From ab initio quantum mechanics to molecular neurobiology: A cation–π binding site in the nicotinic receptor

The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that cation–π interactions may be involved in binding the quaternary ammonium group of the agonist, acetylcholine. Here we show a compelling correlation between: (i) ab initio quantum mechanical predictions of cation–π binding abilities and (ii) EC50 values for acetylcholine at the receptor for a series of tryptophan derivatives that were incorporated into the receptor by using the in vivo nonsense-suppression method for unnatural amino acid incorporation. Such a correlation is seen at one, and only one, of the aromatic residues—tryptophan-149 of the α subunit. This finding indicates that, on binding, the cationic, quaternary ammonium group of acetylcholine makes van der Waals contact with the indole side chain of α tryptophan-149, providing the most precise structural information to date on this receptor. Consistent with this model, a tethered quaternary ammonium group emanating from position α149 produces a constitutively active receptor.

The importance of reactant positioning in enzyme catalysis: A hybrid quantum mechanics/molecular mechanics study of a haloalkane dehalogenase

Hybrid quantum mechanics/molecular mechanics calculations using Austin Model 1 system-specific parameters were performed to study the SN2 displacement reaction of chloride from 1,2-dichloroethane (DCE) by nucleophilic attack of the carboxylate of acetate in the gas phase and by Asp-124 in the active site of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. The activation barrier for nucleophilic attack of acetate on DCE depends greatly on the reactants having a geometry resembling that in the enzyme or an optimized gas-phase structure. It was found in the gas-phase calculations that the activation barrier is 9 kcal/mol lower when dihedral constraints are used to restrict the carboxylate nucleophile geometry to that in the enzyme relative to the geometries for the reactants without dihedral constraints. The calculated quantum mechanics/molecular mechanics activation barriers for the enzymatic reaction are 16.2 and 19.4 kcal/mol when the geometry of the reactants is in a near attack conformer from molecular dynamics and in a conformer similar to the crystal structure (DCE is gauche), respectively. This haloalkane dehalogenase lowers the activation barrier for dehalogenation of DCE by 2–4 kcal/mol relative to the single point energies of the enzyme's quantum mechanics atoms in the gas phase. SN2 displacements of this sort in water are infinitely slower than in the gas phase. The modest lowering of the activation barrier by the enzyme relative to the reaction in the gas phase is consistent with mutation experiments.

How can statistical mechanics contribute to social science?

A model of interdependent decision making has been developed to understand group differences in socioeconomic behavior such as nonmarital fertility, school attendance, and drug use. The statistical mechanical structure of the model illustrates how the physical sciences contain useful tools for the study of socioeconomic phenomena.

Molecular mechanics calculations of the riboacetal internucleotide linkage in double and triple helices.

Structures of Watson-Crick base paired 15-nucleobase oligomer strands in A-type or B-type conformation in which one strand [a strand of alternating nucleotide and riboacetal thymidine nucleoside (RT) units, RP] is DNA and the other is composed of alternating nucleotides and riboacetal nucleosides have been studied by molecular mechanics. Analogously, oligomer strands of RNA in place of DNA have been modeled. The calculations indicate that the RP strand is more stable when complexed in an A-type duplex relative to a B-type form and that this conformational preference is presumably due to the more uniform nature of the former. Nearly planar ribose rings were more commonly observed in the minimized structures of the B-type DNA.RP duplexes as compared with A-type duplexes, despite the fact that planar ribofuranose rings are known to be energetically unfavorable in oligonucleotides. Computed relative stabilities of all duplexes containing the RP strand suggest that such heteroduplexes are less stable than the corresponding double-stranded DNA and double-stranded RNA species. These findings are in agreement with experimental results which show, when equivalent sequences were compared, that a DNA.RNA control forms a more stable duplex than RP hound to a complementary single-stranded RNA strand. In contrast, molecular mechanics studies of complementary triple-helical (DNA)2.RP, (DNA)2.DNA, and (DNA)2.RNA structures indicate that the binding of RP as a Hoogsteen strand stabilizes the underlying duplex to a greater extent compared with native oligonucleotides. These calculations suggest that puckering of the ribose ring in the riboacetal linkage leads to a more favorable interaction with a complementary nucleic acid target than the proposed planar geometry and that this puckering may account for the enhanced binding of RP to a double-stranded target.

Estudo experimental do fenômeno de vibração induzida por vórtices em cilindro rígido livre para oscilar com dois graus de liberdade.

O fenômeno de vibração induzida por vórtices (VIV) é um problema fundamental dentro da Mecânica dos Fluidos e um exemplo importante de interação fluido-estrutura. Esta tese investiga fenômeno de VIV quando um cilindro rígido, submetido a escoamento uniforme, está livre para oscilar na direção transversal e alinhada com a corrente incidente. A tese foi estruturada ao redor de sete perguntas relacionadas ao fenômeno de VIV: 1) O fenômeno e os resultados experimentais são repetitivos? 2) Como ocorre a transição entre ramos de resposta? 3) Qual é o papel da inércia da estrutura oscilante? 4) Qual é o papel de sua rigidez? 5) Quais são as frequências naturais mais importantes da estrutura? 6) Quais padrões de esteira se desenvolvem para VIV com dois graus de liberdade? 7) Quais são os efeitos do movimento na direção alinhada com a corrente no processo de formação e desprendimento de vórtices? O fenômeno de VIV é estudado de maneira experimental em uma base elástica pendular capaz de oscilar com o mesmo momento de inércia e frequência natural nas duas direções. Os experimentos de VIV foram realizados em canal de água recirculante e com diferentes condições de inércia e rigidez. A técnica de velocimetria por imagem de partículas foi usada e permitiu identificar diferentes padrões de esteira de vórtices. Verificou-se que o VIV é repetitivo a nível de amplitudes médias e frequências dominantes. A transição dos ramos pode ocorrer de maneira intermitente ou com histerese. Os parâmetros de inércia e rigidez da estrutura são capazes de mudar o regime de oscilação e, para algumas condições, suprimir as vibrações alinhadas com a corrente. Dentre os padrões de esteira observados, um deles não havia sido relatado na literatura e é definido nesta tese. O novo modo de emissão apresenta dois vórtices com circulação oposta e elevada intensidade emitidos por ciclo. A influência da direção alinhada com o escoamento está relacionada a dois efeitos: a velocidade relativa entre o cilindro e o fluido, responsável pelo aumento da circulação dos vórtices na esteira, e o ângulo de fase do movimento nas direções alinhada e transversal, capaz de mudar o processo de formação dos vórtices.

New Approaches for Teaching Soil and Rock Mechanics Using Information and Communication Technologies

Soil and rock mechanics are disciplines with a strong conceptual and methodological basis. Initially, when engineering students study these subjects, they have to understand new theoretical phenomena, which are explained through mathematical and/or physical laws (e.g. consolidation process, water flow through a porous media). In addition to the study of these phenomena, students have to learn how to carry out estimations of soil and rock parameters in laboratories according to standard tests. Nowadays, information and communication technologies (ICTs) provide a unique opportunity to improve the learning process of students studying the aforementioned subjects. In this paper, we describe our experience of the incorporation of ICTs into the classical teaching-learning process of soil and rock mechanics and explain in detail how we have successfully developed various initiatives which, in summary, are: (a) implementation of an online social networking and microblogging service (using Twitter) for gradually sending key concepts to students throughout the semester (gradual learning); (b) detailed online virtual laboratory tests for a delocalized development of lab practices (self-learning); (c) integration of different complementary learning resources (e.g. videos, free software, technical regulations, etc.) using an open webpage. The complementary use to the classical teaching-learning process of these ICT resources has been highly satisfactory for students, who have positively evaluated this new approach.

SCAPHOID AND LUNATE CARPAL MECHANICS OVER THE SPECTRUM OF HEALTHY FUNCTION

When ligaments within the wrist are damaged, the resulting loss in range of motion and grip strength can lead to reduced earning potential and restricted ability to perform important activities of daily living. Left untreated, ligament injuries ultimately lead to arthritis and chronic pain. Surgical repair can mitigate these issues but current procedures are often non-anatomic and unable to completely restore the wrist’s complex network of ligaments. An inability to quantitatively assess wrist function clinically, both before and after surgery, limits the ability to assess the response to clinical intervention. Previous work has shown that bones within the wrist move in a similar pattern across people, but these patterns remain challenging to predict and model. In an effort to quantify and further develop the understanding of normal carpal mechanics, we performed two studies using 3D in vivo carpal bone motion analysis techniques. For the first study, we measured wrist laxity and performed CT scans of the wrist to evaluate 3D carpal bone positions. We found that through mid-range radial-ulnar deviation range of motion the scaphoid and lunate primarily flexed and extended; however, there was a significant relationship between wrist laxity and row-column behaviour. We also found that there was a significant relationship between scaphoid flexion and active radial deviation range of motion. For the second study, an analysis was performed on a publicly available database. We evaluated scapholunate relative motion over a full range of wrist positions, and found that there was a significant amount of variation in the location and orientation of the rotation axis between the two bones. Together the findings from the two studies illustrate the complexity and subject specificity of normal carpal mechanics, and should provide insights that can guide the development of anatomical wrist ligament repair surgeries that restore normal function.

Bristol's compilation: mechanics' lien law, Torrens land title, builders' directory.

Mode of access: Internet.

Mechanics of pneumatic tires.

Mode of access: Internet.

The Mechanics of supply-demand adjusters for midwestern milk markets /

Cover title.

The theory of functions of a complex variable. [Lectures] New York University, Institute for Mathematics and Mechanics.

"First edition 1948. Second printing 1952."

Selected topics in fluid mechanics, Summer session 1946 [New York University?]

Reproduced from typewritten copy.

Introduction to quantum mechanics : a course at Los Alamos University /

Mode of access: Internet.