Dialectic tensions in the financial markets: a longitudinal study of pre- and post-crisis regulatory technology

This article presents the findings from a longitudinal research study on regulatory technology in the UK financial services industry. The financial crisis with serious corporate and mutual fund scandals raised the profile of compliance as governmental bodies, institutional and private investors introduced a ‘tsunami’ of financial regulations. Adopting a multi-level analysis, this study examines how regulatory technology was used by financial firms to meet their compliance obligations, pre- and post-crisis. Empirical data collected over 12 years examine the deployment of an investment management system in eight financial firms. Interviews with public regulatory bodies, financial institutions and technology providers reveal a culture of compliance with increased transparency, surveillance and accountability. Findings show that dialectic tensions arise as the pursuit of transparency, surveillance and accountability in compliance mandates is simultaneously rationalized, facilitated and obscured by regulatory technology. Responding to these challenges, regulatory bodies continue to impose revised compliance mandates on financial firms to force them to adapt their financial technologies in an ever-changing multi-jurisdictional regulatory landscape

The evolution and adoption of equity crowdfunding: entrepreneur and investor entry into a new market

Equity crowdfunding (ECF) offers entrepreneurs an online social media marketplace where they can access numerous potential investors who, in exchange for an ownership stake, may supply them with finance. In this paper, we describe the evolution of this market in the UK. Using an inductive qualitative longitudinal research design, we analyse the emerging views of entrepreneurs and investors towards ECF. Our interviewees include large and small-scale investors, as well as market participants who have chosen not to invest or raise funds via ECF. We find that the large financial flows to entrepreneurs in the UK via the ECF platforms, nearly half a billion GBP since 2011, have probably been largely incremental to traditional sources of early stage entrepreneurial finance. Moreover, our research indicates that for the most part, investors appear to understand and appropriately evaluate the risks that they are bearing; ECF investments are perceived as a high risk, high return component within individuals’ portfolios. Investors also use their communication with peers and entrepreneurs via the ECF platform as a learning tool. On the entrepreneurs’ side, ECF allows them to test their products, to develop their brand, to build a loyal customer base and to turn customers into investors. We conclude that policymakers, with the support of a locally appropriate regulatory framework, could support equity crowdfunding as one of the market choices available for entrepreneurs looking to start or grow their ventures

Crocodiles in the regulatory swamp: navigating the dangers of outsourcing, SaaS and shadow IT

Corporates are entering the brave new world of the internet and digitization without much regard for the fine print of a growing regulation regime. More traditional outsourcing arrangements are already falling foul of the regulators as rules and supervision intensifies. Furthermore, ‘shadow IT’ is proliferating as the attractions of SaaS, mobile, cloud services, social media, and endless new ‘apps’ drive usage outside corporate IT. Initial cost-benefit analyses of the Cloud make such arrangements look immediately attractive but losing control of architecture, security, applications and deployment can have far reaching and damaging regulatory consequences. From research in financial services, this paper details the increasing body of regulations, their inherent risks for businesses and how the dangers can be pre-empted and managed. We then delineate a model for managing these risks specifically focused on investigating, strategizing and governing outsourcing arrangements and related regulatory obligation

The psychology of post-totalitarianism in Russia

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Determinants of Apoptotic Sensitivity to HSP90 Inhibition In Acute Myeloid Leukemia

Abstract Abstract 2159 Background: Acute myeloid leukemia (AML) is a heterogeneous and intrinsically resistant disease group of malignant hematopoietic disorders that accounts for approximately 80% of all adult leukemias. Heat shock proteins (HSPs) are often overexpressed in AML are their expression is associated with poor-prognosis and resistance to chemotherapy. Among HSPs, HSP90 is the main chaperone required for the stabilization of multiple oncogenic kinases, which contribute to AML pathogenesis, providing a rationale for the use of HSP90 inhibitors in the treatment of AML. Hypothesis: To identify patients with AML who will benefit from HSP90 inhibitor therapy there is a need to discover molecules and pathways in AML cells that confer sensitivity and lead to significant apoptosis upon HSP90 inhibition. Study design and Results: To evaluate the spectrum of sensitivities of AML cells to HSP90 inhibitors, and to investigate a possible relationship between their genetic background and apoptotic sensitivity to HSP90 inhibition, we investigated the effects of HSP90 inhibitors in a set of genetically characterized human AML cells. Addition of several HSP90 inhibitors to each of these cell lines potently inhibited cell growth, with a potency reflective of their affinity for HSP90. Normal peripheral blood leukocytes were unaffected at similar concentrations. HSP90 inhibition was associated with destabilization and subsequent degradation of Akt and c-Raf in all tested cells, as well as of several cell-specific onco-proteins such as mutant Flt3 in MOLM-13, TEL-TRKC in M0-91, AML1-ETO and mutant cKit in Kasumi-1 and SKNO-1, and mutant Jak2 in HEL cells, respectively. Notably, the proclivity for these cells to undergo apoptosis upon HSP90 inhibition varied considerably. The most sensitive cell lines were MOLM-13, MV-4-11 and M0-91 cells, and for each these cell lines we observed near 100% killing of the initial cell population after 48–72 h of HSP90 inhibitor treatment. In contrast, only 20% death was seen in HEL and HL-60 cells under these conditions. We next made use of specific inhibitors of known oncogenic signaling pathways known to be dysregulated in AML to demonstrate that apoptotic sensitivity of AML cells to HSP90 inhibition correlated with PI3K-Akt and STAT5 activation, but not with activation of the Raf-MAPK pathway. Importantly, similar results were observed in cells lines, xenograft models and isogenic cell line systems. We also found that dual activation of these two pathways, especially in the context of Bcl-xL overexpression, lowers the apoptotic threshold of AML when HSP90 is inhibited. Conclusions: We found that activation of oncogenic signaling pathways and expression of leukemogenic anti-apoptotic molecules, most importantly p-Akt, predicts for AML sensitivity to HSP90 inhibitors. Importantly, 50– 70% of patients with AML display phosphorylation of both Thr308 and Ser4 Akt. This molecule contributes to proliferation, survival and drug resistance in AML, and is associated with adverse outcome. Taken together, our findings suggest that AML patients with activation of Akt and STAT5 signaling are most likely to benefit from HSP90 inhibitor therapy, and clinical trials should aim to enroll patients with specific activation of these important signaling pathways. Disclosures: No relevant conflicts of interest to declare

Spatial Variation in Strong Line Ratios and Physical Conditions in Two Strongly Lensed Galaxies at z ∼ 1.4

Upcoming space-based integral field spectrographs will enable spatially resolved spectroscopy of distant galaxies, including at the scale of individual star-forming regions (i.e., down to just tens of parsecs) in galaxies that have been strongly gravitationally lensed. In the meantime, there is only a very small set of lensed galaxies where such spatial detail is possible at wavelengths containing important rest-optical emission lines, even with the Hubble Space Telescope's Wide Field Camera 3 infrared channel grisms. Here, we examine two of these sources, SDSS J1723+3411 and SDSS J2340+2947, using HST WFC3/IR grism data and supporting spatially unresolved spectroscopy from several ground-based instruments to explore the size of spatial variations in observed strong emission-line ratios like O32 and R23, which are sensitive to ionization parameter and metallicity, and the Balmer decrement, which is an indicator of reddening. We find significant spatial variation in the reddening and in the reddening-corrected O32 and R23 values that correspond to spreads of a few tenths of a dex in ionization parameter and metallicity. We also find clear evidence of a negative radial gradient in star formation in SDSS J2340+2947 and tentative evidence of one in SDSS J1723+3411, though its star formation is quite asymmetric. Finally, we find that reddening can vary enough spatially to make spatially resolved reddening corrections necessary in order to characterize gradients in line ratios and the physical conditions inferred from them, necessitating the use of space-based integral field units for future work on larger, more statistically robust samples. © 2021. The American Astronomical Society. All rights reserved..Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species

Acute myeloid leukemia (AML) is a heterogeneous and fatal disease with an urgent need for improved therapeutic regimens given that most patients die from relapsed disease. Irrespective of mutation status, the development of aggressive leukemias is enabled by increasing dependence on signaling networks. We demonstrate that a hyperactive signalosome drives addiction of AML cells to a tumor-specific Hsp90 species (teHsp90). Through genetic, environmental, and pharmacologic perturbations, we demonstrate a direct and quantitative link between hyperactivated signaling pathways and apoptotic sensitivity of AML to teHsp90 inhibition. Specifically, we find that hyperactive JAK-STAT and PI3K-AKT signaling networks are maintained by teHsp90 and, in fact, gradual activation of these networks drives tumors increasingly dependent on teHsp90. Thus, although clinically aggressive AML survives via signalosome activation, this addiction creates a vulnerability that can be exploited with Hsp90-directed therapy