Visual filtering in time and space among persons with Down syndrome.

BACKGROUND: Individuals with Down syndrome (DS) appear to perform at a level that is commensurate with developmental expectations on simple tasks of selective attention. In this study, we examine how their selective attention is impacted by target changes that unfold over both time and space. This increased complexity reflects an attempt at greater ecological validity in an experimental task, as a steppingstone for better understanding attention among persons with DS in real-world environments. METHODS: A modified flanker task was used to assess visual temporal and spatial filtering among persons with DS (n = 14) and typically developing individuals (n = 14) matched on non-verbal mental age (mental age = 8.5 years). Experimental conditions included varying the stimulus onset asynchronies between the onset of the target and flankers, the distances between the target and flankers, and the similarity of the target and flankers. RESULTS: Both the participants with DS and the typically developing participants showed slower reaction times and lower accuracy rates when the flankers appeared closer in time and/or space to the target. CONCLUSION: No group differences were found on a broad level, but the findings suggest that dynamic stimuli may be processed differently by those with DS. Implications of the findings are discussed in relation to the developmental approach to intellectual disability originally articulated by Ed Zigler.

Schizophrenia: a neurodevelopmental disorder--integrative genomic hypothesis and therapeutic implications from a transgenic mouse model.

Schizophrenia is a neurodevelopmental disorder featuring complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain appears to be established during gestation, long before clinical symptoms of the disease appear in early adult life. Many genes are associated with schizophrenia, however, altered expression of no one gene has been shown to be present in a majority of schizophrenia patients. How does altered expression of such a variety of genes lead to the complex set of abnormalities observed in the schizophrenic brain? We hypothesize that the protein products of these genes converge on common neurodevelopmental pathways that affect the development of multiple neural circuits and neurotransmitter systems. One such neurodevelopmental pathway is Integrative Nuclear FGFR1 Signaling (INFS). INFS integrates diverse neurogenic signals that direct the postmitotic development of embryonic stem cells, neural progenitors and immature neurons, by direct gene reprogramming. Additionally, FGFR1 and its partner proteins link multiple upstream pathways in which schizophrenia-linked genes are known to function and interact directly with those genes. A th-fgfr1(tk-) transgenic mouse with impaired FGF receptor signaling establishes a number of important characteristics that mimic human schizophrenia - a neurodevelopmental origin, anatomical abnormalities at birth, a delayed onset of behavioral symptoms, deficits across multiple domains of the disorder and symptom improvement with typical and atypical antipsychotics, 5-HT antagonists, and nicotinic receptor agonists. Our research suggests that altered FGF receptor signaling plays a central role in the developmental abnormalities underlying schizophrenia and that nicotinic agonists are an effective class of compounds for the treatment of schizophrenia.

C60 buckminsterfullerene high yields unraveled.

Recently Irle, Morokuma, and collaborators have carried out a series of quantum chemical molecular dynamics simulations of carbon clustering. The results of these computer experiments are that carbon clusters of size greater than 60 atoms are rapidly formed, anneal to giant fullerenes, and then these fullerenes shrink. The simulation could not be carried to long enough times for the shrinking to reach C60, but they propose reasonably that this shrinking process ultimately forms buckminsterfullerene. However, these simulations do not reveal the force driving the shrinking process. Here, this driving force for shrinking is found to be reactions in which C2 is swapped between fullerenes. The key element is that for typical fullerenes the equilibrium constants for such C2 interchanges are near unity, resulting in expansion of the breadth of the fullerene distribution in an annealing process. When fullerenes of 60 or 70 atoms are populated by shrinking, they fall into the local energy minimum of buckminsterfullerene or D5h C70. This simple mechanism accounts for the high yields (>20%) of buckminsterfullerene that can be achieved in pure carbon systems.

IR kinetic spectroscopy investigation of the CH4 + O(1D) reaction.

The branching of the title reaction into several product channels has been investigated quantitatively by laser infrared kinetic spectroscopy for CH(4) and CD(4). It is found that OH (OD) is produced in 67 +/- 5% (60 +/- 5%) yield compared to the initial O((1)D) concentration. H (D) product is produced in 30 +/- 10%(35 +/- 10%). H(2)CO is produced in 5% yield in the CH(4) system (it was not possible to measure the CD(2)O yield in the CD(4) case). D(2)O is produced in 8% yield in the CD(4) system (it was not feasible to measure the H(2)O yield). The ratio of the overall rate constant of the CD(4) reaction to the overall rate constant of the O((1)D) + N(2)O reaction was determined to be 1.2(5) +/- 0.1. A measurement of the reaction of O((1)D) with NO(2) gave 1.3 x 10(-10) cm(3) molecule(-1) s(-1) relative to the literature values for the rate constants of O((1)D) with H(2) and CH(4). Hot atom effects in O((1)D) reactions were observed.

Chemical sensing with pulsed QC-DFB lasers operating at 15.6 micrometers.

Pulsed thermoelectrically cooled QC-DFB lasers operating at 15.6 micrometers were characterized for spectroscopic gas sensing applications. A new method for wavelength scanning based on repetition rate modulation was developed. A non-wavelength-selective pyroelectric detector was incorporated in the sensor configuration giving the advantage of room-temperature operation and low cost. Absorption lines of CO2 and H2O were observed in ambient air, providing information about the concentration of these species.

Quartz-enhanced photoacoustic spectroscopy.

A new approach to detecting a weak photoacoustic signal in a gas medium is described. Instead of a gas-filled resonant acoustic cavity, the sound energy is accumulated in a high- Q crystal element. Feasibility experiments utilizing a quartz-watch tuning fork demonstrate a sensitivity of 1.2x10(-7) cm(-1) W/ radicalHz . Potential further developments and applications of this technique are discussed.

Absorption spectroscopy with quantum cascade lasers.

Novel pulsed and cw quantum cascade distributed feedback (QC-DFB) lasers operating near lambda=8 micrometers were used for detection and quantification of trace gases in ambient air by means of sensitive absorption spectroscopy. N2O, 12CH4, 13CH4, and different isotopic species of H2O were detected. Also, a highly selective detection of ethanol vapor in air with a sensitivity of 125 parts per billion by volume (ppb) was demonstrated.

Ammonia Detection by use of Near-Infrared Diode-Laser-Based Overtone Spectroscopy.

We describe a portable diode-laser-based sensor for NH(3) detection using vibrational overtone absorption spectroscopy at 1.53 mum. Use of fiber-coupled optical elements makes such a trace gas sensor rugged and easy to align. On-line data acquisition and processing requiring <30 s can be performed with a laptop PC running LabVIEW software. The gas sensor was used primarily for NH(3) concentration measurements with a sensitivity of 0.7 parts per million (signal-to-noise ratio of 3) over a two-week period in a bioreactor being developed at the NASA Johnson Space Center for water treatment technologies to support long-duration space missions. The feasibility of simultaneous, real-time measurements of NH(3) and CO(2) concentrations is also reported.

Spectroscopic detection of biological NO with a quantum cascade laser.

Two configurations of a continuous wave quantum cascade distributed feedback laser-based gas sensor for the detection of NO at a parts per billion (ppb) concentration level, typical of biomedical applications, have been investigated. The laser was operated at liquid nitrogen temperature near lambda = 5.2 microns. In the first configuration, a 100 m optical path length multi-pass cell was employed to enhance the NO absorption. In the second configuration, a technique based on cavity-enhanced spectroscopy (CES) was utilized, with an effective path length of 670 m. Both sensors enabled simultaneous analysis of NO and CO2 concentrations in exhaled air. The minimum detectable NO concentration was found to be 3 ppb with a multi-pass cell and 16 ppb when using CES. The two techniques are compared, and potential future developments are discussed.

Effective utilization of quantum-cascade distributed-feedback lasers in absorption spectroscopy.

A variable duty cycle quasi-cw frequency scanning technique was applied to reduce thermal effects resulting from the high heat dissipation of type I quantum-cascade lasers. This technique was combined with a 100-m path-length multipass cell and a zero-air background-subtraction technique to enhance detection sensitivity to a parts-in-10(9) (ppb) concentration level for spectroscopic trace-gas detection of CH4, N2O, H2O, and C2H5OH in ambient air at 7.9 micrometers. A new technique for analysis of dense high resolution absorption spectra was applied to detection of ethanol in ambient air, yielding a 125-ppb detection limit.

High-power continuous-wave mid-infrared radiation generated by difference frequency mixing of diode-laser-seeded fiber amplifiers and its application to dual-beam spectroscopy.

We report the generation of up to 0.7 mW of narrow-linewidth (<60-MHz) radiation at 3.3 micrometers by difference frequency mixing of a Nd:YAG-seeded 1.6-W Yb fiber amplifier and a 1.5-micrometers diode-laser-seeded 0.6-W Er/Yb fiber amplifier in periodically poled LiNbO3. A conversion efficiency of 0.09%/W (0.47 mWW-2 cm-1) was achieved. A room-air CH4 spectrum acquired with a compact 80-m multipass cell and a dual-beam spectroscopic configuration indicates an absorption sensitivity of +/-2.8 x 10(-5) (+/-1 sigma), corresponding to a sub-parts-in-10(9) (ppb) CH4 sensitivity (0.8 ppb).

Methane concentration and isotopic composition measurements with a mid-infrared quantum-cascade laser.

A quantum-cascade laser operating at a wavelength of 8.1 micrometers was used for high-sensitivity absorption spectroscopy of methane (CH4). The laser frequency was continuously scanned with current over more than 3 cm-1, and absorption spectra of the CH4 nu 4 P branch were recorded. The measured laser linewidth was 50 MHz. A CH4 concentration of 15.6 parts in 10(6) ( ppm) in 50 Torr of air was measured in a 43-cm path length with +/- 0.5-ppm accuracy when the signal was averaged over 400 scans. The minimum detectable absorption in such direct absorption measurements is estimated to be 1.1 x 10(-4). The content of 13CH4 and CH3D species in a CH4 sample was determined.

Mid-infrared difference-frequency generation source pumped by 1.1-1.5 micrometer dual-wavelength fiber amplifier for trace-gas detection.

Continuous-wave mid-infrared radiation near 3.5 micrometers is generated by difference-frequency mixing of the output of a compact 1.1-1.5 micrometer dual-wavelength fiber amplifier in periodically poled LiNbO3. The diode side-pumped amplifier is constructed with double-cladding Yb-doped fiber followed by single-mode Er/Yb codoped fiber. Output powers of as much as 11 microW at 3.4 micrometers are obtained, and spectroscopic detection of CH4 and H2CO is demonstrated.

Room-temperature mid-infrared laser sensor for trace gas detection.

Design and operation of a compact, portable, room-temperature mid-infrared gas sensor is reported. The sensor is based on continuous-wave difference-frequency generation (DFG) in bulk periodically poled lithium niobate at 4.6 mum, pumped by a solitary GaAlAs diode laser at 865 nm and a diode-pumped monolithic ring Nd:YAG laser at 1064.5 nm. The instrument was used for detection of CO in air at atmospheric pressure with 1 ppb precision (parts in 10(9), by mole fraction) and 0.6% accuracy for a signal averaging time of 10 s. It employed a compact multipass absorption cell with a 18-m path length and a thermoelectrically cooled HgCdTe detector. Precision was limited by residual interference fringes arising from scattering in the multipass cell. This is the first demonstration of a portable high-precision gas sensor based on diode-pumped DFG at room temperature. The use of an external-cavity diode laser can provide a tuning range of 700 cm(-1) and allow the detection of several trace gases, including N(2) O, CO(2), SO(2), H(2) CO, and CH(4).

Detection of CO in air by diode-pumped 4.6-microm difference-frequency generation in quasi-phase-matched LiNbO(3).

Detection of CO, N(2)O, and CO(2) in ambient air was performed with a room-temperature cw IR source based on difference-frequency generation in periodically poled LiNbO(3). The source was pumped by a seeded highpower GaAlAs amplif ier at 860 nm and a diode-pumped monolithic Nd:YAG ring laser at 1064 nm. The IR output was tunable between 2160 and 2320 cm(-1) without crystal rotation. The CO detection sensitivity is extrapolated to 5 ppb m/ radicalHz if limited by IR intensity noise.

Continuous-wave tunable 8.7-microm spectroscopic source pumped by fiber-coupled communications lasers.

Tunable narrow-band cw difference-frequency generation at 8.7 microm was demonstrated in silver gallium selenide (AgGaSe(2)) at room temperature. The crystal was pumped by an injection-seeded Er/Yb-codoped fiber amplifier at 1.554 microm and a fiber-coupled diode-pumped monolithic ring Nd:YAG laser at 1.319 microm. The difference-frequency output was used for high-resolution spectroscopy of sulfur dioxide (SO(2)).

Probing chemical reactions: evidence for exploration of an excited potential energy surface at thermal energies.

The reaction K + NaBr --> KBr + Na is probed during the reactive collision by a continuous wave laser tuned to frequencies not resonant with excitation in either reagents or products. Transient [K..Br..Na] absorbs a laser photon giving [K..Br..Na](*), which can decompose to Na(*) + KBr. Emission from excited Na(*) at the sodium D lines provides direct evidence of laser absorption during the reaction. Different excitation spectra were observed, depending on which sodium D line was monitored. This difference is explicable if, in the absence of the laser, the reaction flux partially bifurcates to a second potential energy surface during the reaction.

Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model.

A microscopic mass balance approach has been developed to predict the fraction dose absorbed of suspensions of poorly soluble compounds. The mathematical model includes four fundamental dimensionless parameters to estimate the fraction dose absorbed: initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn). The fraction dose absorbed (F) increases with increasing Is, An, and Dn and with decreasing Do. At higher Dn and lower Do, the fraction dose absorbed reaches the maximal F, which depends only on An. The dissolution number limit on F can appear at both lower Do and lower Dn. Likewise, at higher Do and Dn, the fraction dose absorbed reaches a Do limit. Initial saturation makes a significant difference in F at lower Do and Dn. It is shown that the extent of drug absorption is expected to be highly variable when Dn and Do are approximately one. Furthermore, by calculating these dimensionless groups for a given compound, a formulation scientist can estimate not only the extent of drug absorption but also the effect, if any, of particle size reduction on the extent of drug absorption.