3,4-Diaminopyridine has shown promise in reversing botulinum intoxication, but poor pharmacokinetics and a narrow therapeutic window limit its clinical utility. Thus, we developed a pH-dependent oral ...delivery platform using club moss spore exines. These exine microcapsules slowed 3,4-diaminopyridine absorption, limited its seizure activity, and enabled delivery of doses which prolonged mouse survival after botulism neurotoxin A intoxication.
Invasive electrophysiological and neuroanatomical studies in nonhuman mammalian experimental preparations have helped elucidate the lamina (layer) dependence of neural computations and interregional ...connections. Noninvasive functional neuroimaging can, in principle, resolve cortical laminae (layers), and thus provide insight into human neural computations and interregional connections. However human neuroimaging data are noisy and difficult to interpret; biologically realistic simulations can aid experimental interpretation by relating the neuroimaging data to simulated neural activity. We illustrate the potential of laminar neuroimaging by upgrading an existing large-scale, multiregion neural model that simulates a visual delayed match-to-sample (DMS) task. The new laminar-based neural unit incorporates spiny stellate, pyramidal, and inhibitory neural populations which are divided among supragranular, granular, and infragranular laminae (layers). We simulated neural activity which is translated into local field potential-like data used to simulate conventional and laminar fMRI activity. We implemented the laminar connectivity schemes proposed by Felleman and Van Essen (Cerebral Cortex, 1991) for interregional connections. The hemodynamic model that we employ is a modified version of one due to Heinzle et al. (Neuroimage, 2016) that incorporates the effects of draining veins. We show that the laminar version of the model replicates the findings of the existing model. The laminar model shows the finer structure in fMRI activity and functional connectivity. Laminar differences in the magnitude of neural activities are a prominent finding; these are also visible in the simulated fMRI. We illustrate differences between task and control conditions in the fMRI signal, and demonstrate differences in interregional laminar functional connectivity that reflect the underlying connectivity scheme. These results indicate that multi-layer computational models can aid in interpreting layer-specific fMRI, and suggest that increased use of laminar fMRI could provide unique and fundamental insights to human neuroscience.
•A large-scale neural model of the ventral visual processing pathway was presented.•The multiregion model simulates laminar-based fMRI data as well as neural data.•Task vs. control differences in interarea laminar functional connectivity were shown.
The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of ...the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor.
The CVD of Cu using (hfac)Cu(VTMS) (hfac = hexafluoroacetylacetonate, VTMS = vinyltrimethylsilane) and (hfac)Cu(2-butyne) in the presence of water and other reagents has been studied. The overall CVD ...reaction involving disproportionation of these copper(I) compounds in the presence of water is similar to the overall reaction in the absence of water. The Cu films deposited at low water vapor flow rate (0.2 sccm) exhibited near bulk resistivities (∼2.0 μΩ cm) and dense surface morphologies while the Cu films deposited at higher water vapor flow rate (2.4 sccm) showed significantly higher resistivities (∼12 μΩ cm) and porous morphologies. At higher water flow rates the deposition rate and conductivity of the films were reduced as a result of Cu2O incorporation. The presence of water during CVD is believed to introduce a reaction parallel to the main CVD disproportionation reaction via reaction of water with surface-bound Cu(hfac) and results in the incorporation of copper(I) oxide (Cu2O) in the Cu films. Labeling experiments using H2O18 showed that the oxygen incorporated into the films (SIMS) at high water flow rates was derived from reaction with H2O. The deposition rate enhancements with methanol and dimethyl ether showed similar trends as a function of flow rate but lower overall rate enhancements compared to water. The presence of water is believed to aid the dissociation of the L from the (hfac)CuL by hydrogen bonding with the hfac ligand and/or oxygen donation to the copper(I) center. The incorporation of Cu2O was completely suppressed by introduction of hfacH vapor along with the precursor and water vapor during CVD of Cu.
3,4-Diaminopyridine has shown promise in reversing botulinum intoxication, but poor pharmacokinetics and a narrow therapeutic window limit its clinical utility. Thus, we developed a pH-dependent oral ...delivery platform using club moss spore exines. These exine microcapsules slowed 3,4-diaminopyridine absorption, limited its seizure activity, and enabled delivery of doses which prolonged mouse survival after botulism neurotoxin A intoxication.
Biopolymeric spores and shellac can be rapidly employed to generate a scalable, pH-dependent, controlled-release microcapsule delivery system.
3,4-Diaminopyridine has shown promise in reversing botulinum intoxication, but poor pharmacokinetics and a narrow therapeutic window limit its clinical utility. Thus, we developed a pH-dependent oral ...delivery platform using club moss spore exines. These exine microcapsules slowed 3,4-diaminopyridine absorption, limited its seizure activity, and enabled delivery of doses which prolonged mouse survival after botulism neurotoxin A intoxication.
Endogenous levels of juvenile hormones 0, I, II and III have been measured each day during the 4th, 5th and 6th larval stadia of the Tomato moth,
Lacanobia oleracea, using physico-chemical methods. ...Levels of the same hormones have also been measured at selected times during pupal development, and over the first 5 days of adult life in males, and in mated and virgin females. JH I and JH II were the predominant homologues in this insect in all developmental stages, although JH III was also present in some samples. Hormone levels were relatively high in 4th and 5th instar larvae, but were much reduced in 6th (final) instar larvae. Hormone levels increased in larvae that were about to moult to the subsequent stage. Juvenile hormones were absent in pupae during the first half of pupal development, but increased in pharate adults. Adult males and females contained substantially more hormone than pre-adult stages, although levels in virgin moths were lower than in mated adult females. JH 0 was detected in some extracts of mated adult female moths. These results are discussed in relation to the likely role of juvenile hormones in modulating various aspects of the physiology of this insect.
We present a mathematical framework for simulation of optical fields in complex gravitational-wave interferometers. The simulation framework uses the two-photon formalism for optical fields and ...includes radiation pressure effects, an important addition required for simulating signal and noise fields in next-generation interferometers with high circulating power. We present a comparison of results from the simulation with analytical calculation and show that accurate agreement is achieved.
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