Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g. wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network.Comment: 24 pages, 4 figures, 6 table

Water resources management in a homogenizing world: Averting the Growth and Underinvestment trajectory

Biotic homogenization, a de facto symptom of a global biodiversity crisis, underscores the urgency of reforming water resources management to focus on the health and viability of ecosystems. Global population and economic growth, coupled with inadequate investment in maintenance of ecological systems, threaten to degrade environmental integrity and ecosystem services that support the global socioeconomic system, indicative of a system governed by the Growth and Underinvestment (G&U) archetype. Water resources management is linked to biotic homogenization and degradation of system integrity through alteration of water systems, ecosystem dynamics, and composition of the biota. Consistent with the G&U archetype, water resources planning primarily treats ecological considerations as exogenous constraints rather than integral, dynamic, and responsive parts of the system. It is essential that the ecological considerations be made objectives of water resources development plans to facilitate the analysis of feedbacks and potential trade-offs between socioeconomic gains and ecological losses. We call for expediting a shift to ecosystem-based management of water resources, which requires a better understanding of the dynamics and links between water resources management actions, ecological side-effects, and associated long-term ramifications for sustainability. To address existing knowledge gaps, models that include dynamics and estimated thresholds for regime shifts or ecosystem degradation need to be developed. Policy levers for implementation of ecosystem-based water resources management include shifting away from growth-oriented supply management, better demand management, increased public awareness, and institutional reform that promotes adaptive and transdisciplinary management approaches

Output Fluctuations and Monetary Shocks

Using annual data for Colombia over the last thirty years and a new battery of econometric techniques, we test opposing theories that explain macroeconomic fluctuations: The neoclassical synthesis, which posits that, in the presence of temporary price rigidity, an unanticipated monetary expansion produces output gains that erode over time with increases in the price level; and an alternative explanation, which focuses on "real" technological or preference shocks as the sources of output changes. The coefficients from these systems are used to examine two basic propositions: the long-run neutrality of nominal quantities with respect to permanent movements in the money stock; and the short-run sensitivity of output to inflation.monetary policy exchange rates output capital controls multipliers

Modeling U.S. Soy-Based Markets with Directed Acyclic Graphs and Bernanke Structural VAR Methods: The Impacts of High Soy Meal and Soybean Prices

Advanced methods that combine directed acyclic graphs with Bernanke structural vector autoregression models are applied to a monthly system of three U.S. soy-based markets: for soybeans upstream and for the two soybean co-products soy meal and soy oil further downstream. Analyses of the impulse-response function and forecast error variance decompositions provide updated estimates of market-elasticity parameters that drive these markets and updated policy-relevant information on how these monthly markets run and dynamically interact. Results characterize impacts on the three U.S. soy-based markets of increases in U.S. prices of soy meal and soybeans.Industrial Organization,

OPR

The ability to reproduce a parallel execution is desirable for debugging and program reliability purposes. In debugging (13), the programmer needs to manually step back in time, while for resilience (6) this is automatically performed by the the application upon failure. To be useful, replay has to faithfully reproduce the original execution. For parallel programs the main challenge is inferring and maintaining the order of conflicting operations (data races). Deterministic record and replay (R&R) techniques have been developed for multithreaded shared memory programs (5), as well as distributed memory programs (14). Our main interest is techniques for large scale scientific (3; 4) programming models

A Configurable Transport Layer for CAF

The message-driven nature of actors lays a foundation for developing scalable and distributed software. While the actor itself has been thoroughly modeled, the message passing layer lacks a common definition. Properties and guarantees of message exchange often shift with implementations and contexts. This adds complexity to the development process, limits portability, and removes transparency from distributed actor systems. In this work, we examine actor communication, focusing on the implementation and runtime costs of reliable and ordered delivery. Both guarantees are often based on TCP for remote messaging, which mixes network transport with the semantics of messaging. However, the choice of transport may follow different constraints and is often governed by deployment. As a first step towards re-architecting actor-to-actor communication, we decouple the messaging guarantees from the transport protocol. We validate our approach by redesigning the network stack of the C++ Actor Framework (CAF) so that it allows to combine an arbitrary transport protocol with additional functions for remote messaging. An evaluation quantifies the cost of composability and the impact of individual layers on the entire stack

Output Fluctuations and Monetary Shocks: Evidence from Colombia

Using annual data for Colombia over the last 30 years, we test competing theories that explain macroeconomic fluctuations: the neoclassical synthesis, which posits that in the presence of temporary price rigidity, an unanticipated monetary expansion produces output gains that erode over time with increases in the price level; and an alternative explanation, which focuses on "real" technological or preference shocks as sources of output changes. Coefficients from this system are used to examine the long-run neutrality of nominal quantities with respect to permanent movements in the money stock and the short-run sensitivity of output to inflation.Colombia, inflation, growth, exchange rates,VAR

A reconstructive critique of IPE and GPE from a critical scientific realist perspective: An alternative Keynesian-Kaleckian approach

This paper offers, first, a critique of the relative lack of economic theory in ‘British’ Global Political Economy and then use of neoclassical rational choice theory in American mainstream IPE from the perspective of critical scientific realism. Keynesian economic theories provide perhaps the most obvious alternative. Keynes’ General Theory has been followed by many, forming also the basis of Minsky’s long ignored but now, after the 2008-9 crisis, all of a sudden famous explorations on the mechanisms of financial markets. While a major leap forward, we argue that these theories are historically and conceptually limited. Keynes’ critique of neoclassical economic theory and his alternative theories of particularly the effective demand and of money and credit can be strengthened by following also a neo-Kaleckian approach which avoids some of the inconsistencies of neo-Keynesianism. We indicate where further conceptual work is required and provide several illustrations from the neo-Kaleckian and neo-Keynesian theory to suggest a partial agenda of further scientific work including the explanation of unnecessary and undesired global fluctuations, tendencies and crises and possible collective responses to them. We also suggest the possibility of going beyond Keynes and Kalecki in terms of a general field theory of global political economy that can accommodate the deep normative and institutional underpinnings of the historically evolving planetary political economy