchitecture of the diatom frustule. The biomineralization capacity of marine diatoms, Nitzschia frustulum, was harnessed to biologically manufacture silicon oxide / germanium oxide nanocomposite materials. Germanium was incorporated into living diatom cell mass by a two-stage cultivation process. The micro- and nanostructures of biogenic oxide nanocomposite were characterized by TEM with EDS, and XRD. Furthermore, photoluminescence (PL) measurements were performed on these biogenic nanocomposites with different post processing to study their optoelectronic properties. Strong blue photoluminescence was observed from samples treated with H2O2 and oxygen plasma. A clear blueshift was observed from the biogenic oxides with the addition of germanium. It is believed that self-trapped exciton affected by quantum confinement effect is responsible for the PL from these biogenic oxide nanocomposites.

Zr-based alloy ingots with nominal compositions of Zr52.5Cu17.9Ni14.6Al10.0Ti5.0 (at.%), Vitre-loy 105, were isothermally annealed below the glass-transition temperature at 630 K for 10, 20, 30, 40, and 60 minutes in vacuum to obtain samples with various states of structural relaxation and compared to the as-cast state. Structural studies were performed using time-of-flight neutron diffraction followed by pair distribution function (PDF) analyses. Differential scanning calo-rimetry (DSC) was conducted to examine changes in the specific heat, which were correlated to the amount of structural relaxation in the various samples. These samples exhibited increasing structural relaxation with longer annealing times, which was evidenced in the atomic PDF. Relaxation related to the exothermic peak results in changes in the PDF that are consistent with the elimination of short and long inter-atomic distances. Further annealing led to rearrangements in the second atomic shell that may be related to local phase separation.

Ni/Al nanostructured multilayer foils were machined with femtosecond pulse-length laser irradiation at various fluences. Scanning electron microscopy, back-scattered electron detection, and atomic force microscopy were used to characterize the resulting laser modified regions. We show that material removal at the micron scale is possible with no ignition of a self-propagation reaction emanating from the irradiated areas, a danger minimized by the fact that the extremely short time duration of the pulse produces negligible heat dissipation into the multilayer system. Nevertheless, initial AFM and BSE results give indication that multilayers may be intermixing and reacting locally in areas smaller than the laser beam diameter, though the exact ignition mechanism is still to be determined.