Quantum chemical calculations on thioridazine

Quantum chemical CNDO /2 calculations for the conformational preference of the side chain of thioridazine as a function of angle indicated the crystallographically determined structure gave the lowest energy. There is also a small region of conformational flexibility within the first 90° of rotation of the side chain. This is commensurate with the results which we had obtained previously for our similar calculations for promazine and its Cl and CF₃ derivatives, perazine and its Cl and CF₃ derivatives, and for the hypothetical hitherto unknown N-piperidinopromazine and its Cl and CF₃ derivatives. The conformational profile of thioridazine resembles that of the perazines. The calculated gross atomic populations on the alkyl nitrogen in thioridazine was within the range we had previously found necessary for neuroleptic activity.     

Modification of Escherichia coli single-stranded DNA binding protein with gold nanoparticles for electrochemical detection of DNA hybridization

The unique binding event between Escherichia coli single-stranded DNA binding protein (SSB) and single-stranded oligonucleotides conjugated to gold (Au) nanoparticles is utilized for the electrochemical detection of DNA hybridization. SSB was attached onto a self-assembled monolayer (SAM) of single-stranded oligonucleotide modified Au nanoparticle, and the resulting Au-tagged SSB was used as the hybridization label. Changes in the Au oxidation signal was monitored upon binding of Au tagged SSB to probe and hybrid on the electrode surface. The amplified oxidation signal of Au nanoparticles provided a detection limit of 2.17 pM target DNA, which can be applied to genetic diagnosis applications. This work presented here has important implications with regard to combining a biological binding event between a protein and DNA with a solid transducer and metal nanoparticles.     

Advances in electrochemical detection for study of neurodegenerative disorders

Several severe neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and prion-associated transmissible spongiform encephalopathies, have been linked to dysregulation of specific proteins capable of self-assembly into deleterious fibrillar aggregates termed amyloids. A wide range of analytical techniques has been used to clarify the mechanisms of these protein-misfolding processes, in the hope of developing effective therapeutic treatment. Most of these studies have relied heavily on conventional methods of protein characterization, notably circular dichroism spectroscopy, thioflavin T fluorescence, transmission electron microscopy, and atomic force microscopy, which are particularly suitable for monitoring later-stage aggregate formation. Although electrochemical methods of protein detection have existed for some time, they have only recently gained prominence as a powerful tool for studying the early stages of protein aggregation during which the more toxic soluble amyloid species form. Electrochemical detection methods include direct detection of intrinsic redox-active amino acid residues, protein-catalyzed hydrogen evolution, use of extrinsic β-sheet binding mediators, and impedance spectroscopy. In this review, we evaluate the use of electrochemistry for study of protein aggregation related to neurodegenerative disorders.

Nuclear rotations studied by the time-dependent variational method

A general nuclear rotation including precession and wobbling motion is studied by the time-dependent variational method and a classical equation of motion is derived. The intrinsic wave function associated with the general rotational motion is constructed by making use of the constrained Hartree-Fock method and variables necessary in solving the equation are calculated. The method developed here is applied to a schematic extension of the Nilsson model.     

Functional integral mean field expansions for nuclear many fermion systems

We present a careful analysis of the auxiliary field functional integral formalism for many fermion systems. We examine the limiting procedure used in construction of such integrals and show that a wide flexibility exists with respect to the choice of the one-body field representation upon which mean field expansions are made. We demonstrate the utility of this flexibility in the context of the evaluation of the grand canonical partition function. We examine the zero order. RPA and certain higher-order terms. The above-mentioned flexibility is reflected in the dependence of the results on a trial two-body interaction, different choices of which produce Hartree, Fock, HartreeFock or other forms of the mean field expansions. A standard variational procedure selects the Hartree-Fock as the optimal choice. With this choice we find certain corrections to previously reported RPA contribution for the Hartree mean field. We also indicate the relevance of our formulation for the recent applications of the functional integral mean field approach to nuclear dynamical problems.     

Prospects for production of ultracold $\mathsf{X^{1}\Sigma^{ + }}$ RbCs molecules

Recently, we have reported photoassociation of laser-cooled Rb and Cs atoms, decay of the RbCs photoassociation resonances to high levels of the state, and reexcitation to vibronic levels of the state [Kerman et al. , Phys. Rev. Lett. 92, 033004; 153001 (2004)]. Considering the reexcitation spectrum, we report here a preliminary analysis of perturbations in the c state by high levels of the and low levels of the state. Mixing with the B state provides the singlet character needed to stimulate decay to v = 0 of the ground state. We conclude that an experimental procedure that involves photoassociation of laser-cooled atoms, radiative decay, and stimulated Raman transfer to the ground electronic state is a feasible method for producing translationally, rotationally, vibrationally and electronically cold RbCs molecules. Electronic supplementary material to this article is available at and is accessible for authorized users. Received: 1 September 2004, Published online: 23 November 2004 PACS: 33.80.Ps Optical cooling of molecules; trapping - 34.50.Gb Electronic excitation and ionization of molecules; intermediate molecular states (including lifetimes, state mixing, etc.) - 33.20.Kf Visible spectra - 34.20.-b Interatomic and intermolecular potentials and forces, potential energy surfaces for collisions - 33.15.Pw Fine and hyperfine structure A supplementary table (Tab. I) is only available in electronic form at http: //www.eurphysj.org     

High resolution feshbach spectroscopy of cesium

We measure high-resolution Feshbach resonance spectra for ultracold cesium atoms colliding in different hyperfine and magnetic sublevels. More than 25 resonances are observed for magnetic fields up to 230 G and their positions are measured with an accuracy down to 0.03 G. From these spectra several ground-state molecular interaction parameters can be extracted with sufficient accuracy to permit for the first time an unambiguous and accurate determination of cesium's ultracold collision properties [P. J. Leo, C. J. Williams, and P. S. Julienne, following Letter, Phys. Rev. Lett. 85, 2721 (2000)].     

Insight into Amyloid Formation Using Congo Red as the Electrochemical Probe

The amyloid‐β (Aβ) aggregation pathway is an important target for the discovery of drugs that can prevent or delay the onset of Alzheimer’s disease (AD). The electrochemistry of Congo Red (CR) represents a particularly promising tool for screening of Aβ‐binding therapeutics in a rapid and cost‐effective format. The results of the differential pulse voltammetry (DPV) measurements were confirmed using simultaneous UV‐vis analysis of the same incubated Aβ samples. The early changes in the electrochemical signals were attributed to the interaction of the Aβ oligomers with CR. The electrochemical approach, in principle, allowed monitoring small molecule‐Aβ interactions on the time scale of aggregation.