SUMMARY The genetics of complex disease produce alterations in the molecular interactions of cellular pathways whose collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer’s disease (LOAD), we constructed gene regulatory networks in 1647 post-mortem brain tissues from LOAD patients and non-demented subjects, and demonstrate that LOAD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, we rank-ordered these network structures for relevance to LOAD pathology, highlighting an immune and microglia-specific module dominated by genes involved in pathogen phagocytosis, containing TYROBP as a key regulator and up-regulated in LOAD. Mouse microglia cells over-expressing intact or truncated TYROBP revealed expression changes that significantly overlapped the human brain TYROBP network. Thus the causal network structure is a useful predictor of response to gene perturbations and presents a novel framework to test models of disease mechanisms underlying LOAD.

This paper proposes a framework for gross exports accounting that breaks up a country's gross exports into various value-added components by source and additional double counted terms. By identifying which parts of the official trade data are double counted and the sources of the double counting, it bridges official trade (in gross value terms) and national accounts statistics (in value added terms). Our parsimonious framework integrates all previous measures of vertical specialization and value-added trade in the literature into a unified framework. To illustrate the potential of such a method, we present a number of applications including re-computing revealed comparative advantages and the magnifying impact of multi-stage production on trade costs. -1As different stages of production are now regularly performed in different countries, intermediate inputs cross borders multiple times. As a result, traditional trade statistics become increasingly less reliable as a gauge of the value contributed by any particular country. This paper integrates and generalizes the many attempts in the literature at tracing value added by country and measuring vertical specialization in international trade. We provide a unified conceptual framework that is more comprehensive than the current literature. By design, this is an accounting exercise, and does not directly examine the causes and the consequences of global production chains. However, an accurate and well-defined conceptual framework to account for value added by sources is a necessary step toward a better understanding of all these issues.Supply chains can be described as a system of value-added sources and destinations. Within a supply chain, each producer purchases inputs and then adds value, which is included in the cost of the next stage of production. At each stage, the value-added equals the value paid to the factors of production in the exporting country. However, as all official trade statistics are measured in gross terms, which include both intermediate inputs and final products, they "double count" the value of intermediate goods that cross international borders more than once. Such a conceptual and empirical shortcoming of gross trade statistics, as well as their inconsistency with the System of National Accounts (SNA) accounting standards, has long been recognized by both the economics profession and policy makers. 1 Case studies on global value chains based on detailed micro data for a single product or a single sector in industries such as electronics, apparel, and motor vehicles have provided detailed examples of the discrepancy between gross and value-added trade. While enhancing our intuitive understanding of global production chains in particular industries, they do not offer a comprehensive picture of the gap between value-added and gross trade, and an economy's participation in cross-border production chains. Several researchers have examined the issue of vertical specialization on a systematic basis, including the pioneering effort of Hummels, Ishii...

The views in the paper are solely those of the authors and may not reflect the views of the USITC, its Commissioners, or of any other organization that the authors are affiliated with. The authors thank participants of OECD-World Bank workshop "New metrics for global value chain analysis" in Paris, IEFS China 2010 Conference in Beijing, and seminar at Purdue University for helpful comments and suggestions. The authors are particularly grateful for the constructive discussion with Dr. Kei-Mu Yi at the Federal Reserve Bank of Philadelphia in developing the two-country cases and the relationship between our new measures of vertical specialization and the original HIY measures. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research. NBER working papers are circulated for discussion and comment purposes. They have not been peerreviewed or been subject to the review by the NBER Board of Directors that accompanies official NBER publications.

Manipulating a quantum state via electrostatic gating has been of great importance for many model systems in nanoelectronics. Until now, however, controlling the electron spins or, more specifically, the magnetism of a system by electric-field tuning has proven challenging. Recently, atomically thin magnetic semiconductors have attracted significant attention due to their emerging new physical phenomena. However, many issues are yet to be resolved to convincingly demonstrate gate-controllable magnetism in these two-dimensional materials. Here, we show that, via electrostatic gating, a strong field effect can be observed in devices based on few-layered ferromagnetic semiconducting CrGeTe. At different gate doping, micro-area Kerr measurements in the studied devices demonstrate bipolar tunable magnetization loops below the Curie temperature, which is tentatively attributed to the moment rebalance in the spin-polarized band structure. Our findings of electric-field-controlled magnetism in van der Waals magnets show possibilities for potential applications in new-generation magnetic memory storage, sensors and spintronics.