Social marketing: Immunizing against unethical practice

A simple approach for the catalytic conversion of primary alcohols into their corresponding esters and amides, with evolution of H2 gas using in situ formed ruthenium PNP- and PNN-pincer catalysts, is presented. The evaluation showed conversions for the esterification with turnover numbers as high as 4300, and 4400 for the amidation

The Value of Information Technology-Enabled Diabetes Management

Reviews different technologies used in diabetes disease management, as well as the costs, benefits, and quality implications of technology-enabled diabetes management programs in the United States

Nuevos datos acerca de los repertorios teatrales en el primer catálogo de «El peregrino en su patria»

En este artículo se muestra cómo los títulos que contienen los repertorios de los autores de comedias presentes en El peregrino en su patria de 1604 están dispuestos según un orden cronológico, aunque con algunos matices y no pocas excepciones. Además, se amplían los repertorios descubiertos por Thornton Wilder y se afina la fecha de composición de varias obras, prestando especial atención a textos que se han perdido, como La perdición de España, La gobernadora, La gran pintora, La bella gitana o La toma de Álora. Finalmente, el presente artículo pretende mostrar de un modo práctico cómo una base de datos digital como el Diccionario biográfico de actores del teatro clásico español (DICAT) puede resultar de gran ayuda a la hora de resolver algunos de los problemas clásicos de la filología en general y del teatro del Siglo de Oro en particular.This paper shows that the plays contained in the repertoire of the autores de comedias which appear in El peregrino en su patria (1604) are organised chronologically, although there are some nuances and exceptions. The article also expands the repertoire discovered by Thornton Wilder and sets the date of composition for some plays, paying special attention to lost texts such as La perdición de España, La gobernadora, La gran pintora, La bella gitana or La toma de Álora. Finally, this paper attempts to show in a practical way that a database such as the Diccionario biográfico de actores del teatro clásico español (DICAT) can be extremely helpful when it comes to dealing with some of the philology's classical problems in general and those of the theatre of the Golden Age in particular

The Relationship between Saccadic Choice and Reaction Times with Manipulations of Target Value

Choosing the option with the highest expected value (EV; reward probability × reward magnitude) maximizes the intake of reward under conditions of uncertainty. However, human economic choices indicate that our value calculation has a subjective component whereby probability and reward magnitude are not linearly weighted. Using a similar economic framework, our goal was to characterize how subjective value influences the generation of simple motor actions. Specifically, we hypothesized that attributes of saccadic eye movements could provide insight into how rhesus monkeys, a well-studied animal model in cognitive neuroscience, subjectively value potential visual targets. In the first experiment, monkeys were free to choose by directing a saccade toward one of two simultaneously displayed targets, each of which had an uncertain outcome. In this task, choices were more likely to be allocated toward the higher valued target. In the second experiment, only one of the two possible targets appeared on each trial. In this task, saccadic reaction times (SRTs) decreased toward the higher valued target. Reward magnitude had a much stronger influence on both choices and SRTs than probability, whose effect was observed only when reward magnitude was similar for both targets. Across EV blocks, a strong relationship was observed between choice preferences and SRTs. However, choices tended to maximize at skewed values whereas SRTs varied more continuously. Lastly, SRTs were unchanged when all reward magnitudes were 1×, 1.5×, and 2× their normal amount, indicating that saccade preparation was influenced by the relative value of the targets rather than the absolute value of any single-target. We conclude that value is not only an important factor for deliberative decision making in primates, but also for the selection and preparation of simple motor actions, such as saccadic eye movements. More precisely, our results indicate that, under conditions of uncertainty, saccade choices and reaction times are influenced by the relative expected subjective value of potential movements

Facile synthesis of amides via acceptorless dehydrogenative coupling of aryl epoxides and amines.

The synthesis of amides is significant in a wide variety of academic and industrial fields. We report here a new reaction, namely acceptorless dehydrogenative coupling of epoxides and amines to form amides catalyzed by ruthenium pincer complexes. Various aryl epoxides and amines smoothly convert into the desired amides in high yields with the generation of H2 gas as the only byproduct. Control experiments indicate that amides are generated kinetically faster than side products, possibly because of the facile activation of epoxides by metal-ligand cooperation, as supported by the observation of a ruthenium-enolate species. No alcohol or free aldehyde are involved. A mechanism is proposed involving a dual role of the catalyst, which is responsible for the high yield and selectivity of the new reaction

Metal-Ligand Cooperation with Thiols as Transient Cooperative Ligands: Acceleration and Inhibition Effects in (De)Hydrogenation Reactions.

ConspectusOver the past two decades, we have developed a series of pincer-type transition metal complexes capable of activating strong covalent bonds through a mode of reactivity known as metal-ligand cooperation (MLC). In such systems, an incoming substrate molecule simultaneously interacts with both the metal center and ligand backbone, with one part of the molecule reacting at the metal center and another part at the ligand. The majority of these complexes feature pincer ligands with a pyridine core, and undergo MLC through reversible dearomatization/aromatization of this pyridine moiety. This MLC platform has enabled us to perform a variety of catalytic dehydrogenation, hydrogenation, and related reactions, with high efficiency and selectivity under relatively mild conditions.In a typical catalytic complex that operates through MLC, the cooperative ligand remains coordinated to the metal center throughout the entire catalytic process, and this complex is the only catalytic species involved in the reaction. As part of our ongoing efforts to develop new catalytic systems featuring MLC, we have recently introduced the concept of transient cooperative ligand (TCL), i.e., a ligand that is capable of MLC when coordinated to a metal center, but the coordination of which is reversible rather than permanent. We have thus far employed thiol(ate)s as TCLs, in conjunction with an acridanide-based ruthenium(II)-pincer catalyst, and this has resulted in remarkable acceleration and inhibition effects in various hydrogenation and dehydrogenation reactions. A cooperative thiol(ate) ligand can be installed in situ by the simple addition of an appropriate thiol in an amount equivalent to the catalyst, and this has been repeatedly shown to enable efficient bond activation by MLC without the need for other additives, such as base. The use of an ancillary thiol ligand that is not fixed to the pincer backbone allows the catalytic system to benefit from a high degree of tunability, easily implemented by varying the added thiol. Importantly, thiols are coordinatively labile enough under typical catalytic conditions to leave a meaningful portion of the catalyst in its original unsaturated form, thereby allowing it to carry out its own characteristic catalytic activity. This generates two coexisting catalyst populations─one that contains a thiol(ate) ligand and another that does not─and this may lead to different catalytic outcomes, namely, enhancement of the original catalytic activity, inhibition of this activity, or the occurrence of diverging reactivities within the same catalytic reaction mixture. These thiol effects have enabled us to achieve a series of unique transformations, such as thiol-accelerated base-free aqueous methanol reforming, controlled stereodivergent semihydrogenation of alkynes using thiol as a reversible catalyst inhibitor, and hydrogenative perdeuteration of C═C bonds without using D2, enabled by a combination of thiol-induced acceleration and inhibition. We have also successfully realized the unprecedented formation of thioesters through dehydrogenative coupling of alcohols and thiols, as well as the hydrogenation of organosulfur compounds, wherein the cooperative thiol serves as a reactant or product. In this Account, we present an overview of the TCL concept and its various applications using thiols

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Catalytic Hydrogenation of Thioesters, Thiocarbamates, and Thioamides.

Direct hydrogenation of thioesters with H2 provides a facile and waste-free method to access alcohols and thiols. However, no report of this reaction is documented, possibly because of the incompatibility of the generated thiol with typical hydrogenation catalysts. Here, we report an efficient and selective hydrogenation of thioesters. The reaction is catalyzed by an acridine-based ruthenium complex without additives. Various thioesters were fully hydrogenated to the corresponding alcohols and thiols with excellent tolerance for amide, ester, and carboxylic acid groups. Thiocarbamates and thioamides also undergo hydrogenation under similar conditions, substantially extending the application of hydrogenation of organosulfur compounds

Mechanistic Investigations of Ruthenium Catalyzed Dehydrogenative Thioester Synthesis and Thioester Hydrogenation.

We have recently reported the previously unknown synthesis of thioesters by coupling thiols and alcohols (or aldehydes) with liberation of H2, as well as the reverse hydrogenation of thioesters, catalyzed by a well-defined ruthenium acridine-9H based pincer complex. These reactions are highly selective and are not deactivated by the strongly coordinating thiols. Herein, the mechanism of this reversible transformation is investigated in detail by a combined experimental and computational (DFT) approach. We elucidate the likely pathway of the reactions, and demonstrate experimentally how hydrogen gas pressure governs selectivity toward hydrogenation or dehydrogenation. With respect to the dehydrogenative process, we discuss a competing mechanism for ester formation, which despite being thermodynamically preferable, it is kinetically inhibited due to the relatively high acidity of thiol compared to alcohol and, accordingly, the substantial difference in the relative stabilities of a ruthenium thiolate intermediate as opposed to a ruthenium alkoxide intermediate. Accordingly, various additional reaction pathways were considered and are discussed herein, including the dehydrogenative coupling of alcohol to ester and the Tischenko reaction coupling aldehyde to ester. This study should inform future green, (de)hydrogenative catalysis with thiols and other transformations catalyzed by related ruthenium pincer complexes

Acceptorless dehydrogenative synthesis of primary amides from alcohols and ammonia.

The highly desirable synthesis of the widely-used primary amides directly from alcohols and ammonia via acceptorless dehydrogenative coupling represents a clean, atom-economical, sustainable process. Nevertheless, such a reaction has not been previously reported, and the existing catalytic systems instead generate other N-containing products, e.g., amines, imines and nitriles. Herein, we demonstrate an efficient and selective ruthenium-catalyzed synthesis of primary amides from alcohols and ammonia gas, accompanied by H2 liberation. Various aliphatic and aromatic primary amides were synthesized in high yields, with no observable N-containing byproducts. The selectivity of this system toward primary amide formation is rationalized through density functional theory (DFT) calculations, which show that dehydrogenation of the hemiaminal intermediate into primary amide is energetically favored over its dehydration into imine