bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulse-Momentum Diagrams
Authors: Rosengrant David
Published: December 2010

Multiple representations are a valuable tool to help students learn and understand physics concepts.1 Furthermore, representations help students learn how to think and act like real scientists.2 These representations include: pictures, free-body diagrams,3 energy bar charts,4 electrical circuits, and, more recently, computer simulations and animations.5 However, instructors have limited choices when they want to help their students understand impulse and momentum. One of the only available options is the impulse-momentum bar chart.6 The bar charts can effectively show the magnitude of the momentum as well as help students understand conservation of momentum, but they do not easily show the actual direction. This paper highlights a new representation instructors can use to help their students with momentum and impulse—the impulse-momentum diagram (IMD).
Resonance Effects in Magnetically Driven Mass-Spring Oscillations
Authors: Taylor Ken
Published: December 2010

Resonance effects are among the most intriguing phenomena in physics and engineering. The classical case of a mass-spring oscillator driven at its resonant frequency is one of the earliest examples that students encounter. Perhaps the most commonly depicted method of driving the vibrating system is mechanical. An alternative approach presented in this paper describes an electromagnetic driver that is convenient to use and that provides a frequency resolution of 0.001 Hz. A common mass-spring arrangement suspended vertically with a linear array of permanent magnets located at the bottom of the system is used for illustrating the technique.1
… And now a suspended Cartesian diver
Authors: Fakhruddin Hasan
Published: December 2010

A Cartesian diver can be held suspended in a liquid in which there is a density gradient decreasing from bottom to the top if the density of the diver is between those of the liquid at the top and the bottom. This article adds to a number of Cartesian diver activities published in TPT.1 In a tall beaker of water, a large amount of sugar is added to the bottom. As the sugar dissolves at the bottom, a density gradient, decreasing from bottom to the top, is set up.
Mindset matters
Authors: Cato John
Published: December 2010

We all love those students who just refuse to quit. At sometime during their lives, they adopted a philosophy that they were going to do the best they could, and they recognized that accomplishing their dreams was simply a matter of doing the necessary work in order to be successful. But we also have had those students who didn't even seem to try, and there was very little we could do to get them going. They coasted along, made poor grades, and always seemed to indicate that they weren't going to try. They were “smart,” they never needed to study, and they certainly weren't about to start now no matter what was said to them. Better yet, their struggles weren't their fault, but rather due to “bad teaching.” I thought that was just the way it was going to be.
The Social Sense: Susceptibility to Others’ Beliefs in Human Infants and Adults
Authors: Kovács Ágnes Melinda , Téglás Ernő , Endress Ansgar Denis
Published: December 2010

Mind Reading

One core component of social cognition, especially of the kind practiced by humans, is the capacity to formulate a representation of what someone else believes to be true, even if that belief is not anchored in reality. Holding two such beliefs in mind—one false and one true—is no simple feat, and up until a few years ago, it was generally accepted that such a capacity did not arise until children were 3 to 4 years old. Since then, a flurry of studies, using a variety of interrogation measures, has suggested that much-younger humans might, in fact, possess this capacity, commonly referred to as a theory of mind.

Kovács
et al.

(p.
1830
) devised an ingenious behavioral paradigm and applied it both to adults and to infants, which suggests that the representations of others' beliefs are indeed formed in the same way in adults and in infants.
Boosting CITES
Authors: Phelps Jacob , Webb Edward L. , Bickford David , Nijman Vincent , Sodhi Navjot S.
Published: December 2010

To protect biodiversity, more, improved biological and trade data and analyses are needed.
Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation
Authors: Forneris Federico , Ricklin Daniel , Wu Jin , Tzekou Apostolia , Wallace Rachel S. , Lambris John D. , Gros Piet
Published: December 2010

A Safety Catch on Immune Response

The complement system is an integral part of the innate immune system. When triggered, it initiates a cascade that marks intruders for elimination and stimulates immune responses. The key amplification step is cleavage of a complex comprising the complement fragment C3b and factor B (C3bB) by factor D (FD).

Forneris
et al.

(p.
1816
) now describe the crystal structure of C3bB and its complex with FD. The structures support a mechanism in which membrane-bound C3b stabilizes an open form of factor B (FB) that has its scissile bond accessible. FD binds through a site distant from its catalytic center to the open form of FB, which activates FD. The two conformational equilibria represent a double safety-catch that would allow tight regulation of this immune response pathway.
Dynamics of Magnetic Domain Walls Under Their Own Inertia
Authors: Thomas Luc , Moriya Rai , Rettner Charles , Parkin Stuart S.P.
Published: December 2010

Moving Walls

The current-induced movement of magnetic domain walls in magnetic nanowires is a candidate for a new architecture in logic processing and memory. Controlling the motion and position of the domain walls as they move along the wires in excess of 100 meters per second requires an understanding of the processes involved.

Thomas
et al.

(p.
1810
) investigated the dynamics of magnetic domain wall motion, looking at the acceleration, constant motion, and deceleration processes in detail. The whole process could be described in terms of the inertia of the domain wall. The distance traveled was simply proportional to the length of the current pulse used to move the wall, which should simplify implementation in a circuit or network architecture.
French Nobelist Escapes 'Intellectual Terror' to Pursue Radical Ideas in China
Authors: Enserink Martin
Published: December 2010

Virologist and Nobel laureate Luc Montagnier announced earlier this month that, at age 78, he will take on the leadership of a new research institute at Jiaotong University in Shanghai.
Science
talked to Montagnier last week.
Discoverer Asks for Time, Patience Over Arsenic Bacteria Controversy
Authors: Pennisi Elizabeth
Published: December 2010

Three weeks ago, NASA astrobiology fellow Felisa Wolfe-Simon published a paper in
Science
about bacteria that can use arsenic instead of phosphorus in DNA and other biomolecules. Then came a torrent of criticism that she and her co-authors declined to respond to. Last week, Wolfe-Simon agreed to share some of her thoughts in an interview with
Science
's news department.
Training the Translational Scientist
Authors: Jackson Rebecca D. , Gabriel Sherine , Pariser Anne , Feig Peter
Published: December 2010

A session about educating translational scientists was held at a 2010 NIH forum on promoting collaborations between academia, government, and industry.
Working with the CTSA Consortium: What We Bring to the Table
Authors: Steele Scott J.
Published: December 2010

A session about how CTSA Consortium efforts can foster public-private partnerships was held at a 2010 NIH forum on promoting collaborations among academia, government, and industry.
Insulin Resistance Results in Brain Drain
Authors: Buettner Christoph
Published: December 2010

Insulin regulates brain cholesterol metabolism by modulating the expression of cholesterol-synthesizing enzymes in the central nervous system.
Illuminating Drug Action in the Parkinsonian Brain
Authors: Minzenberg Michael J.
Published: December 2010

Functional MRI can be used to monitor the action of new drugs in the brains of Parkinson's disease patients.
Evaluation of Serum Bactericidal Antibody Assays forHaemophilus influenzaeSerotype a
Authors: Rouphael Nadine G. , Satola Sarah , Farley Monica M. , Rudolph Karen , Schmidt Daniel S. , Gomez-de-León Patricia , Robbins John B. , Schneerson Rachel , Carlone George M. , Romero-Steiner Sandra
Published: December 2010

Haemophilus influenzaetype a (Hia) is an important pathogen for some American Indian, Alaskan native, and Northern Canada aboriginal populations. Assays to measure serum bactericidal activity (SBA) to Hia have not been developed or validated. Here, we describe two methods for the measurement of SBA: SBA with a viability endpoint (CFU counts) and SBA with a fluorometric endpoint using alamarBlue as the metabolic indicator. Both SBA assays measure Hia-specific functional antibody and correlate with anti-Hia IgG enzyme-linked immunosorbent assay (ELISA) concentration of naturally acquired antibodies.
Development of an Immunochromatographic Strip for Simple Detection of Penicillin-Binding Protein 2′
Authors: Matsui Hidehito , Hanaki Hideaki , Inoue Megumi , Akama Hiroyuki , Nakae Taiji , Sunakawa Keisuke , Omura Satoshi
Published: December 2010

Infections with methicillin-resistantStaphylococcus aureus(MRSA) and methicillin-resistant coagulase-negativeStaphylococcus(MR-CNS) are a serious problem in hospitals because these bacteria produce penicillin-binding protein 2′ (PBP2′ or PBP2a), which shows low affinity to β-lactam antibiotics. Furthermore, the bacteria show resistance to a variety of antibiotics. Identification of these pathogens has been carried out mainly by the oxacillin susceptibility test, which takes several days to produce a reliable result. We developed a simple immunochromatographic test that enabled the detection of PBP2′ within about 20 min. Anti-PBP2′ monoclonal antibodies were produced by a hybridoma of recombinant PBP2′ (rPBP2′)-immunized mouse spleen cells and myeloma cells. The monoclonal antibodies reacted only with PBP2′ of whole-cell extracts and showed no detectable cross-reactivity with extracts from other bacterial species tested so far. One of the monoclonal antibodies was conjugated with gold colloid particles, which react with PBP2′, and another antibody was immobilized on a nitrocellulose membrane, which captures the PBP2′-gold colloid particle complex on a nitrocellulose strip. This strip was able to detect 1.0 ng of rPBP2′ or 2.8 × 105to 1.7 × 107CFU of MRSA cells. The cross-reactivity test using 15 bacterial species and aCandida albicansstrain showed no detectable false-positive results. The accuracy of this method in the detection of MRSA and MR-CNS appeared to be 100%, compared with the results obtained by PCR amplification of the PBP2′ gene,mecA. This newly developed immunochromatographic test can be used for simple and accurate detection of PBP2′-producing cells in clinical laboratories.
BBK07 Immunodominant Peptides as Serodiagnostic Markers of Lyme Disease
Authors: Coleman Adam S. , Rossmann Evelyn , Yang Xiuli , Song Haichen , Lamichhane Chinta M. , Iyer Radha , Schwartz Ira , Pal Utpal
Published: December 2010

Lyme disease (LD) is a tick-borne infection caused by the bacterial pathogen
Borrelia burgdorferi
. Current diagnostic tests mostly use borrelial lysates or select antigens to detect serum antibodies against
B. burgdorferi
. These immunoassays are not entirely effective, especially for detection of early infection. We have recently characterized an
in vivo
-induced antigen, BBK07, as a serodiagnostic marker for LD. We now report that in a line blot assay, recombinant BBK07 protein-based detection is 90% sensitive and nearly 100% specific against
B. burgdorferi
infection in humans. Using an overlapping peptide library of 23 peptides encompassing full-length BBK07, we identified the immunodominant epitopes of BBK07 during human infection. We show that a select combination of amino-terminal peptides significantly enhanced BBK07-based diagnostic accuracy compared to that with the full-length protein. Although in enzyme-linked immunosorbent assay (ELISA) studies BBK07 peptides had overall lower sensitivity than established serodiagnostic peptides, such as the VlsE peptide C6 and OspC peptide pepC10, for the detection of early human LD, a subset of serum samples that failed to recognize either VlsE or OspC peptides were preferentially reactive to BBK07 peptides. These results highlight the fact that BBK07 peptides could be useful to complement the efficacy of VlsE and OspC peptide-based serodiagnostic assays. Finally, using a panel of canine sera, we show that BBK07 peptide is also effective for LD diagnosis in infected dogs. Together, our data show that peptides from the
B. burgdorferi
surface protein BBK07 are highly specific and sensitive serodiagnostic markers, and we suggest their future use in LD diagnostic assays.
Low Levels of NF-κB/p65 Mark Anergic CD4+T Cells and Correlate with Disease Severity in Sarcoidosis
Authors: Lee Nam-Sihk , Barber Laura , Kanchwala Ali , Childs Carter J. H. , Kataria Yash P. , Judson Marc A. , Mazer Mark A. , Arce Sergio
Published: December 2010

T lymphocytes from patients with sarcoidosis respond weakly when stimulated with mitogen or antigen. However, the mechanisms responsible for this anergy are not fully understood. Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56LCK, and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4+T cells from patients with sarcoidosis. Baseline expression of p65 in these lymphocytes was reduced in 50% of patients. The reduced levels of p65 in sarcoid CD4+T cells concurred with decreased levels of p50, p105, CD3ζ, p56LCK, IκBα, and NF-ATc2. Polyclonal stimulation of NF-κB-deficient sarcoid T cells resulted in reduced expression of CD69 and CD154, decreased proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN-γ]) production. The clinical significance of these findings is suggested by the association between low p65 levels and the development of more severe and active sarcoidosis. Although correlative, our results support a model in which multiple intrinsic signaling defects contribute to peripheral T-cell anergy and the persistence of chronic inflammation in sarcoidosis.
Escherichia coli
Exports Cyclic AMP via TolC
Authors: Hantke Klaus , Winkler Karin , Schultz Joachim E.
Published: December 2010

In
Escherichia coli
more than 180 genes are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made by intracellular adenylyl cyclases is found in the culture medium. How is cAMP exported from
E. coli
? In a
tolC
mutant, 0.03 mM IPTG (isopropyl-β-
d
-thiogalactopyranoside) was sufficient to induce β-galactosidase compared to 0.1 mM IPTG in the parent strain. In a
cya
mutant unable to produce cAMP about 1 mM extracellular cAMP was required to induce β-galactosidase, whereas in a
cya tolC
mutant 0.1 mM cAMP was sufficient. When cAMP in
E. coli cya
was generated intracellularly by a recombinant, weakly active adenylyl cyclase from
Corynebacterium glutamicum
, the critical level of cAMP necessary for induction of maltose degradation was only achieved in a
tolC
mutant and not in the parent strain. Deletion of a putative cAMP phosphodiesterase of
E. coli
, CpdA, resulted in a slightly similar, yet more diffuse phenotype. The data demonstrate that export of cAMP via TolC is a most efficient way of
E. coli
to lower high concentrations of cAMP in the cell and maintain its sensitivity in changing metabolic environments.
Development and Evaluation of a Real-Time PCR Assay for Detection and Quantification of Blastocystis Parasites in Human Stool Samples: Prospective Study of Patients with Hematological Malignancies
Authors: Poirier Philippe , Wawrzyniak Ivan , Albert Aurélie , El Alaoui Hicham , Delbac Frédéric , Livrelli Valérie
Published: December 2010

Blastocystis
anaerobic parasites are widespread worldwide in the digestive tract of many animal species, including humans. Epidemiological
Blastocystis
studies are often limited by the poor sensitivity of standard parasitological assays for its detection. This report presents a highly sensitive real-time quantitative PCR (qPCR) assay developed to detect
Blastocystis
parasites in stool samples. The assay targets a partial sequence of the
Blastocystis
small ribosomal subunit (SSU) rRNA gene, allowing subtyping (ST) of
Blastocystis
isolates by direct sequencing of qPCR products. This qPCR method was assessed in a prospective study of 186 patients belonging to two cohorts—a group of 94 immunocompromised patients presenting hematological malignancies and a control group of 92 nonimmunocompromised patients. Direct-light microscopy and xenic
in vitro
stool culture analysis showed only 29% and 52% sensitivity, respectively, compared to our qPCR assay. Of the 27 (14.5%)
Blastocystis
-positive patients, 8 (4%) experienced digestive symptoms. No correlation was found between symptomatic patients and immune status, parasite load, or parasite subtypes, although subtyping of all isolates revealed a high (63.0%) prevalence of ST4. Two unexpected avian subtypes were found, i.e., ST6 and ST7, which are frequently isolated in Asia but rarely present in Western countries. In conclusion, this qPCR proved by far the most sensitive of the tested methods and allowed subtype determination by direct sequencing of qPCR products. New diagnostic tools such as the qPCR are essential for evaluating the clinical relevance of
Blastocystis
subtypes and their role in acute or chronic digestive disorders.
Genetic Diversity of Borrelia burgdorferi and Detection of B. bissettii-Like DNA in Serum of North-Coastal California Residents
Authors: Girard Yvette A. , Fedorova Natalia , Lane Robert S.
Published: December 2010

In North America, Lyme borreliosis (LB) is a tick-borne disease caused by infection with the spirochete
Borrelia burgdorferi
. We studied the genetic diversity of LB spirochetes in north-coastal California residents. Spirochete DNA was detected in 23.7% (27/114) of the study subjects using a PCR protocol optimized for increased sensitivity in human sera. Californians were most commonly infected with
B. burgdorferi ospC
genotype A, a globally widespread spirochete associated with high virulence in LB patients. Sequence analysis of
rrf-rrl
and
p66
loci in 11% (3/27) of the PCR-positive study subjects revealed evidence of infection with an organism closely related to
B. bissettii
. This spirochete, heretofore associated with LB only in Europe, is widely distributed among ticks and wildlife in North America. Further molecular testing of sera from residents in areas where LB is endemic is warranted to enhance our understanding of the geographic distribution and frequency of occurrence of
B. bissettii
-like infections.
Evaluation of the Cobas TaqMan MTB Test for Direct Detection of Mycobacterium tuberculosis Complex in Respiratory Specimens
Authors: Yang Yuan-Chieh , Lu Po-Liang , Huang Su Chiao , Jenh Yi-Shan , Jou Ruwen , Chang Tsung Chain
Published: December 2010

The Cobas TaqMan MTB test, based on real-time PCR technology, was evaluated for direct detection of
Mycobacterium tuberculosis
complex (MTBC) in respiratory specimens. A total of 1,093 samples from 446 patients, including 118 acid-fast smear-positive and 975 acid-fast smear-negative specimens, were investigated. Diagnostic cultures performed with 7H11 agar, Löwenstein-Jensen medium, and the Bactec MGIT 960 system were considered the reference methods. When discrepant results between the Cobas TaqMan MTB test and culture occurred, additional results from the BD MGIT TBc identification test and the GenoType Mycobacterium CM test performed on growth-positive and acid-fast-stain-positive MGIT tubes and review of the patient's medical history were used for discrepancy analysis. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the Cobas TaqMan MTB test were 91.5%, 98.7%, 91.5%, and 98.7%, respectively. In general, the performance of the new Cobas TaqMan MTB test was comparable to that of the replaced Cobas Amplicor MTB system. The most prominent feature of the new system was its extraordinarily high sensitivity (79.5%) for detecting MTBC in smear-negative specimens; out of 44 smear-negative but culture-positive specimens, 35 were positive by the new system. The Cobas TaqMan MTB assay, including DNA extraction, can be completed within 3 h.
Detection of Fluoroquinolone-Resistant Organisms from Rectal Swabs by Use of Selective Media Prior to a Transrectal Prostate Biopsy
Authors: Liss Michael A. , Peeples Amy N. , Peterson Ellena M.
Published: December 2010

Sepsis caused by fluoroquinolone-resistant
Escherichia coli
is a risk for patients undergoing an ultrasound-guided, transrectal prostate biopsy. A method incorporating selective broth and media was evaluated using rectal swabs obtained from 136 patients prior to a biopsy procedure. Fluoroquinolone-resistant organisms were isolated from 22% of the patients included in this study.
The Herpes Simplex Virus Type 1 Latency-Associated Transcript Can Protect Neuron-Derived C1300 and Neuro2A Cells from Granzyme B-Induced Apoptosis and CD8 T-Cell Killing
Authors: Jiang Xianzhi , Alami Chentoufi Aziz , Hsiang Chinhui , Carpenter Dale , Osorio Nelson , BenMohamed Lbachir , Fraser Nigel W. , Jones Clinton , Wechsler Steven L.
Published: December 2010

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only HSV-1 gene transcript abundantly expressed throughout latency. LAT null mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis activity is the major LAT factor involved in supporting the wild-type reactivation phenotype. During HSV-1 latency, some ganglionic neurons are surrounded by CD8 T cells, and it has been proposed that these CD8 T cells help maintain HSV-1 latency by suppressing viral reactivations. Surprisingly, despite injection of cytotoxic lytic granules by these CD8 T cells into latently infected neurons, neither apoptosis nor neuronal cell death appears to occur. We hypothesized that protection of latently infected neurons against cytotoxic CD8 T-cell killing is due to LAT's antiapoptosis activity. Since CD8 T-cell cytotoxic lytic granule-mediated apoptosis is critically dependent on granzyme B (GrB), we examined LAT's ability to block GrB-induced apoptosis. We report here that (i) LAT can interfere with GrB-induced apoptosis in cell cultures, (ii) LAT can block GrB-induced cleavage (activation) of caspase-3 both in cell culture and in a cell-free
in vitro
cell extract assay, and (iii) LAT can protect C1300 and Neuro2A cells from cytotoxic CD8 T-cell killing
in vitro
. These findings support the hypothesis that LAT's antiapoptosis activity can protect latently infected neurons from being killed by CD8 T-cell lytic granules
in vivo
.
The Human Cytomegalovirus Protein UL37 Exon 1 Associates with Internal Lipid Rafts
Authors: Williamson Chad D. , Zhang Aiping , Colberg-Poley Anamaris M.
Published: December 2010

The human cytomegalovirus (HCMV) protein UL37 exon 1 (pUL37x1), also known as viral mitochondrion-localized inhibitor of apoptosis (vMIA), sequentially traffics from the endoplasmic reticulum (ER) through mitochondrion-associated membranes (MAMs) to the outer mitochondrial membrane (OMM), where it robustly inhibits apoptosis. Here, we report the association of pUL37x1/vMIA with internal lipid rafts (LRs) in the ER/MAM. The MAM, which serves as a site for lipid transfer and calcium signaling to mitochondria, is enriched in detergent-resistant membrane (DRM)-forming lipids, including cholesterol and ceramide, which are found in lower concentrations in the bulk ER. Sigma 1 receptor (Sig-1R), a MAM chaperone affecting calcium signaling to mitochondria, is anchored in the MAM by its LR association. Because of its trafficking through the MAM and partial colocalization with Sig-1R, we tested whether pUL37x1/vMIA associates with MAM LRs. Extraction with methyl-β-cyclodextrin (MβCD) removed pUL37x1/vMIA from lysed but not intact cells, indicating its association with internal LRs. Furthermore, the isolation of DRMs from purified intracellular organelles independently verified the localization of pUL37x1/vMIA within ER/MAM LRs. However, pUL37x1/vMIA was not detected in DRMs from mitochondria. pUL37x1/vMIA associated with LRs during all temporal phases of HCMV infection, indicating the likely importance of this location for HCMV growth. Although detected during its sequential trafficking to the OMM, the pUL37x1/vMIA LR association was independent of its mitochondrial targeting signals. Rather, it was dependent upon cholesterol binding. These studies suggest a conserved ability of UL37 proteins to interact with cholesterol and LRs, which is functionally distinguishable from their sequential trafficking to mitochondria.
A Single Mutation Responsible for Temperature-Sensitive Entry and Assembly Defects in the VP1-2 Protein of Herpes Simplex Virus
Authors: Abaitua F. , Daikoku T. , Crump C. M. , Bolstad M. , O'Hare P.
Published: December 2010

Evidence for an essential role of the herpes simplex virus type 1 (HSV-1) tegument protein VP1-2 originated from the analysis of the temperature-sensitive (ts) mutanttsB7. At the nonpermissive temperature (NPT),tsB7 capsids accumulate at the nuclear pore, with defective genome release and substantially reduced virus gene expression. We compared the UL36 gene oftsB7 with that of the parental strain HFEM or strain 17 and identified four amino acid substitutions, 1061D → G, 1453Y → H, 2273Y → H, and 2558T → I. We transferred the UL36 gene fromtsB7, HFEM, or strain 17 into a KOS background. While KOS recombinants containing the HFEM or strain 17 UL36 gene exhibited notsdefect, recombinants containing thetsB7 UL36 VP1-2 exhibited a 5-log deficiency at the NPT. Incubation at the NPT resulted in little or no virus gene expression, though limited expression could be detected in a highly delayed fashion. Using shift-down regimes, gene expression recovered and recapitulated the time course normally observed, indicating that the initial block was in a reversible pathway. Using temperature shift-up regimes, a second defect later in the replication cycle was also observed in the KOS.tsviruses. We constructed a further series of recombinants which contained subsets of the four substitutions. A virus containing the wild-type (wt) residue at position 1453 and with the other three residues being fromtsB7 VP1-2 exhibited wt plaquing efficiency. Conversely, a virus containing the three wt residues but the single Y → H change at position 1453 fromtsB7 exhibited a 4- to 5-log drop in plaquing efficiency and was defective at both early and late stages of infection.
Access to RNA Encapsidated in the Nucleocapsid of Vesicular Stomatitis Virus
Authors: Green Todd J. , Rowse Michael , Tsao Jun , Kang Jungsoon , Ge Peng , Zhou Z. Hong , Luo Ming
Published: December 2010

The genomic RNA of negative-strand RNA viruses, such as vesicular stomatitis virus (VSV), is completely enwrapped by the nucleocapsid protein (N) in every stage of virus infection. During viral transcription/replication, however, the genomic RNA in the nucleocapsid must be accessible by the virus-encoded RNA-dependent RNA polymerase in order to serve as the template for RNA synthesis. With the VSV nucleocapsid and a nucleocapsid-like particle (NLP) produced in
Escherichia coli
, we have found that the RNA in the VSV nucleocapsid can be removed by RNase A, in contrast to what was previously reported. Removal of the RNA did not disrupt the assembly of the N protein, resulting in an empty capsid. Polyribonucleotides were reencapsidated into the empty NLP, and the crystal structures were determined. The crystal structures revealed variable degrees of association of the N protein with a specific RNA sequence.
The PA Protein Directly Contributes to the Virulence of H5N1 Avian Influenza Viruses in Domestic Ducks
Authors: Song Jiasheng , Feng Huapeng , Xu Jing , Zhao Dongming , Shi Jianzhong , Li Yanbing , Deng Guohua , Jiang Yongping , Li Xuyong , Zhu Pengyang , Guan Yuntao , Bu Zhigao , Kawaoka Yoshihiro , Chen Hualan
Published: December 2010

During their circulation in nature, H5N1 avian influenza viruses (AIVs) have acquired the ability to kill their natural hosts, wild birds and ducks. The genetic determinants for this increased virulence are largely unknown. In this study, we compared two genetically similar H5N1 AIVs, A/duck/Hubei/49/05 (DK/49) and A/goose/Hubei/65/05 (GS/65), that are lethal for chickens but differ in their virulence levels in ducks. To explore the genetic basis for this difference in virulence, we generated a series of reassortants and mutants of these two viruses. The virulence of the reassortant bearing the PA gene from DK/49 in the GS/65 background increased 10
5
-fold relative to that of the GS/65 virus. Substitution of two amino acids, S224P and N383D, in PA contributed to the highly virulent phenotype. The amino acid 224P in PA increased the replication of the virus in duck embryo fibroblasts, and the amino acid 383D in PA increased the polymerase activity in duck embryo fibroblasts and delayed the accumulation of the PA and PB1 polymerase subunits in the nucleus of virus-infected cells. Our results provide strong evidence that the polymerase PA subunit is a virulence factor for H5N1 AIVs in ducks.
Acquisition of Host-Derived CD40L by HIV-1In Vivoand Its Functional Consequences in the B-Cell Compartment
Authors: Imbeault Michaël , Ouellet Michel , Giguère Katia , Bertin Jonathan , Bélanger Dave , Martin Geneviève , Tremblay Michel J.
Published: December 2010

Aberrant activation of the B-cell compartment and hypergammaglobulinemia were among the first recognized characteristics of HIV-1-infected patients in the early 1980s. It has been demonstrated previously that HIV-1 particles acquire the costimulatory molecule CD40L when budding from activated CD4+T cells. In this paper, we confirmed first that CD40L-bearing virions are detected in the plasma from untreated HIV-1-infected individuals. To define the biological functions of virus-associated CD40L and fully characterize its influence on the activation state of B cells, we conducted a large-scale gene expression analysis using microarray technology on B cells isolated from human tonsillar tissue. Comparative analyses of gene expression profiles revealed that CD40L-bearing virions induce a highly similar response to the one observed in samples treated with a CD40 agonist, indicating that virions bearing CD40L can efficiently activate B cells. Among modulated genes, many cytokines/chemokines (CCL17, CCL22), surface molecules (CD23, CD80, ICAM-1), members of the TNF superfamily (FAS, A20, TNIP1, CD40, lymphotoxin alpha, lymphotoxin beta), transcription factors and associated proteins (NFKB1, NFKBIA, NFKBIE), second messengers involved in CD40 signaling (TRAF1, TRAF3, MAP2K1, phosphatidylinositol 3-kinase), and the activation-induced cytidine deaminase (AID) were identified. Moreover, we show that soluble factors induced upon the exposure of B cells to CD40L-bearing virions can exert chemoattractant properties toward CD4+T cells. We thus propose that a positive feedback loop involving CD40L-bearing HIV-1 particles issued from CD4+T cells productively infected with HIV-1 play a role in the virus-induced dysfunction of humoral immunity by chronically activating B cells through sustained CD40 signaling.
Human Ago2 Is Required for Efficient MicroRNA 122 Regulation of Hepatitis C Virus RNA Accumulation and Translation
Authors: Wilson Joyce A. , Zhang Chao , Huys Adam , Richardson Christopher D.
Published: December 2010

MicroRNA 122 (miR-122) increases the accumulation and translation of hepatitis C virus (HCV) RNA in infected cells through direct interactions with homologous sequences in the 5′ untranslated region (UTR) of the HCV genome. Argonaute 2 (Ago2) is a component of the RNA-induced silencing complex (RISC) and mediates small interfering RNA (siRNA)-directed mRNA cleavage and microRNA translational suppression. We investigated the function of Ago2 in HCV replication to determine whether it plays a role in enhancing the synthesis and translation of HCV RNA that is associated with miR-122. siRNA-mediated depletion of Ago2 in human hepatoma cells reduced HCV RNA accumulation in transient HCV replication assays. The treatment did not adversely affect cell viability, as assessed by cell proliferation, capped translation, and interferon assays. These data are consistent with complementary roles for Ago2 and miR-122 in enhancing HCV RNA amplification. By using a transient HCV replication assay that is dependent on an exogenously provided mutant miR-122, we determined that Ago2 depletion still reduced luciferase expression and HCV RNA accumulation, independently of miR-122 biogenesis. miR-122 has previously been found to stimulate HCV translation. Similarly, Ago2 knockdown also reduced HCV translation, and its depletion reduced the ability of miR-122 to stimulate viral translation. These data suggest a direct role for Ago2 in miR-122-mediated translation. Finally, Ago2 was also necessary for efficient miR-122 enhancement of HCV RNA accumulation. These data support a model in which miR-122 functions within an Ago2-containing protein complex to augment both HCV RNA accumulation and translation.
Hepatitis B Virus Surface Antigen Assembly Function Persists when Entire Transmembrane Domains 1 and 3 Are Replaced by a Heterologous Transmembrane Sequence
Authors: Berkower Ira , Spadaccini Angelo , Chen Hong , Al-Awadi Danah , Muller Jacqueline , Gao Yamei , Feigelstock Dino , Virnik Konstantin , Ni Yisheng
Published: December 2010

Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm subviral particles. The particles are lipoprotein micelles, in which HBsAg is believed to span the lipid layer four times. The first two transmembrane domains, TM1 and TM2, are required for particle assembly. We have probed the requirements for particle assembly by replacing the entire first or third TM domain of HBsAg with the transmembrane domain of HIV gp41. We found that either TM domain of HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with the gp41 domain. The results indicate remarkable flexibility in HBsAg particle formation and provide a novel way to express heterologous membrane proteins that are anchored to a lipid surface by their own membrane-spanning domain. The membrane-proximal exposed region (MPER) of gp41 is an important target of broadly reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may provide a good platform for future vaccine development.
Phosphatidylinositol 4-Kinase III Beta Is a Target of Enviroxime-Like Compounds for Antipoliovirus Activity
Authors: Arita Minetaro , Kojima Hirotatsu , Nagano Tetsuo , Okabe Takayoshi , Wakita Takaji , Shimizu Hiroyuki
Published: December 2010

Enviroxime is an antienterovirus compound that targets viral protein 3A and/or 3AB and suppresses a step in enterovirus replication by unknown mechanism. To date, four antienterovirus compounds, i.e., GW5074, Flt3 inhibitor II, TTP-8307, and AN-12-H5, are known to have similar mutations in the 3A protein-encoding region causing resistance to enviroxime (a G5318A [3A-Ala70Thr] mutation in poliovirus [PV]) and are considered enviroxime-like compounds. Recently, antienterovirus activity of a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor, PIK93, was reported, suggesting that PI4KB is an important host factor targetable by antienterovirus compounds (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we analyzed the inhibitory effects of previously identified enviroxime-like compounds (GW5074 and AN-12-H5) and a newly identified antienterovirus compound, T-00127-HEV1, on phosphoinositide (PI) kinases. We found that T-00127-HEV1 inhibited PI4KB activity with a higher specificity for than other PI kinases, in contrast to GW5074, which had a broad specificity for PI kinases. In contrast, AN-12-H5 showed no inhibitory effect on PI4KB activity and only moderate inhibitory effects on PI 3-kinase activity. Small interfering RNA (siRNA) screening targeting PI kinases identified PI4KB is a target of GW5074 and T-00127-HEV1, but not of AN-12-H5, for anti-PV activity. Interestingly, T-00127-HEV1 and GW5074 did not inhibit hepatitis C virus (HCV) replication, in contrast to a strong inhibitory effect of AN-12-H5. These results suggested that PI4KB is an enterovirus-specific host factor required for the replication process and targeted by some enviroxime-like compounds (T-00127-HEV1 and GW5074) and that enviroxime-like compounds may have targets other than PI kinases for their antiviral effect.
An accurate analytical representation of the bridge function of hard spheres and a question of existence of a general closure to the Ornstein–Zernike equation
Authors: Francová Magda , Malijevský Anatol , Labík Stanislav , Kolafa Jiří
Published: December 2010

The bridge function of hard spheres is accurately calculated from computer simulation data on the pair distribution function via the inverted Ornstein–Zernike equation at reduced densities ρ* ≡ Nσ3/V ranging from 0.2 to 1.02, i.e. from low densities through densities in a vicinity of the phase transition to crystal to densities of metastable fluid region. The data are used to propose an analytical representation of the bridge function as a function of the interparticle distance and density. They are further used to construct the so-called Duh– Haymet plot. It is demonstrated that a “general closure” to the Ornstein–Zernike equation in the form B(r) = f[γ(r)], where γ is the indirect (or series) correlation function, does not match the data. Nor does an extended closure B(r) = f[γ(r),ρ*] even in the simplest case of the one component hard sphere fluid. A relative success of literature closures to the Ornstein–Zernike equation is discussed.
Effects of high-profile collisions on drink-driving penalties and alcohol-related crashes in Japan
Authors: Nakahara Shinji , Ichikawa Masao
Published: December 2010

Background

Japanese road traffic law was amended in 2002 and 2007 to increase the penalties for drink-driving in response to media coverage, publicity campaigns, and debates following high-profile alcohol-related motor-vehicle crashes in 1999 and 2006.

Objective

To test the hypothesis that the proportion of crashes involving drink-driving started to decline before the law amendments, because of changes in social norms and driver behaviour after the high-profile crashes.

Methods

In order to assess the impact of the cases in 1999 and 2006, time-series analyses were used to examine the trends in the proportion of crashes involving drink-driving, and whether there were abrupt changes in the level or slope at the expected time points, using monthly police data for the period between January 1995 and December 2008.

Results

In 1999, the proportion of alcohol-related fatal crashes in which the driver had a blood alcohol concentration (BAC) ≥0.5 mg/ml started to decline with a slope change of −0.09 percentage points per month (95% CI −0.15 to −0.03) but no level change, whereas there were no changes for drivers with a BAC <0.5. In 2006, the trends for drivers with a BAC ≥0.5 or <0.5 showed significant level declines of −3.1 (−5.0 to −1.2) and −1.7 (−2.5 to −0.9) percentage points, respectively, but no slope changes.

Conclusions

Media coverage of high-profile crashes, and subsequent publicity campaigns and debates might have altered social norms and driver behaviour, reducing the proportion of alcohol-related crashes before the introduction of more severe penalties for drink-driving.
PML protein analysis using imaging flow cytometry
Authors: Grimwade Lizz , Gudgin Emma , Bloxham David , Scott Mike A , Erber Wendy N
Published: December 2010

Acute promyelocytic leukaemia (APML) can be promptly diagnosed by detecting abnormal diffuse staining patterns of PML bodies in abnormal promyelocytes using immunofluorescence microscopy. However, this technique is subjective, with low sensitivity. Using samples from 18 patients with acute myeloid leukaemia (AML) (including four with APML), the authors investigated whether imaging flow cytometry could be a viable alternative to this current technique and improve sensitivity levels. Bone marrow/peripheral blood cells were stained with an antibody to PML, and data were acquired on an ImageStream (Amnis Corporation, Seattle, Washington, USA). Using the modulation feature for data analysis, the authors demonstrated that this technique could successfully identify cases of APML. Imaging flow cytometry, by analysing greater numbers of cells and with the potential to include disease-specific antigens, increases the sensitivity of the current immunofluorescence technique. Imaging flow cytometry is an exciting technology that has many possible applications in the diagnosis of haematological malignancies, including the potential to integrate modalities.
Autumnal patterns of nocturnal passerine migration in the St. Lawrence estuary region, Quebec, Canada: a weather radar study
Authors: Gagnon François , Ibarzabal Jacques , Savard Jean-Pierre L. , Bélisle Marc , Vaillancourt Pierre
Published: December 2010

We documented the pattern of nocturnal passerine migration on each side of the St. Lawrence estuary (Côte-Nord north and Gaspésie south), using the Doppler Canadian weather surveillance radar of Val d’Irène (XAM). We examined whether autumnal migrants flew across the St. Lawrence, resulting in a uniform broad-front migration, or avoided crossing it, resulting in a bird concentration along the north coast. We found that a proportion of migrants crossed the estuary but that most followed the north coast. Ranges at which birds were detected were, on average, greater on Côte-Nord, thereby rejecting the uniform broad-front migration hypothesis, inasmuch as reflectivity measurements suggested that bird concentrated along Côte-Nord. The mean flight direction on Côte-Nord was southwest but shifted westward as the night progressed, avoiding crossing the estuary by late night. In Gaspésie, the mean flight direction over land was south and no directional shift was observed throughout the night. Flight altitude reach up to 1000 m above sea level (a.s.l.), but migratory activity was highest in the first 500 m a.s.l. It appears that the St. Lawrence estuary acts as a leading line and a barrier for nocturnal passerine migrants, and likely shapes migration farther south in Canada and in the United States.
Morphometric and genetic analyses of two sympatric morphs of Arctic char (Salvelinus alpinus) in the Canadian High Arctic
Authors: Arbour J. H. , Hardie D. C. , Hutchings J. A.
Published: December 2010

Multivariate morphometric analyses were used to examine variation in head, body, and fin shape between two sympatric morphotypes of Arctic char ( Salvelinus alpinus (L., 1758)) from Lake Hazen, Ellesmere Island, Nunavut, Canada. Population structure of the Lake Hazen Arctic char was examined using five microsatellite loci. The “small” morph was found to have a larger (primarily deeper) head, larger and more elongate fins, and a deeper lateral profile than the “large” morph. The morphs also differed in allometric growth patterns. The large and small morphs do not appear to represent genetically distinct populations. The head morphology of the Lake Hazen small and large morphs exhibited similarities to benthic and pelagic morphs (respectively) from other lakes. We hypothesize that the large morph may be adapted to high-efficiency swimming and that the small morph may be adapted to low-efficiency, high-acceleration swimming. Such functional trade-offs are not uncommon among fish specializing in dispersed or mobile prey (fish and plankton) and benthic prey, respectively. The lack of apparent genetic differentiation between the morphs may suggest that the morphological differences result, to some extent, from phenotypic plasticity. Based on these results and previous analyses, it seems reasonable to conclude that Lake Hazen Arctic char represent a resource polymorphism.
COMBINED CELLULAR AUTOMATON MODEL FOR MIXED TRAFFIC FLOW WITH NON-MOTORIZED VEHICLES
Authors: XIE DONG-FAN , GAO ZI-YOU , ZHAO XIAO-MEI
Published: December 2010

To depict the mixed traffic flow consisting of motorized (m-) and non-motorized (nm-) vehicles, a new cellular automaton model is proposed by combining the NaSch model and the BCA model, and some rules are also introduced to depict the interaction between m-vehicles and nm-vehicles. By numerical simulations, the flux-density relations are investigated in detail. It can be found that the flux-density curves of m-vehicle flow can be classified into two types, corresponding to small and large density regions of nm-vehicles, respectively. In small density region of nm-vehicles, the maximum flux as well as the critical density decreases with the increase of nm-vehicle density. Similar characteristics can also be found in large density region of nm-vehicles. However, compared with the former case, the maximum flux is much lower, the phase transition from free flow to congested flow becomes continuous and thus the corresponding critical points are non-existent. The flux-density curves of nm-vehicle flow can also be classified into two types. And interestingly, the maximum flux and the corresponding density decrease first and keep constant later as the density of m-vehicle increases. Finally, the total transport capacity of the system is investigated. The results show that the maximum capacity can be reached at appropriate proportions for m-vehicles and nm-vehicles, which induces a controlling method to promote the capacity of mixed traffic flow.
SIMULATION STUDY OF TRAFFIC ACCIDENTS IN BIDIRECTIONAL TRAFFIC MODELS
Authors: MOUSSA NAJEM
Published: December 2010

Conditions for the occurrence of bidirectional collisions are developed based on the Simon–Gutowitz bidirectional traffic model. Three types of dangerous situations can occur in this model. We analyze those corresponding to head-on collision; rear-end collision and lane-changing collision. Using Monte Carlo simulations, we compute the probability of the occurrence of these collisions for different values of the oncoming cars' density. It is found that the risk of collisions is important when the density of cars in one lane is small and that of the other lane is high enough. The influence of different proportions of heavy vehicles is also studied. We found that heavy vehicles cause an important reduction of traffic flow on the home lane and provoke an increase of the risk of car accidents.
THE RESEARCH ON STABILITY OF DIFFUSION AND COMPETITION BETWEEN ONLINE TOPICS
Authors: ZHANG YAN-CHAO , LIU YUN , DING FEI , SI XIA-MENG
Published: December 2010

Online topics are becoming an important form of network information communication, and are playing a significant role in consensus formation. When several online topics are published at the same time, the spread of these topics will affect each other. We propose a model to study the development tendency of relationship between two different online topics. We make use of stability theory of differential equations to analyze the model, utilize the phase trajectory to analyze the stability of the equilibrium point, and finally simulate the model with actual data and varied parameters. Simulation results indicate that the proposed model is useful in understanding and explaining the phenomena presented in the diffusion of online topics, especially the interaction and competition among different topics.