Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315

Substituted pyrimidine inhibitors of the Clk and Dyrk kinases have been developed, exploring structure-activity relationships around four different chemotypes. The most potent compounds have low-nanomolar inhibitory activity against Clk1, Clk2, Clk4, Dyrk1A and Dyrk1B. Kinome scans with 442 kinases using agents representing three of the chemotypes show these inhibitors to be highly selective for the Clk and Dyrk families. Further off-target pharmacological evaluation with ML315, the most selective agent, supports this conclusion

TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

YesRecent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD) where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline rich motif. Here, we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2 hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.Faculty of Biological Sciences at the University of Leeds, Wellcome Trust Seed Award, Royal Society Research Grant RG150100, MR/K021303/1, Swedish Research Council (2014-3801) and the Medical Faculty at Lund University

Introduction to the US Definition of Asset-Backed Securities

This chapter examines the definition of asset-backed securities under US securities regulations as of August 2014, together with relevant case law prior to and from 2009 edition of this work

Default Invariance: Naïve Category of Law and Finance

Default invariance is the idea that default does not change at any scale of law and finance. Default is a conserved quantity in a universe where fundamental principles of law and finance operate. It exists at the micro-level as part of the fundamental structure of every financial transaction, and at the macro- level, as a fixed critical point within the relatively stable phases of the law and finance cycle. A key point is that default is equivalent to maximizing uncertainty at the micro-level and at the macro-level, is equivalent to the phase transition where unbearable fluctuations occur in all forms of risk transformation, including maturity, liquidity and credit. As such, default invariance is the glue that links the micro and macro structures of law and finance. In this essay, we apply naïve category theory (NCT), a type of mapping logic, to these types of phenomena. The purpose of using NCT is to introduce a rigorous (but simple) mathematical methodology to law and finance discourse and to show that these types of structural considerations are of prime practical importance and significance to law and finance practitioners. These mappings imply a number of novel areas of investigation. From the micro- structure, three macro-approximations are implied. These approximations form the core analytical framework which we will use to examine the phenomena and hypothesize rules governing law and finance. Our observations from these approximations are grouped into five findings. While the entirety of the five findings can be encapsulated by the three approximations, since the intended audience of this paper is the non-specialist in law, finance and category theory, for ease of access we will illustrate the use of the mappings with relatively common concepts drawn from law and finance, focusing especially on financial contracts, derivatives, Shadow Banking, credit rating agencies and credit crises

US Asset-Backed Securities – Regulatory Reform, Dodd-Frank and Final Rules

This chapter examines the new rules proposed under regulatory reform since the credit crisis of 2008-09, including the major proposals of the Dodd-Frank Act of 2010 and some of the Final Rules thereto

Securitisation law: EU and US disclosure regulations

Providing key guidance on the process of securitisation, this comprehensive title explains in detail exactly what practitioners need to know. Featuring the most up-to-date commentary, Securitisation Law and Practice cuts through this complicated process using practical aids such as flow charts and checklists. The book also contains discussion on the latest case law (including case studies) and critical legal issues. The book also features: (1) Analysis of the recent securities regulations regarding asset-backed securities disclosures in the US and EU, providing an understanding of the differences in regulatory reporting requirements between jurisdictions. (2) Discussion of the various types of asset-backed structures that have been created over the last 30 years. (3) Analysis of the major legal decisions in the US and EU regarding securitisation transactions, including such cases as Enron, Parmalat and the recent sub-prime problem