Systems toxicology: real world applications and opportunities

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity

Pathways Across the Valley of Death: Novel Intellectual Property Strategies for Accelerated Drug Discovery

Drug discovery is stagnating. Government agencies, industry analysts, and industry scientists have all noted that, despite significant increases in pharmaceutical R&D funding, the production of fundamentally new drugs - particularly drugs that work on new biological pathways and proteins - remains disappointingly low. To some extent, pharmaceutical firms are already embracing the prescription of new, more collaborative R&D organizational models suggested by industry analysts. In this Article, we build on collaborative strategies that firms are already employing by proposing a novel public-private collaboration that would help move upstream academic research across the valley of death that separates upstream research from downstream drug candidates. By exchanging trade secrecy for contract-based collaboration, our proposal would both protect intellectual property rights and enable many more researchers to search for potential drug candidates

The Self-Financing Equation in High Frequency Markets

High Frequency Trading (HFT) represents an ever growing proportion of all financial transactions as most markets have now switched to electronic order book systems. The main goal of the paper is to propose continuous time equations which generalize the self-financing relationships of frictionless markets to electronic markets with limit order books. We use NASDAQ ITCH data to identify significant empirical features such as price impact and recovery, rough paths of inventories and vanishing bid-ask spreads. Starting from these features, we identify microscopic identities holding on the trade clock, and through a diffusion limit argument, derive continuous time equations which provide a macroscopic description of properties of the order book. These equations naturally differentiate between trading via limit and market orders. We give several applications (including hedging European options with limit orders, market maker optimal spread choice, and toxicity indexes) to illustrate their impact and how they can be used to the benefit of Low Frequency Traders (LFTs)

Optimal Execution with Dynamic Order Flow Imbalance

We examine optimal execution models that take into account both market microstructure impact and informational costs. Informational footprint is related to order flow and is represented by the trader's influence on the flow imbalance process, while microstructure influence is captured by instantaneous price impact. We propose a continuous-time stochastic control problem that balances between these two costs. Incorporating order flow imbalance leads to the consideration of the current market state and specifically whether one's orders lean with or against the prevailing order flow, key components often ignored by execution models in the literature. In particular, to react to changing order flow, we endogenize the trading horizon $T$. After developing the general indefinite-horizon formulation, we investigate several tractable approximations that sequentially optimize over price impact and over $T$. These approximations, especially a dynamic version based on receding horizon control, are shown to be very accurate and connect to the prevailing Almgren-Chriss framework. We also discuss features of empirical order flow and links between our model and "Optimal Execution Horizon" by Easley et al (Mathematical Finance, 2013).Comment: 31 pages, 8 figure

An assessment of the construct validity of environmental strategy measures

The natural resource-based view of the company is emerging as a dominant paradigm for understanding the intersection of strategic management and the natural environment. Companies that proactively incorporate a natural environment perspective into their enterprise strategies are said to have sustainable competitive advantages. However, defining and measuring environmental strategy has been challenging, with different approaches yielding inconsistent results. Many studies ignore the empirical difficulties of marrying the theoretical connection between the company's resource base and environmental strategy, and its impact on environmental company performance. In this paper, we apply an inductive approach to derive a measure of environmental strategy theoretically congruent with the natural resource-based-view of the firm. We assess its reliability and, using a multi-trait multi-method matrix, confirm the convergent and discriminant validities of this measure against other measures often used by researchers. We also establish predictive validity of our environmental strategy measure for environmental performance. We discuss the implications of the measure for future research and practice.environmental performance; environmental strategies; inductive study; measures;

Exploring the direction on the environmental and business performance relationship at the firm level. Lessons from a literature review

The interest of scientists and companies in understanding the business implications of environmental investment is timely; however, a dilemma remains at the firm level: is the environment a “strategic competitive factor”, as in the “Porter point of view”, or is it a “luxury good”, as in the “Wagner point of view”? Our research contributes to this debate through a review of the papers published in scientific journals between 2000 and 2015 that discussed the direction of the relationship between the environmental and business performances of enterprises. The objectives of the research are: (a) to verify if there is an agreement in the scientific literature of the last 15 years about the “Porter–Wagner dilemma” when focusing at the firm level; (b) to underline the prevalent cause and effect directions of the relationship between environmental and business performance; and (c) to investigate the reasons for any disagreements in this topic among the scientists. The results show that the main agreement regards the positive bi-directional relationship, as a virtuous cyclic approach with mutual effects between business and environmental performance; nevertheless, more complex hypotheses emerge, such as nonlinear and/or conditional relationship, that need to be further explored. On the other hand, the Porter–Wagner dilemma remains, and the main reason for the non-agreement among scientists can be due to the several non-homogeneous variables considered in the analyses. Thereafter, as lesson for scientists, the priority is to share univocal methods to measure firms’ environmental and business performances

Can institutional forces create competitive advantage? An empirical examination of environmental innovation

We examine institutional pressures as antecedents of environmental innovation. Drawing on institutional theory and a resource-based view of the firm, we argue that regulatory and normative forces influence companies' propensity to innovate in environment-related projects. Furthermore, we suggest that this relationship is contingent on the availability and specificity of the companies' resources. These relationships were tested using environmental patents and citations of 340 publicly-traded companies from polluting industries in the U.S. Results suggest that institutional pressures can be a source of competitive advantage, and regulatory forces are becoming more strongly associated with environmental innovations as the intensity of companies' R&D activities increase.environmental innovation; institutional theory; resource-based view;

Abstracts : policy research working paper series - numbers 1989-2015

This paper contains abstracts of Policy Research Working Paper series Numbers 1989-2015.Environmental Economics&Policies,Poverty Assessment,Health Monitoring&Evaluation,Economic Theory&Research,Health Economics&Finance