bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Intermolecular Interactions of Vesicular Stomatitis Virus Nucleoprotein in RNA Encapsidation
Authors: Zhang Xin , Green Todd J. , Tsao Jun , Qiu Shihong , Luo Ming 
Published: November 2007

ABSTRACT

The crystal structure of the vesicular stomatitis virus nucleoprotein (N) in complex with RNA reveals extensive and specific intermolecular interactions among the N molecules in the 10-member oligomer. What roles these interactions play in encapsidating RNA was studied by mutagenesis of the N protein. Three N mutants intended for disruption of the intermolecular interactions were designed and coexpressed with the phosphoprotein (P) in an
Escherichia coli
system previously described (T. J. Green et al., J. Virol. 74:9515-9524, 2000). Mutants N (Δ1-22), N (Δ347-352), and N (320-324, (Ala)
5
) lost RNA encapsidation and oligomerization but still bound with P. Another mutant, N (Ser290→Trp), was able to form a stable ring-like N oligomer and bind with the P protein but was no longer able to encapsidate RNA. The crystal structure of N (Ser290→Trp) at 2.8 Å resolution showed that this mutant can maintain all the same intermolecular interactions as the wild-type N except for a slight unwinding of the N-terminal lobe. These results suggest that the intermolecular contacts among the N molecules are required for encapsidation of the viral RNA.
Infection-Enhancing and -Neutralizing Activities of Mouse Monoclonal Antibodies against Dengue Type 2 and 4 Viruses Are Controlled by Complement Levels
Authors: Yamanaka Atsushi , Kosugi Saori , Konishi Eiji 
Published: November 2007

ABSTRACTDengue viruses are distributed widely in the tropical and subtropical areas of the world and cause dengue fever and its severer form, dengue hemorrhagic fever. While neutralizing antibodies are considered to play a major role in protection from these diseases, antibody-dependent enhancement (ADE) of infection is an important mechanism involved in disease severity, in addition to the involvement of T lymphocytes. Here, we analyzed relationships between neutralizing and enhancing activities at a clonal level using models of dengue type 2 virus (DENV2) and dengue type 4 virus (DENV4). Totals of 33 monoclonal antibodies (MAbs) against DENV2 and 43 against DENV4 were generated, all directed to the envelope protein. In these MAbs, enhancing activities were shown at subneutralizing doses under normal ADE assay conditions where test samples were heat inactivated. However, the inclusion of commercial rabbit complement or fresh sera from healthy humans in the ADE assay system abolished the enhancing activities of all these MAbs. The reductive effect of fresh sera on enhancing activities was significantly reduced by their heat inactivation or the use of C1q- or C3-depleted sera. In some fresh sera, enhancing activities were shown within a range of 20 to 80% of normal complement levels in a dose-dependent fashion. These results indicate that a single antibody species possesses two distinct activities (neutralizing/enhancing), which are controlled by the level of complement, suggesting the involvement of complement in dengue disease severity. Fresh human sera also tended to reduce enhancing activities more effectively in homologous than heterologous combinations of viruses (DENV2/DENV4) and MAbs (against DENV2/DENV4).
Simian Virus 40 DNA Replication Is Dependent on an Interaction between Topoisomerase I and the C-Terminal End of T Antigen
Authors: Khopde Sujata , Simmons Daniel T. 
Published: November 2007

ABSTRACT
Topoisomerase I (topo I) is needed for efficient initiation of simian virus 40 (SV40) DNA replication and for the formation of completed DNA molecules. Two distinct binding sites for topo I have been previously mapped to the N-terminal (residues 83 to 160) and C-terminal (residues 602 to 708) regions of T antigen. By mutational analysis, we identified a cluster of six residues on the surface of the helicase domain at the C-terminal binding site that are necessary for efficient binding to topo I in enzyme-linked immunosorbent assay and far-Western blot assays. Mutant T antigens with single substitutions of these residues were unable to participate normally in SV40 DNA replication. Some mutants were completely defective in supporting DNA replication, and replication was not enhanced in the presence of added topo I. The same mutants were the ones that were severely compromised in binding topo I. Other mutants demonstrated intermediate levels of activity in the DNA replication assay and were correspondingly only partially defective in binding topo I. Mutations of nearby residues outside this cluster had no effect on DNA replication or on the ability to bind topo I. These results strongly indicate that the association of topo I with these six residues in T antigen is essential for DNA replication. These residues are located on the back edges of the T-antigen double hexamer. We propose that topo I binds to one site on each hexamer to permit the initiation of SV40 DNA replication.
New World Clade B Arenaviruses Can Use Transferrin Receptor 1 (TfR1)-Dependent and -Independent Entry Pathways, and Glycoproteins from Human Pathogenic Strains Are Associated with the Use of TfR1
Authors: Flanagan Meg L. , Oldenburg Jill , Reignier Therese , Holt Nathalia , Hamilton Genevieve A. , Martin Vanessa K. , Cannon Paula M. 
Published: November 2007

ABSTRACT
Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, α-dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that other, as-yet-unknown receptors are involved in arenavirus entry. In the present study, we examined the use of TfR1 by the glycoproteins (GPs) from a panel of New World clade B arenaviruses comprising three pathogenic and two nonpathogenic strains. Interestingly, we found that TfR1 was only used by the GPs from the pathogenic viruses, with entry of the nonpathogenic strains being TfR1 independent. The pathogenic GPs could also direct entry into cells by TfR1-independent pathways, albeit less efficiently. A comparison of the abilities of TfR1 orthologs from different species to support arenavirus entry found that the human and feline receptors were able to enhance entry of the pathogenic strains, but that neither the murine or canine forms were functional. Since the ability to use TfR1 is a characteristic feature of the human pathogens, this interaction may represent an important target in the treatment of New World hemorrhagic fevers. In addition, the ability to use TfR1 may be a useful tool to predict the likelihood that any existing or newly discovered viruses in this family could infect humans.
Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins
Authors: Patel Milloni B. , Hoffman Noah G. , Swanstrom Ronald 
Published: November 2007

ABSTRACTThe V3 region of the human immunodeficiency virus type 1 gp120 Env protein is a key domain in Env due to its role in interacting with the coreceptors CCR5 and CXCR4. We examined potential subtype-specific V3 region differences by comparing patterns of amino acid variability and probing for subtype-specific structures using 11 anti-V3 monoclonal antibodies (V3 MAbs). Differences between the subtypes in patterns of variability were most evident in the stem and turn regions of V3 (positions 9 to 24), with the two subtypes being very similar in the base region. The characteristics of the binding of V3 MAbs to Env proteins of the subtype B virus JR-FL and the subtype C virus BR025 suggested three patterns, as each group of MAbs recognized a specific conformation- or sequence-based epitope. Viruses pseudotyped with Env from JR-FL and BR025 were resistant to neutralization by the V3 MAbs, although the replacement of the Env V3 region of the SF162 virus with the JR-FL V3 created a pseudotyped virus that was hypersensitive to neutralization. A single mutation in V3 (H13R) made this chimeric Env selectively resistant to one group of V3 MAbs, consistent with the mAb binding properties. We hypothesize that there are intrinsic differences in V3 conformation between subtype B and subtype C that are localized to the stem and turn regions and that these differences have two important biological consequences: first, subtype B and subtype C V3 regions can have subtype-specific epitopes that will inherently limit antibody cross-reactivity, and second, V3 conformational differences may potentiate the frequent evolution of R5- into X4-tropic variants of subtype B but limit subtype C virus from using the same mechanism to evolve X4-tropic variants as efficiently.
A Novel Block to Mouse Mammary Tumor Virus Infection of Lymphocytes in B10.BR Mice
Authors: Okeoma Chioma M. , Shen Ming , Ross Susan R. 
Published: November 2007

ABSTRACTClassic studies on C57BL-derived mouse strains showed that they were resistant to mouse mammary tumor virus (MMTV) infection. Although one form of resistance mapped to the major histocompatibility complex (MHC) locus, at least one other, unknown gene was implicated in this resistance. We show here that B10.BR mice, which are derived from C57BL mice but have the same MHC locus (H-2k) as susceptible C3H/HeN mice, are resistant to MMTV, and show a lack of virus spread in their lymphoid compartments but not their mammary epithelial cells. Although in vivo virus superantigen (Sag)-mediated activation of T cells was similar in C3H/HeN and B10.BR mice, T cell-dependent B-cell and dendritic cell activation was diminished in the latter. Ex vivo, B10.BR T cells showed a diminished capacity to proliferate in response to the MMTV Sag. The genetic segregation of the resistance phenotype indicated that it maps to a single allele. These data highlight the role of Sag-dependent T-cell responses in MMTV infection and point to a novel mechanism for the resistance of mice to retroviral infection that could lead to a better understanding of the interplay between hosts and pathogens.
The Spike Glycoprotein of Murine Coronavirus MHV-JHM Mediates Receptor-Independent Infection and Spread in the Central Nervous Systems ofCeacam1a−/−Mice
Authors: Miura Tanya A. , Travanty Emily A. , Oko Lauren , Bielefeldt-Ohmann Helle , Weiss Susan R. , Beauchemin Nicole , Holmes Kathryn V. 
Published: November 2007

ABSTRACTThe MHV-JHM strain of the murine coronavirus mouse hepatitis virus is much more neurovirulent than the MHV-A59 strain, although both strains use murine CEACAM1a (mCEACAM1a) as the receptor to infect murine cells. We previously showed thatCeacam1a−/−mice are completely resistant to MHV-A59 infection (E. Hemmila et al., J. Virol. 78:10156-10165, 2004). In vitro, MHV-JHM, but not MHV-A59, can spread from infected murine cells to cells that lack mCEACAM1a, a phenomenon called receptor-independent spread. To determine whether MHV-JHM could infect and spread in the brain independent of mCEACAM1a, we inoculatedCeacam1a−/−mice. AlthoughCeacam1a−/−mice were completely resistant to i.c. inoculation with 106PFU of recombinant wild-type MHV-A59 (RA59) virus, these mice were killed by recombinant MHV-JHM (RJHM) and a chimeric virus containing the spike of MHV-JHM in the MHV-A59 genome (SJHM/RA59). Immunohistochemistry showed that RJHM and SJHM/RA59 infected all neural cell types and induced severe microgliosis in bothCeacam1a−/−and wild-type mice. For RJHM, the 50% lethal dose (LD50) is <101.3in wild-type mice and 103.1inCeacam1a−/−mice. For SJHM/RA59, the LD50is <101.3in wild-type mice and 103.6inCeacam1a−/−mice. This study shows that infection and spread of MHV-JHM in the brain are dependent upon the viral spike glycoprotein. RJHM can initiate infection in the brains ofCeacam1a−/−mice, but expression of mCEACAM1a increases susceptibility to infection. The spread of infection in the brain is mCEACAM1a independent. Thus, the ability of the MHV-JHM spike to mediate mCEACAM1a-independent spread in the brain is likely an important factor in the severe neurovirulence of MHV-JHM in wild-type mice.
A Conserved Motif in Region V of the Large Polymerase Proteins of Nonsegmented Negative-Sense RNA Viruses That Is Essential for mRNA Capping
Authors: Li Jianrong , Rahmeh Amal , Morelli Marco , Whelan Sean P. J. 
Published: November 2007

ABSTRACT
Nonsegmented negative-sense (NNS) RNA viruses cap their mRNA by an unconventional mechanism. Specifically, 5′ monophosphate mRNA is transferred to GDP derived from GTP through a reaction that involves a covalent intermediate between the large polymerase protein L and mRNA. This polyribonucleotidyltransferase activity contrasts with all other capping reactions, which are catalyzed by an RNA triphosphatase and guanylyltransferase. In these reactions, a 5′ diphosphate mRNA is capped by transfer of GMP via a covalent enzyme-GMP intermediate. RNA guanylyltransferases typically have a KxDG motif in which the lysine forms this covalent intermediate. Consistent with the distinct mechanism of capping employed by NNS RNA viruses, such a motif is absent from L. To determine the residues of L protein required for capping, we reconstituted the capping reaction of the prototype NNS RNA virus, vesicular stomatitis virus, from highly purified components. Using a panel of L proteins with single-amino-acid substitutions to residues universally conserved among NNS RNA virus L proteins, we define a new motif, GxxT[n]HR, present within conserved region V of L protein that is essential for this unconventional mechanism of mRNA cap formation.
Strong accountability for network storage
Authors: Yumerefendi Aydan R. , Chase Jeffrey S. 
Published: November 2007

This article presents the design, implementation, and evaluation of CATS, a network storage service with strong accountability properties. CATS offers a simple web services interface that allows clients to read and write opaque objects of variable size. This interface is similar to the one offered by existing commercial Internet storage services. CATS extends the functionality of commercial Internet storage services by offering support for strong accountability.A CATS server annotates read and write responses with evidence of correct execution, and offers audit and challenge interfaces that enable clients to verify that the server is faithful. A faulty server cannot conceal its misbehavior, and evidence of misbehavior is independently verifiable by any participant. CATS clients are also accountable for their actions on the service. A client cannot deny its actions, and the server can prove the impact of those actions on the state views it presented to other clients.Experiments with a CATS prototype evaluate the cost of accountability under a range of conditions and expose the primary factors influencing the level of assurance and the performance of a strongly accountable storage server. The results show that strong accountability is practical for network storage systems in settings with strong identity and modest degrees of write-sharing. We discuss how the accountability concepts and techniques used in CATS generalize to other classes of network services.
Contributing storage using the transparent file system
Authors: Cipar James , Corner Mark D. , Berger Emery D. 
Published: November 2007

Contributory applications allow users to donate unused resources on their personal computers to a shared pool. Applications such as SETI@home, Folding@home, and Freenet are now in wide use and provide a variety of services, including data processing and content distribution. However, while several research projects have proposed contributory applications that support peer-to-peer storage systems, their adoption has been comparatively limited. We believe that a key barrier to the adoption of contributory storage systems is that contributing a large quantity of local storage interferes with the principal user of the machine.
To overcome this barrier, we introduce the Transparent File System (TFS). TFS provides background tasks with large amounts of unreliable storage—all of the currently available space—without impacting the performance of ordinary file access operations. We show that TFS allows a peer-to-peer contributory storage system to provide 40% more storage at twice the performance when compared to a user-space storage mechanism. We analyze the impact of TFS on replication in peer-to-peer storage systems and show that TFS does not appreciably increase the resources needed for file replication.
PARAID
Authors: Weddle Charles , Oldham Mathew , Qian Jin , Wang An-I Andy , Reiher Peter , Kuenning Geoff 
Published: November 2007

Reducing power consumption for server-class computers is important, since increased energy usage causes more heat dissipation, greater cooling requirements, reduced computational density, and higher operating costs. For a typical data center, storage accounts for 27% of energy consumption. Conventional server-class RAIDs cannot easily reduce power because loads are balanced to use all disks, even for light loads.
We have built the power-aware RAID (PARAID), which reduces energy use of commodity server-class disks without specialized hardware. PARAID uses a skewed striping pattern to adapt to the system load by varying the number of powered disks. By spinning disks down during light loads, PARAID can reduce power consumption, while still meeting performance demands, by matching the number of powered disks to the system load. Reliability is achieved by limiting disk power cycles and using different RAID encoding schemes. Based on our five-disk prototype, PARAID uses up to 34% less power than conventional RAIDs while achieving similar performance and reliability.
The jastadd extensible java compiler
Authors: Ekman Torbjörn , Hedin Görel 
Published: November 2007

The JastAdd Extensible Java Compiler is a high quality Java compiler that is easy to extend in order to build static analysis tools for Java, and to extend Java with new language constructs. It is built modularly, with a Java 1.4 compiler that is extended to a Java 5 compiler. Example applications that are built as extensions include an alternative backend that generates Jimple, an extension of Java with AspectJ constructs, and the implementation of a pluggable type system for non-null checking and inferenc.
The system is implemented using JastAdd, a declarative Java-like language. We describe the compiler architecture, the major design ideas for building and extending the compiler, in particular, for dealing with complex extensions that affect name and type analysis. Our extensible compiler compares very favorably concerning quality, speed and size with other extensible Java compiler frameworks. It also compares favorably in quality and size compared with traditional non-extensible Java compilers, and it runs within a factor of three compared to javac.
Statistically rigorous java performance evaluation
Authors: Georges Andy , Buytaert Dries , Eeckhout Lieven 
Published: November 2007

Java performance is far from being trivial to benchmark because it is affected by various factors such as the Java application, its input, the virtual machine, the garbage collector, the heap size, etc. In addition, non-determinism at run-time causes the execution time of a Java program to differ from run to run. There are a number of sources of non-determinism such as Just-In-Time (JIT) compilation and optimization in the virtual machine (VM) driven by timer-based method sampling, thread scheduling, garbage collection, and various.
There exist a wide variety of Java performance evaluation methodologies usedby researchers and benchmarkers. These methodologies differ from each other in a number of ways. Some report average performance over a number of runs of the same experiment; others report the best or second best performance observed; yet others report the worst. Some iterate the benchmark multiple times within a single VM invocation; others consider multiple VM invocations and iterate a single benchmark execution; yet others consider multiple VM invocations and iterate the benchmark multiple times.
This paper shows that prevalent methodologies can be misleading, and can even lead to incorrect conclusions. The reason is that the data analysis is not statistically rigorous. In this paper, we present a survey of existing Java performance evaluation methodologies and discuss the importance of statistically rigorous data analysis for dealing with non-determinism. We advocate approaches to quantify startup as well as steady-state performance, and, in addition, we provide the JavaStats software to automatically obtain performance numbers in a rigorous manner. Although this paper focuses on Java performance evaluation, many of the issues addressed in this paper also apply to other programming languages and systems that build on a managed runtime system.
Lost in translation
Authors: Bierman Gavin M. , Meijer Erik , Torgersen Mads 
Published: November 2007

Current real-world software applications typically involve heavy use of relational and XML data and their query languages. Unfortunately object-oriented languages and database query languages are based on different semantic foundations and optimization strategies. The resulting ''ROX (Relations, Objects, XML) impedance mismatc'' makes life very difficult for developers.
Microsoft Corporation is developing extensions to the .NET framework to facilitate easier processing of non-object-oriented data models. Part of this project (known as "LINQ") includes various extensions to the .NET languages to leverage this support.

In this paper we consider proposals for C
#
3.0, the next version of the C
#
programming language. We give both an informal introduction to the new language features, and a precise formal account by defining a translation from C
#
3.0 to C
#
2.0. This translation also demonstrates how these language extensions do not require any changes to the underlying CLR.
From the editors
Authors: Stafford Tom , Chau Patrick Y. K. , Schwarz Andrew , Lanier Clinton R. 
Published: November 2007

Interesting times and interesting research at Data Base this year. We'll be providing coverage of a new Chinese Information Systems conference, courtesy of Global Co-Editor Patrick Chau. We have an issue on software testing in process with Al Hevner, and this promises to provide some interesting new perspectives on an underutilized but critical research area in our field.
We are expanding our global reach and service dramatically. You'll see important colleagues from distant lands on our masthead as board members, even editors. You'll notice increasing submissions from far parts of the global market. You'll find a new perspective on the practice of scholarship in Information Systems, worldwide, at ACM Data Base!
This issue, welcome Guest Editor Ed Roche, who has brought a globe-spanning body of speculative and futuristic writing about emerging virtual worlds enabled by online technology. Authors from the four corners of the eWorld weigh in with discussions of where the Internet is taking us as an experiential and cultural milieu of modern life. The directions for research provided by this extraordinary overview of an emerging field of inquiry are innovative, visionary and dramatic.
We hope you like it. We hope you'll send us work equally as innovative. We hope you'll tell your friends around the world about how easy it is to access ACM Data Base with our online portal and review system, as well, located at http://www.editorialmanager.com/sigmisdb.