Using Physical Chemistry To Differentiate Nicotinic from Cholinergic Agonists at the Nicotinic Acetylcholine Receptor

The binding of three distinct agonists - acetylcholine (ACh), nicotine, and epibatidine - to the nicotinic acetylcholine receptor has been probed using unnatural amino acid mutagenesis. ACh makes a cation−π interaction with Trp α149, while nicotine employs a hydrogen bond to a backbone carbonyl in the same region of the agonist binding site. The nicotine analogue epibatidine achieves its high potency by taking advantage of both the cation−π interaction and the backbone hydrogen bond. A simple structural model that considers only possible interactions with Trp α149 suggests that a novel aromatic C - H···O=C hydrogen bond further augments the binding of epibatidine. These studies illustrate the subtleties and complexities of the interactions between drugs and membrane receptors and establish a paradigm for obtaining detailed structural information

Biophysical and Structural Characterization of a Robust Octameric Beta-Peptide Bundle

Proteins composed of α-amino acids are essential components of the machinery required for life. Stanley Miller\u27s renowned electric discharge experiment provided evidence that an environment of methane, ammonia, water, and hydrogen was sufficient to produce α-amino acids. This reaction also generated other potential protein building blocks such as the β-amino acid β-glycine (also known as β-alanine); however, the potential of these species to form complex ordered structures that support functional roles has not been widely investigated. In this report we apply a variety of biophysical techniques, including circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, NMR and X-ray crystallography, to characterize the oligomerization of two 12-mer β3-peptides, Acid-1Y and Acid-1Y*. Like the previously reported β3-peptide Zwit-1F, Acid-1Y and Acid-1Y* fold spontaneously into discrete, octameric quaternary structures that we refer to as β-peptide bundles. Surprisingly, the Acid-1Y octamer is more stable than the analogous Zwit-1F octamer, in terms of both its thermodynamics and kinetics of unfolding. The structure of Acid-1Y, reported here to 2.3 Å resolution, provides intriguing hypotheses for the increase in stability. To summarize, in this work we provide additional evidence that nonnatural β-peptide oligomers can assemble into cooperatively folded structures with potential application in enzyme design, and as medical tools and nanomaterials. Furthermore, these studies suggest that nature\u27s selection of α-amino acid precursors was not based solely on their ability to assemble into stable oligomeric structures

Lattice Artefacts In The Non-Abelian Debye Screening Mass In One Loop Order

We compute the electric screening mass in lattice QCD with Wilson fermions at finite temperature and chemical potential to one-loop order, and show that lattice artefacts arising from a finite lattice spacing result in an enhancement of the screening mass as compared to the continuum. We discuss the magnitude of this enhancement as a function of the temperature and chemical potential for lattices with different number of lattice sites in the temporal direction that can be implemented in lattice simulations. Most of the enhancement is found to be due to the fermion loop contribution.Comment: 23 pages, 8 figures, LaTe

Maskless selective growth of InGaAs/InP quantum wires on (100) GaAs

A new fabrication process to create InGaAs/InP quantum wires on (100) GaAs substrates is demonstrated. The process is based on the selectivity of the growth of InP on lines created by focused ion beam bombardment, together with the selectivity of the growth of InGaAs on the InP wires. Intense photoluminescene is observed from the wires and the emission shows clear polarization parallel and perpendicular to the wires. Cathodoluminescene images confirm that the luminescence originates from the wires.Peer reviewe

Designing a memorial place

The design and selection of a memorial stone and the site of the grave, both of which represent the deceased, can be a central issue for people bereaved by traffic accidents. This was revealed in an interview survey of recent Swedish roadside memorials and other memorial places. In this article we consider the design and selection of the memorial stone and gravesite as expressions of continuing care for the deceased and as a way to offer comfort to the bereaved. Materiality, representation and presence will be discussed as crucial parts of the link between the living and the dead. Communicative, spatial and physical values are important also in the professional's design of common public memorial places. Of specific interest for this text are two design practice-based terms, memory object and passage landscape, which may be used by landscape architects when designing memorial places, such as cemeteries and public monuments. Throughout this text, we argue that memorial places like these are capable of bridging the gap between the space of life and the space of death, as well as supporting the regeneration of present memories and the construction of future ones

Non-Perturbative Effects on a Fractional D3-Brane

In this note we study the N=1 abelian gauge theory on the world volume of a single fractional D3-brane. In the limit where gravitational interactions are not completely decoupled we find that a superpotential and a fermionic bilinear condensate are generated by a D-brane instanton effect. A related situation arises for an isolated cycle invariant under an orientifold projection, even in the absence of any gauge theory brane. Moreover, in presence of supersymmetry breaking background fluxes, such instanton configurations induce new couplings in the 4-dimensional effective action, including non-perturbative contributions to the cosmological constant and non-supersymmetric mass terms.Comment: 18 pages, v3: refs adde

Unoriented D-brane Instantons vs Heterotic worldsheet Instantons

We discuss Fermi interactions of four hyperini generated by ``stringy'' instantons in a Type I / Heterotic dual pair on T^4/Z_2.Comment: Minor corrections and clarifications. Added reference

Dispersively detected Pauli Spin-Blockade in a Silicon Nanowire Field-Effect Transistor

We report the dispersive readout of the spin state of a double quantum dot formed at the corner states of a silicon nanowire field-effect transistor. Two face-to-face top-gate electrodes allow us to independently tune the charge occupation of the quantum dot system down to the few-electron limit. We measure the charge stability of the double quantum dot in DC transport as well as dispersively via in-situ gate-based radio frequency reflectometry, where one top-gate electrode is connected to a resonator. The latter removes the need for external charge sensors in quantum computing architectures and provides a compact way to readout the dispersive shift caused by changes in the quantum capacitance during interdot charge transitions. Here, we observe Pauli spin-blockade in the high-frequency response of the circuit at finite magnetic fields between singlet and triplet states. The blockade is lifted at higher magnetic fields when intra-dot triplet states become the ground state configuration. A lineshape analysis of the dispersive phase shift reveals furthermore an intradot valley-orbit splitting $\Delta_{vo}$ of 145 $\mu$eV. Our results open up the possibility to operate compact CMOS technology as a singlet-triplet qubit and make split-gate silicon nanowire architectures an ideal candidate for the study of spin dynamics

Tactile Interactions with a Humanoid Robot : Novel Play Scenario Implementations with Children with Autism

Acknowledgments: This work has been partially supported by the European Commission under contract number FP7-231500-ROBOSKIN. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.The work presented in this paper was part of our investigation in the ROBOSKIN project. The project has developed new robot capabilities based on the tactile feedback provided by novel robotic skin, with the aim to provide cognitive mechanisms to improve human-robot interaction capabilities. This article presents two novel tactile play scenarios developed for robot-assisted play for children with autism. The play scenarios were developed against specific educational and therapeutic objectives that were discussed with teachers and therapists. These objectives were classified with reference to the ICF-CY, the International Classification of Functioning – version for Children and Youth. The article presents a detailed description of the play scenarios, and case study examples of their implementation in HRI studies with children with autism and the humanoid robot KASPAR.Peer reviewedFinal Published versio