Prediction of microRNAs affecting mRNA expression during retinal development.

Background: MicroRNAs (miRNAs) are small RNA molecules (similar to 22 nucleotides) which have been shown to play an important role both in development and in maintenance of adult tissue. Conditional inactivation of miRNAs in the eye causes loss of visual function and progressive retinal degeneration. In addition to inhibiting translation, miRNAs can mediate degradation of targeted mRNAs. We have previously shown that candidate miRNAs affecting transcript levels in a tissue can be deduced from mRNA microarray expression profiles. The purpose of this study was to predict miRNAs which affect mRNA levels in developing and adult retinal tissue and to confirm their expression.

Results: Microarray expression data from ciliary epithelial retinal stem cells (CE-RSCs), developing and adult mouse retina were generated or downloaded from public repositories. Analysis of gene expression profiles detected the effects of multiple miRNAs in CE-RSCs and retina. The expression of 20 selected miRNAs was confirmed by RT-PCR and the cellular distribution of representative candidates analyzed by in situ hybridization. The expression levels of miRNAs correlated with the significance of their predicted effects upon mRNA expression. Highly expressed miRNAs included miR-124, miR-125a, miR-125b, miR-204 and miR-9. Over-expression of three miRNAs with significant predicted effects upon global mRNA levels resulted in a decrease in mRNA expression of five out of six individual predicted target genes assayed.

Conclusions: This study has detected the effect of miRNAs upon mRNA expression in immature and adult retinal tissue and cells. The validity of these observations is supported by the experimental confirmation of candidate miRNA expression and the regulation of predicted target genes following miRNA over-expression. Identified miRNAs are likely to be important in retinal development and function. Misregulation of these miRNAs might contribute to retinal degeneration and disease. Conversely, manipulation of their expression could potentially be used as a therapeutic tool in the future.

Barrier height variations and interface properties of PtSi/Si structures

To study some of the interfacial properties of PtSi/Si diodes, Schottky structures were fabricated on (100) crystalline silicon substrates by conventional thermal evaporation of Pt on Si followed by annealing at different temperatures (from 400 degrees C to 700 degrees C) to form PtSi. The PtSi/n-Si diodes, all yielded Schottky barrier (SB) heights that are remarkably temperature dependent. The temperature range (20-290 K) over which the I-V characteristics were measured in the present study is broader with a much lower limit (20 K), than what is usually reported in literature. These variations in the barrier height are adequately interpreted by introducing spatial inhomogeneity into the barrier potential with a Gaussian distribution having a mean barrier of 0.76 eV and a standard deviation of 30 meV. Multi-frequency capacitance-voltage measurements suggest that the barrier is primarily controlled by the properties of the silicide-silicon interface. The forward C-V characteristics, in particular, show small peaks at low frequencies that can be ascribed to interface states rather than to a series resistance effect.

Characterization of Nickel Germanide Schottky Contacts for the Fabrication of Germanium p-channel MOSFETs

Nickel germanide Schottky contacts, formed by rapid thermal annealing of thin nickel films, have been characterized on n-type germanium wafers for a range of RTA temperatures. The highest Schottky barrier heights for electrons (= 0.6-0.7 eV) were obtained for RTA temperatures of approximately 300°C. For this RTA schedule, the corresponding barrier height for holes is close to zero, ideal for Schottky contacted p-channel germanium MOSFETs. When the RTA temperature was increased to 400oC, a dramatic reduction in electron barrier height (< 0.1 eV) was observed. This RTA schedule, therefore, appears ideal for ohmic source/drain contacts to n channel germanium MOSFETs. From sheet resistance measurements and XRD characterization, nickel germanide formation was found to occur at 300oC and above. The NiGe phase was dominant for RTA temperatures up to at least 435oC.

Local Conentration of Waves due to Abrupt Alongshore Variation of Nearshore Bathymetry

Small-scale physical and numerical experiments were conducted to investigate the local concentration of waves (monochromatic and group) due to abrupt change of nearshore bathymetry in alongshore direction. Wave run-up motions along the shoreline were measured using an image analysis technique to compare localized concentration of wave energy, when waves propagate a over bathymetry composing rhythmic patterns of mild/steep slope bottom configurations. Measured alongshore variation of maximum wave run-up heights showed significant peak near the boundary, which has sudden alongshore change of depth, both under monochromatic and group wave trains. This phenomenon is found to be due to interaction of waves with neashore currents, which is further enhanced by excitation of long wave components by breaking of group waves. Furthermore, this paper discusses results of preliminary experiments carried out to test the effectiveness of several shore protection structure layouts in mitigating such wave concentrations. Numerical simulations were performed by using a model developed based on Nwogu (1993) Boussinesq-type equations; coupled with a transport equation to model energy dissipation due to wave breaking.

Bimodal biometric verification based on face and lips

In this paper, we present a novel approach to person verification by fusing face and lip features. Specifically, the face is modeled by the discriminative common vector and the discrete wavelet transform. Our lip features are simple geometric features based on a lip contour, which can be interpreted as multiple spatial widths and heights from a center of mass. In order to combine these features, we consider two simple fusion strategies: data fusion before training and score fusion after training, working with two different face databases. Fusing them together boosts the performance to achieve an equal error rate as low as 0.4% and 0.28%, respectively, confirming that our approach of fusing lips and face is effective and promising.

Composition profiling of seized ecstasy tablets by Raman spectroscopy

Raman spectroscopy with far-red excitation has been investigated as a simple and rapid technique for composition profiling of seized ecstasy (MDMA, N-methyl-3,4-methylenedioxyamphetamine) tablets. The spectra obtained are rich in vibrational bands and allow the active drug and excipient used to bulk the tablets to be identified. Relative band heights can be used to determine drug/excipient ratios and the degree of hydration of the drug while the fact that 50 tablets per hour can be analysed allows large numbers of spectra to be recorded. The ability of Raman spectroscopy to distinguish between ecstasy tablets on the basis of their chemical composition is illustrated here by a sample set of 400 tablets taken from a large seizure of > 50000 tablets that were found in eight large bags. The tablets are all similar in appearance and carry the same logo. Conventional analysis by GC-MS showed they contained MDMA. Initial Raman studies of samples from each of the eight bags showed that despite some tablet-to-tablet variation within each bag the contents could be classified on the basis of the excipients used. The tablets in five of the bags were sorbitol-based, two were cellulose-based and one bag contained tablets with a glucose excipient. More extensive analysis of 50 tablets from each of a representative series of sample bags gave distribution profiles that showed the contents of each bag were approximately normally distributed about a mean value, rather than being mixtures of several discrete types. Two of the sorbitol-containing sample sets were indistinguishable while a third was similar but not identical to these, in that it contained the same excipient and MDMA with the same degree of hydration but had a slightly different MDMA/sorbitol ratio. The cellulose-based samples were badly manufactured and showed considerable tablet-to-tablet variation in their drug/excipient ratio while the glucose-based tablets had a tight distribution in their drug/excipient ratios. The degree of hydration in the MDMA feedstocks used to manufacture the cellulose-, glucose- and sorbitol-based tablets were all different from each other. This study, because it centres on a single seizure of physically similar tablets with the same active drug, highlights the fact that simple physical descriptions coupled with active drug content do not in themselves fully characterize the nature of the seized materials. There is considerable variation in the composition of the tablets within this single seizure and the fact that this variation can be detected from Raman spectra demonstrates that the potential benefits of obtaining highly detailed spectra can indeed translate into information that is not readily available from other methods but would be useful for tracing of drug distribution networks.

Deep sequencing reveals predominant expression of miR-21 amongst the small non-coding RNAs in retinal microvascular endothelial cells

The retinal vascular endothelium is essential for angiogenesis and is involved in maintaining barrier selectivity and vascular tone. The aim of this study was to identify and quantify microRNAs and other small regulatory non-coding RNAs (ncRNAs) which may regulate these crucial functions. Primary bovine retinal microvascular endothelial cells (RMECs) provide a well-characterized in vitro system for studying angiogenesis. RNA extracted from RMECs was used to prepare a small RNA library for deep sequencing (Illumina Genome Analyzer). A total of 6.8 million reads were mapped to 250 known microRNAs in miRBase (release 16). In many cases, the most frequent isomiR differed from the sequence reported in miRBase. In addition, five novel microRNAs, 13 novel bovine orthologs of known human microRNAs and multiple new members of the miR-2284/2285 family were detected. Several similar to 30 nucleotide sno-miRNAs were identified, with the most highly expressed being derived from snoRNA U78. Highly expressed microRNAs previously associated with endothelial cells included miR-126 and miR-378, but the most highly expressed was miR-21, comprising more than one-third of all mapped reads. Inhibition of miR-21 with an LNA inhibitor significantly reduced proliferation, migration, and tube-forming capacity of RMECs. The independence from prior sequence knowledge provided by deep sequencing facilitates analysis of novel microRNAs and other small RNAs. This approach also enables quantitative evaluation of microRNA expression, which has highlighted the predominance of a small number of microRNAs in RMECs. Knockdown of miR-21 suggests a role for this microRNA in regulation of angiogenesis in the retinal microvasculature. J. Cell. Biochem. 113: 20982111, 2012. (C) 2012 Wiley Periodicals, Inc.

Propagating Wave Phenomena Detected in Observations and Simulations of the Lower Solar Atmosphere

We present high-cadence observations and simulations of the solar photosphere, obtained using the Rapid Oscillations in the Solar Atmosphere imaging system and the MuRAM magnetohydrodynamic (MHD) code, respectively. Each data set demonstrates a wealth of magnetoacoustic oscillatory behavior, visible as periodic intensity fluctuations with periods in the range 110–600 s. Almost no propagating waves with periods less than 140 s and 110 s are detected in the observational and simulated data sets, respectively. High concentrations of power are found in highly magnetized regions, such as magnetic bright points and intergranular lanes. Radiative diagnostics of the photospheric simulations replicate our observational results, confirming that the current breed of MHD simulations are able to accurately represent the lower solar atmosphere. All observed oscillations are generated as a result of naturally occurring magnetoconvective processes, with no specific input driver present. Using contribution functions extracted from our numerical simulations, we estimate minimum G-band and 4170 Å continuum formation heights of 100 km and 25 km, respectively. Detected magnetoacoustic oscillations exhibit a dominant phase delay of −8◦ between the G-band and 4170 Å continuum observations, suggesting the presence of upwardly propagating waves.More than 73% of MBPs (73% from observations and 96% from simulations) display upwardly propagating wave phenomena, suggesting the abundant nature of oscillatory behavior detected higher in the solar atmosphere may be traced back to magnetoconvective processes occurring in the upper layers of the Sun’s convection zone.

Configuration-interaction effects in and intensity dependence of F- multiphoton detachment

Two- and three-photon detachment rates have been obtained for F- using several expansions in the R-matrix Floquet approach. These rates are compared with other theoretical and experimental results. The use of Hartree-Fock wavefunctions for the ground state of F with addition of continuum electrons does not lead to agreement with experiment for two- and three-photon detachment. By adding correlation terms, agreement with experiment and other theoretical results is improved considerably, demonstrating the importance of electron correlation effects. However, convergence with respect to the wavefunction expansion cannot be established, we also study the intensity dependence of multiphoton detachment rates for F- at the Nd-YAG frequency. Due to the ponderomotive shift the three-photon detachment channel closes at an intensity of 8.5 x 10(11) W cm(-2) and the influence of this channel closure on the multiphoton detachment peaks is illustrated by determining the heights of the excess-photon peaks obtained using a Gaussian laser pulse.

Pattern stability and error correction during in-phase and antiphase four-ball juggling

The authors studied pattern stability and error correction during in-phase and antiphase 4-ball fountain juggling. To obtain ball trajectories, they made and digitized high-speed film recordings of 4 highly skilled participants juggling at 3 different heights (and thus different frequencies). From those ball trajectories, the authors determined and analyzed critical events (i.e., toss, zenith, catch, and toss onset) in terms of variability of point estimates of relative phase and temporal correlations. Contrary to common findings on basic instances of rhythmic interlimb coordination, in-phase and antiphase patterns were equally variable (i.e., stable). Consistent with previous findings, however, pattern stability decreased with increasing frequency. In contrast to previous results for 3-ball cascade juggling, negative lag-one correlations for catch-catch intervals were absent, but the authors obtained evidence for error corrections between catches and toss onsets. That finding may have reflected participants' high skill level, which yielded smaller errors that allowed for corrections later in the hand cycle.

Interceptive skills in children aged 9-11 years, diagnosed with Autism Spectrum Disorder

Growing evidence suggests that significant motor problems are associated with a diagnosis of Autism Spectrum Disorders (ASD), particularly in catching tasks. Catching is a complex, dynamic skill that involves the ability to synchronise one's own movement to that of a moving target. To successfully complete the task, the participant must pick up and use perceptual information about the moving target to arrive at the catching place at the right time. This study looks at catching ability in children diagnosed with ASD (mean age 10.16 ± 0.9 years) and age-matched non-verbal (9.72 ± 0.79 years) and receptive language (9.51 ± 0.46) control groups. Participants were asked to "catch" a ball as it rolled down a fixed ramp. Two ramp heights provided two levels of task difficulty, whilst the sensory information (audio and visual) specifying ball arrival time was varied. Results showed children with ASD performed significantly worse than both the receptive language (p =.02) and non-verbal (p =.02) control groups in terms of total number of balls caught. A detailed analysis of the movement kinematics showed that difficulties with picking up and using the sensory information to guide the action may be the source of the problem. © 2013 Elsevier Ltd.

Tip leakage flow and heat transfer on turbine blade tip and casing, Part 1: Effect of tip clearance height and rotation speed

Steady simulations were performed to investigate tip leakage flow and heat transfer characteristics on the rotor blade tip and casing in a single-stage gas turbine engine. A typical high-pressure gas turbine stage was modeled with a pressure ratio of 3.2. The predicted isentropic Mach number and adiabatic wall temperature on the casing showed good agreement with available experimental data under similar operating condition. The present numerical study focuses extensively on the effects of tip clearance heights and rotor rotational speeds on the blade tip and casing heat transfer characteristics. It was observed that the tip leakage flow structure is highly dependent on the height of the tip gap and the speed of the rotor. In all cases, the tip leakage flow was seen to separate and recirculate just around the corner of the pressure side of the blade tip. This region of re-circulating flow enlarges with increasing clearance heights. The separated leakage flow reattaches afterwards on the tip surface. Leakage flow reattachment was shown to enhance surface heat transfer at the tip. The interaction between tip leakage flow and secondary flows that is induced by the relative casing motion is found to significantly influence the blade tip and casing heat transfer distribution. A region of critical heat transfer exists on the casing near the blade tip leading edge and along the pressure-side edge for all the clearance heights that were investigated. At high rotation speed, the region of critical heat transfer tends to move towards the trailing edge due to the change in inflow angle.

The Source of 3 Minute Magnetoacoustic Oscillations in Coronal Fans

We use images of high spatial, spectral, and temporal resolution, obtained using both ground- and space-based instrumentation, to investigate the coupling between wave phenomena observed at numerous heights in the solar atmosphere. Analysis of 4170 Å continuum images reveals small-scale umbral intensity enhancements, with diameters ~0."6, lasting in excess of 30 minutes. Intensity oscillations of ˜3 minutes are observed to encompass these photospheric structures, with power at least three orders of magnitude higher than the surrounding umbra. Simultaneous chromospheric velocity and intensity time series reveal an 87?±8? out-of-phase behavior, implying the presence of standing modes created as a result of partial wave re?ection at the transition region boundary. We ?nd a maximum waveguide inclination angle of˜40? between photospheric and chromospheric heights, combined with a radial expansion factor of <76%. An average blueshifted Doppler velocity of ˜1.5 km s-1, in addition to a time lag between photospheric and chromospheric oscillatory phenomena, con?rms the presence of upwardly propagating slow-mode waves in the lower solar atmosphere. Propagating oscillations in EUV intensity are detected in simultaneous coronal fan structures, with a periodicity of 172±17 s and a propagation velocity of 45±7 km s-1. Numerical simulations reveal that the damping of the magnetoacoustic wave trains is dominated by thermal conduction. The coronal fans are seen to anchor into the photosphere in locations where large-amplitude umbral dot (UD) oscillations manifest. Derived kinetic temperature and emission measure time series display prominent outof-phase characteristics, and when combined with the previously established sub-sonic wave speeds, we conclude that the observed EUV waves are the coronal counterparts of the upwardly propagating magnetoacoustic slow modes detected in the lower solar atmosphere. Thus, for the ?rst time, we reveal how the propagation of 3 minute magnetoacoustic waves in solar coronal structures is a direct result of amplitude enhancements occurring in photospheric UDs.photospheric UDs.