Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate‐driven synthesis of β‐enaminones and N‐aryl pyrroles from indolizines and nitrosoarenes; aryl‐substituted indolizines lead to β‐enaminones in a regio‐ and diastereoselective manner, whereas alkyl‐substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the β‐enaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.This work was generously supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICIU; grant no. CTQ2017-88171-P), the Generalitat Valenciana (GV; grant no. AICO/2017/007), and the Instituto de Síntesis Orgánica (ISO). M.J.G.-S. is grateful to the ISO for a predoctoral grant (contract no. I-PAS-11/16)

A note on Armstrong numbers

In this article, student Satvik Kaushik investigates Armstrong numbers. Mathematical investigation is a powerful way for students to learn more about concepts that interest them. In mathematical investigations, students are expected to pose their own problems after initial exploration of the mathematical situation. The exploration of the situation, the formulation of problems and their solution give opportunity for the development of independent mathematical thinking and in engaging in mathematical processes such as organizing and recording data, pattern searching, conjecturing, inferring, justifying and explaining conjectures and generalizations. It is these thinking processes which enable an individual to learn more mathematics, apply mathematics in other disciplines and in everyday situations and to solve mathematical (and nonmathematical) problems

Possible potentials responsible for stable circular relativistic orbits

Bertrand's theorem in classical mechanics of the central force fields attracts us because of its predictive power. It categorically proves that there can only be two types of forces which can produce stable, circular orbits. In the present article an attempt has been made to generalize Bertrand's theorem to the central force problem of relativistic systems. The stability criterion for potentials which can produce stable, circular orbits in the relativistic central force problem has been deduced and a general solution of it is presented in the article. It is seen that the inverse square law passes the relativistic test but the kind of force required for simple harmonic motion does not. Special relativistic effects do not allow stable, circular orbits in presence of a force which is proportional to the negative of the displacement of the particle from the potential center.Comment: 11 pages, Latex fil

Impedimetric and Plasmonic Sensing of Collagen I Using a Half-Antibody-Supported, Au-Modified, Self-Assembled Monolayer System

This research presents an electrochemical immunosensor for collagen I detection using a self-assembled monolayer (SAM) of gold nanoparticles (AuNPs) and covalently immobilized half-reduced monoclonal antibody as a receptor; this allowed for the validation of the collagen I concentration through two different independent methods: electrochemically by Electrochemical Impedance Spectroscopy (EIS), and optically by Surface Plasmon Resonance (SPR). The high unique advantage of the proposed sensor is based on the performance of the stable covalent immobilization of the AuNPs and enzymatically reduced half-IgG collagen I antibodies, which ensured their appropriate orientation onto the sensor’s surface, good stability, and sensitivity properties. The detection of collagen type I was performed in a concentration range from 1 to 5 pg/mL. Moreover, SPR was utilized to confirm the immobilization of the monoclonal half-antibodies and sensing of collagen I versus time. Furthermore, EIS experiments revealed a limit of detection (LOD) of 0.38 pg/mL. The selectivity of the performed immunosensor was confirmed by negligible responses for BSA. The performed approach of the immunosensor is a novel, innovative attempt that enables the detection of collagen I with very high sensitivity in the range of pg/mL, which is significantly lower than the commonly used enzyme-linked immunosorbent assay (ELISA)

Strategic optimization framework considering unobservability in multi-voltage active distribution networks

An increase in the share of weather-dependent generation at low voltage levels necessitates incorporating the low-voltage network in optimizing a distribution network. Optimization in a multi-voltage network requires significant computation time and effort due to many nodes operating at different voltage levels. This research proposes a decomposition and strategic optimization method to reduce the computation requirements for such large multi-voltage distribution networks. The proposed algorithm reduces the space complexity and the computation time required for solving the optimization routines of these multi-voltage distribution networks. A virtual transformer model incorporates tap-changer as a continuous variable in the semidefinite programming power flow optimization model. The zero-duality gap condition for multiple virtual transformers is proven empirically. Compared to a centralized optimization using the same power flow model, the proposed framework reduced the computation time by 96%.</p

Cost-effectiveness of interventions to control cardiovascular diseases and type 2 diabetes mellitus in South Asia: protocol for a systematic review.

INTRODUCTION: While a number of strategies are being implemented to control cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM), the cost-effectiveness of these in the South Asian context has not been systematically evaluated. We aim to systematically review the economic (cost-effectiveness) evidence available on the individual-, group- and population-level interventions for control of CVD and T2DM in South Asia. METHODS AND ANALYSIS: This review will consider all relevant economic evaluations, either conducted alongside randomised controlled trials or based on decision modelling estimates. These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries (India, Bangladesh, Pakistan, Sri Lanka, Nepal, Maldives, Bhutan and Afghanistan). We will identify relevant papers by systematically searching all major databases and registries. Selected articles will be screened by two independent researchers. Methodological quality of the studies will be assessed using a modified Drummond and a Phillips checklist. Cochrane guidelines will be followed for bias assessment in the effectiveness studies. RESULTS: Results will be presented in line with the PRISMA (Preferred Reporting Items for Systematic review and Meta-analysis) checklist, and overall quality of evidence will be presented as per the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION: The study has received ethics approval from the All India Institute of Medical Sciences, New Delhi, India. The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia. STUDY REGISTRATION NUMBER: PROSPERO CRD42013006479

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BackgroundIn 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions.MethodsData on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared.ResultsOf the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34).ConclusionAbout one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions.Level of evidencePrognostic and Epidemiological Study, level III