Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Δ2-isoxazoline derivatives as potent and selective agonists of α7 nicotinic acetylcholine receptors

A set of racemic spirocyclic quinuclidinyl‐Δ²‐isoxazoline derivatives was synthesized using a 1,3‐dipolar cycloaddition‐based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (α7) and heteromeric (α4β2) nicotinic acetylcholine receptors. Δ²‐Isoxazolines 3 a (3‐Br), 6 a (3‐OMe), 5 a (3‐Ph), 8 a (3‐OnPr), and 4 a (3‐Me) were the ligands with the highest affinity for the α7 subtype (K_i values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM , respectively), and showed excellent α7 versus α4β2 subtype selectivity. These compounds, tested in electrophysiological experiments against human α7 and α4β2 receptors stably expressed in cell lines, behaved as partial α7 agonists with varying levels of potency. The two enantiomers of (±)‐3‐methoxy‐1‐oxa‐2,7‐diaza‐7,10‐ethanospiro[4.5]dec‐2‐ene sesquifumarate 6 a were prepared using (+)‐dibenzoyl‐L ‐ or (?)‐dibenzoyl‐D ‐tartaric acid as resolving agents. Enantiomer (R)‐(?)‐ 6 a was found to be the eutomer, with K_i values of 4.6 and 48.7 nM against rat and human α7 receptors, respectively.     

The infusion of calcium gluconate in coronary disease patients induces myocardial ischemia via a possible adenosine-mediated mechanism

The development of spontaneous mammary tumors was observed for about 2 years in a group of 25 female Sprague-Dawley rats aged over 1 year at the beginning of the study. All younger females in our animal facility were similarly monitored. In old females, the incidence of spontaneous mammary tumors was 64%. The parity of rats did not protect them from tumorigenesis, but the proportion of malignant tumors was higher in virgin (57%) than in parous (13%) rats. Activities of cytochrome P450IA1-dependent enzyme (aryl hydrocarbon hydroxylase, AHH) and NADPH-cytochrome P450 reductase (NCR) were determined in microsome fractions isolated from livers, lungs, uteri and tumors of rats. AHH and NCR activities in tumors and uteri were low compared to those in livers or lungs. In tumors, the activity distributions were wide, even in different tumors of the same animal the AHH activities varied as widely as between different animals. The activities in benign and malignant tumors were not statistically significantly different. No correlation with liver, lung or uterine activities was found either. With ageing of the rat, the AHH activities in tumors, liver and lungs decreased. The behavior of AHH in spontaneous mammary tumors in rats seems to be similar to that found in chemically induced tumors and seems to show individual regulation, possibly altered by tumorigenesis in each individual tumor.     

Interannual variability of surface heat fluxes in the Adriatic Sea in the period 1998-2001 and comparison with observations

Surface heat fluxes of the Adriatic Sea are estimated for the period 1998-2001 through bulk formulae with the goal to assess the uncertainties related to their estimations and to describe their interannual variability. In addition a comparison to observations is conducted. We computed the components of the sea surface heat budget by using two different operational meteorological data sets as inputs: the ECMWF operational analysis and the regional limited area model LAMBO operational forecast. Both results are consistent with previous long-term climatology and short-term analyses present in the literature. In both cases we obtained that the Adriatic Sea loses 26 W/m2 on average, that is consistent with the assessments found in the literature. Then we conducted a comparison with observations of the radiative components of the heat budget collected on offshore platforms and one coastal station. In the case of shortwave radiation, results show a little overestimation on the annual basis. Values obtained in this case are 172 W/m2 when using ECMWF data and 169 W/m2 when using LAMBO data. The use of either Schiano's or Gilman's and Garrett's corrections help to get even closer values. More difficult is to assess the comparison in the case of longwave radiation, with relative errors of an order of 10-20%.     

The role of personality in shaping social networks and mediating behavioral change

In this paper, we exploit different facets of the Friends and Family study to deal with two personality-related tasks of paramount importance for the user modeling and ubiquitous computing fields. First, we propose and validate an approach for automatic classification of personality traits based on the ego-networks’ structural characteristics. Our classification results show that (i) mobile phones-based behavioral data can be superior to survey ones for the purposes of personality classification from structural network properties and (ii) particular feature set/network type combinations promise to perform better with given personality traits. Then, we investigate the mediating role played by personality in the context of inducing behavioral change, specifically increasing daily physical activity using social strategies (social comparison and peer pressure). Our results confirm the role played by Extraversion and Neuroticism. Extroverts exposed to a social comparison strategy are positively associated with an increase in physical activity level, while they tend to decrease physical activity level if they are exposed to a peer pressure intervention strategy. Regarding Neuroticism dimension, neurotic people tend to increase their physical daily activity level if they are exposed to a social comparison strategy. Our findings may have implications in designing personality-based behavioral change strategies and suggest to incorporate users’ personality models in the implementation of persuasive systems.     

Automatic differentiation of rigid body dynamics for optimal control and estimation

Abstract

Many algorithms for control, optimization and estimation in robotics depend on derivatives of the underlying system dynamics, e.g. to compute linearizations, sensitivities or gradient directions. However, we show that when dealing with rigid body dynamics, these derivatives are difficult to derive analytically and to implement efficiently. To overcome this issue, we extend the modelling tool ‘RobCoGen’ to be compatible with Automatic Differentiation. Additionally, we propose how to automatically obtain the derivatives and generate highly efficient source code. We highlight the flexibility and performance of the approach in two application examples. First, we show a trajectory optimization example for the quadrupedal robot HyQ, which employs auto-differentiation on the dynamics including a contact model. Second, we present a hardware experiment in which a six-DoF robotic arm avoids a randomly moving obstacle in a go-to task by fast, dynamic replanning.     

Robot impedance control and passivity analysis with inner torque and velocity feedback loops

Impedance control is a well-established technique to control interaction forces in robotics. However, real implementations of impedance control with an inner loop may suffer from several limitations. In particular, the viable range of stable stiffness and damping values can be strongly affected by the bandwidth of the inner control loops (e.g., a torque loop) as well as by the filtering and sampling frequency. This paper provides an extensive analysis on how these aspects influence the stability region of impedance parameters as well as the passivity of the system. This will be supported by both simulations and experimental data. Moreover, a methodology for designing joint impedance controllers based on an inner torque loop and a positive velocity feedback loop will be presented. The goal of the velocity feedback is to increase (given the constraints to preserve stability) the bandwidth of the torque loop without the need of a complex controller.     

Anomalous Monism in a Digital Universe

Bermúdez (Philosophy of psychology: a contemporary introduction, Routledge, London, 2005) identifies the “Interface Problem” as the central problem in the philosophy of psychology: how commonsensical psychological explanations can be integrated with lower-level (cognitive, biological, etc.) explanations? In particular, since folk psychology is meant to provide causal explanations on a par with, say, neurobiological explanations, the question of how to understand the relation between the two layers arises naturally. Donald Davidson claimed that the interface problem is actually ill-posed and put forward his version of the “Autonomy Picture”, the view known as anomalous monism. This work reviews Davidson’s proposal in the light of digital universes: we model the key claims of the theory using cellular automata and show that Davidson’s original version of the Autonomy Picture (which differs, in some respects, from what is discussed by Bermúdez) is immune to two arguments against autonomy.