Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely reported in patients after recovery from COVID-19, but ...some of these patients do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells in culture and that transcription of the integrated sequences might account for some of the positive PCR tests seen in patients. In support of this hypothesis, we found that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells. We found target site duplications flanking the viral sequences and consensus LINE1 endonuclease recognition sequences at the integration sites, consistent with a LINE1 retrotransposon-mediated, target-primed reverse transcription and retroposition mechanism. We also found, in some patient-derived tissues, evidence suggesting that a large fraction of the viral sequences is transcribed from integrated DNA copies of viral sequences, generating viral-host chimeric transcripts. The integration and transcription of viral sequences may thus contribute to the detection of viral RNA by PCR in patients after infection and clinical recovery. Because we have detected only subgenomic sequences derived mainly from the 3' end of the viral genome integrated into the DNA of the host cell, infectious virus cannot be produced from the integrated subgenomic SARS-CoV-2 sequences.
The Routledge Handbook of Differentiation in the European Union offers an essential collection of groundbreaking chapters reflecting on the causes and consequences of this complex phenomenon.
This ...handbook is essential reading and an authoritative reference for scholars, students, researchers and practitioners involved in, and actively concerned about, research in the study of European integration. As European differentiation is multifaceted and involves a wide range of actors and policies, it will be of further interest to those working on countries and/or in policy areas where differentiation is an increasingly relevant feature.
With contributions from key experts in this subfield of European Studies, it will become a key volume used for those interested in learning the nuts and bolts of differentiation as a mechanism of (dis)integration in the European Union, especially in the light of Brexit. Organized around five key themes, it offers an authoritative "encyclopaedia" of differentiation and addresses questions such as:
How can one define differentiation in the European Union in the light of the most recent events?
Does differentiation create more challenges or opportunities for the European Union?
Is Europe moving away from an "ever closer Union" and heading towards an "ever more differentiated Union", especially as leading political figures across Europe favour the use of differentiation to reconcile divergences between member states?
This article examines the determinants of public opinion on differentiated integration (DI) in the European Union (EU). Specifically, it tests whether citizen attitudes are informed by the national ...experience of opt‐outs and exclusions from full participation in EU policies. The study generally finds that support for DI strongly depends on the mode of DI. Even though ‘multi‐speed DI’ is only temporary, it is evaluated more critically than durable treaty opt‐outs establishing ‘multi‐tier DI’. We suggest that citizens from opt‐out countries oppose multi‐speed DI out of concern that it would render their exemptions temporary, whereas citizens from new member states tend to be critical towards the often involuntary and discriminatory transitional arrangements that were imposed by the old member states.
This article addresses major information systems integration problems, approaches, technologies, and tools within the context of Model‐Driven Software Engineering. The Guaraná integration platform is ...introduced as an innovative platform amongst state‐of‐the‐art technologies available for enterprises to design and implement integration solutions. In this article, we present its domain‐specific modeling language and its industrial cloud‐based web development platform, which supports the design and implementation of integration solutions. A real‐world case study is described and analyzed; then, we delve into its design and implementation, to finally disclose ten measures that empirically help estimating the amount of effort involved in the development of integration solutions.
Using a novel common econometric specification, we examine the measurement of three important effects in international trade that historically have been addressed largely separately: the (partial) ...effects on trade of economic integration agreements, international borders, and bilateral distance. First, recent studies focusing on precise and unbiased estimates of effects of economic integration agreements (EIAs) on members׳ trade may be biased upward owing to inadequate control for time-varying exogenous unobservable country-pair-specific changes in bilateral export costs (possibly decreasing the costs of international relative to intranational trade); we find evidence of this bias using a properly specified gravity equation. Second, our novel methodology yields statistically significant estimates of the declining effect of “international borders” on world trade, now accounting for endogenous EIA formations and unobserved country-pair heterogeneity in initial levels. Third, we confirm recent evidence providing a solution to the “distance-elasticity puzzle,” but show that these estimates of the declining effect of distance on international trade are biased upward by not accounting for endogenous EIA formations and unobserved country-pair heterogeneity. We conclude our study with numerical general equilibrium comparative statics illustrating a substantive difference on trade effects of EIAs with and without allowance for the declining effects of international borders on world trade.
This article explores how practice theory can be recruited for the study of European integration. New generations of EU researchers are fascinated by the prospect of leaving the armchair and studying ...the people and artefacts that make the EU on an everyday level. This article surveys key practice‐oriented, anthropological and micro‐sociological studies of the EU and European integration and shows how their findings challenge more traditional understandings of the dynamics of European integration. Moving beyond a stock‐taking, the article distinguishes between ‘ordering’ and ‘disordering’ practices and explores the potential of a practice turn in EU studies for both theory (overcoming dualism, replacing substantialism with processualism and rethinking power) and methods (including unstructured interviews, fieldwork and participant observation). A practice turn will force us to rethink core assumptions about the EU and allow us to grasp otherwise uncharted performances and social activities that are crucial for European integration.
A reprint of the classic text, this book popularized compact modeling of electronic and semiconductor devices and components for college and graduate-school classrooms, and manufacturing engineering, ...over a decade ago. The first comprehensive book on MOS transistor compact modeling, it was the most cited among similar books in the area and remains the most frequently cited today. The coverage is device-physics based and continues to be relevant to the latest advances in MOS transistor modeling. This is also the only book that discusses in detail how to measure device model parameters required for circuit simulations.
Evidence suggests that many organizations are finding it hard to implement a CRM strategy. This article reports on the research conducted over the last five years that explores how organizations can ...successfully develop a CRM strategy. We propose a multi-layered framework for mapping and understanding the inter-relationships between complex variables relating to CRM strategy implementation. The concept of ‘affordance’ is delineated and applied to culture, people, processes and technology. Evidence from three case studies suggests that a multi-layered, interdisciplinary framework can assist companies in developing their CRM strategy through a greater understanding of how different variables interact in a constantly changing environment.
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