On a conjecture of Goodearl: Jacobson radical non-nil algebras of Gelfand-Kirillov dimension 2

For an arbitrary countable field, we construct an associative algebra that is graded, generated by finitely many degree-1 elements, is Jacobson radical, is not nil, is prime, is not PI, and has Gelfand-Kirillov dimension two. This refutes a conjecture attributed to Goodearl

Identification of an active metabolite of PAR-1 antagonist RWJ-58259 and synthesis of analogues to enhance its metabolic stability

The discontinuation of PAR-1 antagonist RWJ-58259 beyond use as a biological probe is most likely due to it's short half-life in vivo. However, retention of significant in vivo activity beyond the point where most of the RWJ-58259 had been consumed implies the generation of an active metabolite. Herein we describe the biological activity of a predicted metabolite of RWJ-58259 and the synthesis of analogues designed to enhance the metabolic stability of RWJ-58259

Synthesis of novel and potent vorapaxar analogues

Vorapaxar is a first-in-class PAR-1 antagonistic drug based on the ent-himbacine scaffold. Detailed in this article are enantioselective and racemic routes to various novel vorapaxar analogues. Biological testing revealed these compounds to have moderate to excellent potencies against PAR-1 with the most potent analogue demonstrating an IC50 of 27 nM

TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells.

The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an αvβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2- and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin αv and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer.Medical Research Council UK (MRC) CASE studentship with Novartis awarded to RCC, MRC Centenary Award awarded to NS and RCC, and MRC Career Development Award G0800340 to CJS

A NOTE ON NIL AND JACOBSON RADICALS IN GRADED RINGS

It was shown by Bergman that the Jacobson radical of a Z-graded ring is homogeneous. This paper shows that the analogous result holds for nil rings, namely, that the nil radical of a Z-graded ring is homogeneous. It is obvious that a subring of a nil ring is nil, but generally a subring of a Jacobson radical ring need not be a Jacobson radical ring. In this paper it is shown that every subring which is generated by homogeneous elements in a graded Jacobson radical ring is always a Jacobson radical ring. It is also observed that a ring whose all subrings are Jacobson radical rings is nil. Some new results on graded-nil rings are also obtained

Author Correction: Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes

Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-017-13675-8, published online 01 November 201

Estruturação dos objetivos de aprendizagem para ambientes de educação on-line

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Ciência da Computação.O objetivo deste trabalho é prover o processo e a avaliação funcional dos componentes que compõem um ambiente de e-aprendizagem baseado em Objetos de aprendizagem, apresentando as definições, propriedades e aplicações dos Objetos de aprendizagem, que se referem à criação e reutilização dos objetos para desenvolver ambientes de aprendizagem. Os padrões utilizados para desenvolvimento de conteúdos estruturados para ambientes de aprendizagem para Web também serão descritos. Também é abordado o potencial da Web semântica, a qual transforma a Web em um meio em que a informação é interpretada, trocada e processada. Apresentar como a linguagem XML e a orientação a objeto se relacionam com os Objetos de aprendizagem é outro tópico abordado. O trabalho inclui, ainda, um protótipo para um ambiente de aprendizagem online utilizando os objetos de aprendizagem

Evaluation schemes in the ring of quaternionic polynomials

In this paper we focus on computational aspects associated with polynomial problems in the ring of one-sided quaternionic polynomials. The complexity and error bounds of quaternion arithmetic are considered and several evaluation schemes are analyzed from their complexity point of view. The numerical stability of generalized Horner’s and Goertzel’s algorithms to evaluate polynomials with quaternion floating-point coefficients is addressed. Numerical tests illustrate the behavior of the algorithms from the point of view of performance and accuracy.Research at CMAT was financed by Portuguese Funds through FCT - Fundação para a Ciência e a Tecnologia, within the Project UID/MAT/00013/2013. Research at NIPE was carried out within the funding with COMPETE reference number POCI-01-0145-FEDER-006683 (UID/ECO/03182/2013), with the FCT/MEC’s (Fundação para a Ciência e a Tecnologia, I.P.) financial support through national funding and by the ERDF through the Operational Programme on “Competitiveness and Internationalization - COMPETE 2020” under the PT2020 Partnership Agreement.info:eu-repo/semantics/publishedVersio