bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Sequence Element Directing Translation Reinitiation in RNA of the Calicivirus Rabbit Hemorrhagic Disease Virus
Authors: Meyers Gregor 
Published: June 2007

ABSTRACT
The calicivirus minor capsid protein VP2 is expressed via reinitiation of protein synthesis after termination of translation of the preceding VP1 gene. A sequence element of about 80 nucleotides denoted “termination upstream ribosomal binding site” (TURBS) (25) is crucial for reinitiation. Deletion mapping in the TURBS of a rabbit calicivirus identified two short sequence motifs that were crucial for VP2 expression. Motif 1 is conserved among caliciviruses and is complementary to a sequence in the 18S rRNA. Single-residue exchanges in this motif severely impaired reinitiation when they affected the putative rRNA binding, whereas an exchange preserving complementarity had only a minor effect. Single exchanges in motif 2 were rather well tolerated, but the introduction of double exchanges almost blocked VP2 expression. In contrast, the deletion analyses showed that the RNA between the two motifs is of minor importance. The distance between motif 2 and the start site was found to be important, since deletions of increasing length in this sequence or upstream positioning of the start codon reduced VP2 expression stepwise to low levels, whereas multiple-nucleotide exchanges in this region were tolerated. The low flexibility of the arrangement of TURBS motif 2 and the start codon stand in marked contrast to the requirements with regard to the location of the stop codon of the preceding VP1 gene, which could be moved far downstream with continuous reduction, but without loss, of VP2 translation. The sequence mapping resulted in a refined model of the reinitiation mechanism leading to VP2 expression.
In Vivo and In Vitro Intragenomic Rearrangement of TT Viruses
Authors: Leppik Ludmila , Gunst Karin , Lehtinen Matti , Dillner Joakim , Streker Karin , de Villiers Ethel-Michele 
Published: June 2007

ABSTRACT

The in vitro replication of the Torque teno virus (TT virus) tth8 full-length genome and particle formation in a Hodgkin's lymphoma-derived cell line after transfection with cloned viral DNA were demonstrated. Analyses of the transcription patterns of tth8 and tth7 TT virus isolates in a number of lymphoma and T-cell leukemia cell lines indicated differential additional splicing events and intragenomic rearrangement generating open reading frames which could not be deducted from the genomic sequence. We also demonstrated the presence of rearranged TT virus genomes in vivo in sera taken from pregnant mothers whose children later developed childhood leukemia, as well as sera from control mothers. Control experiments using religated cloned genomic tth8 DNA mixed with cellular DNA did not result in such subviral molecules. These subviral isolates ranged from 172 bp to full-length TT virus genomes. Possible in vivo selection for specific rearranged molecules was indicated by the presence of one isolate (561 bp) in 11 serum samples. It remains to be clarified whether selected rearranged subviral components resulting from specific TT virus types may contribute to the initiation of disease. These data demonstrate new features of TT viruses suggesting possible similarities to plant viruses of the family
Geminiviridae
, as well as raise questions about the documented plurality and diversity of anelloviruses.
A New Generation of Modified Live-Attenuated Avian Influenza Viruses Using a Two-Strategy Combination as Potential Vaccine Candidates
Authors: Song Haichen , Nieto Gloria Ramirez , Perez Daniel R. 
Published: June 2007

ABSTRACTIn light of the recurrent outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI), there is a pressing need for the development of vaccines that allow rapid mass vaccination. In this study, we introduced by reverse genetics temperature-sensitive mutations in the PB1 and PB2 genes of an avian influenza virus, A/Guinea Fowl/Hong Kong/WF10/99 (H9N2) (WF10). Further genetic modifications were introduced into the PB1 gene to enhance the attenuated (att) phenotype of the virus in vivo. Using theattWF10 as a backbone, we substituted neuraminidase (NA) for hemagglutinin (HA) for vaccine purposes. In chickens, a vaccination scheme consisting of a single dose of anattH7N2 vaccine virus at 2 weeks of age and subsequent challenge with the wild-type H7N2 LPAI virus resulted in complete protection. We further extended our vaccination strategy against the HPAI H5N1. In this case, we reconstituted anattH5N1 vaccine virus, whose HA and NA genes were derived from an Asian H5N1 virus. A single-dose immunization in ovo with theattH5N1 vaccine virus in 18-day-old chicken embryos resulted in more than 60% protection for 4-week-old chickens and 100% protection for 9- to 12-week-old chickens. Boosting at 2 weeks posthatching provided 100% protection against challenge with the HPAI H5N1 virus for chickens as young as 4 weeks old, with undetectable virus shedding postchallenge. Our results highlight the potential of liveattavian influenza vaccines for mass vaccination in poultry.
Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane
Authors: Frieman Matthew , Yount Boyd , Heise Mark , Kopecky-Bromberg Sarah A. , Palese Peter , Baric Ralph S. 
Published: June 2007

ABSTRACT
The host innate immune response is an important deterrent of severe viral infection in humans and animals. Nuclear import factors function as key gatekeepers that regulate the transport of innate immune regulatory cargo to the nucleus of cells to activate the antiviral response. Using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model, we demonstrate that SARS-COV ORF6 protein is localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells, where it binds to and disrupts nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane. Retention of import factors at the ER/Golgi membrane leads to a loss of STAT1 transport into the nucleus in response to interferon signaling, thus blocking the expression of STAT1-activated genes that establish an antiviral state. We mapped the region of ORF6, which binds karyopherin alpha 2, to the C terminus of ORF6 and show that mutations in the C terminus no longer bind karyopherin alpha 2 or block the nuclear import of STAT1. We also show that N-terminal deletions of karyopherin alpha 2 that no longer bind to karyopherin beta 1 still retain ORF6 binding activity but no longer block STAT1 nuclear import. Recombinant SARS-CoV lacking ORF6 did not tether karyopherin alpha 2 to the ER/Golgi membrane and allowed the import of the STAT1 complex into the nucleus. We discuss the likely implications of these data on SARS-CoV replication and pathogenesis.
An Adenovirus Vector-Mediated Reverse Genetics System for Influenza A Virus Generation
Authors: Ozawa Makoto , Goto Hideo , Horimoto Taisuke , Kawaoka Yoshihiro 
Published: June 2007

ABSTRACT
Plasmid-based reverse genetics systems allow the generation of influenza A virus entirely from cloned cDNA. However, since the efficiency of virus generation is dependent on the plasmid transfection efficiency of cells, virus generation is difficult in cells approved for vaccine production that have low transfection efficiencies (e.g., Vero cells). Here we established an alternative reverse genetics system for influenza virus generation by using an adenovirus vector (AdV) which achieves highly efficient gene transfer independent of cell transfection efficiency. This AdV-mediated reverse genetics system will be useful for generating vaccine seed strains and for basic influenza virus studies.
Elite and Leadership Change in Liberal Democracies
Authors: Pakulski Jan , Higley John 
Published: June 2007

AbstractThis article presents and assesses the thesis that a shift in the character of governing elites and leaders has been occurring in several important liberal democracies during recent years. Ascendant elites are more leonine and top leaders are more pugnacious. We attribute the shift to strong centripetal pressures that now impinge on elites and leaders, and we ask about the shift's consequences for the operation of liberal democracies.
Nordic Elites in Comparative Perspective
Authors: Ruostetsaari Ilkka 
Published: June 2007

AbstractThe article compares the Nordic, i.e., Danish, Finnish, Norwegian and Swedish, elite structures based on power studies which were completed in these countries in the 2000s. Despite differences in data collection methods, all of these studies employ the positional approach, and the composition of national elites is defined identically. Moreover, the four Nordic countries are associated with largely common history and political culture. The Nordic elites will be compared on the grounds of three dimensions, i.e. openness of recruitment into the elites, interaction between various elite groups, and interaction between the elites and the people. We will ask in what way the Nordic elite structures have changed as far as these dimensions are concerned and how many elites exist in the Nordic countries, i.e., one power elite or several mutually competitive elites.
Elite Integration and Institutional Trust in Norway
Authors: Gulbrandsen Trygve 
Published: June 2007

AbstractIn modern elite theory accommodation and compromise between national elite groups are seen as preconditions for the continuance and stability of a democratic society. It is claimed that elite accommodation is facilitated to the extent that the elites are integrated. In this article trust between the various elite groups and their respective institutions is investigated as a core aspect of elite integration. The analyses presented in the article demonstrate that in general there is a relatively high level of institutional trust among national elite groups in Norway. There is, however, some variation in how much trust the various elite groups accord the institutions to which other elite groups belong, and this is explained by (1) the extent to which one elite identifies with the functions of other elites, (2) has a similar ideological orientation, and (3) has social contact with members of other elites.
From Vietnam to Iraq: American Elites' Views on the Use of Military Force
Authors: Moore Gwen , Mack Stephanie 
Published: June 2007

AbstractIn this paper we present trends in US elites' opinions on the use of military force abroad in the period from the end of US military involvement in Vietnam in 1975 to 2004 during the 'war on terror.' With data from quadrennial surveys of US elites' foreign policy attitudes sponsored by the Chicago Council on Foreign Relations since 1975, we ask whether elites have become more militaristic or whether such views have been a long term characteristic of US elites. We find support for the view of United States leaders as prone to the use of military might, even without the support of allies. Yet the findings also indicate that American elites have held this military view of reality for a long time.
Political Elites in the Commonwealth of Independent States: Recruitment and Rotation Tendencies
Authors: Gaman-Golutvina Oxana 
Published: June 2007

AbstractThis paper deals with the process of elite recruitment in the Commonwealth of Independent States (CIS). The analysis of CIS countries' experiences allows a correlation to be drawn between the model of elite organization and the political and economic policies they pursue. As a rule, based on the mold of traditionalist (patron-client) relations, elites act as the agents of de-modernization and re-traditionalization. Organized on the principles of rational bureaucracy, elites are able to ensure modernization. Looking at the evolution of the CIS countries from this angle, the author investigates three groups of states. Two of these represent an almost 'ideal type' or 'clean' example of implementing the reference model. Byelorussia, at one end of the spectrum, is an example of a bureaucratically run state. On the other side of this spectrum are the countries of post-Soviet Central Asia, Azerbaijan, and Georgia, which embody the model of the clannish elite. The third group of countries are those states maintaining an in-between position within the proposed line of analysis, or those post-Soviet polities marked by a complicated plexus and sometimes also by an acute struggle between different models (Russia, Ukraine, Armenia, and Moldova).
The American Territorial Presence in Asia
Authors: Badgley John H. 
Published: June 2007

The system of states that has evolved since World War II has not resolved the basic political problems facing Asia. Furthermore, American efforts to sustain, and hopefully stabilize, the non-Communist regimes have entangled the United States unnecessarily in the domestic political processes of several Asian countries. Resurgent forces of ethnic and local identity increasingly challenge the authority of central governments and bring into question the efficacy of anti-pluralist, nationalistic schemes. The foreseeable future appears laden with struggles by these classic forces, which dominated pre-colonial Asia and now underlie ideological and nationalist conflicts. Regional competition between traditional ethnic enemies, as well as between larger Asian powers, is reasserting itself, calling into question the efforts by the superpowers, and the United Nations, to play dominant roles in the settlement of these conflicts. More certain is a constant secondary role by the United States, due to its technological superiority, economic abundance, and cultural vigor. The kind of American presence in Asia over the next two decades will be significantly modified. While military assistance may, in many cases, continue, termination of alliances on mainland Asia may eventually follow the withdrawal from Vietnam. The major motive for the American desire to disengage flows from domestic pressures. However, the quest for relaxation of tension with China will help account for the new American tolerance of political change in Asia.
The Presence in Southern Asia of Outside Powers
Authors: Wriggins W. Howard 
Published: June 2007

In considering the presence of outside powers in South and Southeast Asia, this discussion covers a spectrum of phenomena included in the often-used but highly ambiguous concept of "presence." It examines the major different forms of outside "presence" in Pakistan, India, Burma, Thailand, Malaysia, Indonesia, and the Philippines. It then notes the shifting preponderant foreign presence in Pakistan, the diminishing American presence in both Pakistan and India, the rising Soviet military assistance presence in India, and the lack of foreign presence in Burma. There is an expectation that the American presence in Thailand will decline and growing anxiety there about likely Vietnam presence in the future, particularly among ethnic minorities on Thailand's frontiers. A Japanese presence, in the form of commercial activity, at the very least, is growing rapidly—in Thailand and Indonesia, particularly—and will grow further. The Chinese presence is more a problem for the eighties than for the seventies, except in countries with Chinese minorities, where anxieties persist and may increase. The Soviet presence is also widely expected to grow, both militarily and in terms of economic activity over the decade.
The Role of Japan and the Future of American Relations with the Far East
Authors: Johnson U. Alexis 
Published: June 2007

American interest and involvement in Asia is not a recent aberration, but a continuing phenomenon going back to the days of the China Clippers and extending through the period when the United States followed a policy of isolation in other areas. Today Japan is the leading nation in Asia, vastly superior economically and technically to other states in the area. Linked to the United States by a Mutual Defense Treaty, Japan has substantial armed forces capable of assuring the country's immediate conventional defense. In his State of the Union message, President Nixon recognized this primacy, stating "Japanese-American friendship and coöperation are the linchpin for peace in the Pacific." Japan is contributing to the development of the free states of Asia through increasing economic and technical coöperation. We welcome this policy and will not ask Japan to assume security responsibilities inconsistent with the felt concerns of the Japanese people. Looking at the region as a whole, the ultimate ideal is a community of the free states of Asia coöperating for their common interests in the political, economic, and security fields, with which we are associated only to the degree that these states desire our association. Japan must play a major role in any such community.
The Psychology of Political Activity
Authors: Levy Sheldon G. 
Published: June 2007

This study examines the attitudes of citizens to actions that might be taken under hypothetical conditions of governmental oppression. A technique called Polarized Sub group Analysis (PSA) was used to divide a national sample of adults into groups that varied in the amount of systemic pun ishment that they had experienced. Those who had experi enced greater amounts of systemic punishment were less politi cally active and more rigid in the modes of action that they had utilized. They were more rigid psychologically and had higher levels of endorsement of official internal and international uses of force. A theory of reduced alternatives is proposed, which hypothe sizes that systemic punishment leads to a reduction in political activity as well as behavioral and psychological rigidity. It is this rigidity that leads to anxiety over complex situations and increased dependency upon and subsequent identification with authority to reduce the anxiety. This identification then re sults in greater endorsement of official uses of force, as well as reduced opposition to governmental oppression. Opposition to government requires a wide range of political alternatives, which reduces anxiety and dependence and the need for identi fication. The conditions under which withdrawal (alienation) may occur are briefly discussed. Evidence is given that non- whites in the United States do not identify with authority.
The entire organization of transcription units on the Bacillus subtilis genome
Authors: Kobayashi Hirokazu , Akitomi Joe , Fujii Nobuyuki , Kobayashi Kazuo , Altaf-Ul-Amin Md , Kurokawa Ken , Ogasawara Naotake , Kanaya Shigehiko 
Published: June 2007

AbstractBackgroundIn the post-genomic era, comprehension of cellular processes and systems requires global and non-targeted approaches to handle vast amounts of biological information.ResultsThe present study predicts transcription units (TUs) inBacillus subtilis, based on an integrated approach involving DNA sequence and transcriptome analyses. First, co-expressed gene clusters are predicted by calculating the Pearson correlation coefficients of adjacent genes for all the genes in a series that are transcribed in the same direction with no intervening gene transcribed in the opposite direction. Transcription factor (TF) binding sites are then predicted by detecting statistically significant TF binding sequences on the genome using a position weight matrix. This matrix is a convenient way to identify sites that are more highly conserved than others in the entire genome because any sequence that differs from a consensus sequence has a lower score. We identify genes regulated by each of the TFs by comparing gene expression between wild-type and TF mutants using a one-sided test. By applying the integrated approach to 11 σ factors and 17 TFs ofB. subtilis, we are able to identify fewer candidates for genes regulated by the TFs than were identified using any single approach, and also detect the known TUs efficiently.ConclusionThis integrated approach is, therefore, an efficient tool for narrowing searches for candidate genes regulated by TFs, identifying TUs, and estimating roles of the σ factors and TFs in cellular processes and functions of genes composing the TUs.
External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer
Authors: Booth Christopher M , Dranitsaris George , Gainford M Corona , Berry Scott , Fralick Michael , Fralick John , Sue Joanna , Clemons Mark 
Published: June 2007

Abstract

Background
Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer.

Methods
A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario.

Results
During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast), the median time to funding approval was 31 months (range 14–46). Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each) than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56).

Conclusion
Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all) of these external factors may play in the debate over priority-setting.