bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding of very low birth weight infants born to HCMV‐seropositive mothers in Germany, Austria and Switzerland
Authors: Buxmann Horst , Falk Maike , Goelz Rangmar , Hamprecht Klaus , Poets Christian F , Schloesser Rolf L
Published: July 2010

Aim:  To evaluate the enteral feeding practice of preterm infants <32 weeks (W) gestational age (GA) or <1500 g birth weight (BW) from human cytomegalovirus (HCMV)‐seropositive mothers in Germany, Austria and Switzerland.

Methods:  This prospective cross‐sectional study included all neonatal units (NU) admitting preterm infants <32W or <1500 g BW in Germany, Austria and Switzerland. In June and July 2009, an anonymized questionnaire was sent via e‐mail, asking whether mothers of the above patients were screened for HCMV, and about the enteral feeding protocol for preterm infants <32W GA or <1500 g BW from HCMV‐seropositive mothers.

Results:  During the study period, 58.6% of the questionnaires (123/210) from Germany, 50% (13/26) from Austria and 50% (6/12) from Switzerland were returned, yielding a total of 6232 preterm infants for analysis. Formula was given to the mentioned preterm infants in 28.5% (35/123) of the German NUs but not in Austria or Switzerland. Untreated breast milk was given in 66.6% (4/6) of the Swiss, 14.6% (18/123) of the German and no Austrian NU. Long‐term pasteurized breast milk was given in 32.5% (40/123) of the German and 38.5% (5/13) of the Austrian NUs, but not in Switzerland. Short‐term pasteurized breast milk was given only in 5.7% (7/123) of German NUs. Freeze‐thawed breast milk was given in Germany (4.9%; 6/123), Austria (61.5%; 8/13) and Switzerland (16.7%; 1/6).

Conclusion:  Preterm infants <32W GA or <1500 g BW born to HCMV‐seropositive mothers are fed according to different regimes in German‐speaking countries. About 28.5% of the German VLBW‐infants receive formula, which is not recommended.
Structure, location and interactions of G‐quadruplexes
Authors: Huppert Julian L.
Published: July 2010

Four‐stranded G‐rich DNA structures called G‐quadruplexes have been the subject of increasing interest recently. Experimental and computational techniques have been used to implicate them in important biological processes such as transcription and translation. In this minireview, I discuss how they form, what structures they adopt and with what stability. I then discuss the computational approaches used to predict them on a genomic scale and how the information derived can be combined with experiments to understand their biological functions. Other minireviews in this series deal with G‐quadruplex nucleic acids and human disease [Wu Y & Brosh RM Jr (2010) FEBS J] and making sense of G‐quadruplex and i‐motif function in oncogene promoters [Brooks TA et al. (2010) FEBS J].
Making sense of G‐quadruplex and i‐motif functions in oncogene promoters
Authors: Brooks Tracy A. , Kendrick Samantha , Hurley Laurence
Published: July 2010

The presence and biological importance of DNA secondary structures in eukaryotic promoters are becoming increasingly recognized among chemists and biologists as bioinformatics in vitro and in vivo evidence for these structures in the c‐Myc, c‐Kit, KRAS, PDGF‐A, hTERT, Rb, RET and Hif‐1α promoters accumulates. Nevertheless, the evidence remains largely circumstantial. This minireview differs from previous ones in that here we examine the diversity of G‐quadruplex and i‐motif structures in promoter elements and attempt to categorize the different types of arrangements in which they are found. For the c‐Myc G‐quadruplex and Bcl‐2 i‐motif, we summarize recent biological and structural studies.
Beneficial effects of omega‐3 fatty acids in cardiovascular disease
Authors: Freeman Lisa M.
Published: July 2010

There is a large body of evidence supporting beneficial effects of omega‐3 fatty acids for both primary and secondary prevention of cardiac disease in people. However, evidence is increasing for the use of omega‐3 fatty acids in dogs with cardiac disease as well. Omega‐3 fatty acids’ anti‐inflammatory and anti‐arrhythmic effects may be beneficial in managing the loss of lean body mass and arrhythmias that are common in heart failure. However, omega‐3 fatty acids also may have positive effects on myocardial energy metabolism, endothelial function, heart rate and blood pressure, and immune function. Additional research is needed to determine optimal indications, doses and formulations for dogs and cats with cardiac disease.
Deciphering STAT3 Signaling in the Heart: Plasticity and Vascular Inflammation
Authors: Kurdi Mazen , Booz George W.
Published: July 2010

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays a critical role in heart development and protection. New developments in understanding its molecular chemistry have revealed the importance of STAT3 in controlling mitochondrial respiration, independent of its function as a transcription factor, and in modulating inflammatory signaling through interactions with other transcription factors and cofactors. The purpose of this article is 2‐fold. First, the authors summarize some recent insights into the function of STAT3. Second, the authors seek to illustrate the complexity of targeting a particular cellular protein for therapeutic purposes and the need to consider context when attempting to decipher the role of a particular signaling pathway in the heart. In this case, inflammation, aging, hypertrophy, and heart failure provide new environments that certainly impact on the functioning of STAT3 and on the gene profile linked to its activation. Congest Heart Fail. 2010;16:234–238. © 2010 Wiley Periodicals, Inc.
Ruthenium plaque radiation therapy for iris and iridociliary melanomas
Authors: Razzaq Lubna , Keunen Jan E.E. , Schalij‐Delfos Nicoline E. , Creutzberg Carien L. , Ketelaars Martijn , de Keizer Rob J.W.
Published: July 2010

Purpose:  To determine the long‐term effects of ruthenium‐106 plaque radiation therapy for iris and iridociliary melanomas in terms of tumour regression and complications.

Methods:  Between 1 November 1997 and 31 December 2007, 36 patients with an iris or iridociliary melanoma were treated with Ruthenium‐106 (Ru‐106) ophthalmic plaque radiation therapy. The median follow‐up was 6.5 years with a range of 2–11 years. The mean tumour apex dose was 151.5 Gy. Main outcome measures were local tumour control and radiation‐related ocular complications.

Results:  The mean age of the patients at the time of treatment was 54 years (range 14–82). The tumours had a median largest basal dimension of 4.8 mm (range 3–11) and a prominence of 2.3 mm (range 0.8–5), with a median involvement of three clock hours (range 1–6). The tumours were confined to the iris in 14 patients (39%), extended into the anterior ciliary body in 12 (33%), while the anterior ciliary body tumour extended into the iris in ten patients (28%). Tumours regressed in all patients (100%) with a mean regression of 80% of the original tumour size at 7 years of follow‐up. Radiation‐related complications included corneal erosions on the first postoperative day in nine patients (25%), cataract in four of 11 patients free of cataract before treatment (36%) and postradiation glaucoma in one patient (3%). Visual acuity of 20/200 or worse was present in one of 20 patients (5%) at 6 years of follow‐up. Local recurrences occurred in two patients (5%), 2 and 5 years after the radiation therapy respectively, and both underwent enucleation. Distant metastases occurred in one of these enucleated patients (3%) 2 years after treatment.

Conclusion:  Ru‐106 plaque radiation therapy for iris and iridociliary melanoma resulted in good local tumour control and preservation of visual acuity with few and treatable side‐effects.
Trailing Edge Noise Model Validation and Application to Airfoil
Optimization
Authors: Bertagnolio F. , Madsen H. Aa. , Bak C.
Published: July 2010

The aim of this article is twofold. First, an existing trailing edge noise model is validated by comparing with airfoil surface pressure fluctuations and far field sound pressure levels measured in three different experiments. The agreement is satisfactory in one case but poor in two other cases. Nevertheless, the model reproduces the main tendencies observed in the measurements with respect to varying flow conditions. Second, the model is implemented into an airfoil design code that is originally used for aerodynamic optimization. An existing wind turbine airfoil is optimized in order to reduce its noise emission, trying at the same time to preserve some of its aerodynamic and geometric characteristics. The new designs are characterized by less cambered airfoils and flatter suction sides. The resulting noise reductions seem to be mainly achieved by a reduction in the turbulent kinetic energy across the boundary layer near the trailing edge and to a lesser extent by a smaller boundary layer displacement thickness.
A Solar Thermal Electrolytic Reactor for Studying the Production of Metals From Their Oxides
Authors: Krenzke P. , Krueger K. , Leonard N. , Duncan S. , Palumbo R. D. , Möller S.
Published: July 2010

A solar thermal electrolytic reactor was developed for studying at a 10 kW scale how a solar reactor’s electrolytic cell design and operating variables influence the performance of a solar process for producing metals from their oxides. Current versus voltage maps as well as current versus time for specified voltages were obtained for the electrolysis of ZnO and MgO within the temperature range of 1200–1500 K and various electrolytic cell configurations. An example of a map is presented. The data from maps and steady-state runs were used to illustrate how we quantify the influence of the cell’s operating temperature and current density on process performance. We also illustrate how one design variable, the cell’s electrolyte, influences process performance.
Wedge Indentation Fracture of Cortical Bone: Experimental Data and Predictions
Authors: Kasiri Saeid , Reilly Ger , Taylor David
Published: July 2010

The fracture of bone due to indentation with a hard, sharp object is of significance in surgical procedures and certain trauma situations. In the study described below, the fracture of bovine bone under indentation was measured experimentally and predicted using the theory of critical distances (TCDs), a theory, which predicts failure due to cracking in the vicinity of stress concentrations. The estimated indentation fracture force was compared with the experimental results in three different cutting directions. Under indentation, the material experiences high levels of compression and shear, causing cracks to form and grow. The direction of crack growth was highly dependent on the bone’s microstructure: major cracks grew in the weakest possible structural direction. Using a single value of the critical distance (L=320 μm), combined with a multiaxial failure criterion, it was possible to predict the experimental failure loads with less than 30% errors. Some differences are expected between the behavior of human bone and the bovine bone studied here, owing to its plexiform microstructure.
Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients
Authors: Rouleau Leonie , Farcas Monica , Tardif Jean-Claude , Mongrain Rosaire , Leask Richard L.
Published: July 2010

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and τ=4.5 dyn/cm2, 9 dyn/cm2, and 18 dyn/cm2) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.
High-aspect-ratio deep Si etching in SF6/O2 plasma. II. Mechanism of lateral etching in high-aspect-ratio features
Authors: Maruyama Takahiro , Narukage Takeshi , Onuki Ryota , Fujiwara Nobuo
Published: July 2010

In this article, the authors focus on the profiles formed by high-aspect-ratio deep Si etching with SF6/O2 plasma mixtures. One of the most serious problems for deep Si etching processes is lateral etching in the upper regions of sidewalls. This lateral etching seems to depend on time (or etched depth) rather than aspect ratio (depth/width). Reducing the SF6:O2 ratio and lowering the temperature not only reduced the scope of lateral etching but also produced features that were more strongly tapered with depth. Results of simulation indicated that the distribution of radicals during the formation of a hole plays a significant role in determining the characteristics of the hole. In fact, the addition of SiFx radicals from the top of the hole is markedly effective in reducing lateral etching without sacrificing shape in the vicinity of the bottom of the hole. However, the distribution of radicals alone cannot explain the time dependence of lateral etching. The results of experiments with masks having various shapes shows that scattered ions at the facets of the mask are mainly responsible for lateral etching. The time dependence of lateral etching is due to expansion of the mask facets over time.
New Opportunities for an Ancient Material
Authors: Omenetto Fiorenzo G. , Kaplan David L.
Published: July 2010

Insight into Silks

Silkworms have been cultivated for thousands of years and their silk has been used to make fabrics for clothing, bed sheets, shirts, dresses, and for other applications like sutures. Spider silk is harder to harvest, and thus has not found such widespread use, but its fantastic combination of properties has made it a tempting material to study in detail.
Omenetto and Kaplan
(p.
528
) review our understanding of silk chemistry, the limitations in being able to reconstitute silks and to generate them synthetically, and a range of applications that have been developed using silk materials.
Early Chordate Origins of the Vertebrate Second Heart Field
Authors: Stolfi Alberto , Gainous T. Blair , Young John J. , Mori Alessandro , Levine Michael , Christiaen Lionel
Published: July 2010

Building the Heart

The multichambered heart of birds and mammals develops through addition of second heart field (SHF)–derived precursor cells to a primary heart tube.

Stolfi
et al.

(p.
565
) show that, in the simple chordate
Ciona intestinalis
, the heart and atrial siphon muscle (ASM) precursors arise from common progenitors following asymmetric cell divisions and that the transcription factor COE (Collier/Olf1/EBF) is involved in this fate choice. The ASM precursors express molecular markers of the vertebrate pharyngeal mesoderm that gives rise to the SHF and lower jaw muscles, suggesting that the origins of both can be traced back to the last common ancestor of tunicates and vertebrates.
Strain-Induced Pseudo–Magnetic Fields Greater Than 300 Tesla in Graphene Nanobubbles
Authors: Levy N. , Burke S. A. , Meaker K. L. , Panlasigui M. , Zettl A. , Guinea F. , Neto A. H. Castro , Crommie M. F.
Published: July 2010

Straining Graphene's Electronic States

The conduction electrons in graphene, single sheets of graphite, can have very high mobilities. Under the influence of an applied magnetic field, a series of energy steps, or Landau levels, can be observed that correspond to the conduction electrons traveling in cyclotron orbits. Recent theoretical work has indicated that if graphene layers are strained, the strain field creates a pseudomagnetic field that should also lead to observable Landau levels.

Levy
et al.

(p.
544
) used scanning tunneling microscopy to probe the energy levels of graphene grown on a platinum surface, which forms highly strained “nanobubbles.” The strain is equivalent to applying very high magnetic fields (in excess of 300 tesla). Thus, the electronic properties of graphene can indeed be modified using applied strain.
Reconstructing the Lung
Authors: Wagner William R. , Griffith Bartley P.
Published: July 2010

Engineering functional lung tissue on the structural scaffold of the native organ in rodents points to a possible strategy for lung regeneration.
Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice
Authors: Ye Jianqiang , Shao Hongxia , Hickman Danielle , Angel Matthew , Xu Kemin , Cai Yibin , Song Haichen , Fouchier Ron A. M. , Qin Aijian , Perez Daniel R.
Published: July 2010

Highly pathogenic avian H5N1 influenza viruses are endemic in poultry in Asia and pose a pandemic threat to humans. Since the deployment of vaccines against a pandemic strain may take several months, adequate antiviral alternatives are needed to minimize the effects and the spread of the disease. Passive immunotherapy is regarded as a viable alternative. Here, we show the development of an IgA monoclonal antibody (DPJY01 MAb) specific to H5 hemagglutinin. The DPJY01 MAb showed a broad hemagglutination inhibition (HI) profile against Asian H5N1 viruses of clades 0, 1.0, 2.1, 2.2, and 2.3 and also against H5 wild bird influenza viruses of the North American and Eurasian lineages. DPJY01 MAb displayed also high neutralization activityin vitroandin vivo. In mice, DPJY01 MAb provided protection via a single dose administered intranasally before or after inoculation with a sublethal dose of H5N1 viruses of clades 1.0 and 2.2. Pretreatment with 50 mg of DPJY01 MAb kg of body weight at either 24, 48, or 72 h before highly pathogenic H5N1 virus (A/Vietnam/1203/2004 [H5N1]) inoculation resulted in complete protection. Treatment with 50 mg/kg at either at 24, 48, or 72 h after H5N1 inoculation provided 100%, 80%, and 60% protection, respectively. These studies highlight the potential use of DPJY01 MAb as an intranasal antiviral treatment for H5N1 influenza virus infections.
Mycobacterium avium
Complex Cervical Lymphadenitis in an Immunocompetent Adult
Authors: Christensen Joshua B. , Koeppe John
Published: July 2010

Nontuberculosis mycobacterial cervical lymphadenitis is a relatively common disease in immunocompetent children but a rare disease in immunocompetent adults. We report the diagnosis and treatment of
Mycobacterium avium
complex cervical lymphadenitis in an adult female. Our evaluation of immune competence, including gamma interferon (IFN-γ) and interleukin-12 (IL-12) signaling, found no evidence of deficiency.
Screening of Predicted Secreted Antigens from
Mycobacterium bovis
Identifies Potential Novel Differential Diagnostic Reagents
Authors: Jones Gareth J. , Hewinson R. Glyn , Vordermeier H. Martin
Published: July 2010

To date, the most promising vaccination strategies for the control of bovine tuberculosis (TB) focus on improving the efficacy of
M
ycobacterium
bovis
bacillus Calmette-Guérin (BCG). However, vaccination with BCG results in sensitization of animals to bovine tuberculin and compromises tests currently used for diagnosis of bovine TB infection. Thus, the development of specific diagnostic reagents capable of discriminating between infected and uninfected vaccinated animals (DIVA) is of high priority. To test the hypothesis that
M. bovis
-secreted proteins are likely to contain immunogenic antigens that can be used to increase the specificity of diagnostic tests, we screened 379 pools of overlapping peptides representing 119 antigens for their ability to stimulate a gamma inferferon (IFN-γ) response
in vitro
using whole blood from both TB reactor and BCG-vaccinated animals. Peptide pools representing antigens Rv3020c and Rv2346c induced responses in 61% and 57% of the TB reactor animals, respectively, without inducing responses in any BCG-vaccinated animal studied. Furthermore, individual peptides contained within pools recognized by BCG vaccinates were identified that were specific and induced IFN-γ responses in TB reactor animals. From these results, we constructed a cocktail of nine peptides representing multiple antigen targets that was recognized by 54% of TB reactor animals but also failed to induce responses in any BCG-vaccinated animal studied. In summary, we have identified three peptide cocktails for prioritization in larger trials to discriminate between
M. bovis
infection and BCG vaccination.
Multicenter Study Evaluating Performance of the Smart Group B Streptococcus (GBS) Assay Using an Enrichment Protocol for Detecting GBS Colonization in Patients in the Antepartum Period
Authors: Jordan Jeanne A. , Hall Geraldine , Davis Thomas
Published: July 2010

Group B streptococcus (GBS) remains the leading cause of infectious morbidity and mortality in infants born in the United States, especially among black infants. Because a newborn can acquire GBS during and after delivery, the Centers for Disease Control and Prevention (CDC) recommends that pregnant women be screened for rectovaginal GBS colonization during the antepartum period between weeks 35 and 37 of gestation and, if they are colonized, that intrapartum antibiotic prophylaxis be administered. A prospective investigational study was undertaken from 2 May 2006 to 14 August 2006 at three sites to establish the performance characteristics of the Smart GBS LB assay on the SmartCycler II system for detecting GBS colonization in subjects in the antepartum period from combined vaginal/rectal swab-based specimens after broth enrichment. Results were compared to broth enrichment culture and to the predicate device, the BD GeneOhm StrepB direct assay. The collected specimens were randomized for swab testing order. Each swab sample was processed simultaneously by culture, Smart GBS LB assay, and the BD GeneOhm StrepB assay. A total of 310 subjects were enrolled, with 306 subject results included in the study. Compared to enrichment culture, the Smart GBS LB assay demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 98.6%, 90.4%, 77.1%, and 99.5%, respectively. The Smart GBS LB assay demonstrated substantially equivalent or better performance than culture or the predicate device. Screening of broth enrichment fluids by nucleic acid amplification testing requires careful handling during sample processing to avoid possible contamination.
Agar-Based Disk Diffusion Assay for Susceptibility Testing of Dermatophytes
Authors: Nweze E. I. , Mukherjee P. K. , Ghannoum M. A.
Published: July 2010

Currently, no agar-based susceptibility testing method has been standardized for testing dermatophytes. We describe a newly developed agar-based method employing disk diffusion assay to test the susceptibility of 47 isolates of dermatophytes against 8 antifungals. Our results show that the method is reproducible, is simple, and could be used to determine the antifungal susceptibility of dermatophytes.
Comparison of Citrated Human Blood, Citrated Sheep Blood, and Defibrinated Sheep Blood Mueller-Hinton Agar Preparations for Antimicrobial Susceptibility Testing of
Streptococcus pneumoniae
Isolates
Authors: Satzke Catherine , Seduadua Anna , Chandra Reginald , Carapetis Jonathan R. , Mulholland E. Kim , Russell Fiona M.
Published: July 2010

The use of Mueller-Hinton agar supplemented with citrated human or citrated sheep blood was compared with the use of routinely used Mueller-Hinton agar supplemented with defibrinated sheep blood for antimicrobial susceptibility testing of
Streptococcus pneumoniae
. The alternate supplements were found to be unsatisfactory, particularly for testing resistant isolates, and therefore are not recommended.
Novel Phosphoprotein-Interacting Region in Nipah Virus Nucleocapsid Protein and Its Involvement in Viral Replication
Authors: Omi-Furutani Mio , Yoneda Misako , Fujita Kentaro , Ikeda Fusako , Kai Chieko
Published: July 2010

The interaction of Nipah virus (NiV) nucleocapsid (N) protein with phosphoprotein (P) during nucleocapsid assembly is the essential process in the viral life cycle, since only the encapsidated RNA genome can be used for replication. To identify the region responsible for N-P interaction, we utilized fluorescent protein tags to visualize NiV N and P proteins in live cells and analyzed their cellular localization. N protein fused to monomeric enhanced cyan fluorescence protein (N-ECFP) exhibited a dotted pattern in transfected cells, while P protein fused to monomeric red fluorescent protein (P-mRFP) showed diffuse distribution. When the two proteins were coexpressed, P-mRFP colocalized with N-ECFP dots. N-ECFP mutants with serial amino acid deletions were generated to search for the region(s) responsible for this N-P colocalization. We found that, in addition to the 467- to 496-amino-acid (aa) region reported previously, aa 135 to 146 were responsible for the N-P colocalization. The residues crucial for N-P interaction were further investigated by introducing alanine substitutions into the untagged N protein. Alanine scanning in the region of aa 135 to 146 has revealed that there are distinct regions essential for the interaction of N-P and the function of N. This is the first study to visualize Nipah viral proteins in live cells and to assess the essential domain of N protein for the interaction with P protein.
P Body-Associated Protein Mov10 Inhibits HIV-1 Replication at Multiple Stages
Authors: Burdick Ryan , Smith Jessica L. , Chaipan Chawaree , Friew Yeshitila , Chen Jianbo , Venkatachari Narasimhan J. , Delviks-Frankenberry Krista A. , Hu Wei-Shau , Pathak Vinay K.
Published: July 2010

Recent studies have shown that APOBEC3G (A3G), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is localized to cytoplasmic mRNA-processing bodies (P bodies). However, the functional relevance of A3G colocalization with P body marker proteins has not been established. To explore the relationship between HIV-1, A3G, and P bodies, we analyzed the effects of overexpression of P body marker proteins Mov10, DCP1a, and DCP2 on HIV-1 replication. Our results show that overexpression of Mov10, a putative RNA helicase that was previously reported to belong to the DExD superfamily and was recently reported to belong to the Upf1-like group of helicases, but not the decapping enzymes DCP1a and DCP2, leads to potent inhibition of HIV-1 replication at multiple stages. Mov10 overexpression in the virus producer cells resulted in reductions in the steady-state levels of the HIV-1 Gag protein and virus production; Mov10 was efficiently incorporated into virions and reduced virus infectivity, in part by inhibiting reverse transcription. In addition, A3G and Mov10 overexpression reduced proteolytic processing of HIV-1 Gag. The inhibitory effects of A3G and Mov10 were additive, implying a lack of functional interaction between the two inhibitors. Small interfering RNA (siRNA)-mediated knockdown of endogenous Mov10 by 80% resulted in a 2-fold reduction in virus production but no discernible impact on the infectivity of the viruses after normalization for the p24 input, suggesting that endogenous Mov10 was not required for viral infectivity. Overall, these results show that Mov10 can potently inhibit HIV-1 replication at multiple stages.
Introduction of the Six Major Genomic Deletions of Modified Vaccinia Virus Ankara (MVA) into the Parental Vaccinia Virus Is Not Sufficient To Reproduce an MVA-Like Phenotype in Cell Culture and in Mice
Authors: Meisinger-Henschel Christine , Späth Michaela , Lukassen Susanne , Wolferstätter Michael , Kachelriess Heike , Baur Karen , Dirmeier Ulrike , Wagner Markus , Chaplin Paul , Suter Mark , Hausmann Jürgen
Published: July 2010

Modified vaccinia virus Ankara (MVA) has a highly restricted host range in cell culture and is apathogenic
in vivo
. MVA was derived from the parental chorioallantois vaccinia virus Ankara (CVA) by more than 570 passages in chicken embryo fibroblast (CEF) cells. During CEF cell passaging, six major deletions comprising 24,668 nucleotides occurred in the CVA genome. We have cloned both the MVA and the parental CVA genome as bacterial artificial chromosomes (BACs) and have sequentially introduced the six major MVA deletions into the cloned CVA genome. Reconstituted mutant CVA viruses containing up to six major MVA deletions showed no detectable replication restriction in 12 of 14 mammalian cell lines tested; the exceptions were rabbit cell lines RK13 and SIRC. In mice, CVA mutants with up to three deletions showed slightly enhanced virulence, suggesting that gene deletion in replicating vaccinia virus (VACV) can result in gain of fitness
in vivo
. CVA mutants containing five or all six deletions were still pathogenic, with a moderate degree of attenuation. Deletion V was mainly responsible for the attenuated phenotype of these mutants. In conclusion, loss or truncation of all 31 open reading frames in the six major deletions is not sufficient to reproduce the specific MVA phenotype of strong attenuation and highly restricted host range. Mutations in viral genes outside or in association with the six major deletions appear to contribute significantly to this phenotype. Host range restriction and avirulence of MVA are most likely a cooperative effect of gene deletions and mutations involving the major deletions.
Estimating Frequencies of Minority Nevirapine-Resistant Strains in Chronically HIV-1-Infected Individuals Naïve to Nevirapine by Using Stochastic Simulations and a Mathematical Model
Authors: Gadhamsetty Saikrishna , Dixit Narendra M.
Published: July 2010

Nevirapine forms the mainstay of our efforts to curtail the pediatric AIDS epidemic through prevention of mother-to-child transmission of HIV-1. A key limitation, however, is the rapid selection of HIV-1 strains resistant to nevirapine following the administration of a single dose. This rapid selection of resistance suggests that nevirapine-resistant strains preexist in HIV-1 patients and may adversely affect outcomes of treatment. The frequencies of nevirapine-resistant strainsin vivo, however, remain poorly estimated, possibly because they exist as a minority below current assay detection limits. Here, we employ stochastic simulations and a mathematical model to estimate the frequencies of strains carrying different combinations of the common nevirapine resistance mutations K103N, V106A, Y181C, Y188C, and G190A in chronically infected HIV-1 patients naïve to nevirapine. We estimate the relative fitness of mutant strains from an independent analysis of previous competitive growth assays. We predict that single mutants are likely to preexist in patients at frequencies (∼0.01% to 0.001%) near or below current assay detection limits (>0.01%), emphasizing the need for more-sensitive assays. The existence of double mutants is subject to large stochastic variations. Triple and higher mutants are predicted not to exist. Our estimates are robust to variations in the recombination rate, cellular superinfection frequency, and the effective population size. Thus, with 107to 108infected cells in HIV-1 patients, even when undetected, nevirapine-resistant genomes may exist in substantial numbers and compromise efforts to prevent mother-to-child transmission of HIV-1, accelerate the failure of subsequent antiretroviral treatments, and facilitate the transmission of drug resistance.
Lipids and Proteins Act in Opposing Manners To Regulate Polyomavirus Infection
Authors: Qian Mengding , Tsai Billy
Published: July 2010

How receptors control virus infection is poorly understood. Polyomavirus (Py) binds to the sialic acid-galactose moiety on receptors to gain entry into host cells and cause infection. We previously demonstrated that the sialic acid-galactose-containing glycolipids called gangliosides GD1a and GT1b promote Py infection, in part, by sorting the virus from the endolysosomes to the endoplasmic reticulum (ER), a critical infection route. Whether these glycolipids act as Py entry receptors, however, is not clear. Additionally, as the majority of glycoproteins also harbor terminal sialic acid-galactose residues, their roles in Py infection are also not well established. Using a ganglioside-deficient cell line, we show that GD1a is the functional entry receptor for Py. GD1a binds to Py on the plasma membrane, and the receptor-virus complex is internalized and transported to the late endosomes and then the ER to initiate infection. In contrast, our findings indicate that glycoproteins act as decoy receptors, restricting the ER transport and infection of Py. Thus, glycolipids and glycoproteins, two major constituents of the plasma membrane, execute opposing functions in regulating infection by a defined virus.
Comparison of Immune Restoration in Early versus Late Alpha Interferon Therapy against Hepatitis C Virus
Authors: Abdel-Hakeem Mohamed S. , Bédard Nathalie , Badr Gamal , Ostrowski Mario , Sékaly Rafick P. , Bruneau Julie , Willems Bernard , Heathcote E. Jenny , Shoukry Naglaa H.
Published: July 2010

Early alpha interferon (IFN-α) therapy against hepatitis C virus (HCV) rescues polyfunctional, virus-specific memory CD8+T cells, but whether immune restoration is possible during late therapy remains controversial. We compared immune restoration of HCV-specific memory T cells in patients who cleared HCV infection spontaneously and following early or late IFN therapy. Multifunctional CD4+and CD8+memory T cells were detected in spontaneous resolvers and in individuals treated early following an acute infection. In contrast, limited responses were detected in patients treated during chronic infection, and the phenotype of HCV-specific cells was influenced by autologous viral sequences. Our data suggest that irreversible damage to the HCV-specific memory T-cell response is associated with chronic HCV infection.
Role of the Innate Immune Response and Tumor Immunity Associated with Simian Virus 40 Large Tumor Antigen
Authors: Lowe Devin B. , Shearer Michael H. , Aldrich Joel F. , Winn Richard E. , Jumper Cynthia A. , Kennedy Ronald C.
Published: July 2010

We examined properties of the innate immune response against the tumor-specific antigen simian virus 40 (SV40) large tumor antigen (Tag) following experimental pulmonary metastasis in naive mice. Approximately 14 days after mKSA tumor cell challenge, expression of inflammatory mediators such as tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and RANTES was upregulated in splenocytes harvested from mice, as assessed by flow cytometry and antibody array assays. This response was hypothesized to activate and induce tumor-directed NK cell lysis since IL-2-stimulated NK cells mediated tumor cell destructionin vitro. The necessary function of NK cells was further validatedin vivothrough selected antibody depletion of NK cells, which resulted in an overwhelming lung tumor burden relative to that in animals receiving a control rabbit IgG depletion regimen. Interestingly, mice achieved increased protection from experimental pulmonary metastasis when NK cells were further activated indirectly throughin vivoadministration of poly(I:C), a Toll-like receptor 3 (TLR3) agonist. In a separate study, mice receiving treatments of poly(I:C) and recombinant SV40 Tag protein immunization mounted effective tumor immunity in an established experimental pulmonary metastasis setting. Initiating broad-based immunity with poly(I:C) was observed to induce a Th1 bias in the SV40 Tag antibody response that led to successful antitumor responses not observed in animals treated only with poly(I:C) or SV40 Tag. These data have direct implications for immunotherapeutic strategies incorporating methods to elicit inflammatory reactions, particularly NK cell-driven lysis, against malignant cell types that express a tumor-specific antigen such as SV40 Tag.
Analysis of A47, an Immunoprevalent Protein of Vaccinia Virus, Leads to a Reevaluation of the Total Antiviral CD8+T Cell Response
Authors: Yuen Tracy J. , Flesch Inge E. A. , Hollett Natasha A. , Dobson Bianca M. , Russell Tiffany A. , Fahrer Aude M. , Tscharke David C.
Published: July 2010

Vaccinia virus (VACV) is the prototypic orthopoxvirus and was the live vaccine used to eradicate smallpox. In addition, VACV is a possible vector for recombinant vaccines. Despite these reasons for study, the roles of many VACV genes are unknown, and some fundamental aspects, such as the total size of immune responses, remain poorly characterized. VACV gene A47L is of interest because it is highly transcribed, has no sequence similarity to any nonpoxvirus gene, and contains a larger-than-expected number of CD8+T cell epitopes. Here it is shown that A47L is not required for growthin vitroand does not contribute to virulence in mice. However, we confirmed that this one protein primes CD8+T cells to three different epitopes in C57BL/6 mice. In the process, one of these epitopes was redefined and shown to be the most dominant in A47 and one of the more highly ranked in VACV as a whole. The relatively high immunogenicity of this epitope led to a reevaluation of the total CD8+T cell response to VACV. By the use of two methods, the true size of the response was found to be around double previous estimates and at its peak is on the order of 60% of all CD8+T cells. We speculate that more CD8+T cell epitopes remain to be mapped for VACV and that underestimation of responses is unlikely to be unique to VACV, so there would be merit in revisiting this issue for other viruses.
Widespread Infection with Homologues of Human Parvoviruses B19, PARV4, and Human Bocavirus of Chimpanzees and Gorillas in the Wild
Authors: Sharp Colin P. , LeBreton Matthew , Kantola Kalle , Nana Ahmadou , Diffo Joseph Le Doux , Djoko Cyrille F. , Tamoufe Ubald , Kiyang John A. , Babila Tafon G. , Ngole Eitel Mpoudi , Pybus Oliver G. , Delwart Eric , Delaporte Eric , Peeters Martine , Soderlund-Venermo Maria , Hedman Klaus , Wolfe Nathan D. , Simmonds Peter
Published: July 2010

Infections with human parvoviruses B19 and recently discovered human bocaviruses (HBoVs) are widespread, while PARV4 infections are transmitted parenterally and prevalent specifically in injecting drug users and hemophiliacs. To investigate the exposure and circulation of parvoviruses related to B19 virus, PARV4, and HBoV in nonhuman primates, plasma samples collected from 73 Cameroonian wild-caught chimpanzees and gorillas and 91 Old World monkey (OWM) species were screened for antibodies to recombinant B19 virus, PARV4, and HBoV VP2 antigens by enzyme-linked immunosorbent assay (ELISA). Moderate to high frequencies of seroreactivity to PARV4 (63% and 18% in chimpanzees and gorillas, respectively), HBoV (73% and 36%), and B19 virus (8% and 27%) were recorded for apes, while OWMs were uniformly negative (for PARV4 and B19 virus) or infrequently reactive (3% for HBoV). For genetic characterization, plasma samples and 54 fecal samples from chimpanzees and gorillas collected from Cameroonian forest floors were screened by PCR with primers conserved within
Erythrovirus
,
Bocavirus
, and PARV4 genera. Two plasma samples (chimpanzee and baboon) were positive for PARV4, while four fecal samples were positive for HBoV-like viruses. The chimpanzee PARV4 variant showed 18% and 15% nucleotide sequence divergence in NS and VP1/2, respectively, from human variants (9% and 7% amino acid, respectively), while the baboon variant was substantially more divergent, mirroring host phylogeny. Ape HBoV variants showed complex sequence relationships with human viruses, comprising separate divergent homologues of HBoV1 and the recombinant HBoV3 species in chimpanzees and a novel recombinant species in gorillas. This study provides the first evidence for widespread circulation of parvoviruses in primates and enables future investigations of their epidemiology, host specificity, and (co)evolutionary histories.
KALUZA–KLEIN THEORY WITH TORSION CONFINED TO THE EXTRA DIMENSION
Authors: SHANKAR KARTHIK H. , WALI KAMESHWAR C.
Published: July 2010

Here we consider a variant of the five-dimensional Kaluza–Klein (KK) theory within the framework of Einstein–Cartan formalism that includes torsion. By imposing a set of constraints on torsion and Ricci rotation coefficients, we show that the torsion components are completely expressed in terms of the metric. Moreover, the Ricci tensor in 5D corresponds exactly to what one would obtain from torsion-free general relativity on a 4D hypersurface. The contributions of the scalar and vector fields of the standard KK theory to the Ricci tensor and the affine connections are completely nullified by the contributions from torsion. As a consequence, geodesic motions do not distinguish the torsion free 4D spacetime from a hypersurface of 5D spacetime with torsion satisfying the constraints. Since torsion is not an independent dynamical variable in this formalism, the modified Einstein equations are different from those in the general Einstein–Cartan theory. This leads to important cosmological consequences such as the emergence of cosmic acceleration.
VARIABLE SEPARATION AND ALGEBRAIC-GEOMETRIC SOLUTIONS OF MODIFIED TODA LATTICE EQUATION
Authors: LUO LIN , FAN ENGUI
Published: July 2010

In this paper, we derive a modified Toda lattice hierarchy by resorting to the Lenard operator pairs. The hyper-elliptic curve and Abel–Jacobi coordinates are then introduced to linearize the associated flow, from which some algebraic-geometric solutions of the modified Toda lattice are explicitly constructed in terms of Riemann theta functions by using Jacobi inversion technique.
COVERT COMMUNICATIONS BASED ON SIGNAL OVERLAY
Authors: ROY ARNAB , DOHERTY JOHN F.
Published: July 2010

A covert communication technique based on the principle of signal overlay is presented here. A weak narrow-band signal is added to the primary signal and shares the same frequency band. Covertness of the overlay signal is ensured by careful signal design. At the receiver a stationary filtering approach is ineffective in separating the signals. However, the recently introduced raised cosine empirical mode decomposition technique is ideally suited to separate these time-varying signals with overlapping frequency components. An application to commercial frequency modulation overlay is presented with associated analysis and empirical performance results.
Electron Transport in Carbon Nanotubes
Authors: Ilani Shahal , McEuen Paul L.
Published: July 2010

Over the past decade, transport measurements on individual single-wall nanotubes have played a prominent role in developing our understanding of this novel carbon conductor. These measurements have identified both metallic and semiconducting nanotubes, determined their dominant electronic scattering mechanisms, and elucidated in great detail the properties of their quantized energy spectrum. Recent technological breakthroughs in nanotube device fabrication and electronic measurement have made possible experiments of unprecedented precision that reveal new and surprising phenomena. In this review, we present the fundamental properties of nanotubes side by side with the newest discoveries and also discuss some of the most exciting emerging directions.
FeAs-Based Superconductivity: A Case Study of the Effects of Transition Metal Doping on BaFe2As2
Authors: Canfield Paul C. , Bud'ko Sergey L.
Published: July 2010

The recently discovered FeAs-based superconductors are a new, promising set of materials for technological and basic research. They offer transition temperatures as high as 55 K as well as essentially isotropic, and extremely large, upper, superconducting critical fields, in excess of 40 T at 20 K. In addition, they may well provide insight into exotic superconductivity that extends beyond just FeAs-based superconductivity, perhaps even shedding light on the still-perplexing CuO-based high-Tc materials. Whereas superconductivity can be induced in the RFeAsO (R = rare earth) and AEFe2As2 (AE = Ba, Sr, Ca) families by several means, transition metal (TM) doping of BaFe2As2 [e.g., Ba(Fe1–xTMx)2As2] offers the easiest experimental access to a wide set of materials and states. In this review, we present an overview and summary of the effect of TM-doping (TM = Co, Ni, Cu, Pd, and Rh) on BaFe2As2. The resulting phase diagrams reveal the nature of the interaction between the structural, magnetic, and superconducting phase transitions in these compounds and delineate a region of phase space that allows for the stabilization of superconductivity.
Physics of Cellular Movements
Authors: Sackmann Erich , Keber Felix , Heinrich Doris
Published: July 2010

The survival of cells depends on perpetual active motions, including (a) bending excitations of the soft cell envelopes, (b) the bidirectional transport of materials and organelles between the cell center and the periphery, and (c) the ongoing restructuring of the intracellular macromolecular scaffolds mediating global cell changes associated with cell adhesion locomotion and phagocytosis. Central questions addressed are the following: How can this bustling motion of extremely complex soft structures be characterized and measured? What are the major driving forces? Further topics include (a) the active dynamic control of global shape changes by the interactive coupling of the aster-like soft scaffold of microtubules and the network of actin filaments associated with the cell envelope (the actin cortex) and (b) the generation of propulsion forces by solitary actin gelation waves propagating within the actin cortex.
Molecular Theories of Segmental Dynamics and Mechanical Response in Deeply Supercooled Polymer Melts and Glasses
Authors: Chen Kang , Saltzman Erica J. , Schweizer Kenneth S.
Published: July 2010

We review recent progress in developing statistical mechanical theories for the slow activated segmental dynamics and mechanical response of deeply supercooled polymer melts and glasses. The focus is polymer-based predictive approaches and uniquely macromolecular aspects. We summarize the central concepts that underlie two prominent polymer theories in the molten state and critically discuss their key predictions and confrontation with experiment. The influence of anisotropic conformation and interchain packing on the emergence of activated glassy dynamics in oriented polymer liquid crystals and deformed rubber networks is discussed. In quenched nonequilibrium glass, the temperature dependence of segmental relaxation qualitatively changes, and physical aging commences. A very recent theory for the dramatic effects of external stress on polymer glasses is summarized, including acceleration of relaxation, yielding, plastic flow, and strain hardening. The review concludes with a discussion of some outstanding theoretical challenges.