Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Role of π-π interactions and chain flexibility in dispersion and dynamic-mechanical properties of nanocomposites with multiple wall carbon nanotubes

Two polymers of same functional group were used; one with greater chain flexibility, PA 6.6, and the other with two benzene rings in the main chain, PA 6I-6T (aPA), to evaluate how the structure influences on the nanoparticle dispersion homogeneity and on dynamic-mechanical properties. In the aPA nanocomposites, good dispersion and homogeneous distribution were observed for all CNT concentrations. However, PA 6.6 nanocomposites showed agglomerated regions in all formulations. The interfacial energy of the aPA/CNT was five times lower than that of PA6.6/CNT, resulting in greater compatibility in this nanocomposite. An increase of up to 26% was observed with 2.5% of CNT in aPA nanocomposites storage modulus. In the samples with PA 6.6, the increase was at most 5%. Even with greater flexibility of PA 6.6 macromolecules, the π-π interaction between the aPA aromatic rings and CNTs might be the decisive factor for dispersion improvement and positively influence on the dynamic-mechanical properties of these nanocomposites. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48195.     

Vitamin E acetate addition to poly(d,l)lactic acid modifies its mechanical behavior without affecting biocompatibility

Mechanical properties of poly(d,l )lactic acid films enriched with Vitamin E and Vitamin E Acetate (5–40% w/w) were investigated. The addition of both formulations resulted in increased polymer Young's modulus and tensile strength. Human foreskin fibroblasts and murine pre‐osteoblasts were used to assess the biocompatibility of polymers. Pre‐osteoblasts adhesion and proliferation were strongly decreased by Vitamin E, whereas Vitamin E Acetate did not alter cell proliferation. Collagen deposition was lower onto Vitamin E blended polymers than onto native and Vitamin E Acetate blended ones. Fibroblasts adhesion and proliferation were increased by both Vitamin E and Vitamin E Acetate addition. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39970.     

Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level. To this goal, we tested the ability of curcumin, a nutraceutical already used with relevant results in animal models as well as in clinics in other diseases, in the Gunn rat, the spontaneous model of neonatal hyperbilirubinemia. Curcumin treatment fully abolished the landmark cerebellar hypoplasia of Gunn rat, restoring the histological features, and reverting the behavioral abnormalities present in the hyperbilirubinemic rat. The protection was mediated by a multi-target action on the main bilirubin-induced pathological mechanism ongoing CNS damage (inflammation, redox imbalance, and glutamate neurotoxicity). If confirmed by independent studies, the result suggests the potential of curcumin as an alternative/complementary approach to bilirubin-induced brain damage in the clinical scenario.     

Strong normalization property for second order linear logic

The paper contains the first complete proof of strong normalization (SN) for full second order linear logic (LL): Girard’s original proof uses a standardization theorem which is not proven. We introduce sliced pure structures (sps), a very general version of Girard’s proof-nets, and we apply to sps Gandy’s method to infer SN from weak normalization (WN). We prove a standardization theorem for sps: if WN without erasing steps holds for an sps, then it enjoys SN. A key step in our proof of standardization is a confluence theorem for sps obtained by using only a very weak form of correctness, namely acyclicity slice by slice. We conclude by showing how standardization for sps allows to prove SN of LL, using as usual Girard’s reducibility candidates.     

Enhancement of interconnected power system stability using a control strategy involving static phase shifters

The static phase shifting transformer is one of the potential options of the recently proposed FACTS (flexible AC transmission systems). Promising results have been obtained for enhancing the small-disturbance and the transient stability of interconnected power systems.

In this paper, the important concept of involving in the same control strategy both generating units and static phase shifters has been considered. A systematic procedure for designing co-ordinated and decentralized controllers of these components is provided to assure a satisfactory dynamic performance of an interconnected power system under both small and large perturbations. The approach uses optimal control theory as a basis for the co-ordination of static phase shifter and governor controllers. A suboptimal decentralized control scheme is derived from the designed optimal controller by using a ‘minimum norm’ nearness criterion. The resulting feedback control signals for each generating unit and for each phase shifter is expressed in terms of measurable and local variables only.

Test results show the effectiveness of the proposed control strategy and the usefulness of control actions on static phase shifters.     

Allocation and scheduling of Conditional Task Graphs

We propose an original, complete and efficient approach to the allocation and scheduling of Conditional Task Graphs (CTGs). In CTGs, nodes represent activities, some of them are branches and are labeled with a condition, arcs rooted in branch nodes are labeled with condition outcomes and a corresponding probability. A task is executed at run time if the condition outcomes that label the arcs in the path to the task hold at schedule execution time; this can be captured off-line by adopting a stochastic model. Tasks need for their execution either unary or cumulative resources and some tasks can be executed on alternative resources. The solution to the problem is a single assignment of a resource and of a start time to each task so that the allocation and schedule is feasible in each scenario and the expected value of a given objective function is optimized. For this problem we need to extend traditional constraint-based scheduling techniques in two directions: (i) compute the probability of sets of scenarios in polynomial time, in order to get the expected value of the objective function; (ii) define conditional constraints that ensure feasibility in all scenarios. We show the application of this framework on problems with objective functions depending either on the allocation of resources to tasks or on the scheduling part. Also, we present the conditional extension to the timetable global constraint. Experimental results show the effectiveness of the approach on a set of benchmarks taken from the field of embedded system design. Comparing our solver with a scenario based solver proposed in the literature, we show the advantages of our approach both in terms of execution time and solution quality.     

Attitude, knowledge, and skill competencies for practice in professional geropsychology: Implications for training and building a geropsychology workforce.

Professional geropsychology is a growing area of practice and training. To meet the mental health needs of an aging population, increasing numbers of psychologists need to develop competence to work with older adults, their families, and related care systems. The Pikes Peak model for geropsychology training (Knight, Karel, Hinrichsen, Qualls, & Duffy, 2009) delineates attitude, knowledge, and skill competencies for professional geropsychology practice and makes recommendations for training. In this paper, we define and illustrate the Pikes Peak geropsychology practice competencies through a case example. In the case, an older man with complex needs seeks care through a generalist psychologist in an outpatient setting. The attitudes, knowledge, and skills that the psychologist needs to consider, and implications for training, are reviewed. Training recommendations and resources are provided, with a focus on the training needs of psychologists who wish to expand their practices to include older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Projective Architecture

Michele Sbacchi investigates the real influence of the notion of projection on architectural design before and during the age of Guarini. He takes into consideration concepts such as light and shadow, abstract line, plane, section, projective geometry and perspective. To do this he looks at the ideas of Gregorius Saint Vincent, Alberti, Guarini, Desargues and de l’Orme, among others.     

Two new measures of attitudes about the acceptability of teen dating aggression.

Aggression in dating relationships is associated with attitudes that justify its use. Attitudes about dating aggression are targeted by prevention efforts, contributing to a need to measure these attitudes sensitively, accurately, and multidimensionally. We describe two new measures of attitudes about aggression, each tapping different attitudinal components, and compare their psychometric properties with an existing scale. The 1st assesses attitudes about physical aggression in provocative situations. The 2nd taps attitudes about verbally aggressive, controlling, and jealous tactics against a dating partner. Data from 2,313 high school students were factor analyzed and cross-validated for each new scale. Compared with an existing measure, the scales had comparable levels of reliability and validity and improved response distributions. A 2nd-order factor analysis lends support to a multidimensional view of attitudes about dating aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)