bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure of Memory: Evidence concerning the Recall of Surface and Background Colour of Shapes
Authors: Wilton Richard N.
Published: September 2011

In the first of four experiments, two groups of subjects were shown a series of cards, each displaying a different shape. For one group the shapes were of different colours, and each was located on either a black or a white background. For the other group a shape was black or white, and its background was coloured. Subjects in both groups were instructed to memorize the colour and brightness (black or white) assigned to each shape. Recall of the colours, in response to the names of the shapes, was superior for the group for which the shapes themselves had been coloured. In the other three experiments the finding was extended, with the aim of limiting possible explanations of the effect. One of these experiments showed that the effect is obtained when the relevant stimuli are imagined rather than being physically shown to a subject. This suggests that the effect is not the result of processes of attention that are dependent upon the perceptual analysis of a display. In discussion, it is argued that the effect may shed light on the constraints that govern the process of association. One hypothesis that specifically accounts for the results is that the structure of memory for visually presented information is that of a network of propositions.
Psychometric Functions for the Discrimination of Differences in Intensity of Gaussian Noise
Authors: Irwin R. J.
Published: September 2011

A new theory of sensory functioning by Laming predicts how the shape of the psychometric function depends on the context in which a signal is presented. The discrimination of intensities of noise was therefore studied with four different stimulus configurations. In one, observers discriminated between two separate noise samples that differed in intensity. In accordance with the theory, a normal probability integral provided a better fit to each observer's data than either of two other functions: a normal integral with respect to the square of the difference, or a normal integral with respect to the fourth power of the difference. In a second task, observers detected an increment in a continuous noise. For eight out of nine sets of data, a square-law function provided a better fit than either a normal integral or fourth-power function. A third task asked observers to decide which of two noises was amplitude modulated. The predicted square-law function provided the best fit for four out of five observers. In a fourth task, one observer detected an interval of amplitude modulation in a continuous noise. As predicted by the theory, a fourth-power function provided the best fit. In addition, Weber fractions for difference discriminations decreased approximately with the square root of sample duration for durations up to 300 msec, whereas Weber fractions for increment detections decreased approximately directly with duration for durations up to 100 msec. The results are usually in qualitative agreement with the theory and often in quantitative agreement as well.
The Effects of Surface Detail on Object Categorization and Naming
Authors: Price Cathy J. , Humphreys Glyn W.
Published: September 2011

Three experiments are reported examining the effects of surface colour and brightness/texture gradients (photographic detail) on object classification and naming. Objects were drawn from classes with either structurally similar or structurally dissimilar exemplars. In Experiment 1a, object naming was facilitated by both congruent surface colour and photographic detail, with the effects of these two variables combining under-additively. In addition incongruent colour disrupted naming accuracy. These effects tended to be larger on objects from structurally similar classes than on objects from structurally dissimilar classes. Experiment 1b examined superordinate classification. There were again advantages due to congruent colour and photographic detail on responses to objects from both structurally similar and structurally dissimilar classes. Incongruent colour disrupted classification accuracy on structurally distinct but not structurally similar items. For structurally similar items, the advantages of congruent surface attributes on classification were smaller than on naming, but this was not the case for structurally dissimilar items. Experiment 2 examined subordinate classification of structurally similar objects. Now effects of congruent and incongruent colour, but not of photographic detail, were found. Experiment 3 showed that congruent and incongruent colour effects occur only when the colours occupy the internal surfaces of objects. The results suggest that surface details can affect object recognition and naming, depending upon: (1) the degree to which objects must be differentiated for a correct response to be made, and (2) the nature of the rate-limiting process determining performance.
Attention, spatial integration, and the tail of response time distributions in Stroop task performance
Authors: Roelofs Ardi
Published: September 2011

A few studies have examined selective attention in Stroop task performance through ex-Gaussian analyses of response time (RT) distributions. It has remained unclear whether the tail of the RT distribution in vocal responding reflects spatial integration of relevant and irrelevant attributes, as suggested by Spieler, Balota, and Faust (2000). Here, two colour–word Stroop experiments with vocal responding are reported in which the spatial relation between colour and word was manipulated. Participants named colours (e.g., green; say “green”) while trying to ignore distractors that were incongruent or congruent words (e.g., red or green), or neutral series of Xs. The vocal RT was measured. Colour words in colour, white words superimposed onto colour rectangles (Experiment 1), and colour rectangles combined with auditory words (Experiment 2) yielded Stroop effects in both the leading edge and the tail of the RT distributions. These results indicate that spatial integration is not necessary for effects in the tail to occur in vocal responding. It is argued that the findings are compatible with an association of the tail effects with task conflict.
The Effects of Acute Exercise on Temporal Generalization
Authors: Lambourne Kate
Published: September 2011

Sixteen healthy college students performed a multiple-trial referenced temporal generalization task and an episodic temporal generalization task before and during moderate-intensity aerobic exercise. The same tasks were performed in a resting control condition. Working memory tasks were also administered before, during, and after exercise to determine whether exercise affected working memory processes. Temporal generalization gradients demonstrated leftward shifts during exercise when compared to rest, indicating that the subject perceived intervals to elapse more slowly. This finding is consistent with an increased pacemaker speed. Subjective lengthening of stimuli as the task progressed did not occur during exercise or rest. No significant differences were observed on the episodic timing task, nor were any differences found on the working memory tasks. These findings provide support for the notion that exercise influences the internal clock in a manner similar to other arousal-inducing manipulations.
TheQuadro da Portegoin Sixteenth-Century Venetian Art*
Authors: Schmitter Monika
Published: September 2011

During the sixteenth century a symbiotic relationship developed between the form, use, and symbolic associations of the Venetian portego, the central reception and entertainment hall of Venetian palaces, and the paintings that were increasingly commissioned to ornament these spaces. The intended placement of the paintings affected their size, format, composition, subject matter, and contemporary interpretation. At the same time, the works of art themselves reflected upon and helped to define the social meanings of the space and the activities taking place there. Analyzing documentary sources and surviving paintings reveals the degree to which we can speak of thequadro da portegoas a distinctive type of Venetian painting.
Dead Infants, Cruel Mothers, and Heroic Popes: The Visual Rhetoric of Foundling Care at the Hospital of Santo Spirito, Rome*
Authors: Presciutti Diana Bullen
Published: September 2011

The fresco cycle painted at the behest of Pope Sixtus IV in the late 1470s in the main ward of the hospital of Santo Spirito in Rome comprises an extended pictorial biography of Sixtus, prefaced by scenes representing the legendary foundation of the hospital by his predecessor Innocent III. The legend, which tells how Innocent established Santo Spirito as a foundling hospital in response to the discovery of victims of infanticide in the Tiber River, positions the pope as the savior of the city's unwanted children. This article elucidates how the construction andrenovatioof the hospital is presented in the cycle as a generative product of papal will, with the care of foundlings situated as an integral part of the image of the pope as both Father of the Church and restorer of past glory to the city of Rome. While the frescoes engage with both widespread conventions for representing infanticide and commonplace notions of the social value of caring for abandoned children, I demonstrate that the ideologically potent visual rhetoric of foundling care was also flexible, and could be adapted to meet the specific needs of a particular institutional and patronal context.
Curiosity, Contingency, and Cultural Diversity: Montaigne's Readings at the Vatican Library*
Authors: Rigolot François
Published: September 2011

One of the key episodes of Michel de Montaigne's trip to Rome (1580–81) was his visit to the Vatican Library, which he comments upon in hisJournal de voyage,posthumously published. Strangely enough, few scholars have paid close attention to what Montaigne says about the selection of manuscripts and printed material he consulted there on 6 March 1581. He claims that he was given free access to thatWunderkammer,and scholarly research shows that his wish list indeed reflected his taste for irony, humor, and cultural diversity, ranging from Greco-Roman manuscripts to Egyptian papyrus and a Chinese booklet. At the same time, a case could be made for interpreting the selection, not as Montaigne's, but as the library custodian's, with Aquinas's sermons, anti-Lutheran material, and documents used at the Council of Trent. This paper tries to sort out to what extent the selection of books and items that Montaigne saw at the Vatican Library can be considered as the meeting ground between the interests of Montaigne himself as skeptic and the agenda of the Counter-Reformation.
PTTG1/securin modulates microtubule nucleation and cell migration
Authors: Moreno-Mateos Miguel A. , Espina Águeda G. , Torres Belén , del Estal María M. Gámez , Romero-Franco Ana , Ríos Rosa M. , Pintor-Toro José A.
Published: September 2011

Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference–mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.
Splice isoform estrogen receptors as integral transmembrane proteins
Authors: Kim Kyung Hee , Toomre Derek , Bender Jeffrey R.
Published: September 2011

In addition to enhancing or repressing transcription, steroid hormone receptors rapidly transduce kinase activation signals. On ligand engagement, an N-terminus–truncated splice isoform of estrogen receptor (ER) α, ER46, triggers membrane-initiated signals, resulting in endothelial nitric oxide synthase (eNOS) activation and endothelial NO production. The orientation of ER46 at the plasma membrane is incompletely defined. With the use of ecliptic pHluorin-fused ER46, total internal reflection fluorescence microscopy in live human endothelial cells illustrates that ER46 can topologically conform to a type I transmembrane protein structure. Mutation of isoleucine-386 at the center of ER46's transmembrane hydrophobic core prevents membrane spanning, obscures the N-terminal ectodomain, and effects a marked reduction in membrane-impermeant estrogen binding with diminished rapid eNOS activation and NO production, despite maintained genomic induction of an estrogen response element–luciferase reporter. Thus there exist pools of transmembrane steroid hormone receptors that are efficient signaling molecules and potential novel therapeutic targets.
An Efficient and Economical Rapid-Tooling Method for Die-Sinking Electrical Discharge Machining
Authors: Gu Lin , Li Lei , Zhao Wansheng , Rjaurkar Kamlakar P.
Published: September 2011

This paper reports on the efficiency and economy of bundled electrode in die-sinking electrical discharge machining (EDM). Bundled electrode was fabricated by putting several thin tubular or cylindrical cell electrodes together and forming an approximate 3D end-face geometry by adjusting the length of each cell electrode. This method of electrode design and fabrication significantly reduced the fabrication time and cost compared to that of traditional cutting method. The bundled electrode allows better flushing of dielectric fluid to facilitate removal of more heat and debris from the inter electrode gap. Experiments were conducted to demonstrate the advantages of bundled electrode in rough machining with large peak current. It was also found that the relative higher tool wear ratio could be reduced by using graphite cell electrodes. Additionally, time and cost of tools preparation as well as the machining time between EDM with bundled electrode and solid die-sinking electrode were compared by machining a 3-blade cavity component.
A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization
Authors: Gkikopoulos Triantaffyllos , Schofield Pieta , Singh Vijender , Pinskaya Marina , Mellor Jane , Smolle Michaela , Workman Jerry L. , Barton Geoffrey J. , Owen-Hughes Tom
Published: September 2011

Three chromatin remodeling enzymes in yeast drive higher-order chromatin compaction.
Efficient Dehydrogenation of Formic Acid Using an Iron Catalyst
Authors: Boddien Albert , Mellmann Dörthe , Gärtner Felix , Jackstell Ralf , Junge Henrik , Dyson Paul J. , Laurenczy Gábor , Ludwig Ralf , Beller Matthias
Published: September 2011

Iron-catalyzed hydrogen generation raises prospects for a cheap hydrogen storage medium.
Generating Helices in Nature
Authors: Forterre Yoel , Dumais Jacques
Published: September 2011

A general model accounts for different types of helical shapes that can result from bilayers of stretchable, bendable sheets.
Consequent Capture of Strange Fish
Reactions
The Private Life of Atoms

by Peter Atkins

Oxford University Press, Oxford, 2011. 199 pp. $24.95, £16.99. ISBN 9780199695126.
Authors: Tang Samantha , Poliakoff Martyn
Published: September 2011

Atkins aims to help readers imagine what occurs on the molecular scale when atoms are drawn into a variety of combinations.
The Sperm's Sweet Tooth
Authors: Wassarman Paul M.
Published: September 2011

Human sperm bind to a sugar moiety present on glycoproteins of the egg's outer coat.
Aboriginal Genome Shows Two-Wave Settlement of Asia
Authors: Gibbons Ann
Published: September 2011

In a paper published online this week in
Science
, geneticists report that they have sequenced the first complete genome of an Australian Aboriginal.
Type-Specific Human Papillomavirus E6/E7 mRNA Detection by Real-Time PCR Improves Identification of Cervical Neoplasia
Authors: Andersson Elin , Kärrberg Cecilia , Rådberg Thomas , Blomqvist Lennart , Zetterqvist Britt-Marie , Ryd Walter , Lindh Magnus , Horal Peter
Published: September 2011

DNA-based human papillomavirus (HPV) assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of the oncoproteins E6 and E7 show higher specificity but lack either detection of all high-risk HPV genotypes or the capacity to specify the detected genotypes. Therefore, a real-time PCR assay detecting type-specific E6/E7 mRNA was developed and the clinical performance evaluated. A total of 210 cervical LBC (liquid-based cytology) samples from 204 women were analyzed for HPV DNA and mRNA with the in-house real-time PCR as well as PreTect HPV-Proofer. The sensitivity of real-time PCR mRNA detection to identify histologically confirmed CIN2+ (cervical intraepithelial neoplasia, grade 2 or higher) was 0.91, compared to 0.95 for DNA analysis. The specificity was 0.68 compared to 0.38, and the positive predictive value (PPV) was higher for mRNA (0.67 versus 0.52) without any loss in negative predictive value (NPV). The sensitivity of the real-time PCR mRNA test was somewhat higher than that for PreTect HPV-Proofer (0.83 versus 0.75) in analyses for the same genotypes. The specificities were similar (0.76 versus 0.77). In analyses for mRNA of the eight most common genotypes in cervical cancer (HPV16, -18, -31, -33, -35, -45, -52, and -58), the sensitivity of detection of CIN2+ lesions was 0.87 and the specificity 0.74, with a PPV of 0.70. In conclusion, real-time PCR for detection of HPV E6/E7 mRNA transcripts can be a sensitive and specific tool in screening and investigation of cervical neoplasia. The composition of HPV types in mRNA testing needs to be further investigated to optimize sensitivity and specificity.
Evaluation of Aspergillus PCR Protocols for Testing Serum Specimens
Authors: White P. Lewis , Mengoli Carlo , Bretagne Stéphane , Cuenca-Estrella Manuel , Finnstrom Niklas , Klingspor Lena , Melchers Willem J. G. , McCulloch Elaine , Barnes Rosemary A. , Donnelly J. Peter , Loeffler Juergen
Published: September 2011

A panel of human serum samples spiked with various amounts of
Aspergillus fumigatus
genomic DNA was distributed to 23 centers within the European
Aspergillus
PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most
Aspergillus
PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance.
Epidemic Methicillin-Susceptible Staphylococcus aureus Lineages Are the Main Cause of Infections at an Iranian University Hospital
Authors: Havaei Seyed Asghar , Vidovic Sinisa , Tahmineh Narimani , Mohammad Kazemi , Mohsen Karbalaei , Starnino Stefania , Dillon Jo-Anne R.
Published: September 2011

The majority of
Staphylococcus aureus
infections from Isfahan, Iran, were caused by epidemic methicillin-susceptible
S. aureus
(MSSA) lineages, sequence type 8 (ST8), ST22, ST30, and ST6. The predominant methicillin-resistant
S. aureus
strain was ST239. We observed a high prevalence of Panton-Valentine leukocidin-positive MSSA strains (19.7%), which is a matter of considerable concern, since these strains have the ability to cause severe infections.
A Novel Pancreatropic Coxsackievirus Vector Expressing Glucagon-Like Peptide 1 Reduces Hyperglycemia in Streptozotocin-Treated Mice
Authors: Dan Meixia , Chantler Janet K.
Published: September 2011

A coxsackievirus vector, vCVB(dm) (v stands for vector, CVB stands for group B coxsackievirus, and dm stands for double mutant), has been produced from a unique strain of coxsackievirus B3 (CVB3) containing 2 mutations that confer the property of highly selective pancreatropism. This vector has been tested as a delivery vehicle for glucagon-like peptide 1 (GLP-1), a peptide that enhances pancreatic regeneration following tissue damage. vCVB(dm) is a live vector comprising the entire plus-strand RNA genome with a multiple cloning site (MCS) inserted between the P1 and P2 gene regions. The MCS is flanked by sequences encoding the cleavage site for viral protease 2Apro that processes the polyprotein to release the incorporated gene. Our studies show that this vector selectively delivers GLP-1 to the pancreas where it is expressed in foci scattered throughout the acinar tissue for 4 or 5 days. Moreover, expression is associated with new beta cell clusters in juxtaposition to vector-infected cells. Inoculation of streptozotocin (STZ)-treated mice with vCVB(dm)GLP-1 was found to suppress development of hyperglycemia and increase insulin production relative to mice treated with STZ alone or with empty vector. This vector has the advantage of exclusively targeting pancreas and has potential use for short-term gene delivery to this tissue. The lack of viral integration provides a significant safety feature, making this vector a possible option for use as a therapeutic tool for pancreas-related diseases, including type 1 and 2 diabetes, pancreatitis, and pancreatic cancer.
DNA Damage Response Signaling Triggers Nuclear Localization of the Chicken Anemia Virus Protein Apoptin
Authors: Kucharski Thomas J. , Gamache Isabelle , Gjoerup Ole , Teodoro Jose G.
Published: September 2011

The chicken anemia virus (CAV) protein Apoptin is a small, 13.6-kDa protein that has the intriguing activity of inducing G
2
/M arrest and apoptosis specifically in cancer cells by a mechanism that is independent of p53. The activity of Apoptin is regulated at the level of localization. Whereas Apoptin is cytoplasmic in primary cells and does not affect cell growth, in transformed cells it localizes to the nucleus, where it induces apoptosis. The properties of cancer cells that are responsible for activating the proapoptotic activities of Apoptin remain unclear. In the current study, we show that DNA damage response (DDR) signaling is required to induce Apoptin nuclear localization in primary cells. Induction of DNA damage in combination with Apoptin expression was able to induce apoptosis in primary cells. Conversely, chemical or RNA interference (RNAi) inhibition of DDR signaling by ATM and DNA-dependent protein kinase (DNA-PK) was sufficient to cause Apoptin to localize in the cytoplasm of transformed cells. Furthermore, the nucleocytoplasmic shuttling activity of Apoptin is required for DDR-induced changes in localization. Interestingly, nuclear localization of Apoptin in primary cells was able to inhibit the formation of DNA damage foci containing 53BP1. Apoptin has been shown to bind and inhibit the anaphase-promoting complex/cyclosome (APC/C). We observe that Apoptin is able to inhibit formation of DNA damage foci by targeting the APC/C-associated factor MDC1 for degradation. We suggest that these results may point to a novel mechanism of DDR inhibition during viral infection.
Hepatocytes Traffic and Export Hepatitis B Virus Basolaterally by Polarity-Dependent Mechanisms
Authors: Bhat Purnima , Snooks Michelle J. , Anderson David A.
Published: September 2011

Viruses commonly utilize the cellular trafficking machinery of polarized cells to effect viral export. Hepatocytes are polarizedin vivo, but mostin vitrohepatocyte models are either nonpolarized or have morphology unsuitable for the study of viral export. Here, we investigate the mechanisms of trafficking and export for the hepadnaviruses hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) in polarized hepatocyte-derived cell lines and primary duck hepatocytes. DHBV export, but not replication, was dependent on the development of hepatocyte polarity, with export significantly abrogated over time as primary hepatocytes lost polarity. Using Transwell cultures of polarized N6 cells and adenovirus-based transduction, we observed that export of both HBV and DHBV was vectorially regulated and predominantly basolateral. Monitoring of polarized N6 cells and nonpolarized C11 cells during persistent, long-term DHBV infection demonstrated that newly synthesized sphingolipid and virus displayed significant colocalization and fluorescence resonance energy transfer, implying cotransportation from the Golgi complex to the plasma membrane. Notably, 15% of virus was released apically from polarized cells, corresponding to secretion into the bile ductin vivo, also in association with sphingolipids. We conclude that DHBV and, probably, HBV are reliant upon hepatocyte polarity to be efficiently exported and this export is in association with sphingolipid structures, possibly lipid rafts. This study provides novel insights regarding the mechanisms of hepadnavirus trafficking in hepatocytes, with potential relevance to pathogenesis and immune tolerance.
Localization of Sequences in a Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 That Inhibits Apoptosis and Interferes with Notch1-Mediated
trans
-Activation of the bICP0 Promoter
Authors: Sinani Devis , Jones Clinton
Published: September 2011

Bovine herpesvirus 1 (BHV-1) infection induces clinical symptoms in the upper respiratory tract, inhibits immune responses, and can result in life-threatening secondary bacterial infections. Following acute infection, BHV-1 establishes latency in sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs, resulting in virus transmission. The latency-related (LR) RNA is abundantly expressed in latently infected sensory neurons, suggesting that LR gene products regulate the latency-reactivation cycle. An LR mutant virus with stop codons at the amino terminus of the first open reading frame (ORF) in the LR gene (ORF2) does not reactivate from latency, in part because it induces higher levels of apoptosis in infected neurons. ORF2 inhibits apoptosis in transiently transfected cells, suggesting that it plays an important role in the latency-reactivation cycle. ORF2 also interacts with Notch1 or Notch3 and consequently inhibits their ability to
trans
-activate the bICP0 early and glycoprotein C promoters. In this study, we identified ORF2 sequences that were necessary for inhibiting cold shock-induced apoptosis or Notch1-mediated
trans
-activation of the bICP0 early promoter and stimulation of productive infection. Relative to ORF2 sequences necessary for inhibiting apoptosis, distinct domains in ORF2 were important for interfering with Notch1-mediated
trans
-activation. Five consensus protein kinase A and/or protein kinase C phosphorylation sites within ORF2 regulate the steady-state levels of ORF2 in transfected cells. A nuclear localization signal in ORF2 was necessary for inhibiting Notch1-mediated
trans
-activation but not apoptosis. In summary, ORF2 has more than one functional domain that regulates its stability and functional properties.
Nonconsensus West Nile Virus Genomes Arising during Mosquito Infection Suppress Pathogenesis and Modulate Virus Fitness
In Vivo
Authors: Ebel Gregory D. , Fitzpatrick Kelly A. , Lim Pei-Yin , Bennett Corey J. , Deardorff Eleanor R. , Jerzak Greta V. S. , Kramer Laura D. , Zhou Yangsheng , Shi Pei-Yong , Bernard Kristen A.
Published: September 2011

West Nile virus (WNV) is similar to other RNA viruses in that it forms genetically complex populations within hosts. The virus is maintained in nature in mosquitoes and birds, with each host type exerting distinct influences on virus populations. We previously observed that prolonged replication in mosquitoes led to increases in WNV genetic diversity and diminished pathogenesis in mice without remarkable changes to the consensus genome sequence. We therefore sought to evaluate the relationships between individual and group phenotypes in WNV and to discover novel viral determinants of pathogenesis in mice and fitness in mosquitoes and birds. Individual plaque size variants were isolated from a genetically complex population, and mutations conferring a small-plaque and mouse-attenuated phenotype were localized to the RNA helicase domain of the NS3 protein by reverse genetics. The mutation, an Asp deletion, did not alter type I interferon production in the host but rendered mutant viruses more susceptible to interferon compared to wild type (WT) WNV. Finally, we used an
in vivo
fitness assay in
Culex quinquefasciatus
mosquitoes and chickens to determine whether the mutation in NS3 influenced fitness. The fitness of the NS3 mutant was dramatically lower in chickens and moderately lower in mosquitoes, indicating that RNA helicase is a major fitness determinant of WNV and that the effect on fitness is host specific. Overall, this work highlights the complex relationships that exist between individual and group phenotypes in RNA viruses and identifies RNA helicase as an attenuation and fitness determinant in WNV.
Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation
Authors: Mostafa Heba H. , Thompson Thornton W. , Kushnir Anna S. , Haenchen Steve D. , Bayless Adam M. , Hilliard Joshua G. , Link Malen A. , Pitcher Lisa A. , Loveday Emma , Schaffer Priscilla A. , Davido David J.
Published: September 2011

In cell culture experiments, phosphorylation appears to be a critical regulator of the herpes simplex virus 1 (HSV-1) immediate-early (IE) protein, ICP0, which is an E3 ubiquitin ligase that transactivates viral gene expression. Three major regions of phosphorylation in ICP0 (amino acids 224 to 232, 365 to 371, and 508 to 518) have been identified, and mutant viruses that block phosphorylation sites within each region (termed Phos 1, 2, and 3, respectively) have been constructed. Previous studies indicated that replication of Phos 1 is significantly reduced compared to that of wild-type virus in cell culture (C. Boutell, et al., J. Virol. 82:10647–10656, 2008). To determine the effects these phosphorylation site mutations have on the viral life cycle
in vivo
, mice were ocularly infected with wild-type HSV-1, the Phos mutants, or their marker rescue counterparts. Subsequently, viral replication, establishment of latency, and viral explant-induced reactivation of these viruses were examined. Relative to wild-type virus, Phos 1 eye titers were reduced as much as 7- and 18-fold on days 1 and 5 postinfection, respectively. Phos 2 eye titers showed a decrease of 6-fold on day 1 postinfection. Titers of Phos 1 and 2 trigeminal ganglia were reduced as much as 16- and 20-fold, respectively, on day 5 postinfection. Additionally, the reactivation efficiencies of Phos 1 and 2 were impaired relative to wild-type HSV-1, although both viruses established wild-type levels of latency
in vivo
. The acute replication, latency, and reactivation phenotypes of Phos 3 were similar to those of wild-type HSV-1. We conclude from these studies that phosphorylation is likely a key modulator of ICP0's biological activities in a mouse ocular model of HSV-1 infection.
Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response
Authors: Liu Ting-Kai , Zhang Yi-Bing , Liu Ying , Sun Fan , Gui Jian-Fang
Published: September 2011

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) inhibits protein synthesis by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). In fish species, in addition to PKR, there exists a PKR-like protein kinase containing Z-DNA binding domains (PKZ). However, the antiviral role of fish PKZ and the functional relationship between fish PKZ and PKR remain unknown. Here we confirmed the coexpression of fish PKZ and PKR proteins in
Carassius auratus
blastula embryonic (CAB) cells and identified them as two typical interferon (IFN)-inducible eIF2α kinases, both of which displayed an ability to inhibit virus replication. Strikingly, fish IFN or all kinds of IFN stimuli activated PKZ and PKR to phosphorylated eIF2α. Overexpression of both fish kinases together conferred much more significant inhibition of virus replication than overexpression of either protein, whereas morpholino knockdown of both made fish cells more vulnerable to virus infection than knockdown of either. The antiviral ability of fish PKZ was weaker than fish PKR, which correlated with its lower ability to phosphorylate eIF2α than PKR. Moreover, the independent association of fish PKZ or PKR reveals that each of them formed homodimers and that fish PKZ phosphorylated eIF2α independently on fish PKR and vice versa. These results suggest that fish PKZ and PKR play a nonredundant but cooperative role in IFN antiviral response.
The Interaction of Alphavirus E1 Protein with Exogenous Domain III Defines Stages in Virus-Membrane Fusion
Authors: Roman-Sosa Gleyder , Kielian Margaret
Published: September 2011

Alphaviruses such as Semliki Forest virus (SFV) are enveloped viruses that infect cells through a low-pH-triggered membrane fusion reaction mediated by the transmembrane fusion protein E1. E1 drives fusion by insertion of its hydrophobic fusion loop into the cell membrane and refolding to a stable trimeric hairpin. In this postfusion conformation, the immunoglobulin-like domain III (DIII) and the stem region pack against the central core of the trimer. Membrane fusion and infection can be specifically inhibited by exogenous DIII, which binds to an intermediate in the E1 refolding pathway. Here we characterized the properties of the E1 target for interaction with exogenous DIII. The earliest target for DIII binding was an extended membrane-inserted E1 trimer, which was not detectable by assays for the stable postfusion hairpin. DIII binding provided a tool to detect this extended trimer and to define a series of SFV fusion-block mutants. DIII binding studies showed that the mutants were blocked in distinct steps in fusion protein refolding. Our results suggested that formation of the initial extended trimer was reversible and that it was stabilized by the progressive fold-back of the DIII and stem regions.
A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge
Authors: Bolles Meagan , Deming Damon , Long Kristin , Agnihothram Sudhakar , Whitmore Alan , Ferris Martin , Funkhouser William , Gralinski Lisa , Totura Allison , Heise Mark , Baric Ralph S.
Published: September 2011

Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.
NONPLANAR INTEGRABILITY: BEYOND THE SU(2) SECTOR
Authors: DE MELLO KOCH ROBERT , MOHAMMED BADR AWAD ELSEID , SMITH STEPHANIE
Published: September 2011

We compute the one-loop anomalous dimensions of restricted Schur polynomials with a classical dimension Δ~O(N). The operators that we consider are labeled by Young diagrams with two long columns or two long rows. Simple analytic expressions for the action of the dilatation operator are found. The projection operators needed to define the restricted Schur polynomials are constructed by translating the problem into a spin chain language, generalizing earlier results obtained in the SU(2) sector of the theory. The diagonalization of the dilatation operator reduces to solving five term recursion relations. The recursion relations can be solved exactly in terms of products of symmetric Kravchuk polynomials with Hahn polynomials. This proves that the dilatation operator reduces to a decoupled set of harmonic oscillators and therefore it is integrable, extending a similar conclusion reached for the SU(2) sector of the theory.
ELECTRONIC TRANSPORT IN METALLIC SYSTEMS AND GENERALIZED KINETIC EQUATIONS
Authors: KUZEMSKY A. L.
Published: September 2011

This paper reviews some selected approaches to the description of transport properties, mainly electroconductivity, in crystalline and disordered metallic systems. A detailed qualitative theoretical formulation of the electron transport processes in metallic systems within a model approach is given. Generalized kinetic equations which were derived by the method of the nonequilibrium statistical operator are used. Tight-binding picture and modified tight-binding approximation (MTBA) were used for describing the electron subsystem and the electron-lattice interaction correspondingly. The low- and high-temperature behavior of the resistivity was discussed in detail. The main objects of discussion are nonmagnetic (or paramagnetic) transition metals and their disordered alloys. The choice of topics and the emphasis on concepts and model approach makes it a good method for a better understanding of the electrical conductivity of the transition metals and their disordered binary substitutional alloys, but the formalism developed can be applied (with suitable modification), in principle, to other systems. The approach we used and the results obtained complements the existent theories of the electrical conductivity in metallic systems. The present study extends the standard theoretical format and calculation procedures in the theories of electron transport in solids.
MULTIFUNCTIONAL HYDROXYCAMPTOTHECIN-CAPPED Fe3O4 NANOPARTICLES FOR INHIBITING OF CANCER DRUG RESISTANCE
Authors: ZHANG GEN , JIANG HUI , WANG XUEMEI
Published: September 2011

In this study, we have explored the multifunctional hydroxycamptothecin (HCPT)-capped Fe 3 O 4 nanoparticles efficiently targeting adriamycin-resistant K562 cells (KA cells), inducing apoptosis, making hole on KA cell membrane, photothermal therapy and low hemolysis activity. The HCPT functionalized Fe 3 O 4 nanoparticles were characterized by the transmission electron microscopy (TEM) and high performance liquid chromatographic (HPLC) study. Meanwhile, the apoptotic staining and the DNA fragmentation clearly illustrate that the apoptosis rate apparently increased after the treatment with HCPT-capped Fe 3 O 4 (HCPT- Fe 3 O 4) nanoparticles, compared with that of the only HCPT treatment in KA cells. Moreover, our observations also demonstrate the possibility of the photothermal therapy to kill KA cells by using HCPT- Fe 3 O 4 nanoparticles with semiconductor laser. In addition, the blood compatibility of the HCPT- Fe 3 O 4 nanoparticles was tested by hemolysis assay on washing the isolated rat erythrocytes. The results indicate that HCPT- Fe 3 O 4 nanoparticles did not cause aggregation behavior at lower concentration. Thus, it is evident that the HCPT functionalized Fe 3 O 4 nanoparticles could readily induce cellular apoptosis and low hemolysis activity, which could be further utilized for the efficient multimode therapy of cancers.
Absence of Host Cation Segregation in the (Gd,Y)3Al5O12 Mixed Garnet Optical Ceramics
Authors: Boulon Georges , Epicier Thierry , Zhao Wei , Chani Valery I. , Yanagida Takayuki , Yoshikawa Akira
Published: September 2011

Recently non-uniform distribution of dopants in transparent optical ceramics was observed. It was demonstrated that dopants with low segregation coefficients (K<0.2) with respect to the melt crystal growth are segregated to the grain boundaries when the grains of the ceramics are developed. This communication discusses segregation of host cations that form crystal matrix. Experimental examination of spatial distribution of Gd3+ and Y3+ host cations in Ce3+-doped (Gd,Y)3Al5O12 ceramic sample demonstrated that no detectable redistribution of Gd3+ and Y3+ cations in the vicinity of the grain boundaries was detected. These results are in good agreement with comparable segregation behavior of Gd3+ and Y3+ [K(Y3+)≈K(Gd3+)] when the garnet solidification is performed from liquid phase. This observation also confirms qualitative match of segregation in liquid and solid states.
Different Resistive Switching Characteristics of a Cu/SiO2/Pt Structure
Authors: Liu Chih-Yi , Sung Po-Wei
Published: September 2011

A 20-nm SiO2 thin film was deposited using a radio-frequency magnetron sputter to form a Cu/SiO2/Pt structure. Resistance of the Cu/SiO2/Pt device was reversibly switched between the high resistance-state and the low resistance-state using dc voltages. The switching behaviors and the conduction mechanisms suggested that a conducting filament model would best explain the resistance switching. Both unipolar and bipolar switching behaviors were observed in the identical device by using different voltage operations. The detailed switching mechanism can not be differentiated by the switching behaviors directly. This study adopted current sweeping mode, reset current, and sweeping speed to distinguish the conducting model from the thermochemical and the electrochemical reactions.
Structure and Microwave Dielectric Property Relations in Barium Cobalt Magnesium Niobate Ceramics
Authors: Chen Ching-Tien , Huang Chi-Yuen , Lin Yong-Ming , Lee Chun-Te
Published: September 2011

The effects of cobalt substitution for magnesium on the microstructure and microwave dielectric properties of Ba(Mg1/3Nb2/3)O3 are investigated using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), Raman spectra, and microwave dielectric properties measurement. The structure of NbO6 octahedra displays a significant effect on the relative dielectric constant (εr) and the quality factor (Q ×f). The cobalt substitution shows a great quantity of nucleation of ordered domains, and result in a higher ordering degree. However, an annealing treatment also results in a higher ordering degree because of the growth of ordered domains. A compounds with near-zero τf can be obtained by the cobalt substitution. The Ba(Mg1-x
Co
x
)1/3Nb2/3O3 ceramic with cobalt substitution at x = 0.5 has the 32.2 of εr, 40,275 GHz of Q ×f, and 5.4 ppm/°C of τf, and it is suitable for microwave resonator application. This study indicates that the cobalt substitution cause a variant of the ordering degree, and consequently has a significant effect on the microwave dielectric properties.
Design of Plasmonic Racetrack Resonators with a Trench Structure
Authors: Okamoto Hiroyuki , Yamaguchi Kenzo , Haraguchi Masanobu , Okamoto Toshihiro , Sun Cheng
Published: September 2011

The authors present a plasmonic racetrack resonator with a trench structure. The depth of the structure and the length of the racetrack straightaways both significantly influence the characteristics of the plasmonic racetrack resonator. The optimum depth of the structure and length of the straightaways have been numerically evaluated by the finite-difference time-domain method. The quality factor of the plasmonic racetrack resonator is 38. As compared to the output intensity of a plasmonic ring resonator with a trench structure, the output intensity of the proposed plasmonic racetrack resonator is greater by one order of magnitude.
Improved Photovoltaic Effects of a Vertical-Type InGaN/GaN Multiple Quantum Well Solar Cell
Authors: Bae Si-Young , Shim Jae-Phil , Lee Dong-Seon , Jeon Seoung-Ran , Namkoong Gon
Published: September 2011

We investigated the photovoltaic performance of InGaN/GaN multiple quantum well (MQW) solar cells by comparing vertical-type and conventional lateral-type solar cells. We found that both bottom reflector and front surface texturing of vertical-type InGaN/GaN MQW solar cells enhanced light absorption by 45%, leading to an enhancement of the short circuit current density (J
SC) by 1.6 times, compared to that of a lateral-type structure. For the vertical-type InGaN/GaN solar cell, Ag was used for bottom reflectors and pyramid textured surfaces were formed by KOH etching after a lift-off process, whereas lateral-type structures were fabricated on sapphire substrates having smooth surfaces. As a result, the vertical InGaN/GaN MQW solar cells showed a high fill factor of 80.0% and conversion efficiency of 2.3%; in contrast, the conventional lateral structure produced a fill factor of 77.6% and a conversion efficiency of 1.4%.
Fiber Transmission Characteristics of Parabolic Pulses Generated by Optical Pulse Synthesizer
Authors: Kashiwagi Ken , Ishizu Hiroyuki , Kurokawa Takashi
Published: September 2011

We generated parabolic pulses by using an optical pulse synthesizer and investigated their fiber transmission characteristics in detail. The generated pulses had a rms difference of less than 0.03 between the target pulse shapes and their shapes. We transmitted them through standard single-mode fibers and dispersion-shifted fibers to evaluate the influences of their dispersions and nonlinearities on the pulse shapes. We compared the experimental results with simulated results calculated by the split-step Fourier method. The two results were well matched with each other. In the high power regime, the pulses experienced the higher order nonlinearities and were strongly distorted.