bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actively Learning Object Names Across Ambiguous Situations
Authors: Kachergis George , Yu Chen , Shiffrin Richard M. 
Published: January 2013

AbstractPrevious research shows that people can use the co‐occurrence of words and objects in ambiguous situations (i.e., containing multiple words and objects) to learn word meanings during a brief passive training period (Yu & Smith, 2007). However, learners in the world are not completely passive but can affect how their environment is structured by moving their heads, eyes, and even objects. These actions can indicate attention to a language teacher, who may then be more likely to name the attended objects. Using a novel active learning paradigm in which learners choose which four objects they would like to see named on each successive trial, this study asks whether active learning is superior to passive learning in a cross‐situational word learning context. Finding that learners perform better in active learning, we investigate the strategies and discover that most learners use immediate repetition to disambiguate pairings. Unexpectedly, we find that learners who repeat only one pair per trial—an easy way to infer this pair—perform worse than those who repeat multiple pairs per trial. Using a working memory extension to an associative model of word learning with uncertainty and familiarity biases, we investigate individual differences that correlate with these assorted strategies.
Human Semi‐Supervised Learning
Authors: Gibson Bryan R. , Rogers Timothy T. , Zhu Xiaojin 
Published: January 2013

AbstractMost empirical work in human categorization has studied learning in either fully supervised or fully unsupervised scenarios. Most real‐world learning scenarios, however, are semi‐supervised: Learners receive a great deal of unlabeled information from the world, coupled with occasional experiences in which items are directly labeled by a knowledgeable source. A large body of work in machine learning has investigated how learning can exploit both labeled and unlabeled data provided to a learner. Using equivalences between models found in human categorization and machine learning research, we explain how these semi‐supervised techniques can be applied to human learning. A series of experiments are described which show that semi‐supervised learning models prove useful for explaining human behavior when exposed to both labeled and unlabeled data. We then discuss some machine learning models that do not have familiar human categorization counterparts. Finally, we discuss some challenges yet to be addressed in the use of semi‐supervised models for modeling human categorization.
Bilateral Trade and the Eurozone: Evidence from New Member Countries
Authors: Jagelka Tomáš 
Published: January 2013

AbstractThe question of whether and how much currency unions increase bilateral trade among their members has garnered much attention since Rose’s seminal article. The answer is as pertinent now as ever for both the Eurozone’s existing and future members as the financial crisis shook the very foundations of the European Monetary Union (EMU) and brought its shortcomings into the spotlight. This paper analyses the issue using the gravity equation with country pair and time fixed effects. For a sample of the four new members of the EMU – Slovakia, Slovenia, Malta and Cyprus – which has, to the author’s knowledge, not been studied thus far due to their recent joining, and controls drawn from the European Union, this paper finds a positive relationship between joining the EMU and trade with EMU partners but not with non‐EMU partners.
Genetic Types, Gene Repertoire, and Evolution of Isolates of the Salmonella enterica Serovar 4,5,12:i:− Spanish Clone Assigned to Different Phage Types
Authors: García Patricia , Malorny Burkhard , Hauser Elisabeth , Mendoza M. Carmen , Rodicio M. Rosario 
Published: January 2013

ABSTRACT

Salmonella enterica
subsp.
enterica
4,[5],12:i:− is one of the most prevalent serovars associated with human infections worldwide. Two multidrug-resistant clones, designated Spanish and European clones, are recognized as having importance for public health and are subject to control measures in the European Union. In this study, 23 clinical isolates belonging to the Spanish clone were characterized by multilocus sequence typing, multiple-locus variable number tandem repeat analysis (MLVA), PCR amplification and sequencing, and a DNA microarray targeting 263 genes, in order to provide new insights into their origins and further evolution. The derived data were compared with information available from other studies for
S
. 4,[5],12:i:− isolates of both the Spanish and the European clones, to identify differential molecular markers which could be potentially used as surveillance tools in the control of dissemination of this serovar. The isolates analyzed were assigned to sequence type 19 and to 17 MLVA patterns, with 3-13-16-NA-311 being the most prevalent. Highly similar virulence, metabolic, and prophage-associated gene profiles were identified, but DNA mobility markers distinguished five genotypes. Two types of deletions, caused by insertion of IS
26
, presumably donated by pUO-STmR/RV1-like plasmids typically found in the Spanish clone, affected the
fljAB
operon and surrounding DNA. The Spanish and European clones differ in sequence type, MLVA patterns, gene repertoire, and
fljAB
deletion type. The observed variability supports an independent evolution of the two successful monophasic clones from different
Salmonella enterica
serovar Typhimurium ancestors and can be taken into consideration for epidemiological surveillance.
Evaluation of Epstein-Barr Virus, Human Herpesvirus 6 (HHV-6), and HHV-8 Antiviral Drug Susceptibilities by Use of Real-Time-PCR-Based Assays
Authors: Bounaadja Lotfi , Piret Jocelyne , Goyette Nathalie , Boivin Guy 
Published: January 2013

ABSTRACT

Evaluation of candidate antiviral drugs against Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and HHV-8 is hampered by the lack of convenient laboratory assays. We developed real-time quantitative PCR assays performed on supernatants of lymphoma cell lines and determined the 50% inhibitory concentrations (IC
50
s) of nucleoside, nucleotide, and pyrophosphate analogues against these herpesviruses.
An N-Terminal Amphipathic Helix in Dengue Virus Nonstructural Protein 4A Mediates Oligomerization and Is Essential for Replication
Authors: Stern Omer , Hung Yu-Fu , Valdau Olga , Yaffe Yakey , Harris Eva , Hoffmann Silke , Willbold Dieter , Sklan Ella H. 
Published: January 2013

ABSTRACT
Dengue virus (DENV) causes dengue fever, a major health concern worldwide. We identified an amphipathic helix (AH) in the N-terminal region of the viral nonstructural protein 4A (NS4A). Disruption of its amphipathic nature using mutagenesis reduced homo-oligomerization and abolished viral replication. These data emphasize the significance of NS4A in the life cycle of the dengue virus and demarcate it as a target for the design of novel antiviral therapy.
Timeless-Dependent DNA Replication-Coupled Recombination Promotes Kaposi's Sarcoma-Associated Herpesvirus Episome Maintenance and Terminal Repeat Stability
Authors: Dheekollu Jayaraju , Chen Horng-Shen , Kaye Kenneth M. , Lieberman Paul M. 
Published: January 2013

ABSTRACT
Kaposi's Sarcoma-associated herpesvirus (KSHV) is maintained as a stable episome in latently infected pleural effusion lymphoma (PEL) cells. Episome maintenance is conferred by the binding of the KSHV-encoded LANA protein to the viral terminal repeats (TR). Here, we show that DNA replication in the KSHV TR is coupled with DNA recombination and mediated in part through the cellular replication fork protection factors Timeless (Tim) and Tipin. We show by two-dimensional (2D) agarose gel electrophoresis that replication forks naturally stall and form recombination-like structures at the TR during an unperturbed cell cycle. Chromatin immunoprecipitation (ChIP) assays revealed that Tim and Tipin are selectively enriched at the KSHV TR during S phase and in a LANA-dependent manner. Tim depletion inhibited LANA-dependent TR DNA replication and caused the loss of KSHV episomes from latently infected PEL cells. Tim depletion resulted in the aberrant accumulation of recombination structures and arrested MCM helicase at TR. Tim depletion did not induce the KSHV lytic cycle or apoptotic cell death. We propose that KSHV episome maintenance requires Tim-assisted replication fork protection at the viral terminal repeats and that Tim-dependent recombination-like structures form at TR to promote DNA repeat stability and viral genome maintenance.
T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses
In Vitro
Authors: Baranovich Tatiana , Wong Sook-San , Armstrong Jianling , Marjuki Henju , Webby Richard J. , Webster Robert G. , Govorkova Elena A. 
Published: January 2013

ABSTRACT

Several novel anti-influenza compounds are in various phases of clinical development. One of these, T-705 (favipiravir), has a mechanism of action that is not fully understood but is suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the mechanism of T-705 activity against influenza A (H1N1) viruses by applying selective drug pressure over multiple sequential passages in MDCK cells. We found that T-705 treatment did not select specific mutations in potential target proteins, including PB1, PB2, PA, and NP. Phenotypic assays based on cell viability confirmed that no T-705-resistant variants were selected. In the presence of T-705, titers of infectious virus decreased significantly (
P
< 0.0001) during serial passage in MDCK cells inoculated with seasonal influenza A (H1N1) viruses at a low multiplicity of infection (MOI; 0.0001 PFU/cell) or with 2009 pandemic H1N1 viruses at a high MOI (10 PFU/cell). There was no corresponding decrease in the number of viral RNA copies; therefore, specific virus infectivity (the ratio of infectious virus yield to viral RNA copy number) was reduced. Sequence analysis showed enrichment of G→A and C→T transversion mutations, increased mutation frequency, and a shift of the nucleotide profiles of individual NP gene clones under drug selection pressure. Our results demonstrate that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705. Our findings also explain the broad spectrum of activity of T-705 against viruses of multiple families.
Comparative Proteomic Analysis of HIV-1 Particles Reveals a Role for Ezrin and EHD4 in the Nef-Dependent Increase of Virus Infectivity
Authors: Brégnard Christelle , Zamborlini Alessia , Leduc Marjorie , Chafey Philippe , Camoin Luc , Saïb Ali , Benichou Serge , Danos Olivier , Basmaciogullari Stéphane 
Published: January 2013

ABSTRACT

Nef is a human immunodeficiency virus type 1 (HIV-1) auxiliary protein that plays an important role in virus replication and the onset of acquired immunodeficiency. Although known functions of Nef might explain its contribution to HIV-1-associated pathogenesis, how Nef increases virus infectivity is still an open question.
In vitro
, Nef-deleted viruses have a defect that prevents efficient completion of early steps of replication. We have previously shown that this restriction is not due to the absence of Nef in viral particles. Rather, a loss of function in virus-producing cells accounts for the lower infectivity of
nef
-deleted viruses compared to wild-type (WT) viruses. Here we used DiGE and iTRAQ to identify differences between the proteomes of WT and
nef
-deleted viruses. We observe that glucosidase II is enriched in WT virions, whereas Ezrin, ALG-2, CD81, and EHD4 are enriched in
nef
-deleted virions. Functional analysis shows that glucosidase II, ALG-2, and CD81 have no or only Nef-independent effect on infectivity. In contrast, Ezrin and EHD4 are involved in the ability of Nef to increase virus infectivity (referred to thereafter as Nef potency). Indeed, simultaneous Ezrin and EHD4 depletion in SupT1 and 293T virus-producing cells result in an ∼30 and ∼70% decrease of Nef potency, respectively. Finally, while Ezrin behaves as an inhibitory factor counteracted by Nef, EHD4 should be considered as a cofactors required by Nef to increase virus infectivity.
Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques
Authors: Xu Yin , Weatherall Chris , Bailey Michelle , Alcantara Sheilajen , De Rose Robert , Estaquier Jerome , Wilson Kim , Suzuki Kazuo , Corbeil Jacques , Cooper David A. , Kent Stephen J. , Kelleher Anthony D. , Zaunders John 
Published: January 2013

ABSTRACT

T follicular helper (Tfh) cells are a specialized subset of memory CD4
+
T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1
high
CD127
low
memory CD4
+
T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4
+
memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir.
Toscana Virus NSs Protein Promotes Degradation of Double-Stranded RNA-Dependent Protein Kinase
Authors: Kalveram Birte , Ikegami Tetsuro 
Published: January 2013

ABSTRACT

Toscana virus (TOSV), which is transmitted by
Phlebotomus
spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the Mediterranean. Like other members of the genus
Phlebovirus
of the family
Bunyaviridae
, TOSV encodes a nonstructural protein (NSs) in its small RNA segment. Although the NSs of Rift Valley fever virus (RVFV) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon promoter, and promotes the proteasomal degradation of double-stranded RNA-dependent protein kinase (PKR), little is known about the functions of NSs proteins encoded by less-pathogenic members of this genus. In this study we report that TOSV is able to downregulate PKR with similar efficiency as RVFV, while infection with the other phleboviruses—i.e., Punta Toro virus, sandfly fever Sicilian virus, or Frijoles virus—has no effect on cellular PKR levels. In contrast to RVFV, however, cellular transcription remains unaffected during TOSV infection. TOSV NSs protein promotes the proteasome-dependent downregulation of PKR and is able to interact with kinase-inactive PKR in infected cells.
PEGylation of Vesicular Stomatitis Virus Extends Virus Persistence in Blood Circulation of Passively Immunized Mice
Authors: Tesfay Mulu Z. , Kirk Amber C. , Hadac Elizabeth M. , Griesmann Guy E. , Federspiel Mark J. , Barber Glen N. , Henry Stephen M. , Peng Kah-Whye , Russell Stephen J. 
Published: January 2013

ABSTRACTWe are developing oncolytic vesicular stomatitis viruses (VSVs) for systemic treatment of multiple myeloma, an incurable malignancy of antibody-secreting plasma cells that are specifically localized in the bone marrow. One of the presumed advantages for using VSV as an oncolytic virus is that human infections are rare and preexisting anti-VSV immunity is typically lacking in cancer patients, which is very important for clinical success. However, our studies show that nonimmune human and mouse serum can neutralize clinical-grade VSV, reducing the titer by up to 4 log units in 60 min. In addition, we show that neutralizing anti-VSV antibodies negate the antitumor efficacy of VSV, a concern for repeat VSV administration. We have investigated the potential use of covalent modification of VSV with polyethylene glycol (PEG) or a function-spacer-lipid (FSL)–PEG construct to inhibit serum neutralization and to limit hepatosplenic sequestration of systemically delivered VSV. We report that in mice passively immunized with neutralizing anti-VSV antibodies, PEGylation of VSV improved the persistence of VSV in the blood circulation, maintaining a more than 1-log-unit increase in VSV genome copies for up to 1 h compared to the genome copy numbers for the non-PEGylated virus, which was mostly cleared within 10 min after intravenous injection. We are currently investigating if this increase in PEGylated VSV circulating half-life can translate to increased virus delivery and better efficacy in mouse models of multiple myeloma.
Characterization of the Bhanja Serogroup Viruses (Bunyaviridae): a Novel Species of the Genus Phlebovirus and Its Relationship with Other Emerging Tick-Borne Phleboviruses
Authors: Matsuno Keita , Weisend Carla , Travassos da Rosa Amelia P. A. , Anzick Sarah L. , Dahlstrom Eric , Porcella Stephen F. , Dorward David W. , Yu Xue-Jie , Tesh Robert B. , Ebihara Hideki 
Published: January 2013

ABSTRACT

Bhanja virus (BHAV) and its antigenically close relatives Forecariah virus (FORV), Kismayo virus (KISV), and Palma virus (PALV) are thought to be members of the family
Bunyaviridae
, but they have not been assigned to a genus or species. Despite their broad geographical distribution and reports that BHAV causes sporadic cases of febrile illness and encephalitis in humans, the public health importance of the Bhanja serogroup viruses remains unclear, due in part to the lack of sequence and biochemical information for the virus proteins. In order to better define the molecular characteristics of this group, we determined the full-length sequences of the L, M, and S genome segments of multiple isolates of BHAV as well as FORV and PALV. The genome structures of these Bhanja viruses are similar to those of viruses belonging to the genus
Phlebovirus
. Functional domains and amino acid motifs in the viral proteins that are conserved among other known phleboviruses were also identified in proteins of the BHAV group. Phylogenetic and serological analyses revealed that the BHAVs are most closely related to the novel emerging tick-borne phleboviruses severe fever with thrombocytopenia syndrome virus and Heartland virus, which have recently been implicated as causing severe acute febrile illnesses associated with thrombocytopenia in humans in China and the United States. Our results indicate that the Bhanja serogroup viruses constitute a single novel species in the genus
Phlebovirus
. The results of this study should facilitate epidemiological surveillance for other, similar tick-borne phleboviruses that may represent unrecognized causes of febrile illness in humans.
Adaptation to the Interferon-Induced Antiviral State by Human and Simian Immunodeficiency Viruses
Authors: Bitzegeio Julia , Sampias Marissa , Bieniasz Paul D. , Hatziioannou Theodora 
Published: January 2013

ABSTRACT

The production of type I interferon (IFN) is an early host response to different infectious agents leading to the induction of hundreds of IFN-stimulated genes (ISGs). The roles of many ISGs in host defense are unknown, but their expression results in the induction of an “antiviral state” that inhibits the replication of many viruses. Here we show that prototype primate lentiviruses human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaques (SIV
MAC
and SIV
MNE
) can replicate in lymphocytes from their usual hosts (humans and macaques, respectively), even when an antiviral state is induced by IFN-α treatment. In contrast, HIV-1 and SIV
MAC
/SIV
MNE
replication was hypersensitive to IFN-α in lymphocytes from unnatural hosts, indicating that the antiviral state can effectively curtail the replication of primate lentiviruses in hosts to which they are not adapted. Most of the members of a panel of naturally occurring HIV-1 and HIV-2 strains behaved like prototype strains and were comparatively insensitive to IFN-α in human lymphocytes. Using chimeric viruses engineered to overcome restriction factors whose antiretroviral specificities vary in a species-dependent manner, we demonstrate that differential HIV-1 and SIV
MAC
sensitivities to IFN-α in lymphocytes from humans and macaques could not be ascribed to TRIM5, APOBEC3, tetherin, or SAMHD1. Single-cycle infection experiments indicated that at least part of this species-specific, IFN-α-induced restriction of primate lentivirus replication occurs early in the retroviral life cycle. Overall, these studies indicate the existence of undiscovered, IFN-α-inducible antiretroviral factors whose spectrum of activity varies in a species-dependent manner and to which at least some HIV/SIV strains have become adapted in their usual hosts.
Does Microenvironment Contribute to the Etiology of Estrogen Receptor–Negative Breast Cancer?
Authors: Barcellos-Hoff Mary Helen 
Published: January 2013

Abstract
What dictates the prevalence of certain types of breast cancer, which are classified by markers, particularly estrogen receptor (ER), expression profiles such as basal or luminal, and genetic alterations such as HER2 amplification, in particular populations is not well understood. It is increasingly evident that microenvironment disruption is highly intertwined with cancer progression. Here, the idea that microenvironment shapes the course of carcinogenesis, and hence breast cancer subtype, is discussed. Aggressive, basal-like, ER-negative breast tumors occur in younger women, African-American women, women who carry BRCA1 mutation, and women exposed to ionizing radiation. Recent experimental studies using ionizing radiation, a well-documented environmental exposure, suggest that certain processes in the microenvironment strongly favor the development of ER-negative tumors. Understanding the contribution of tissue microenvironment during carcinogenesis could lead to prevention strategies that are personalized to age, agent, and exposure to reduce the risk of aggressive breast cancer. Clin Cancer Res; 19(3); 541–8. ©2012 AACR.