Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

An analytical approach to solution of two- point boundary condition problems in optimal guidance Summary report, May 1965 - Apr. 1966

Analytical approaches to path-adaptive guidance functions, circular orbit trajectories, and use of Fortran-compiled program

Imaging geometry through dynamics: the observable representation

For many stochastic processes there is an underlying coordinate space, $V$, with the process moving from point to point in $V$ or on variables (such as spin configurations) defined with respect to $V$. There is a matrix of transition probabilities (whether between points in $V$ or between variables defined on $V$) and we focus on its ``slow'' eigenvectors, those with eigenvalues closest to that of the stationary eigenvector. These eigenvectors are the ``observables,'' and they can be used to recover geometrical features of $V$

A l% and 1cm Perspective Leads to a Novel CDOM Absorption Algorithm

A next-generation in-water profiler designed to measure the apparent optical properties of seawater was developed and validated across a wide dynamic range of water properties. This new Compact-Optical Profiling System (C-OPS) design uses a novel, kite-shaped, free-falling backplane with adjustable buoyancy and is based on 19 state-of-the-art microradiometers, spanning 320-780 nm. Data collected as part of the field commissioning were of a previously unachievable quality and showed that systematic uncertainties in the sampling protocols were discernible at the 1% optical and 1cm depth resolution levels. A sensitivity analysis as a function of three water types, established by the peak in the remote sensing reflectance spectra, revealed which water types and spectral domains were the most indicative of data acquisition uncertainties. The unprecedented vertical resolution of C-OPS measurements provided near-surface data products at the spectral endpoints with a quality level that has not been obtainable. The improved data allowed development of an algorithm for predicting the spectral absorption due to chromophoric dissolved organic matter (CDOM) using ratios of diffuse attenuation coefficients with over 99% of the variance in the data explained

Federal Listing of Prairie Grouse: Lessons from the Attwater’s Prairie Chicken

Considerable controversy has often surrounded proposals to confer official status (i.e., list) species under the authority of the Endangered Species Act (ESA) of 1973 as amended or its precursors. Recent proposals to list the lesser prairie-chicken (Tympanuchus pallidicinctus), the western sage grouse (Centrocercus urophasianus phaios), and the Gunnison sage grouse (C. minimus) were met with strong opposition by those concerned with prospects of an increased regulatory environment associated with such an action. The Attwater\u27s prairie-chicken (T. cupido attwateri) was one of the first species listed under The Endangered Species Conservation Act of 1966, the first federal effort to specifically protect endangered species. Federal listing benefited the Attwater\u27s by raising awareness of its status and by authorizing additional sources of funding for its management. While concern over an increased regulatory environment associated with the endangered status of the Attwater\u27s probably has always existed among property owners and land managers, conflicts involving this bird have been few and local in scope. Maintaining good working relationships and respect for all affected interests, including property owners and land managers, has been paramount in Attwater\u27s recovery efforts. However, these efforts at times have been hampered by lightning-rod issues pertaining to other species. Despite 35 years of ESA protection, the Attwater\u27s prairie-chicken remains perilously close to extinction. Based on these experiences, federal listing should be viewed neither as a panacea nor as a demon, but rather as a tool in species recovery

Paediatric nonbronchoscopic bronchoalveolar lavage: Overview and recommendations for clinical practice

NB-BAL is an effective procedure for the diagnosis of pulmonary disease processes in ventilated infants and children. This procedure is, however, not without risks to both patients and staff. Numerous complications of NB-BAL exist, with hypoxia being the most common. As a result, care should be taken in performing NB-BAL on haemodynamically unstable patients; patients with coagulation defects; and patients with cardiac or brain abnormalities. This paper presents an overview of paediatric nonbronchoscopic bronchoalveolar lavage (NB-BAL) including: the rationale for NB-BAL; the complications associated with the procedure; indications and contraindications. It also recommends an evidence-based clinical guideline for performing the procedure in the paediatric intensive care unit. By following the NB-BAL guidelines presented in this paper, one can ensure that an effective specimen is obtained from the lower respiratory tract, whilst minimising the risk to the patient

Derivative analysis of spectral absorption by photosynthetic pigments in the western Sargasso Sea

Concurrent measurements of the spectral absorption coefficient and photosynthetic pigmentation of natural particulates were performed to determine the principal pigments responsible for the absorption of spectral irradiance in seawater. The spectral absorption coefficient, Ap(λ), was then analyzed by taking the second and fourth derivatives with respect to wavelength. The wavelength and magnitude of these derivative values provide useful information regarding the identification and quantification of phytoplankton pigments responsible for a given spectral signature. Linear relationships were examined and established between derivative values at selected wavelengths and concentrations of the major tetrapyrrole pigments, specifically chlorophylls a, b, and c. The correlation between derivative values near 526 nm and concentrations of photosynthetic carotenoids was poor and presumably caused by the broad absorption spectra of these pigments. A comparison of the measured particulate absorption coefficient with the absorption coefficient reconstructed for the phytoplankton component revealed that detritus can be a major source of light absorption. The method described here provides a rapid means of obtaining estimates of photosynthetic pigment concentrations in natural samples where absorption can be strongly influenced by detrital matter

Perinatal neurosteroid levels influence GABAergic interneuron localization in adult rat prefrontal cortex

Neurosteroids are a class of steroids synthesized de novo in the brain, several of which are potent modulators of GABAA receptor function. In developing brain GABAA receptor, stimulation plays a trophic role. Cortical levels of the GABAergic neurosteroid 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) vary dramatically across development; during the second week of life, elevated levels of 3α,5α-THP are associated with decreased GABAA receptor function. To determine whether alteration of endogenous 3α,5α-THP levels during development alters GABAergic interneurons in prefrontal cortex (PFC) at maturity, rat pups were exposed to 3α,5α-THP (10 mg/kg) on postnatal day 1 (P1), P2, and P5. On P80, frontal cortex tissue was assayed for GABAergic cell localization (parvalbumin and calbindin immunoreactivity), agonist-dependent [3H] dizocilpine (MK-801) binding to NMDA receptors in cortical homogenates, muscimol-mediated 36Cl- influx into synaptoneurosomes, and 3α,5α-THP levels. The localization of parvalbumin-labeled cells was markedly altered; the ratio of cell number in the deep layers (V-VI) versus superficial layers (I-III) of adult PFC increased twofold in animals exposed to 3α,5α-THP on P1 or P5. Relative microtubule-associated protein-2 and calbindin immunoreactivity were not altered by perinatal 3α,5α-THP administration. Agonist-dependent [3H]MK-801 binding was decreased in PFC but not parietal cortex homogenates, whereas muscimolmediated 36Cl- influx and 3α,5α-THP levels were unchanged in frontal cortex of adult males exposed to 3α,5α-THP on P5. These data are consistent with a change in the distribution of a subset of interneurons in response to neurosteroid exposure and suggest that GABAergic neurosteroids are critical for normal development of GABAergic systems in the PFC