Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants.

The quinoxaline nonnucleoside RT inhibitor (NNRTI) (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4- dihydroquinoxaline-2(1H)-thione (HBY 097) was used to select for drug-resistant HIV-1 variants in vitro. The viruses first developed mutations affecting the NNRTI-binding pocket, and five of six strains displayed the RT G190-->E substitution, which is characteristic for HIV-1 resistance against quinoxalines. In one variant, a new mutant (G190-->Q) most likely evolved from preexisting G190-->E mutants. The negative charge introduced by the G190-->E substitution was maintained at that site of the pocket by simultaneous selection for V179-->D together with G190-->Q. After continued exposure to the drug, mutations at positions so far known to be specific for resistance against nucleoside RT inhibitors (NRTIs) (L74-->V/I and V75-->L/I) were consistently detected in all cultures. The inhibitory activities of the cellular conversion product of 2',3'-dideoxyinosine (ddI, didanosine), 2',3'-dideoxyadenosine (ddA) and of 2',3'-didehydro-3'-deoxythymidine (d4T, stavudine) against these late-passage viruses were shown to be enhanced with the L74-->V/I RT mutant virus as compared with the wild-type (wt) HIV-1MN isolate. Clonal analysis proved linkage of the codon 74 and codon 75 mutations to the NNRTI-specific mutations in all RT gene fragments. The nonnucleoside- and nucleoside-resistance mutation sites are separated by approximately 35 A. We propose that the two sites "communicate" through the template-primer which is situated in the DNA-binding cleft between these two sites. Quinoxalines cause high selective pressure on HIV-1 replication in vitro; however, the implication of these findings for the treatment of HIV-1 infection has yet to be determined.

Does Müller cell differentiation occur prior to the emergence of synapses in embryonic turtle retina?

Müller cells are the main glial cells in the retina, and are related to plexiform layer activity. Recent studies have demonstrated that Müller cells are involved in the synaptic conservation, plasticity, development and metabolism of glutamate. During turtle retinal development, layers, cells and synapses appear at different times. The aim of this research is to study the emergence of Müller cells during embryonic development and their relationship with the synaptogenesis. The authors used retinas from Trachemys scripta elegans embryos at stages S14, 18, 20, 23, and 26. Some retinas were processed with immunocytochemistry in order to detect the presence of glutamine synthetase in Müller cells, which was used as a marker of these cells. Other retinas from the same stages were processed for ultrastructural studies. Samples were observed in confocal and transmission electron microscopes, respectively. The present results show that glutamine synthetase expression in Müller cells occurs at S18, before the emergence of the retinal layers and the early synapses.

Industries and Citizens’ Groups Networks in EU Food Policy: The Emergence of ‘Unholy Alliances’ in Multilevel Governance? Brugges Political Research Paper No. 30, September 2013

Food policy is one the most regulated policy fields at the EU level. ‘Unholy alliances’ are collaborative patterns that temporarily bring together antagonistic stakeholders behind a common cause. This paper deals with such ‘transversal’ co-operations between citizens’ groups (NGOs, consumers associations…) and economic stakeholders (food industries, retailers…), focusing on their ambitions and consequences. This paper builds on two case studies that enable a more nuanced view on the perspectives for the development of transversal networks at the EU level. The main findings are that (i) the rationale behind the adoption of collaborative partnerships actually comes from a case-by-case cost/benefit analysis leading to hopes of improved access to institutions; (ii) membership of a collaborative network leads to a learning process closely linked to the network’s performance; and (iii) coalitions can have a better reception — rather than an automatic better access — depending on several factors independent of the stakeholders themselves.

Regional business cycles and the emergence of sheltered economies in the southern periphery of Europe. Bruges European Economic Research (BEER) Papers 7/November 2006

Recent research has highlighted that in the last few years the evolution of regional disparities in many European states has become pro-cyclical. This represents a change with respect to the predominantly anti-cyclical pattern of the 1960s and 1970s. This paper addresses the question of whether and when this change has taken place in the southern periphery of Europe, before analyzing the factors that may have played a role in such a change. The analysis relies on a regional database that includes the evolution of the GDP per capita of NUTS II regions in five European countries (France, Greece, Italy, Portugal, and Spain) between 1980 and 2000. The results of the analysis support the hypothesis of a change towards a pro-cyclical evolution of regional disparities in the cases of Italy, Portugal, and Spain, but not in those of Greece and France. A relationship between these pro-cyclical patters and the emergence of less dynamic sheltered economies is also detected in peripheral regions. This lack of dynamism is related to the fact that numerous peripheral areas in southern Europe have become increasingly dependent on factors such as transfers or public investment and employment, and therefore are less exposed to changes in market conditions.

The Emergence of Open Hardware Phenomena in Different Technological Environments

Dannie Jost gave an introductory presentation on the emergence on open hardware phenomena, including synthetic biology and other technological environments at the HEPTech Workshop on Open Hardware on June 13 held at the GSI, Darmstadt (Germany). The workshop was organized by CERN and GSI. This event addressed the OSHW phenomenon and its implications for academia and industry with special attention to knowledge and technology transfer issues. Consideration was given to the various aspects of open source hardware development, and how these are dealt with in academia and industry. Presentations from legal experts, academics, practitioners and business provided input for the discussions and exchange of ideas.

Social services in international perspective : the emergence of the sixth system /

"SRS 76-05704."

Reconsidering the Emergence of the Gay Novel in English and German /

In Reconsidering the Emergence of the Gay Novel in English and German, James P. Wilper examines a key moment in the development of the modern gay novel by analyzing four novels by German, British, and American writers. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

Mapping the emergence of heart disease in a black, urban population in Africa: The Heart of Soweto Study

Background: There is increasing evidence that many populations in the developing world are in epidemiologic transition with the subsequent emergence of more affluent disease states. The Heart of Soweto Study will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of I million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 prevalent cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 incident cases. Sub-studies of the relationship between HIV status and H D and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a developing world community in epidemiologic transition. Initially documented Population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

The emergence of order in random walk resource discovery protocols

While others have attempted to determine, by way of mathematical formulae, optimal resource duplication strategies for random walk protocols, this paper is concerned with studying the emergent effects of dynamic resource propagation and replication. In particular, we show, via modelling and experimentation, that under any given decay (purge) rate the number of nodes that have knowledge of particular resource converges to a fixed point or a limit cycle. We also show that even for high rates of decay - that is, when few nodes have knowledge of a particular resource - the number of hops required to find that resource is small.