bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine-Induced Control of Viral Shedding following Rhesus Cytomegalovirus Challenge in Rhesus Macaques
Authors: Abel Kristina , Martinez Joy , Yue Yujuan , Lacey Simon F. , Wang Zhongde , Strelow Lisa , Dasgupta Anindya , Li Zhongqi , Schmidt Kimberli A. , Oxford Kristie L. , Assaf Basel , Longmate Jeffrey A. , Diamond Don J. , Barry Peter A.
Published: December 2010

The use of animal models of human cytomegalovirus (HCMV) infection is critical to refine HCMV vaccine candidates. Previous reports have demonstrated that immunization of rhesus monkeys against rhesus cytomegalovirus (RhCMV) can reduce both local and systemic replication of RhCMV following experimental RhCMV challenge. These studies used prime/boost combinations of DNA expression plasmids alone or DNA priming and boosting with either inactivated virion particles or modified vaccinia virus Ankara (MVA) expressing the same antigens. Viral outcomes included reduced RhCMV replication at the site of subcutaneous inoculation and RhCMV viremia following intravenous inoculation. Since shedding of cytomegalovirus from mucosal surfaces is critical for horizontal transmission of the virus, DNA priming/MVA boosting was evaluated for the ability to reduce oral shedding of RhCMV following subcutaneous challenge. Of six rhesus monkeys vaccinated exclusively against RhCMV glycoprotein B (gB), phosphoprotein 65 (pp65), and immediate-early 1 (IE1), half showed viral loads in saliva that were lower than those of control monkeys by 1 to 3 orders of magnitude. Further, there was a strong association of memory pp65 T cell responses postchallenge in animals exhibiting the greatest reduction in oral shedding. These results highlight the fact that a DNA/MVA vaccination regimen can achieve a notable reduction in a critical parameter of viral replication postchallenge. The recently completed clinical trial of a gB subunit vaccine in which the rate of HCMV infection was reduced by 50% in the individuals receiving the vaccine is consistent with the results of this study suggesting that additional immunogens are likely essential for maximum protection in an outbred human population.
Experimental Adaptation of an RNA Virus Mimics Natural Evolution
Authors: Hajimorad M. R. , Wen R.-H. , Eggenberger A. L. , Hill J. H. , Maroof M. A. Saghai
Published: December 2010

Identification of virulence determinants of viruses is of critical importance in virology. In search of such determinants, virologists traditionally utilize comparative genomics between a virulent and an avirulent virus strain and construct chimeras to map their locations. Subsequent comparison reveals sequence differences, and through analyses of site-directed mutants, key residues are identified. In the absence of a naturally occurring virulent strain, an avirulent strain can be functionally converted to a virulent variant via an experimental evolutionary approach. However, the concern remains whether experimentally evolved virulence determinants mimic those that have evolved naturally. To provide a direct comparison, we exploited a plant RNA virus, soybean mosaic virus (SMV), and its natural host, soybean. Through a serial
in vivo
passage experiment, the molecularly cloned genome of an avirulent SMV strain was converted to virulent variants on functionally immune soybean genotypes harboring resistance factor(s) from the complex
Rsv1
locus. Several of the experimentally evolved virulence determinants were identical to those discovered through a comparative genomic approach with a naturally evolved virulent strain. Thus, our observations validate an experimental evolutionary approach to identify relevant virulence determinants of an RNA virus.
Rhesus and Human Cytomegalovirus Glycoprotein L Are Required for Infection and Cell-to-Cell Spread of Virus but Cannot Complement Each Other
Authors: Bowman J. Jason , Lacayo Juan C. , Burbelo Peter , Fischer Elizabeth R. , Cohen Jeffrey I.
Published: December 2010

Rhesus cytomegalovirus (RhCMV), the homolog of human cytomegalovirus (HCMV), serves as a model for understanding the pathogenesis of HCMV and for developing candidate vaccines. In order to develop a replication-defective virus as a vaccine candidate, we constructed RhCMV with glycoprotein L (gL) deleted. RhCMV gL was essential for viral replication, and virus with gL deleted could only replicate in cells expressing RhCMV gL. Noncomplementing cells infected with RhCMV with gL deleted released intact, noninfectious RhCMV particles that were indistinguishable from wild-type RhCMV by electron microscopy and could be rescued by treatment of cells with polyethylene glycol. In addition, noncomplementing cells infected with RhCMV with gL deleted produced levels of gB, the major target of neutralizing antibodies, at levels similar to those observed in cells infected with wild-type RhCMV. Since RhCMV and HCMV gL share 53% amino acid identity, we determined whether the two proteins could complement the heterologous virus. Cells transfected with an HCMV bacterial artificial chromosome with gL deleted yielded virus that could replicate in human cells expressing HCMV gL. This is the second HCMV mutant with an essential glycoprotein deleted that has been complemented in cell culture. Finally, we found that HCMV gL could not complement the replication of RhCMV with gL deleted and that RhCMV gL could not complement the replication of HCMV with gL deleted. These data indicate that RhCMV and HCMV gL are both essential for replication of their corresponding viruses and, although the two gLs are highly homologous, they are unable to complement each another.
West Nile Virus Differentially Modulates the Unfolded Protein Response To Facilitate Replication and Immune Evasion
Authors: Ambrose Rebecca L. , Mackenzie Jason M.
Published: December 2010

For intracellular survival it is imperative that viruses have the capacity to manipulate various cellular responses, including metabolic and biosynthetic pathways. The unfolded protein response (UPR) is induced by various external and internal stimuli, including the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Our previous studies have indicated that the replication and assembly of the flavivirus West Nile virus strain Kunjin virus (WNV
KUN
) is intimately associated with the ER. Thus, we sought to determine whether the UPR was induced during WNV
KUN
infection. WNV
KUN
induces UPR signaling during replication, which is coordinated with peak replication. Interestingly, signaling is biased toward the ATF6/IRE-1 arm of the response, with high levels of Xbp-1 activation but negligible eukaryotic translation initiation factor 2α phosphorylation and downstream transcription. We show that the PERK-mediated response may partially regulate replication, since external UPR stimulation had a limiting effect on early replication events and cells deficient for PERK demonstrated increased replication and virus release. Significantly, we show that the WNV
KUN
hydrophobic nonstructural proteins NS4A and NS4B are potent inducers of the UPR, which displayed a high correlation in inhibiting Jak-STAT signaling in response to alpha interferon (IFN-α). Sequential removal of the transmembrane domains of NS4A showed that reducing hydrophobicity decreased UPR signaling and restored IFN-α-mediated activation. Overall, these results suggest that WNV
KUN
can stimulate the UPR to facilitate replication and that the induction of a general ER stress response, regulated by hydrophobic WNV
KUN
proteins, can potentiate the inhibition of the antiviral signaling pathway.
Antiviral RNA Interference Responses Induced by Semliki Forest Virus Infection of Mosquito Cells: Characterization, Origin, and Frequency-Dependent Functions of Virus-Derived Small Interfering RNAs
Authors: Siu Ricky W. C. , Fragkoudis Rennos , Simmonds Peter , Donald Claire L. , Chase-Topping Margo E. , Barry Gerald , Attarzadeh-Yazdi Ghassem , Rodriguez-Andres Julio , Nash Anthony A. , Merits Andres , Fazakerley John K. , Kohl Alain
Published: December 2010

RNA interference (RNAi) is an important mosquito defense mechanism against arbovirus infection. In this paper we study the processes underlying antiviral RNAi in
Aedes albopictus
-derived U4.4 mosquito cells infected with Semliki Forest virus (SFV) (
Togaviridae
;
Alphavirus
). The production of virus-derived small interfering RNAs (viRNAs) from viral double-stranded RNA (dsRNA) is a key event in this host response. dsRNA could be formed by RNA replication intermediates, by secondary structures in RNA genomes or antigenomes, or by both. Which of these dsRNAs is the substrate for the generation of viRNAs is a fundamental question. Here we used deep sequencing of viRNAs and bioinformatic analysis of RNA secondary structures to gain insights into the characteristics and origins of viRNAs. An asymmetric distribution of SFV-derived viRNAs with notable areas of high-level viRNA production (hot spots) and no or a low frequency of viRNA production (cold spots) along the length of the viral genome with a slight bias toward the production of genome-derived viRNAs over antigenome-derived viRNAs was observed. Bioinformatic analysis suggests that hot spots of viRNA production are rarely but not generally associated with putative secondary structures in the SFV genome, suggesting that most viRNAs are derived from replicative dsRNA. A pattern of viRNAs almost identical to those of
A. albopictus
cells was observed for
Aedes aegypti
-derived Aag2 cells, suggesting common mechanisms that lead to viRNA production. Hot-spot viRNAs were found to be significantly less efficient at mediating antiviral RNAi than cold-spot viRNAs, pointing toward a nucleic acid-based viral decoy mechanism to evade the RNAi response.
Differential Effects of Human Immunodeficiency Virus Type 1 Vpu on the Stability of BST-2/Tetherin
Authors: Andrew Amy J. , Miyagi Eri , Strebel Klaus
Published: December 2010

BST-2/CD317/tetherin is a host factor that inhibits the release of HIV-1 and other unrelated viruses. A current model proposes that BST-2 physically tethers virions to the surface of virus-producing cells. The HIV-1-encoded Vpu protein effectively antagonizes the activity of BST-2. How Vpu accomplishes this task remains unclear; however, it is known that Vpu has the ability to down-modulate BST-2 from the cell surface. Here we analyzed the effects of Vpu on BST-2 by performing a series of kinetic studies with HeLa, 293T, and CEMx174 cells. Our results indicate that the surface downregulation of BST-2 is not due to an accelerated internalization or reduced recycling of internalized BST-2 but instead is caused by interference with the resupply of newly synthesized BST-2 from within the cell. While our data confirm previous reports that the high-level expression of Vpu can cause the endoplasmic reticulum (ER)-associated degradation of BST-2, we found no evidence that Vpu targets endogenous BST-2 in the ER in the course of a viral infection. Instead, we found that Vpu acts in a post-ER compartment and increases the turnover of newly synthesized mature BST-2. Our observation that Vpu does not affect the recycling of BST-2 suggests that Vpu does not act directly at the cell surface but may interfere with the trafficking of newly synthesized BST-2 to the cell surface, resulting in the accelerated targeting of BST-2 to the lysosomal compartment for degradation.
Rice Dwarf Viruses with Dysfunctional Genomes Generated in Plants Are Filtered Out in Vector Insects: Implications for the Origin of the Virus
Authors: Pu Yingying , Kikuchi Akira , Moriyasu Yusuke , Tomaru Masatoshi , Jin Yan , Suga Haruhisa , Hagiwara Kyoji , Akita Fusamichi , Shimizu Takumi , Netsu Osamu , Suzuki Nobuhiro , Uehara-Ichiki Tamaki , Sasaya Takahide , Wei Taiyun , Li Yi , Omura Toshihiro
Published: December 2010

Rice dwarf virus
(RDV), with 12 double-stranded RNA (dsRNA) genome segments (S1 to S12), replicates in and is transmitted by vector insects. The RDV-plant host-vector insect system allows us to examine the evolution, adaptation, and population genetics of a plant virus. We compared the effects of long-term maintenance of RDV on population structures in its two hosts. The maintenance of RDV in rice plants for several years resulted in gradual accumulation of nonsense mutations in S2 and S10, absence of expression of the encoded proteins, and complete loss of transmissibility. RDV maintained in cultured insect cells for 6 years retained an intact protein-encoding genome. Thus, the structural P2 protein encoded by S2 and the nonstructural Pns10 protein encoded by S10 of RDV are subject to different selective pressures in the two hosts, and mutations accumulating in the host plant are detrimental in vector insects. However, one round of propagation in insect cells or individuals purged the populations of RDV that had accumulated deleterious mutations in host plants, with exclusive survival of fully competent RDV. Our results suggest that during the course of evolution, an ancestral form of RDV, of insect virus origin, might have acquired the ability to replicate in a host plant, given its reproducible mutations in the host plant that abolish vector transmissibility and viability in nature.
Initiation of Epstein-Barr Virus Lytic Replication Requires Transcription and the Formation of a Stable RNA-DNA Hybrid Molecule at OriLyt
Authors: Rennekamp Andrew J. , Lieberman Paul M.
Published: December 2010

The genetic elements of herpesvirus origins of lytic replication have been characterized in detail; however, much remains to be elucidated concerning their functional role in replication initiation. In the case of the Epstein-Barr virus (EBV), we have found that in addition to the two well-defined critical elements required for lytic replication (the upstream and downstream essential elements, UEE and DEE), the origin of lytic replication (OriLyt) also requires the presence of a GC-rich RNA in
cis
. The
BHLF1
transcript is similar to the essential
K5
transcript identified at the Kaposi's sarcoma-associated herpesvirus OriLyt. We have found that truncation of the
BHLF1
transcript or deletion of the TATA box, but not the putative ATG initiation codon, reduce OriLyt function to background levels. By using an antibody specific for RNA-DNA hybrid molecules, we found the
BHLF1
RNA stably annealed to its DNA template during the early steps of lytic reactivation. Furthermore, expression of human RNase H1, which degrades RNA in RNA-DNA hybrids, drastically reduces OriLyt-dependent DNA replication as well as recruitment of the viral single-stranded DNA binding protein BALF2 to OriLyt. These studies suggest that a GC-rich OriLyt transcript is an important component of gammaherpesvirus lytic origins and is required for initial strand separation and loading of core replication proteins.
Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1
Authors: Changela Anita , Wu Xueling , Yang Yongping , Zhang Baoshan , Zhu Jiang , Nardone Glenn A. , O'Dell Sijy , Pancera Marie , Gorny Miroslaw K. , Phogat Sanjay , Robinson James E. , Stamatatos Leonidas , Zolla-Pazner Susan , Mascola John R. , Kwong Peter D.
Published: December 2010

Monoclonal antibody 2909 belongs to a class of potently neutralizing antibodies that recognize quaternary epitopes on HIV-1. Some members of this class, such as 2909, are strain specific, while others, such as antibody PG16, are broadly neutralizing; all, however, recognize a region on the gp120 envelope glycoprotein that includes two loops (V2 and V3) and forms appropriately only in the oligomeric HIV-1 spike (gp120
3
/gp41
3
). Here we present the crystal structure of 2909 and report structure-function analysis with antibody chimeras composed of 2909 and other members of this antibody class. The 2909 structure was dominated by a heavy-chain third-complementarity-determining region (CDR H3) of 21 residues, which comprised 36% of the combining surface and formed a β-hairpin club extending ∼20 Å beyond the rest of the antibody. Sequence analysis and mass spectrometry identified sites of tyrosine sulfation at the middle and top of CDR H3; substitutions with phenylalanine either ablated (middle substitution) or substantially diminished (top substitution) neutralization. Chimeric antibodies composed of heavy and light chains, exchanged between 2909 and other members of the class, indicated a substantial lack of complementation. Comparison of 2909 to PG16 (which is tyrosine sulfated and the only other member of the class for which a structure has previously been reported) showed that both utilize protruding, anionic CDR H3s for recognition. Thus, despite some diversity, members of this class share structural and functional similarities, with conserved features of the CDR H3 subdomain likely reflecting prevalent solutions by the human immune system for recognition of a quaternary site of HIV-1 vulnerability.
Preferential Induction of Protective T Cell Responses to Theiler's Virus in Resistant (C57BL/6 × SJL)F1 Mice
Authors: Jin Young-Hee , Kang Hyun Seok , Mohindru Mani , Kim Byung S.
Published: December 2010

Infection of the central nervous system (CNS) with Theiler's murine encephalomyelitis virus (TMEV) induces an immune-mediated demyelinating disease in susceptible mouse strains such as SJL/J (H-2s) but not in strains such as C57BL/6 (H-2b). In addition, it has been shown that (C57BL/6 × SJL/J)F1 mice (F1 mice), which carry both resistant and susceptible MHC haplotypes (H-2b/s), are resistant to both viral persistence and TMEV-induced demyelinating disease. In this study, we further analyzed the immune responses underlying the resistance of F1 mice. Our study shows that the resistance of F1 mice is associated with a higher level of the initial virus-specific H-2b-restricted CD8+T cell responses than of the H-2s-restricted CD8+T cell responses. In contrast, pathogenic Th17 responses to viral epitopes are lower in F1 mice than in susceptible SJL/J mice. Dominant effects of resistant genes expressed in antigen-presenting cells of F1 mice on regulation of viral replication and induction of protective T cell responses appear to play a crucial role in disease resistance. Although the F1 mice are resistant to disease, the level of viral RNA in the CNS was intermediate between those of SJL/J and C57BL/6 mice, indicating the presence of a threshold of viral expression for pathogenesis.
Roles of VP4 and NSP1 in Determining the Distinctive Replication Capacities of Simian Rotavirus RRV and Bovine Rotavirus UK in the Mouse Biliary Tract
Authors: Feng Ningguo , Sen Adrish , Wolf Marie , Vo Phuoc , Hoshino Yasutaka , Greenberg Harry B.
Published: December 2010

Rotavirus replication and virulence are strongly influenced by virus strain and host species. The rotavirus proteins VP3, VP4, VP7, NSP1, and NSP4 have all been implicated in strain and species restriction of replication; however, the mechanisms have not been fully determined. Simian (RRV) and bovine (UK) rotaviruses have distinctive replication capacities in mouse extraintestinal organs such as the biliary tract. Using reassortants between UK and RRV, we previously demonstrated that the differential replication of these viruses in mouse embryonic fibroblasts is determined by the respective NSP1 proteins, which differ substantially in their abilities to degrade interferon (IFN) regulatory factor 3 (IRF3) and suppress the type I IFN response. In this study, we used an
in vivo
model of rotavirus infection of mouse gallbladder with UK × RRV reassortants to study the genetic and mechanistic basis of systemic rotavirus replication. We found that the low-replication phenotype of UK in biliary tissues was conferred by UK
VP4
and that the high-replication phenotype of RRV was conferred by RRV
VP4
and
NSP1
. Viruses with RRV
VP4
entered cultured mouse cholangiocytes more efficiently than did those with UK
VP4
. Reassortants with RRV
VP4
and UK
NSP1
genes induced high levels of expression of IRF3-dependent p54 in biliary tissues, and their replication was increased 3-fold in IFN-α/β and -γ receptor or STAT1 knockout (KO) mice compared to wild-type mice. Our data indicate that systemic rotavirus strain-specific replication in the murine biliary tract is determined by both viral entry mediated by
VP4
and viral antagonism of the host innate immune response mediated by
NSP1
.
Appraising the Roles of CBLL1 and the Ubiquitin/Proteasome System for Flavivirus Entry and Replication
Authors: Fernandez-Garcia Maria-Dolores , Meertens Laurent , Bonazzi Matteo , Cossart Pascale , Arenzana-Seisdedos Fernando , Amara Ali
Published: December 2010

The ubiquitin ligase CBLL1 (also known as HAKAI) has been proposed to be a critical cellular factor exploited by West Nile virus (WNV) for productive infection. CBLL1 has emerged as a major hit in a recent RNA interference screen designed to identify cellular factors required for the early stages of the WNV life cycle. Follow-up experiments showed that HeLa cells knocked down for CBLL1 by a small interfering RNA (siRNA) failed to internalize WNV particles and resisted infection. Furthermore, depletion of a free-ubiquitin pool by the proteasome inhibitor MG132 abolished WNV endocytosis, suggesting that CBLL1 acts in concert with the ubiquitin proteasome system to mediate virus internalization. Here, we examined the effect of CBLL1 knockdown and proteasome inhibitors on infection by WNV and other flaviviruses. We identified new siRNAs that repress the CBLL1 protein and strongly inhibit the endocytosis of
Listeria monocytogenes
, a bacterial pathogen known to require CBLL1 to invade host cells. Strikingly, however, we detected efficient WNV, dengue virus, and yellow fever virus infection of human cells, despite potent downregulation of CBLL1 by RNA interference. In addition, we found that the proteasome inhibitors MG132 and lactacystin did not affect WNV internalization but strongly repressed flavivirus RNA translation and replication. Together, these data do not support a requirement for CBLL1 during flavivirus entry and rather suggest an essential role of the ubiquitin/proteasome pathway for flavivirus genome amplification.
ASYMPTOTIC APPROXIMATION OF THE MODAL ACOUSTIC IMPEDANCE OF A CIRCULAR MEMBRANE
Authors: RDZANEK WOJCIECH P. , RDZANEK WITOLD J. , SZEMELA KRZYSZTOF
Published: December 2010

The Neumann boundary value problem of the Helmholtz equation of a vibrating circular membrane embedded into a flat rigid baffle is solved. The membrane is excited asymmetrically and radiates acoustic waves into the half-space above the baffle. A set of elementary asymptotic equations for modal radiation self-impedance and mutual impedance is presented. The equations are necessary for numerical computations of the radiated active and reactive acoustic power including the acoustic attenuation. A few equations available in the literature are collected. All the missing equations have been obtained using the methods of analysis of contour integral and stationary phase. The presented equations cover a wide frequency band, with the exception of the lowest frequencies and the frequencies close to coincidence.
STARTING A NEW COMPANY — WHICH TYPES OF PERSONAL EXPERIENCE HELP?
Authors: MERZ CHRISTIN , SCHROETER ANDREAS , WITT PETER
Published: December 2010

This paper investigates the relationship between different types of personal experience and start-up success. We propose four extensions to earlier studies on the subject. First, we distinguish between management, technical, industry, and entrepreneurial experience of founders. Second, we consider decreasing marginal effects of different types of experience on start-up success. Third, our measures for start-up success correspond to the different stages of the entrepreneurial process. Fourth, we measure the "breadth" of experience in different fields in addition to the "depth" of experience per field. In the empirical part of the paper, we test all hypotheses using a sample of 137 German start-ups.
THE INTERPLAY BETWEEN ORIENTATIONS: ENTREPRENEURIAL, TECHNOLOGY AND CUSTOMER ORIENTATIONS IN SOFTWARE COMPANIES
Authors: HAKALA HENRI , KOHTAMÄKI MARKO
Published: December 2010

This study examines the interplay between entrepreneurial, technology and customer orientations and company performance using data from 164 software companies. To conduct the analysis, the study applies PLS (partial least squares) modeling to understand the direct and indirect effects of entrepreneurial, customer and technology orientations on the performance of a software company. The results indicate that entrepreneurial and customer orientations directly affect performance, but, in this context, they do not support the view that a technology orientation directly enhances performance. More importantly, results suggest that an entrepreneurial orientation positively affects both customer and technology orientations. It appears that software companies need a capability to serve customers well, but also need to recognize new business opportunities from within their current customer relationships. The results suggest that to achieve high levels of performance, software companies need to balance the elements of entrepreneurial proactiveness and innovation with customer needs.
Intermediation Spread, Bank Supervision, and Financial Stability
Authors: Özyıldırım Süheyla
Published: December 2010

This paper models the effect of bank competition and deposit insurance premiums on the spread between lending and deposit rates. In developing economies, low spreads do not always indicate bank efficiency; they may be the result of high risk taking. This paper shows that imposing upper and lower limits on banks' spreads and adjusting deposit insurance premiums when violation of these limits occurs leads to a more stable but relatively large intermediation costs. In developing economies, such an outcome would be considered more desirable because it insulates existing financial intermediaries and investors against macroeconomic disturbances.
Non-Normality and Risk in Developing Asian Markets
Authors: Alles Lakshman , Murray Louis
Published: December 2010

This paper examines whether additional risk factors such as the variance, skewness, and coskewness of returns offer an appropriate explanation of company returns in less developed capital markets. Arguments for considering some additional factors in pricing models to better deal with such situations are presented. Using individual company returns from a range of developing Asian capital markets, empirical tests examine the importance of these extra risk factors. Results indicate that both individually and when in combination, variance and coskewness are significantly related to returns in these markets. Skewness is less consistently important. Robustness tests confirm that these measures tend not to capture size or book to market factors.
The Impact of Non-trading Periods on the Measurement of Volatility
Authors: Wang Yaw-Huei , Hsiao Yu-Jen
Published: December 2010

Based upon the theory of the "arrival of news", the main purpose of this paper is to investigate the impact of non-trading periods on the measurement of volatility for the S&P 500, FTSE 100, and TAIEX indices. Using an adaptation of the GJR (1,1) model, we find that both weekday holiday periods and half-day trading periods have significant impacts on the estimation of volatility for the S&P 500 and FTSE 100 indices. On the other hand, weekends have significant impacts for the TAIEX index. Our findings imply that for the UK and US markets, much less relevant information is produced during weekends, while more relevant information continues to be produced during other types of non-trading periods. However, the weekend volatility of the Taiwan market is specially driven because the US macro news is announced on Fridays and the trading time of the US market is later than that of the Taiwan market without any overlapping.
Research of Building Intelligent Investment Decision Mode for Investment Portfolio — Using Taiwan Electronic Stock as an Example
Authors: Ho Wen-Rong Jerry , Liu C. H. , Chen H. W.
Published: December 2010

This research uses all of the listed electronic stocks in the Taiwan Stock Exchange as a sample to test the performance of the return rate of stock prices. In addition, this research compares it with the electronic stock returns. The empirical result shows that no matter which kind of stock selection strategy we choose, a majority of the return rate is higher than that of the electronics index. Evident in the results, the predicted effect of BPNN is better than that of the general average decentralized investment strategy. Furthermore, the low price-to-earning ratio and the low book-to-market ratio have a significant long-term influence.
POLY(ETHYLENE CO-VINYL ACETATE)-ASSISTED ONE-STEP TRANSFER OF ULTRA-LARGE GRAPHENE
Authors: HAN GANG HEE , SHIN HYEON-JIN , KIM EUN SUNG , CHAE SEUNG JIN , CHOI JAE-YOUNG , LEE YOUNG HEE
Published: December 2010

One-step roll-to-roll lamination transfer of graphene was achieved by poly(ethylene co-vinyl acetate) as a binding material which has thermoplastic property and wide rubbery-plateau region between T g ~T m . The transferred graphene film has a transmittance of 96.7% at 550 nm and 1.96 kΩ/sq of sheet resistance measured by simple 4-probe method. Standard deviation was found to be 0.198 kΩ/sq.
ANNEALING BEHAVIORS OF TiO2-SHEATHED SnO2 NANORODS
Authors: JIN CHANGHYUN , LEE JUNGKEUN , KIM HYUNSU , PARK SUNGHOON , JEONG BONGYONG , LEE CHONGMU
Published: December 2010

We report the preparation and thermal annealing of SnO 2-core/ TiO 2-shell nanorods using a two-step process comprising the thermal evaporation of Sn powders and the sputter-deposition of TiO 2. X-ray diffraction analysis revealed that the shells were crystallized by annealing. Photoluminescence measurements showed that the major yellow emission of the SnO 2 nanorods was enhanced in intensity by sheathing them with TiO 2 and was further enhanced by annealing. A reducing atmosphere was found to be more efficient in enhancing the yellow emission by annealing than an oxidative atmosphere. The origin of the emission enhancement by coating and annealing is also discussed.
PRESENTATION OF BIOACTIVE EPITOPES WITH FREE N-TERMINI ON SELF-ASSEMBLING PEPTIDE NANOFIBERS
Authors: LIU YANFEI , ZHAO XIAOJUN
Published: December 2010

Branched self-assembling peptides bearing epitopes with free N-termini were designed. A lysine residue was used as branch point to present more than one epitopes in a single peptide. Atomic force microscope, circular dichroism and Fourier transform infrared spectroscopy data indicate that the N-terminus attached epitope sequences do not prevent the formation of the β-sheets and the self-assembling of these peptides into stable nanofibers in aqueous solutions. Rheology experiments show that these peptides could form self-supporting scaffolds once electrostatic repulsions were screened by electrolytes. Fluorescence spectra measurements upon binding of FITC-avidin to surfaces of nanofibers were performed to investigate the effect of charged aspartic acid residues in RGD epitopes at the lysine branching on packing and accessibility of the epitopes. Results show that the electrostatic interaction between hydrophilic side chains at branching and nanofiber surfaces may significantly affect the conformational freedom and accessibility of the epitopes at the periphery of the nanofibers. Cell entrapment experiments reveal that the attached RGD epitopes with free N-termini are biological active.
TOPOLOGICAL ASPECTS OF THE DVORETZKY THEOREM
Authors: BURAGO DMITRI , IVANOV SERGEI , TABACHNIKOV SERGE
Published: December 2010

We explore possibilities and limitations of a purely topological approach to the Dvoretzky theorem.
STABILITY OF ANOSOV HAMILTONIAN STRUCTURES
Authors: MERRY WILL J. , PATERNAIN GABRIEL P.
Published: December 2010

Let (Mn, g) denote a closed Riemannian manifold (n ≥ 3) which admits a metric of negative curvature (not necessarily equal to g). Let ω1 := ω0 + π*σ denote a twisted symplectic form on TM, where σ ∈ Ω2(M) is a closed 2-form and ω0 is the symplectic structure on TM obtained by pulling back the canonical symplectic form dx ∧ dp on T*M via the Riemannian metric. Let Σk be the hypersurface [Formula: see text]. We prove that if n is odd and the Hamiltonian structure (Σk, ω1) is Anosov with C1 weak bundles, then (Σk, ω1) is stable if and only if it is contact. If n is even and in addition the Hamiltonian structure is 1/2-pinched, then the same conclusion holds. As a corollary, we deduce that if g is negatively curved, strictly 1/4-pinched and σ is not exact then the Hamiltonian structure (Σk, ω1) is never stable for all sufficiently large k.
ELIASHBERG'S PROOF OF CERF'S THEOREM
Authors: GEIGES HANSJÖRG , ZEHMISCH KAI
Published: December 2010

Following a line of reasoning suggested by Eliashberg, we prove Cerf's theorem that any diffeomorphism of the 3-sphere extends over the 4-ball. To this end we develop a moduli-theoretic version of Eliashberg's filling-with-holomorphic-discs method.
Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake
Authors: Zimnicka Adriana M. , Ivy Kristin , Kaplan Jack H.
Published: December 2010

Copper is an essential micronutrient in humans and is required for a wide range of physiological processes, including neurotransmitter biosynthesis, oxidative metabolism, protection against reactive oxygen species, and angiogenesis. The first step in the acquisition of dietary copper is absorption from the intestinal lumen. The major human high-affinity copper uptake protein, human copper transporter hCTR1, was recently shown to be at the basolateral or blood side of both intestinal and renal epithelial cell lines and thus does not play a direct role in this initial step. We sought to functionally identify the major transport pathways available for the absorption of dietary copper across the apical intestinal membrane using Caco2 cells, a well-established model for human enterocytes. The initial rate of apical copper uptake into confluent monolayers of Caco2 cells is greatly elevated if amino acids and serum proteins are removed from the growth media. Uptake from buffered saline solutions at neutral pH (but not at lower pH) is inhibited by either d- or l-histidine, unaltered by the removal of sodium ions, and inhibited by ∼90% when chloride ions are replaced by gluconate or sulfate. Chloride-dependent copper uptake occurs with Cu(II) or Cu(I), although Cu(I) uptake is not inhibited by histidine, nor by silver ions. A well-characterized inhibitor of anion exchange systems, DIDS, inhibited apical copper uptake by 60–70%, while the addition of Mn(II) or Fe(II), competitive substrates for the divalent metal transporter DMT1, had no effect on copper uptake. We propose that anion exchangers play an unexpected role in copper absorption, utilizing copper-chloride complexes as pseudo-substrates. This pathway is also observed in mouse embryonic fibroblasts, human embryonic kidney cells, and Cos-7 cells. The special environment of low pH, low concentration of protein, and protonation of amino acids in the early intestinal lumen make this pathway especially important in dietary copper acquisition.
NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of basal and acute regulation of NHE3 activity
Authors: Sarker Rafiquel , Valkhoff Vera E. , Zachos Nicholas C. , Lin Rong , Cha Boyoung , Chen Tian-e , Guggino Sandra , Zizak Mirza , de Jonge Hugo , Hogema Boris , Donowitz Mark
Published: December 2010

Na+/H+ exchanger 3 (NHE3) is expressed in the brush border (BB) of intestinal epithelial cells and accounts for the majority of neutral NaCl absorption. It has been shown that the Na+/H+ exchanger regulatory factor (NHERF) family members of multi-PDZ domain-containing scaffold proteins bind to the NHE3 COOH terminus and play necessary roles in NHE3 regulation in intestinal epithelial cells. Most studies of NHE3 regulation have been in cell models in which NHERF1 and/or NHERF2 were overexpressed. We have now developed an intestinal Na+ absorptive cell model in Caco-2/bbe cells by expressing hemagglutinin (HA)-tagged NHE3 with an adenoviral infection system. Roles of NHERF1 and NHERF2 in NHE3 regulation were determined, including inhibition by cAMP, cGMP, and Ca2+ and stimulation by EGF, with knockdown (KD) approaches with lentivirus (Lenti)-short hairpin RNA (shRNA) and/or adenovirus (Adeno)-small interfering RNA (siRNA). Stable infection of Caco-2/bbe cells by NHERF1 or NHERF2 Lenti-shRNA significantly and specifically reduced NHERF protein expression by >80%. NHERF1 KD reduced basal NHE3 activity, while NHERF2 KD stimulated NHE3 activity. siRNA-mediated (transient) and Lenti-shRNA-mediated (stable) gene silencing of NHERF2 (but not of NHERF1) abolished cGMP- and Ca2+-dependent inhibition of NHE3. KD of NHERF1 or NHERF2 alone had no effect on cAMP inhibition of NHE3, but KD of both simultaneously abolished the effect of cAMP. The stimulatory effect of EGF on NHE3 was eliminated in NHERF1-KD but occurred normally in NHERF2-KD cells. These findings show that both NHERF2 and NHERF1 are involved in setting NHE3 activity. NHERF2 is necessary for cGMP-dependent protein kinase (cGK) II- and Ca2+-dependent inhibition of NHE3. cAMP-dependent inhibition of NHE3 activity requires either NHERF1 or NHERF2. Stimulation of NHE3 activity by EGF is NHERF1 dependent.
Prostaglandin F2αstimulates PI3K/ERK/mTOR signaling and skeletal myotube hypertrophy
Authors: Markworth James F. , Cameron-Smith David
Published: December 2010

Cyclooxygenase (COX) enzymes mediate the synthesis of proinflammatory prostaglandin (PG) species from cellular arachidonic acid. COX/PGs have been implicated in skeletal muscle growth/regeneration; however, the mechanisms by which PGs influence skeletal muscle adaptation are poorly understood. The present study aimed to investigate PGF2αsignaling and its role in skeletal myotube hypertrophy. PGF2αor the FP receptor agonist fluprostenol increased C2C12 myotube diameter. This effect was abolished by the FP receptor antagonist AL8810 and mammalian target of rapamycin (mTOR) inhibition. PGF2αstimulated time- and dose-dependent increases in the phosphorylation of extracellular receptor kinase (ERK)1/2 (Thr202/Tyr204), p70S6 kinase (p70S6K) (Thr389 and Thr421/Ser424), and eukaryotic initiation factor 4G (eIF4G) (Ser1108) without influencing Akt (Ser473). Pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the ERK inhibitor PD98059 blocked F prostanoid receptor signaling responses, whereas rapamycin blocked heightened p70S6K/eIF4G phosphorylation without influencing ERK1/2 phosphorylation. These data suggest that activation of the F prostanoid receptor is coupled to C2C12 myotube growth and intracellular signaling via a PI3K/ERK/mTOR-dependent pathway.
Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells
Authors: Nørsett Kristin G. , Steele Islay , Duval Cedric , Sammut Stephen J. , Murugesan Senthil V. M. , Kenny Susan , Rainbow Lucille , Dimaline Rod , Dockray Graham J. , Pritchard D. Mark , Varro Andrea
Published: December 2010

Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biopsies from subjects with elevated plasma gastrin, the abundances of PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared with subjects with plasma concentrations in the reference range. In patients with hypergastrinemia due to autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1, uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy. Immunohistochemistry revealed localization of PAI-1 to parietal cells and enterochromaffin-like cells in micronodular neuroendocrine tumors in hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI-1-luciferase promoter-reporter construct transfected into AGS-GR cells. There was time- and concentration-dependent increase of PAI-1-luciferase expression in response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways. In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-GR cell migration and invasion, and small interfering RNA treatment increased responses to gastrin. We conclude that elevated plasma gastrin concentrations are associated with increased expression of gastric PAI-1, which may act to restrain gastrin-stimulated cell migration and invasion.
Decrease in the density of t-tubular L-type Ca2+ channel currents in failing ventricular myocytes
Authors: Horiuchi-Hirose Miwa , Kashihara Toshihide , Nakada Tsutomu , Kurebayashi Nagomi , Shimojo Hisashi , Shibazaki Toshihide , Sheng Xiaona , Yano Shiharu , Hirose Masamichi , Hongo Minoru , Sakurai Takashi , Moriizumi Tetsuji , Ueda Hideho , Yamada Mitsuhiko
Published: December 2010

In some forms of cardiac hypertrophy and failure, the gain of Ca2+-induced Ca2+ release [CICR; i.e., the amount of Ca2+ released from the sarcoplasmic reticulum normalized to Ca2+ influx through L-type Ca2+ channels (LTCCs)] decreases despite the normal whole cell LTCC current density, ryanodine receptor number, and sarcoplasmic reticulum Ca2+ content. This decrease in CICR gain has been proposed to arise from a change in dyad architecture or derangement of the t-tubular (TT) structure. However, the activity of surface sarcolemmal LTCCs has been reported to increase despite the unaltered whole cell LTCC current density in failing human ventricular myocytes, indicating that the “decreased CICR gain” may reflect a decrease in the TT LTCC current density in heart failure. Thus, we analyzed LTCC currents of failing ventricular myocytes of mice chronically treated with isoproterenol (Iso). Although Iso-treated mice exhibited intact t-tubules and normal LTCC subunit expression, acute occlusion of t-tubules of isolated ventricular myocytes with osmotic shock (detubulation) revealed that the TT LTCC current density was halved in Iso-treated versus control myocytes. Pharmacological analysis indicated that kinases other than PKA or Ca2+/calmodulin-dependent protein kinase II insufficiently activated, whereas protein phosphatase 1/2A excessively suppressed, TT LTCCs in Iso-treated versus control myocytes. These results indicate that excessive β-adrenergic stimulation causes the decrease in TT LTCC current density by altering the regulation of TT LTCCs by protein kinases and phosphatases in heart failure. This phenomenon might underlie the decreased CICR gain in heart failure.
Functional plasticity of mitochondrion-rich cells in the skin of euryhaline medaka larvae (Oryzias latipes) subjected to salinity changes
Authors: Shen Wan-Ping , Horng Jiun-Lin , Lin Li-Yih
Published: December 2010

A noninvasive technique, the scanning ion-selective electrode technique (SIET) was applied to measure Na+and Cl−transport by the yolk-sac skin and individual mitochondrion-rich cells (MRCs) in intact medaka larvae ( Oryzias latipes ). In seawater (SW)-acclimated larvae, significant outward Na+and Cl−gradients were measured at the yolk-sac surface, indicating secretions of Na+and Cl−from the yolk-sac skin. With Na+pump immunostaining and microscopic observation, two groups of MRCs were identified on the yolk-sac skin of SW-larvae. These were single MRCs (s-MRCs), which do not have an accompanying accessory cell (AC), and multicellular complex MRCs (mc-MRCs), which usually consist of an MRC and an accompanying AC. The percentage of mc-MRC was ∼60% in 30 parts per thousand of SW, and it decreased with the decrease of external salinity. By serial SIET probing over the surface of the MRCs and adjacent keratinocytes (KCs), significant outward fluxes of Na+and Cl−were detected at the apical opening (membrane) of mc-MRCs, whereas only outward Cl−flux, but not Na+flux, was detected at s-MRCs. Treatment with 100 μM ouabain or bumetanide effectively blocked the Na+and Cl−secretion. Following freshwater (FW) to SW transfer, Na+and Cl−secretions by the yolk-sac skin were fully developed in 5 h and 2 h, respectively. In contrast, both Na+and Cl−secretions downregulated rapidly after SW to FW transfer. Sequential probing at individual MRCs found that Na+and Cl−secretions declined dramatically after SW to FW transfer and Na+/Cl−uptake was detected at the same s-MRCs and mc-MRCs after 5 h. This study provides evidence demonstrating that ACs are required for Na+excretion and MRCs possess a functional plasticity in changing from a Na+/Cl−-secreting cell to a Na+/Cl−-absorbing cell.
Adrenocorticotropic hormone and corticosterone responses to acute hypoxia in the neonatal rat: effects of body temperature maintenance
Authors: Bruder Eric D. , Kamer Kimberli J. , Guenther Mitchell A. , Raff Hershel
Published: December 2010

The corticosterone response to acute hypoxia in neonatal rats develops in the 1st wk of life, with a shift from ACTH independence to ACTH dependence. Acute hypoxia also leads to hypothermia, which may be protective. There is little information about the endocrine effects of body temperature maintenance during periods of neonatal hypoxia. We hypothesized that prevention of hypothermia during neonatal hypoxia would augment the adrenocortical stress response. Rat pups separated from their dams were studied at postnatal days 2 and 8 ( PD2 and PD8). In one group of pups, body temperature was allowed to spontaneously decrease during a 30-min prehypoxia period. Pups were then exposed to 8% O2 for 3 h and allowed to become spontaneously hypothermic or externally warmed (via servo-controlled heat) to maintain isothermia. In another group, external warming was used to maintain isothermia during the prehypoxia period, and then hypoxia with or without isothermia was applied. Plasma ACTH and corticosterone and mRNA expression of genes for upstream proteins involved in the steroidogenic pathway were measured. Maintenance of isothermia during the prehypoxia period increased baseline plasma ACTH at both ages. Hypothermic hypoxia caused an increase in plasma corticosterone; this response was augmented by isothermia at PD2, when the response was ACTH-independent, and at PD8, when the response was ACTH-dependent. In PD8 rats, isothermia also augmented the plasma ACTH response to hypoxia. We conclude that maintenance of isothermia augments the adrenocortical response to acute hypoxia in the neonate. Prevention of hypothermia may increase the stress response during neonatal hypoxia, becoming more pronounced with increased age.
Renal programming: cause for concern?
Authors: Kett Michelle M. , Denton Kate M.
Published: December 2010

Development of the kidney can be altered in utero in response to a suboptimal environment. The intrarenal factors that have been most well characterized as being sensitive to programming events are kidney mass/nephron endowment, the renin-angiotensin system, tubular sodium handling, and the renal sympathetic nerves. Newborns that have been subjected to an adverse intrauterine environment may thus begin life at a distinct disadvantage, in terms of renal function, at a time when the kidney must take over the primary role for extracellular fluid homeostasis from the placenta. A poor beginning, causing renal programming, has been linked to increased risk of hypertension and renal disease in adulthood. However, although a cause for concern, increasingly, evidence demonstrates that renal programming is not a fait accompli in terms of future cardiovascular and renal disease. A greater understanding of postnatal renal maturation and the impact of secondary factors (genes, sex, diet, stress, and disease) on this process is required to predict which babies are at risk of increased cardiovascular and renal disease as adults and to be able to devise preventative measures.