On the high affinity of 8-cyclohexylcaffeine for the presynaptic inhibitory adenosine receptor present in rat motor nerve terminals

Rat neuromuscular junction was used to study the characteristics of presynaptic A1 adenosine receptors. We investigated the ability of the 8-substituted caffeine, 8-cyclohexylcaffeine (CHC), as well as of 1,3,8-substituted xanthines, 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) and 8-p-sulfophenyl-1-isoamyl-3-isobutylxanthine (SPIIBX) to antagonize the inhibitory effect of 2-chloroadenosine on the amplitude of nerve-evoked twitches of the rat phrenic-hemidiaphragm, and we compared the affinity of these xanthines with that of 1,3-dipropyl-8-cyclopenthylxanthine (DPCPX). CHC, DPSPX and SPIIBX in a near parallel manner shifted to the right the log concentration-response curve for the inhibitory effect of 2-chloroadenosine on nerve-evoked twitch amplitude. Linear Schild plots with slopes near to unity were obtained for all these xanthines. The order of potency of the xanthines was DPCPX (Ki = 0.53 nM) > DPSPX (38 nM) = CHC (41 nM) > SPIIBX (404 nM). The affinities of DPSPX and SPIIBX for the A1 receptor at the rat neuromuscular junction are in agreement with the affinities described for A1 receptors at brain membranes. The now reported affinity of CHC for the presynaptic A1 receptor is 683 times higher than that obtained in binding studies in rat brain membranes, and is only 49 times higher than that obtained in functional assays (adenylate cyclase activity) in non-neuronal preparations (rat fat cells).     

Guidelines for nonspecific bronchial provocation tests

This study evaluated the effects of a predialysis patient education programme on functioning and well-being in 28 uraemic patients. The programme consisted of four group sessions with the following themes: renal disease and dietary restriction, active renal replacement therapy, physical exercise, and the impact of chronic renal failure on economy, family and social life. Three to 9 months after having started dialysis the patients were evaluated regarding symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status. Twenty-eight patients already on dialysis treatment informed according to conventional routines constituted the comparison group. There were no significant differences between the groups regarding age, sex, educational or social background, duration of kidney disease, choice of dialysis treatment, cause of renal disease and laboratory tests except for s-urea. The patients who participated in the education programme scored significantly better mood, less mobility problems (HI), less functional disabilities (SIP) and lower levels of anxiety (STAI) compared to the comparison group. There were no significant differences between the two groups regarding symptoms and overall health. The differences between the groups prevailed during the first 6 months on dialysis treatment, after which the differences disappeared. In the comparison group age correlated significantly to anxiety and overall SIP, which was not the case in the experimental group. In conclusion, the experimental group that participated in a predialysis patient education programme, showed better functional and emotional well-being than the non-educated comparison group. The positive effects of participating in an education programme prevailed during the first 6 months of dialysis treatment. Moreover, the younger patients seemed especially to benefit from participation in a predialysis patient education programme. It is suggested that patient education should be ongoing for patients with end-stage renal failure initiated during the predialysis stage and continued after maintenance dialysis has been established.     

Fujisaki–Okamoto hybrid encryption revisited

At Crypto’99, Fujisaki and Okamoto [11] presented a generic transformation from weak secure asymmetric and symmetric schemes into an IND-CCA hybrid encryption scheme in the Random Oracle Model, which has been extensively used in several cryptographic scenarios. The work we present here forms part of the careful revision of the provable security techniques initiated by Shoup in [25] insofar as we find some ambiguities in the proof of this generic conversion, which can lead to false claims. Consequently, the original conversion is modified and the class of asymmetric primitives that can be used is shortened. Furthermore, the concept of easily verifiable primitive is formalized, showing its connection with the gap problems introduced in [18]. Using these ideas, a completely new security proof for the modified transformation is given, which is phrased using currently widely accepted techniques. The reduction thereby obtained turns out to be tight, enhancing the concrete security claimed in the original work for the easily verifiable primitives. For the remaining primitives, the concrete security is improved at the cost of stronger assumptions. Finally, the resistance of the new conversion against reject timing attacks is addressed.     

A metamodeling approach for the identification of organizational smells in multi-agent systems: application to ASPECS

Software Quality is one of the most important subjects in the Process Development Software, especially in large and complex systems. Much effort has been devoted to the development of techniques and concepts to improve software quality over the years. We are especially interested on smells, which represent anomalies or flaws in the design/code that can have serious consequences in maintenance or future development of the systems. These techniques have a strong development in the Object Oriented paradigm, however, very few studies were conducted in the agent oriented paradigm. In this paper we focus on the detection of design smells applied to multi-agent systems models based on the organizational approach, named Organizational Design Smells (ODS). Early and automatic detection of these ODS allows reducing the costs and development times, while increasing the final product’s quality. To achieve this objective, validation rules were defined based in the EVL language. The approach is illustrated with two examples, their validation rules, and the refactoring solutions proposed.     

A novel multi-class SVM model using second-order cone constraints

In this work we present a novel maximum-margin approach for multi-class Support Vector Machines based on second-order cone programming. The proposed method consists of a single optimization model to construct all classification functions, in which the number of second-order cone constraints corresponds to the number of classes. This is a key difference from traditional SVM, where the number of constraints is usually related to the number of training instances. This formulation is extended further to kernel-based classification, while the duality theory provides an interesting geometric interpretation: the method finds an equidistant point between a set of ellipsoids. Experiments on benchmark datasets demonstrate the virtues of our method in terms of predictive performance compared with various other multicategory SVM approaches.     

A comparative study of many-objective evolutionary algorithms for the discovery of software architectures

During the design of complex systems, software architects have to deal with a tangle of abstract artefacts, measures and ideas to discover the most fitting underlying architecture. A common way to structure such complex systems is in terms of their interacting software components, whose composition and connections need to be properly adjusted. Along with the expected functionality, non-functional requirements are key at this stage to guide the many design alternatives to be evaluated by software architects. The appearance of Search Based Software Engineering (SBSE) brings an approach that supports the software engineer along the design process. Evolutionary algorithms can be applied to deal with the abstract and highly combinatorial optimisation problem of architecture discovery from a multiple objective perspective. The definition and resolution of many-objective optimisation problems is currently becoming an emerging challenge in SBSE, where the application of sophisticated techniques within the evolutionary computation field needs to be considered. In this paper, diverse non-functional requirements are selected to guide the evolutionary search, leading to the definition of several optimisation problems with up to 9 metrics concerning the architectural maintainability. An empirical study of the behaviour of 8 multi- and many-objective evolutionary algorithms is presented, where the quality and type of the returned solutions are analysed and discussed from the perspective of both the evolutionary performance and those aspects of interest to the expert. Results show how some many-objective evolutionary algorithms provide useful mechanisms to effectively explore design alternatives on highly dimensional objective spaces.     

Bicriteria Optimization Model for Locating Maritime Container Depots: Application to the Port of Valencia

Since the location of container depots has an impact on maritime logistics costs, the container depot location problem is usually treated as a cost minimization problem. But the location of the container depots also has a serious environmental impact, given the heavy traffic load inherent to these operations and the setting up and maintenance of the depots. In this paper a bicriteria optimization model for designing a network of depots in a hinterland is proposed and its application to the Port of Valencia, Spain is reported. The two objectives considered are (1) the total cost of the network and (2) the environmental impact of the container depots and the transport operations associated with them. An Analytic Hierarchy Process (AHP) has been used to determine the environmental impact of each depot, and the ε-constraint method to obtain the optimal Pareto set of the problem. The results clearly show that trade-offs are possible between both objective functions and that, for our case study, the proposed approach can obtain solutions that are more cost-effective and have lower environmental impacts than those currently existing.     

A Numerical Approximation‐Based Controller for Mobile Robots with Velocity Limitation

In this paper the problem of trajectory tracking considers that the values of the control actions do not exceed a maximum allowable value and the zero convergence of tracking errors is demonstrated. The control law is based on a linear algebra approach. First, the desired trajectories of some state variables are determined by analyzing the conditions for a system of linear equations to have an exact solution. Therefore, the control signals are obtained by solving the system of linear equations. The optimal controller parameters are selected through nonlinear programming so as to prevent the saturation of the control actions. Experimental results are presented and discussed, demonstrating the controller's good performance. Finally, the performance of the proposed controller is compared with a fuzzy controller, and all the results are validated through experimental laboratory tests.     

Performance limitations for single-input LTI plants controlled over SNR constrained channels with feedback

This paper studies control problems for discrete-time single-input linear time-invariant plants when controlled over a signal-to-noise ratio (SNR) constrained channel. Our focus is on the performance limitations in an architecture that uses channel feedback. We explicitly characterize the interplay between stabilization, optimal performance, and SNR constraints, highlighting the way in which plant dynamical features affect the best achievable performance. We also apply our results to the study of networked control systems where communication takes place over a power constrained erasure channel. In that scenario, we first show that stabilization problems, and problems involving stationary second-order moments, can be dealt with by focusing on a related SNR constrained networked situation. This observation allows one to obtain results valid in the alternative scenario as corollaries of the results obtained when a single SNR constraint is present.     

Associations of subclinical hypocalcemia with fertility in a herd of grazing dairy cows

The main objective was to assess the associations of subclinical hypocalcemia (SCH), diagnosed at parturition (SCH-0) and 7 d in milk (SCH-7), with fertility in a herd of grazing dairy cows. Additional objectives were to characterize Ca concentration on 0 and 7 d in milk (DIM), assessing the risk factors for SCH-0 and SCH-7 and also the relationship with health status (metritis, endometritis, subclinical ketosis, and culling). A prospective observational study was carried out in a dairy farm in Argentina. Holstein cows (n = 126) were body condition scored (BCS, 1–5) on ?21 ± 3, 0, 7 ± 3, and 28 ± 7 DIM and blood was collected on 0 and 7 ± 3 DIM to determine Ca and β-hydroxybutyrate concentrations. Calcium concentrations <2.0 and <2.14 mmol/L were used to define SCH-0 and SCH-7, respectively. The associations of SCH with (1) the odds for pregnancy to first service (P1AI) and pregnancy by 100 DIM (P100) were evaluated by logistic models, (2) the services per pregnancy was evaluated by a Poisson regression model, and (3) the hazards of insemination and pregnancy were evaluated with proportional hazards regression models whereas median days from calving to first insemination and to pregnancy were estimated by Kaplan-Meier method. Additionally, Ca concentration was assessed by linear regression models, and the associations of SCH-0 and SCH-7 with the odds for metritis, endometritis, subclinical ketosis, and culling were evaluated by logistic models. Calcium concentrations were similar at 0 and 7 DIM (2.40 vs. 2.41 mmol/L, respectively); they were higher in cows calving in fall than in summer (2.58 vs. 2.24 mmol/L), and they also were higher in primiparous than in multiparous cows (2.53 vs. 2.28 mmol/L, respectively). The proportion of cows having SCH-0 and SCH-7 was 27.3 and 39.3%, respectively. Fall-calving cows had lower odds for SCH-0 [odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.12–0.86] than summer-calving cows, multiparous cows had higher odds for SCH-0 (OR = 3.96, 95% CI = 1.09–14.39) than primiparous cows, and cows with prepartum BCS ≥3.00 had higher odds for SCH-0 (OR = 4.03, 95% CI = 1.17–13.89) than in cows with BCS <3.00. Conversely, parity and prepartum BCS were not important predictors for SCH-7. Surprisingly, SCH-0 was not a risk factor for SCH-7. Cows with SCH-0 had lower odds for P1AI (OR = 0.26, 95% CI = 0.07–0.99) than normocalcemic cows, given that P1AI was 14 versus 38%, respectively. The hazard of first service was not associated with SCH-0 (hazard ratio = 1.03, 95% CI = 0.63–1.70) but cows with SCH-0 had lower hazard of pregnancy (hazard ratio = 0.39, 95% CI = 0.16–0.98) and took 32 d longer to get pregnant (105 vs. 73) than normocalcemic cows. Conversely, SCH-7 was not associated with fertility. Finally, SCH-0 and SCH-7 were associated with the odds for subclinical ketosis and metritis, respectively. In conclusion, SCH-0 but not SCH-7 is associated with reduced fertility in a herd of grazing dairy cows, but both were associated with health status.