Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture

Strategic argument mapping

Includes bibliographical references (p. 38)

The BTeV Software Tutorial Suite

The BTeV Collaboration is starting to develop its C++ based offline software suite, an integral part of which is a series of tutorials. These tutorials are targeted at a diverse audience, including new graduate students, experienced physicists with little or no C++ experience, those with just enough C++ to be dangerous, and experts who need only an overview of the available tools. The tutorials must both teach C++ in general and the BTeV specific tools in particular. Finally, they must teach physicists how to find and use the detailed documentation. This report will review the status of the BTeV experiment, give an overview of the plans for and the state of the software and will then describe the plans for the tutorial suite.Comment: Submitted to the proceedings of CHEP03, paper number THLT00

Identifying common problems in the acquisition and deployment of large-scale software projects in the US and UK healthcare systems

Public and private organizations are investing increasing amounts into the development of healthcare information technology. These applications are perceived to offer numerous benefits. Software systems can improve the exchange of information between healthcare facilities. They support standardised procedures that can help to increase consistency between different service providers. Electronic patient records ensure minimum standards across the trajectory of care when patients move between different specializations. Healthcare information systems also offer economic benefits through efficiency savings; for example by providing the data that helps to identify potential bottlenecks in the provision and administration of care. However, a number of high-profile failures reveal the problems that arise when staff must cope with the loss of these applications. In particular, teams have to retrieve paper based records that often lack the detail on electronic systems. Individuals who have only used electronic information systems face particular problems in learning how to apply paper-based fallbacks. The following pages compare two different failures of Healthcare Information Systems in the UK and North America. The intention is to ensure that future initiatives to extend the integration of electronic patient records will build on the ‘lessons learned’ from previous systems

The emerging legal framework for private sector development in Viet Nam's transitional economy

A major objective of Viet Nam's transition to a market economy has been to reactivate the private sector in a mixed economy. Several new laws have been introduced in the past five years to implement this policy and to create an enabling environment for the private sector. The author reviews some of the more important laws and regulations that affect Viet Nam's private sector activities, including laws on real property, intellectual property, companies, domestic investment, foreign investment, bankruptcy, contracts, and dispute resolution. Anti-monopoly law has not yet been introduced in Viet Nam. The issue of competition is addressed in the context of trade law, the relative roles of the state and private sector, and restrictions in company law. These areas all establish the foundation of a legal framework for a market economy. The author concludes that Viet Nam's legal framework, like China's, is still influenced by ideology, which causes problems in such areas as private ownership of real property and with such fundamental legal concepts as"due process of law."It is noted that the private sector is constrained by the lack of an independent judiciary, the absence of private land ownership, other uncertainties in property law that limit the develpoment of financial markets, and the inherent bias of the system in favor of the state sector (and collective ownership). Also noted is a law-abiding attitude, equally important to development has been slow to develop. The author goes on to point out that the foreign investment process is too complicated, and its company law too restrictive. A first priority should be to strreamline regulations, as well as liberalize trade policy and increase efforts in privatization of state enterprises. In this respect the author notes that export processing zones may be a useful interim instrument to attract foreign investment but should be phased out over time. More important in the long term is a good investment climate resting on a strong legal foundation.Legal Products,Environmental Economics&Policies,Banks&Banking Reform,Municipal Housing and Land,Municipal Financial Management,Environmental Economics&Policies,Banks&Banking Reform,Municipal Housing and Land,Legal Products,Municipal Financial Management

Targeted cortical reorganization using optogenetics in non-human primates.

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation

Rethinking Freedom of Contract: A Bankruptcy Paradigm

This Article tests the limits of private contracting by examining what it means to contract about bankruptcy. Bankruptcy law if governed by a statutory code that defines the relationship between debtors and creditors when a debtor enters the bankruptcy regulatory scheme. May debtors and creditors contract in advance to change that relationship? Or would these contracts be Faustian bargains that the state should not enforce? Both courts and scholars are in conflict, yet the answer is critical because it affects not only bankruptcy costs but also the structuring of corporate reorganizations and securitization transactions. I maintain that the threshold question--what freedom should parties or should not be allowed to contractually alter statutory schemes. I then apply those principles to a model of prebankruptcy contracting by taking into account the policies underlying the bankruptcy code and also by analyzing the extent to which, under contract law, externalities should render a contract unenforceable. I conclude that, within defined limits, bankruptcy law should be viewed as default provisions and not as mandatory rules. Finally I show that my model of prebankruptcy contracting can have important applications, not only to making corporate reorganizations and securitizations transactions more efficient but also to understanding when parties should be allowed to contract about statutory schemes generally and when externalities should override freedom of contract

Empirical analysis of credit relationships in small firms financing : sampling design and descriptive statistics

Despite the relevance of credit financing for the profit and risk situation of commercial banks only little empirical evidence on the initial credit decision and monitoring process exists due to the lack of appropriate data on bank debt financing. The present paper provides a systematic overview of a data set generated during the Center for Financial Studies research project on "Credit Management" which was designed to fill this empirical void. The data set contains a broad list of variables taken from the credit files of five major German banks. It is a random sample drawn from all customers which have engaged in some form of borrowing from the banks in question between January 1992 and January 1997 and which meet a number of selection criteria. The sampling design and data collection procedure are discussed in detail. Additionally, the project's research agenda is described and some general descriptive statistics of the firms in our sample are provided

Common DNA sequence variation influences 3-dimensional conformation of the human genome.

BACKGROUND:The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. RESULTS:To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. CONCLUSION:Our results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized