Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors

We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC50 for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC50 of ACh dose-response relationship in the expected direction but does not completely convert the EC50 of the dose- response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors

Achieving peak brightness in an atom laser

In this paper we present experimental results and theory on the first continuous (long pulse) Raman atom laser. The brightness that can be achieved with this system is three orders of magnitude greater than has been previously demonstrated in any other continuously outcoupled atom laser. In addition, the energy linewidth of a continuous atom laser can be made arbitrarily narrow compared to the mean field energy of a trapped condensate. We analyze the flux and brightness of the atom laser with an analytic model that shows excellent agreement with experiment with no adjustable parameters.Comment: 4 pages, 4 black and white figures, submitted to Physical Revie

A detector for continuous measurement of ultra-cold atoms in real time

We present the first detector capable of recording high-bandwidth real time atom number density measurements of a Bose Einstein condensate. Based on a two-color Mach-Zehnder interferometer, our detector has a response time that is six orders of magnitude faster than current detectors based on CCD cameras while still operating at the shot-noise limit. With this minimally destructive system it may be possible to implement feedback to stabilize a Bose-Einstein condensate or an atom laser.Comment: 3 pages, 3 figures, submitted to optics letter

Semiclassical limits to the linewidth of an atom laser

We investigate the linewidth of a quasi-continuous atom laser within a semiclassical framework. In the high flux regime, the lasing mode can exhibit a number of undesirable features such as density fluctuations. We show that the output therefore has a complicated structure that can be somewhat simplified using Raman outcoupling methods and energy-momentum selection rules. In the weak outcoupling limit, we find that the linewidth of an atom laser is instantaneously Fourier limited, but, due to the energy `chirp' associated with the draining of a condensate, the long-term linewidth of an atom laser is equivalent to the chemical potential of the condensate source. We show that correctly sweeping the outcoupling frequency can recover the Fourier-limited linewidth.Comment: 9 Figure

Quantum projection noise limited interferometry with coherent atoms in a Ramsey type setup

Every measurement of the population in an uncorrelated ensemble of two-level systems is limited by what is known as the quantum projection noise limit. Here, we present quantum projection noise limited performance of a Ramsey type interferometer using freely propagating coherent atoms. The experimental setup is based on an electro-optic modulator in an inherently stable Sagnac interferometer, optically coupling the two interfering atomic states via a two-photon Raman transition. Going beyond the quantum projection noise limit requires the use of reduced quantum uncertainty (squeezed) states. The experiment described demonstrates atom interferometry at the fundamental noise level and allows the observation of possible squeezing effects in an atom laser, potentially leading to improved sensitivity in atom interferometers.Comment: 8 pages, 8 figures, published in Phys. Rev.

Regions of β4·β2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors

AbstractFifteen chimeric nicotinic receptors β subunits were constructed consisting of N-terminal neuronal β4 sequences and C-terminal β2 sequences. Responses to cytisine, nicotine, or tetramethylammonium were compared to acetylcholine responses for these subunits expressed in Xenopus oocytes with α3 subunits. The results show that (i) two residues in the extracellular domain of chimeric β4·β2 subunits (108β2F/β4V, 110β2S/β4T) account for much of the relative cytisine sensitivity; and (ii) four extracellular residues of chimeric β4·β2 subunits (112β2A/β4V, 113β2V/β4I and 115β2S/β4R, 116β2Y/β4S) account for most of the relative tetramethylammonium sensitivity. The data did not permit localization of nicotine sensitivity to any particular region

Mutations Linked to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Affect Allosteric Ca²⁺ Activation of the α4β2 Nicotinic Acetylcholine Receptor

Extracellular Ca²⁺ robustly potentiates the acetylcholine response of α4β2 nicotinic receptors. Rat orthologs of five mutations linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)—α4(S252F), α4(S256L), α4(+L264), β2(V262L), and β2(V262M)—reduced 2 mM Ca²⁺ potentiation of the α4β2 1 mM acetylcholine response by 55 to 74%. To determine whether altered allosteric Ca²⁺ activation or enhanced Ca²⁺ block caused this reduction, we coexpressed the rat ADNFLE mutations with an α4 N-terminal mutation, α4(E180Q), that abolished α4β2 allosteric Ca²⁺ activation. In each case, Ca²⁺ inhibition of the double mutants was less than that expected from a Ca²⁺ blocking mechanism. In fact, the effects of Ca²⁺ on the ADNFLE mutations near the intracellular end of the M2 region—α4(S252F) and α4(S256L)—were consistent with a straightforward allosteric mechanism. In contrast, the effects of Ca²⁺ on the ADNFLE mutations near the extracellular end of the M2 region—α4(+L264)β2, β2(V262L), and β2(V262M)—were consistent with a mixed mechanism involving both altered allosteric activation and enhanced block. However, the effects of 2 mM Ca²⁺ on the α4β2, α4(+L264)β2, and α4β2(V262L) single-channel conductances, the effects of membrane potential on the β2(V262L)-mediated reduction in Ca²⁺ potentiation, and the effects of eliminating the negative charges in the extracellular ring on this reduction failed to provide any direct evidence of mutant-enhanced Ca²⁺ block. Moreover, analyses of the α4β2, α4(S256L), and α4(+L264) Ca²⁺ concentration-potentiation relations suggested that the ADNFLE mutations reduce Ca²⁺ potentiation of the α4β2 acetylcholine response by altering allosteric activation rather than by enhancing block

Using Insights from Cognitive Neuroscience to Investigate the Effects of Event-Driven Process Chains on Process Model Comprehension

Business process models have been adopted by enterprises for more than a decade. Especially for domain experts, the comprehension of process models constitutes a challenging task that needs to be mastered when creating or reading these models. This paper presents the results we obtained from an eye tracking experiment on process model comprehension. In detail, individuals with either no or advanced expertise in process modeling were confronted with models expressed in terms of Event-driven Process Chains (EPCs), reflecting different levels of difficulty. The first results of this experiment confirm recent findings from one of our previous experiments on the reading and comprehension of process models. On one hand, independent from their level of exper-tise, all individuals face similar patterns, when being confronted with process models exceeding a certain level of difficulty. On the other, it appears that process models expressed in terms of EPCs are perceived differently compared to process models specified in the Business Process Model and Notation (BPMN). In the end, their generalization needs to be confirmed by additional empirical experiments. The presented expe-riment continues a series of experiments that aim to unravel the factors fostering the comprehension of business process models by using methods and theories stemming from the field of cognitive neuroscience and psychology