N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

Targeting NF-κB-Inducing Kinase (NIK) in Immunity,Inflammation, and Cancer

NF-κB-inducing kinase (NIK), the essential upstream kinase, which regulates activation of the noncanonical NF-κB pathway, has important roles in regulating immunity and inflammation. In addition, NIK is vital for maintaining cellular health through its control of fundamental cellular processes, including differentiation, growth, and cell survival. As such aberrant expression or regulation of NIK is associated with several disease states. For example, loss of NIK leads to severe immune defects, while the overexpression of NIK is observed in inflammatory diseases, metabolic disorders, and the development and progression of cancer. This review discusses recent studies investigating the therapeutic potential of NIK inhibitors in various diseases.     

Assessing the Novelty of Computer-Generated Narratives Using Empirical Metrics

Novelty is a key concept to understand creativity. Evaluating a piece of artwork or other creation in terms of novelty requires comparisons to other works and considerations about the elements that have been reused in the creative process. Human beings perform this analysis intuitively, but in order to simulate it using computers, the objects to be compared and the similarity metrics to be used should be formalized and explicitly implemented. In this paper we present a study on relevant elements for the assessment of novelty in computer-generated narratives. We focus on the domain of folk-tales, working with simple plots and basic narrative elements: events, characters, props and scenarios. Based on the empirical results of this study we propose a set of computational metrics for the automatic assessment of novelty. Although oriented to the implementation of our own story generation system, the measurement methodology we propose can be easily generalized to other creative systems.     

Stereoselective Synthesis of Pyrroloquinolines by a Brønsted Acid Catalyzed [4+2]‐Heterocyclization of Indole‐7‐Carbaldehydes,Anilines and Electron‐Rich Alkenes

The pyrrolo[3,2,1‐ij]quinoline heterocyclic core is found in the structure of a variety of compounds with interesting applications and then, new efficient and flexible strategies to construct this skeleton are required. Here, a new diastereoselective tetrafluoroboric acid (HBF₄)‐catalyzed three‐component coupling reaction of 1H‐indole‐7‐carbaldehyde derivatives, anilines and electron‐rich alkenes to give pyrrolo[3,2,1‐ij]quinolines is described. The reaction involves an unusual [4+2]‐heterocyclization between an in situ formed imine and an alkene. The new catalytic method, where water is the only by‐product, is efficient, robust and flexible, and allows for multigram‐scale synthesis.

     

Accelerated aging of elastomeric composites with vulcanized ground scraps

The aim of this work is to study the effect of thermal aging on the mechanical, dynamic‐mechanical, and chemical properties of SBR (styrene‐butadiene rubber) composites filled with SBR industrial rubber scraps. Eight composites with varying proportions (10–80 phr) of the SBR ground scraps (SBR‐r) were prepared and subjected to accelerated aging in an air‐oven. The composites were evaluated, and the results were compared with a control sample (base formulation with 0 phr of SBR‐r), before and after thermal aging. The accelerated aging led to a decrease in the mechanical properties as a result of an increase in the stiffness of the material, related to an increase in the crosslink density. However, these properties were not affected by the addition of rubber scraps up to 50 phr, either before or after aging. The increase in the glass transition temperature of the composites after aging, measured using dynamic mechanical analysis, confirmed the occurrence of a postcrosslinking process. Fourier transform infrared spectroscopy and crosslink density revealed that the aging mechanism was dependent on the SBR‐r content. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Mechanism of degradation of nitrilotriacetic acid by heterogeneous photocatalysis over TiO2 and platinized TiO2

TiO₂-heterogeneous photocatalysis of nitrilotriacetic acid (NTA) at pH 2.5 was studied to establish the kinetic regime and the reaction mechanism. Pure Degussa P-25 and Hombikat UV100 commercial samples were compared. A Langmuirian behavior was observed over P-25. Platinization of the Hombikat sample (0.5 wt.%) caused an important increase on the photocatalytic rate with a change in the kinetics from zero order in the pure precursors to first order in the platinized sample. The nature of the intermediates and their evolution with time were compared on all systems. Glycine, iminodiacetic and oxamic acids have been identified in different proportions, together with ammonium and glycolic acid, depending on the catalyst used. The rapid depletion of NTA was not accompanied by a corresponding total organic carbon (TOC) reduction, but 84% of TOC decrease was obtained on P25 after 24 h, a very reasonable result for refractory compounds. A detailed mechanism is proposed for the photocatalytic reaction, suggested to be the same over the three catalysts here tested.     

The effects of tasks on integrating information from multiple documents.

The authors examine 2 issues: (a) how students integrate information from multiple scientific documents to describe and explain a physical phenomenon that represents a subset of the information in the documents; and (b) the role of 2 sorts of tasks to achieve this type of integration, either writing an essay on a question requiring integration across texts or answering shorter intratext questions that require students to integrate information within a single text, while superficial and deep comprehension measurements are obtained. Undergraduate students answered 1 of the 2 types of questions, and their reading times were recorded. Half of the sample thought aloud. Results showed that the integration question increased integration and decreased the processing of isolated units of information, which enhanced deep learning, whereas no differences between the 2 sorts of tasks on memory recall were apparent. This research also provides evidence for the discrepancy between training and posttraining effects (R. A. Schmidt & R. A. Bjork, 1992). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of barley and triticale as feed ingredients in growing Iberian pigs: amino acid and carbohydrate ileal digestibility

BACKGROUND: Iberian pig production is linked to the use of the Mediterranean woodland, where the use of local feed resources is of paramount importance for the sustainability of the system. The aim of the present work was to explore the potential of triticale cv. Camarma as compared to barley cv. Esgueva in Iberian pig feeding by studying their respective ileal digestibilities of amino acids and carbohydrates in animals cannulated at the end of the ileum. RESULTS: Leu, Met and Tyr had (P < 0.05) greater standardised ileal digestibilities (SID) in pigs fed triticale diet. There was a trend (P = 0.07) towards greater SID of Thr in pigs fed the barley diet. The least digestible indispensable amino acids were Ile (74.6% SID) for barley and Thr (78.9% SID) for triticale. Except for β‐glucans, apparent ileal digestibilities (AIDs) of individual non‐starch polysaccharide (NSP), sugars and starch were greater in pigs fed triticale (P < 0.05). Nevertheless, total amounts of NSP digested were greater in pigs fed the barley diet (P < 0.05). CONCLUSION: Overall, triticale cv. Camarma had greater amino acid and carbohydrate AID than barley cv. Esgueva and may represent a valuable grain for Iberian pig feeding. Copyright © 2008 Society of Chemical Industry     

Use of dendrochronological method in Pinus halepensis to estimate the soil erosion in the South East of Madrid (Spain)

The rate of soil erosion in pine forests (Pinus halepensis) located in the Southeast of Madrid has been estimated using dendrochronological analysis based on the change in ring-growth pattern from concentric to eccentric when the root is exposed. Using 49 roots spread across five inclined areas, it has been found that the length and direction of the hillsides, as well as their vegetation cover affect the rate of erosion, while the slope itself does not. The erosion rates found for the different areas studied vary between 3.5 and 8.8 mm year(-1), that is between 40 and 101 t ha(-1) year(-1) respectively. These values are between 2 and 3 times greater than those predicted by USLE, for which this equation underestimates soil loss for Central Spain's Mediterranean conditions. Nonetheless, both methods (using dendrochronology to determine actual soil loss and theoretical prediction with USLE) are able to establish the same significant differences among the areas studied, allowing for the comparative estimate of the severity of the area's erosion problem.