Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

rdgE: a novel retinal degeneration mutation in Drosophila melanogaster

We report isolating the Drosophila retinal degeneration E (rdgE) mutation. The hypomorphic rdgE1 allele causes rapid photoreceptor degeneration in light and a slower rate of degeneration when the flies are raised in constant darkness. The rdgE1 flies exhibited an electrophysiological light response that decreased with age, coinciding with the degeneration. This suggests that degeneration caused the loss of the light response. We determined that the ninaE (rhodopsin) mutation, but not norpA [phospholipase C (PLC)], slowed the rdgE-dependent degeneration. This was consistent with the light-enhanced degeneration, but revealed that the degeneration is independent of the PLC-mediated phototransduction cascade. Transmission electron microscopy revealed that rdgE1 photoreceptors exhibited a number of vesicular transport defects including unpacking/vesiculation of rhabdomeres, endocytosis of novel vesicles by photoreceptors, a buildup of very large multivesicular bodies, and an increased amount of rough endoplasmic reticulum. We determined that the rdgE null phenotype is a late embryonic lethality. Therefore, rdgE+ is required in cells outside of the retina, quite possibly in a large number of neurons. Thus, rdgE may define a mutational class that exhibits both light-enhanced retinal degeneration and a recessive null lethality by perturbing neuronal membrane biosynthesis and/or recycling.     

The effects of instructional match and content overlap on generalized reading performance

This study examined the effects of instructional match and content overlap on students' ability to generalize from passage reading instruction. Four students with mild disabilities served as participants. Using a multielement design, students were instructed with passages at two levels of text difficulty (instructionally matched vs. instructionally mismatched), and generalization was assessed with passages at two levels of similarity to those instructed (low vs. high content overlap). Results indicated that students' oral reading accuracy and fluency showed the greatest degree of generalization when instructional materials were matched to the students' skill level and assessment materials were similar to those used during instruction. Moreover, these results were maintained at 1-month follow-up. The implications of these findings for classroom reading instruction and the assessment of students' reading skills are discussed.     

Thermal alteration of a cyclic fatty acid produced by a flaxseed extract

Methyl 8-[2-(cis-pent-2′-enyl)-3-oxo-cis-cyclopent-4-enyl] octanoate (I) is the methyl ester of a cyclic fatty acid synthesized enzymically from an incubation of linolenic acid with an extract of flaxseed (Linum usitatissimum L.). A proposed trivial name for I is methyl 12-oxo-cis-10, 15-phytodienoate (12-oxo-PDA). The evidence presented indicated that compound I has thecis configuration of the carbon chains with respect to the cyclopentenone ring. Treatment with acid, base, or heat isomerized I to a second product (II) that has thetrans configuration of the carbon chains. Prolonged heat treatment of II yielded a third cyclic product, methyl 12-oxo-9(13),cis-15-phytodienoate (III).     

Traveling-wave analysis of a bifilar scanning helical antenna

The bifilar scanning helical antenna is analyzed by considering the structure to carry a single traveling wave. It is shown that the relative phase velocity (v/c) must equal unity to yield the scanning features shown by numerical experiment. This is at complete odds with monofilament helices (Kraus), which display a slow wave structure     

10GBASE-T:基于铜质电缆的10Gb以太网指南

10GBASE-T面临着回波、近端串扰、远端串扰、Alien串扰等信道损耗带来的挑战。10Gb以太网切实可行且万事俱备自从2002年批准10Gb以太网通信标准以来,业界总是预测"明年"将会最终推出10Gb以太网。然而,自诞生以来,10Gb以太网的发展就因为其无法利用各种低速以太网标准成熟的传输方式而受到阻碍。     

Development and validation of a Monte Carlo simulation of photon transport in an Anger camera

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.