Isomeric Xylene Molecules in the Terahertz Far Infrared Regime Computational Chemistry and Spectral Modeling View

The theoretical assignments of spectral peaks of liquid phase ortho , meta , and para xylene recorded with far infrared FIR and THz spectroscopy in the spectral range between 550 and 50 cm amp; 8722;1 is done with density functional theory DFT calculations. As THz spectroscopic techniques drastically evolved in recent years, the critical focus of this paper lies on the applicability of theoretical concepts, used as computational standard in near and mid IR spectra, to the FIR THz region. An evaluation of the choice of functionals, basis sets, and appropriate scaling factors as well as the tractability of the liquid phase in a polarizable continuum model is performed. Alongside a new analysis procedure based on spectral Hard Modeling has been developed. DFT line spectra are fitted to experimental FIR spectra where a quantitative track record allows for meaningful comparisons. With all these tools we are able to reproduce experimental spectra in an optically appealing way and we can explain trends for each spectrum as well as across the row of the isomer

Nicotine binding to brain receptors requires a strong cation–π interaction

Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine (ACh) receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the largest source of preventable mortality in developed countries. Stress reduction, pleasure, improved cognition and other central nervous system effects are strongly associated with smoking. However, if nicotine activated ACh receptors found in muscle as potently as it does brain ACh receptors, smoking would cause intolerable and perhaps fatal muscle contractions. Despite extensive pharmacological, functional and structural studies of ACh receptors, the basis for the differential action of nicotine on brain compared with muscle ACh receptors has not been determined. Here we show that at the α4β2 brain receptors thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation–π interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle type ACh receptor is largely due to the fact that this key interaction is absent, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates α4β2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. ACh receptors are established therapeutic targets for Alzheimer’s disease, schizophrenia, Parkinson’s disease, smoking cessation, pain, attention-deficit hyperactivity disorder, epilepsy, autism and depression. Along with solving a chemical mystery in nicotine addiction, our results provide guidance for efforts to develop drugs that target specific types of nicotinic receptors

The Use and Characterization of Aluminum Based Metallic Paints in Early Twentieth Century Paintings

This paper presents the results of research into the composition and use of metallic aluminum paints in three paintings by Australian artists from the first half of the twentieth century as well as a contemporary can of aluminum stove paint. A brief history of the development of aluminum paint and its uses is presented. The material characteristics of aluminum powders and binders used with them are described, as well as the effects variations of components have on resulting paint films. Analyses found leafing aluminum flakes and nitrocellulose binder on two paintings and identified coumarone as the binder for the stove pain

Electromagnetic Pulse Sounding for Surveying Underground Water

This project supported in part by the Office of Water Resources Research U. S. Department of the Interior Washington, D. C. under Project B-028-OHIOA number of approaches have been explored for measuring the water content of soil electrically. In contrast with traditional measurements, which utilize electric currents at DC or at specific frequencies, our techniques have been based on the transmission and reflection of sharp, regularly repeated pulses. Such pulse measurements can be shown to be equivalent to measuring the electrical properties at all frequencies in a very wide band, and therefore the possibility of extracting the desired information is much greater than with single-frequency measurements. Because the information content of the signal is great, data processing can be used to extract those features which relate most directly to moisture content and reject those which appear to depend more on soil inhomogenieties. For example, it was found that the attenuation in the frequency band of approximately 10 to 20 MHz had a much higher correlation with soil moisture than that in other frequency bands for the actual field conditions under which our measurements were made. This information content increase is obtained by means of sophisticated research equipment. The measurements reported herein were made and processed under real-time computer control. They include the signal scattered from known buried targets, transmission measurements through the ground, and the measurement of reflections in a coaxial test cell, all with pulses containing very wide frequency bands. The results are encouraging in that definite correlations with moisture were found. Unfortunately the one-year time limitation of this effort, much of it spent in instrumentation development, was insufficient to allow testing these correlations quantitatively over extended time periods or in a variety of locations. Thus the techniques must be evaluated at present as promising, but not fully proven. It should be noted that, while the research system to obtain this information is complex, field equipment based on these techniques need not be unduly complicated or expensive. Once the features relating to moisture content under the greatest variety of field conditions are identified, means for extracting this information more simply should be devised. This is proposed as the objective for continuation of this effort.Summary -- Introduction -- 1. The Measuring System -- 2. Data Processing -- 3. Underground Moisture Content Monitoring by Measurement of Buried Target Signatures -- 4. Sampled Moisture Conditions -- 5. Underground Propagation Experiment -- 6. Reflection Measurements on Soil Samples in a Vertical Coaxial Test Cell -- 7. Propagation Calculations -- Conclusions -- Recommendations -- References -- Appendix I - Transmission Measurements using a Buried Antenn

α4* Nicotinic Receptors in preBotzinger Complex Mediate Cholinergic/Nicotinic Modulation of Respiratory Rhythm

Acetylcholine and nicotine can modulate respiratory patterns by acting on nicotinic acetylcholine receptors (nAChRs) in the preBötzinger complex (preBötC). To further explore the molecular composition of these nAChRs, we studied a knock-in mouse strain with a leucine-to-alanine mutation in the M2 pore-lining region (L9′A) of the nAChR α4 subunit; this mutation renders α4-containing receptors hypersensitive to agonists. We recorded respiratory-related rhythmic motor activity from hypoglossal nerve (XIIn) and patch-clamped preBötC inspiratory neurons in an in vitro medullary slice preparation from neonatal mice. Nicotine affected respiratory rhythm at concentrations ∼100-fold lower in the homozygous L9′A knock-in mice compared with wild-type mice. Bath application of 5 nm nicotine increased the excitability of preBötC inspiratory neurons, increased respiratory frequency, and induced tonic/seizure-like activities in XIIn in L9′A mice, effects similar to those induced by 1 μm nicotine in wild-type mice. In L9′A mice, microinjection of low nanomolar concentrations of nicotine into the preBötC increased respiratory frequency, whereas injection into the ipsilateral hypoglossal (XII) nucleus induced tonic/seizure-like activity. The α4*-selective nAChR antagonist dihydro-β-erythroidine produced opposite effects and blocked the nicotinic responses. These data, showing that nAChRs in the preBötC and XII nucleus in L9'A mice are hypersensitive to nicotine and endogenous ACh, suggest that functional α4* nAChRs are present in the preBötC. They mediate cholinergic/nicotinic modulation of the excitability of preBötC inspiratory neurons and of respiratory rhythm. Furthermore, functional α4* nAChRs are present in XII nucleus and mediate cholinergic/nicotinic modulation of tonic activity in XIIn

Probing the Effects of Residues Located Outside the Agonist Binding Site on Drug-Receptor Selectivity in the Nicotinic Receptor

The nicotinic acetylcholine receptors (nAChRs) are a family of closely related but pharmacologically distinct neurotransmitter-gated ion channels. They are therapeutic targets for a wide range of neurological disorders, and a key issue in drug development is selective targeting among the more than 20 subtypes of nAChRs that are known. The present work evaluates a proposed hydrogen bonding interaction involving a residue known as the “loop B glycine” that distinguishes receptors that are highly responsive to ACh and nicotine from those that are much less so. We have performed structure–function studies on the loop B site, including unnatural amino acid mutagenesis, in three different nAChR subtypes and found that the correlation between agonist potency and this residue is strong. Low potency receptor subtypes have a glycine at this key site, and mutation to a residue with a side chain converts a low potency receptor to a high potency receptor. Innately high potency receptors have a lysine at the loop B site and show a decrease in potency for the reverse mutation (i.e., introducing a glycine). This residue lies outside of the agonist binding site, and studies of other residues at the agonist binding site show that the details of how changes at the loop B glycine site impact agonist potency vary for differing receptor subtypes. This suggests a model in which the loop B residue influences the global shape of the agonist binding site rather than modulating any specific interaction

Differential Expression and Function of Nicotinic Acetylcholine Receptors in Subdivisions of Medial Habenula

Neuronal nAChRs in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway are key mediators of nicotine's aversive properties. In this paper, we report new details regarding nAChR anatomical localization and function in MHb and IPN. A new group of knock-in mice were created that each expresses a single nAChR subunit fused to GFP, allowing high-resolution mapping. We find that α3 and β4 nAChR subunit levels are strong throughout the ventral MHb (MHbV). In contrast, α6, β2, β3, and α4 subunits are selectively found in some, but not all, areas of MHbV. All subunits were found in both ChAT-positive and ChAT-negative cells in MHbV. Next, we examined functional properties of neurons in the lateral and central part of MHbV (MHbVL and MHbVC) using brain slice patch-clamp recordings. MHbVL neurons were more excitable than MHbVC neurons, and they also responded more strongly to puffs of nicotine. In addition, we studied firing responses of MHbVL and MHbVC neurons in response to bath-applied nicotine. Cells in MHbVL, but not those in MHbVC, increased their firing substantially in response to 1 μm nicotine. Additionally, MHbVL neurons from mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline. Last, we characterized rostral and dorsomedial IPN neurons that receive input from MHbVL axons. Together, our data provide new details regarding neurophysiology and nAChR localization and function in cells within the MHbV

Coordination crosslinking of helical substituted oligoamide nanorods with Cu II

Substituted oligoamides are short sequences of unnatural amino acids. Oligoamides made entirely of amp; 946;3 amino acids yield helical monomers that, if N acylated, assemble into nanorod structures via a supramolecular assembly motif. In this work, coordination crosslinking was used to create complex nanomaterials fromoligoamides WKLWEL KE and WELWEL EE the letters denote the analogous amp; 945; amino acids . Upon Cu II addition, atomic force microscopy and small angle neutron scattering revealedmorphologic changes specific to KE but absent in EE. Vibration spectroscopymeasurements revealed that Cu II can coordinate to the amine moieties of the side chains, without direct effect on the backboneamides. While coordination in excess solvent lead to regular nanostructures, fast drying of the sample yielded oligoamide templated crystallization of CuCl2. The metal coordination crosslinking of supramolecular assemblies as reported here is the first realization of a metallosupramolecular framework structur