bluuebunny/crossref_metadata_2025 huggingface dataset:
An MRI-Compatible Needle Manipulator Concept Based on Elastically Averaged Dielectric Elastomer Actuators for Prostate Cancer Treatment: An Accuracy and MR-Compatibility Evaluation in Phantoms
Authors: Plante Jean-Sébastien , Tadakuma Kenjiro , DeVita Lauren M. , Kacher Daniel F. , Roebuck Joseph R. , DiMaio Simon P. , Jolesz Ferenc A. , Dubowsky Steven
Published: September 2009

A parallel manipulator concept using bistable polymer actuators has been developed to perform prostate cancer biopsy, and deliver therapy within the bore of a magnetic resonance imaging (MRI) scanner. The dielectric elastomer actuators (DEAs) used in this manipulator concept are promising for MRI-compatible robotics because they do not interfere with the high magnetic fields of MRI while having good mechanical performance and being low cost. In the past, these actuators have been plagued by robustness problems when used in a continuous manner. Recent studies show that reliability significantly improves when DEAs are used in a bistable manner, as proposed here. This paper investigates the potential of the proposed manipulator concept by evaluating the positioning accuracy and MRI compatibility of a laboratory prototype, developed for clinically relevant design criteria. An analytical model of the manipulator kinematics is presented. Analytical and experimental results validate that the proposed technology can provide an accurate needle placement required to perform prostate cancer treatments. The prototype’s MRI compatibility is validated in a 3 T clinical MRI scanner. The parallel manipulator concept using bistable polymer actuators is shown to be a viable approach to perform MRI-guided needle insertions for prostate cancer biopsy and therapy.
An Ultraminiature MEMS Pressure Sensor With High Sensitivity for Measurement of Intramuscular Pressure (IMP) in Patients With Neuromuscular Diseases
Authors: Sezen A. S. , Rajamani R. , Morrow D. , Kaufman K. R. , Gilbert B. K.
Published: September 2009

An ultraminiature micropressure sensor to accurately measure intramuscular pressure has been developed. The MEMS sensor is fabricated through surface micromachining and consists of a capacitive array of eight 150 μm diameter sensing membranes connected in parallel. The membranes have been vacuum-sealed via a subsequent deposition and patterning batch microfabrication step. A deep reactive ion etcher (DRIE) based postfabrication self-release has been utilized to fabricate individual devices. Each device has an outline that incorporates specially designed “anchor” structures that are utilized to attach on the muscle tissue during measurements to minimize the effect of muscle contractions on sensor readings. Electrical isolation of the wire bonds and bonding pads has been accomplished by utilizing glob-topping technique. The fabricated sensor performance has been experimentally validated inside a pressure chamber. The current sensors have 0.2 mm Hg pressure resolution in the ±19 mm Hg dynamic range with negligible hysteresis and show a flat frequency response in the 0–5.5 Hz experimental test range.
Formation of Uniform Microspheres Using a Perforated Silicon Membrane: A Preliminary Study
Authors: Song K.-Y. , Chiao M. , Stoeber B. , Häfeli U. , Gupta M. M. , Zhang W. J.
Published: September 2009

This paper presents a new method to generate uniform microspheres with biodegradable poly(lactic-co-glycolic acid) (PLGA) material using microelectromechanical system technology. The general idea with this method is such that a liquid phase containing the dissolved microsphere matrix material reaches a continuous phase after a silicon membrane with micron-sized perforations, where microdroplets are formed. After the droplet is detached from the membrane, the solvent diffuses out of the droplets into a continuous phase leading to the formation of solid microspheres. The experiment was performed to verify this method with some promising result. It has been shown that with this method, about 90% of the microspheres are in the range from 1 to 2 μm, which seems to be better than the result obtained with other methods using glass or ceramic membranes. The microsphere with such a size range is useful for intravascular applications and pharmaceutical drug delivery with a slow release of the drug at narrowly defined rates.
An Inexpensive Weight Bearing Indicator With Load Range Capability for Rehabilitation of Patients With Lower Extremity Injuries
Authors: Walczyk Daniel F. , Ziomek William T.
Published: September 2009

This paper investigates the mechanical behavior and design of a patent pending device called a load range weight bearing indicator (LWBI), which provides upper and lower range indication to patients with lower extremity injuries as part of a partial weight bearing rehabilitation. The LWBI consists of two opposing stacks (a.k.a. double stack) of snap domes—bistable mechanical elements that snap through only when a threshold weight is applied—sandwiched between a load transfer plate and base plate. The mechanical behavior of a LWBI has been characterized by testing single and double stacks of snap domes in a rigid aluminum fixture using a universal testing machine. Single stacks of two to eight snap domes each exhibited very predictable and repeatable buckling behavior (i.e., stack buckling load is simply the sum of individual snap dome buckling loads) when deflected at speeds typical for patients walking with a regular gait. The double stack configuration only works when supporting legs of the opposing snap dome stacks are offset by half the angle between adjacent legs. The lower load stack buckles first, while the higher load stack buckles at its threshold load because of the very low force required to keep the lower load stack collapsed. While the presence of a spacer has little effect on the double stack buckling behavior under controlled rate deflection in a precision test fixture, it was required for proper functioning of a LWBI prototype probably because of looser dimensional tolerances. The type of substrate that snap dome stacks are in contact with has little effect on the buckling loads as long as the material is not too soft. Finally, the speed of deflection within the expected range of ambulating patients has an insignificant effect on the LWBI’s buckling behavior. A LWBI prototype was designed based on the observed characteristics of the snap dome double stack with a spacer plate between the upper and lower load stacks. The prototype was installed in a recess in the insole of a biomechanical shoe beneath the patient’s heel. The shoe with LWBI was tested by various subjects pushing on a force plate and the upper and lower buckling loads were clearly indicated to the subject by audible and tactile click and measured as ground reaction force versus time. Future work will focus on further testing of the device and refinement of the design for various medical appliances.
A Magnetic Resonance-Compatible Loading Device for Dynamically Imaging Shortening and Lengthening Muscle Contraction Mechanics
Authors: Silder Amy , Westphal Christopher J. , Thelen Darryl G.
Published: September 2009

The purpose of this study was to design and test a magnetic resonance (MR)-compatible device to induce either shortening or lengthening muscle contractions for use during dynamic MR imaging. The proposed device guides the knee through cyclic flexion-extension, while either elastic or inertial loads are imposed on the hamstrings. Ten subjects were tested in a motion capture laboratory to evaluate the repeatability of limb motion and imposed loads. Image data were subsequently obtained for all ten subjects using cine phase contrast imaging. Subjects achieved ∼30 deg of knee joint motion, with individual subjects remaining within ∼1 deg of their average motion across 56 repeated cycles. The maximum hamstring activity and loading occurred when the knee was flexed for the elastic loading condition (shortening contraction), and extended for the inertial loading condition (lengthening contraction). Repeat MR image acquisitions of the same loading condition resulted in similar tissue velocities, while spatial variations in velocity data were clearly different between loading conditions. The proposed device can enable dynamic imaging of the muscle under different types of loads, which has the potential to improve our understanding of basic muscle mechanics, identify potential causes of muscle injury, and provide a basis for quantitatively assessing injury effects at the tissue level. Slight modifications to the device design and/or subject positioning could allow for imaging of the quadriceps or the knee.
Comment on “Energy Uptake and Allocation During Ontogeny”
Authors: Sousa Tânia , Marques Gonçalo M. , Domingos Tiago
Published: September 2009

Hou
et al
. (Reports, 31 October 2008, p. 736) presented a model for energy uptake and allocation over an organism’s growth and development. However, their model does not account for allocation to reproduction (essential to adults) and growth without assimilation (essential to embryos) and is therefore only applicable to organisms growing with abundant food in the juvenile stage.
Comment on “Energy Uptake and Allocation During Ontogeny”
Authors: Makarieva Anastassia M. , Gorshkov Victor G. , Li Bai-Lian
Published: September 2009

We demonstrate that the model of energy allocation during ontogeny of Hou
et al
. (Reports, 31 October 2008, p. 736) fails to account for the observed elevation of metabolic rate in growing organisms compared with similarly sized adults of different species. The basic model assumptions of the three-quarter power scaling for resting metabolism and constancy of the mass-specific maintenance metabolism need to be reassessed.
Shor’s Quantum Factoring Algorithm on a Photonic Chip
Authors: Politi Alberto , Matthews Jonathan C. F. , O'Brien Jeremy L.
Published: September 2009

A quantum algorithm to factor numbers is implemented on an optical chip.
Realization of an Excited, Strongly Correlated Quantum Gas Phase
Authors: Haller Elmar , Gustavsson Mattias , Mark Manfred J. , Danzl Johann G. , Hart Russell , Pupillo Guido , Nägerl Hanns-Christoph
Published: September 2009

Stability Through Confinement

With the ability to vary experimental parameters—including particle density, geometry, interaction strength, and sign—cold atoms trapped in optical lattices are ideal test systems to probe many-body quantum physics. However, due to dissipation processes most of the scenarios studied to date have necessarily looked at ground state phases.

Haller
et al.

(p.
1224
) describe a technique in which confinement of the atoms to low dimensions, using a confinement-induced resonance, can stabilize excited states with tunable interactions. The ability to create these metastable states will allow a much wider range of quantum systems to be explored.
Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate
Authors: Hait Nitai C. , Allegood Jeremy , Maceyka Michael , Strub Graham M. , Harikumar Kuzhuvelil B. , Singh Sandeep K. , Luo Cheng , Marmorstein Ronen , Kordula Tomasz , Milstien Sheldon , Spiegel Sarah
Published: September 2009

Epigenetic Signals

The lipid sphingosine-1-phosphate (S1P) is a signaling molecule that binds to receptors on the cell surface to initiate biochemical changes that control a range of biological processes from growth and survival to immune reactions.

Hait
et al.

(p.
1254
) report that S1P can also function by direct binding to the nuclear enzymes, histone deacetylases (HDACs) 1 and 2. The enzyme that generates S1P, sphingosine kinase 2 (ShpK2) is present in the nucleus in complexes with HDAC1 and HDAC2. Generation of S1P and its binding to HDACs inhibited deacetylation of histone. Such histone modification is an epigenetic mechanism that controls gene transcription. Thus, generation of S1P in the nucleus appears to be a signaling mechanism by which cells can control gene expression in response to various stimuli.
Threats to Freshwater Fish
Authors: Magurran Anne E.
Published: September 2009

Insights into how small, isolated fish populations persist in the wild could aid conservation efforts.
Re-viewing an Old Comet Reservoir
Authors: Duncan Martin
Published: September 2009

Simulations show that the inner Oort Cloud is the source of many more long-period comets than expected.
Positive Interactions Promote Public Cooperation
Authors: Rand David G. , Dreber Anna , Ellingsen Tore , Fudenberg Drew , Nowak Martin A.
Published: September 2009

Carrots Are Better Than Sticks

The challenge of dealing with freeloaders—who benefit from a common good but refuse to pay their “fair share” of the costs—has often been met in theoretical and laboratory studies by sanctioning costly punishment, in which contributors pay a portion of their benefit so that freeloaders lose theirs.

Rand
et al.

(p.
1272
; see the news story by

Pennisi

and the cover) added a private interaction session after each round of the public goods game during which participants were allowed to reward or punish other members of their group. The outcome showed that reward was as effective as punishment in maintaining a cooperative mindset, and doing so via rewarding interactions allowed the entire group to prosper because less is lost to the costs of punishing.
Galvanizing Science Departments
Authors: Wieman Carl
Published: September 2009

Countless reports have stressed the economic and broad societal benefits to be gained from improved science, technology, engineering, and math (STEM) education for all students. At the higher education level, there is extensive evidence that innovative teaching methods improve student learning and are practical to implement. Yet these methods remain at the periphery, and the traditional lecture model continues to dominate, particularly at large research universities. This fact poses a major problem for improving science education at all levels, because these institutions generally set the norms for how to teach science and what it means to learn science. To effectively change STEM education at the university level, a majority of the faculty in a given university department must become collectively engaged in implementing new curricula and teaching methods. In other words, an entire department must be the unit of change.
Last Chance to Save the 'Panda of Indochina'
Authors: Stone Richard
Published: September 2009

At an emergency meeting in Vientiane last month, researchers hammered out a set of measures that, if implemented within the next year, could give the saola, a rare ungulate no scientist has ever glimpsed in the wild, a shot at survival.
On the Origin of Cooperation
Authors: Pennisi Elizabeth
Published: September 2009

How did cooperation evolve when cheaters—those who benefit without making sacrifices—can threaten its stability? In the ninth essay in
Science
's series in honor of the Year of Darwin, Elizabeth Pennisi discusses the genetic nuts and bolts of cooperation in systems from microbes to humans.
Multiplex Screening of Surface Proteins fromMycoplasma mycoidessubsp.mycoidesSmall Colony for an Antigen Cocktail Enzyme-Linked Immunosorbent Assay
Authors: Neiman Maja , Hamsten Carl , Schwenk Jochen M. , Bölske Göran , Persson Anja
Published: September 2009

A recombinant antigen cocktail enzyme-linked immunosorbent assay (ELISA) for diagnosis of contagious bovine pleuropneumonia (CBPP) was developed after careful selection of antigens among one-third of the surface proteome proteins of the infectious agentMycoplasma mycoidessubsp.mycoidessmall colony (M. mycoidesSC). First, a miniaturized and parallelized assay system employing antigen suspension bead array technology was used to screen 97 bovine sera for humoral immune responses toward 61 recombinant surface proteins fromM. mycoidesSC. Statistical analysis of the data resulted in selection of eight proteins that showed strong serologic responses in CBPP-affected sera and minimal reactivity in negative control sera, withPvalues of <10−6. Only minor cross-reactivity to hyperimmune sera against other mycoplasmas was observed. When applied in an ELISA, the cocktail of eight recombinant antigens allowed a fivefold signal separation between 24 CBPP-affected and 23 CBPP-free sera from different geographical origins. No false-positive results and only two false-negative results were obtained. In conclusion, the selected recombinant mycoplasma antigens qualified as highly specific markers for CBPP and could be employed in both a suspension bead array platform and a cocktail ELISA setting. This set of proteins and technologies therefore offers a powerful combination to drive and further improve serological assays toward reliable, simple, and cost-effective diagnosis of CBPP.
Use of Toll-Like Receptor Assays To Detect and Identify Microbial Contaminants in Biological Products
Authors: Huang Li-Yun , DuMontelle James L. , Zolodz Melissa , Deora Aparna , Mozier Ned M. , Golding Basil
Published: September 2009

Toll-like receptor (TLR)-expressing cells, for the first time, detected and identified a microbial contaminant in a product made inEscherichia coliusing an old manufacturing process. It was suspected of having a microbial contaminant(s) because, although it tested negative by standard pyrogen assays, it was associated with adverse events in early clinical trials. The assay readout is the induction of NF-κB and/or cytokines in response to TLR activation. Four coded samples, labeled A to D, including a sample prepared by the older manufacturing process, were submitted. The cell lines were activated only by samples B and D. Sample D stimulated only Mono-Mac 6 and HEK-human TLR4 (hTLR4) cells and was later identified as lipopolysaccharide. Except for TLR3 cells, sample B stimulated cells bearing the different TLRs (TLRs 2, 4, 5, 7, 8, and 9) and nontransfected HEK293 cells. These data suggested that flagellin was the microbial contaminant, since TLR5, the receptor for flagellin, is known to be expressed constitutively on HEK293 cells. Moreover, purified flagellin fromSalmonella entericaserovar Typhimurium behaved like sample B, stimulating HEK293 and HEK-hTLR5 cells but not HEK-hTLR3 cells, and this stimulation by flagellin and sample B was blocked by an anti-hTLR5 neutralizing antibody. Western blots showed bands positive for flagellin and sample B with the molecular sizes expected for the flagellins fromS. Typhimurium andE. coli, respectively. Mass spectrometry data were consistent with the presence of flagellin in the manufacturer's sample B. Taken together, these data indicate that the microbial contaminant in sample B was flagellin and may have been associated with adverse events when the recombinant product was administered.
Identification of Respiratory Viruses in Adults: Nasopharyngeal versus Oropharyngeal Sampling
Authors: Lieberman David , Lieberman Devora , Shimoni Avi , Keren-Naus Ayelet , Steinberg Rachel , Shemer-Avni Yonat
Published: September 2009

The optimal method for identifying respiratory viruses in adults has not been established. The objective of the study was to compare the sensitivities of three sampling methods for this purpose. One thousand participants (mean age, 63.1 ± 17.8 years) were included. Of these, 550 were patients hospitalized for acute febrile lower respiratory tract infections and 450 were controls. Oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), and nasopharyngeal washings (NPW) were obtained from each participant and were tested for 12 respiratory viruses by a multiplex hydrolysis probes-based quantitative real-time reverse transcription-PCR. Patients were defined as positive for a specific virus if the virus was identified by at least one sampling method. In all, 251 viruses were identified in 244 participants. For the detection of any virus, the sensitivity rates for OPS, NPS, and NPW were 54.2%, 73.3%, and 84.9%, respectively (for OPS versus NPS and NPW,
P
< 0.00001; for NPS versus NPW,
P
< 0.003). Maximal sensitivity was obtained only with sampling by all three methods. The same gradation of sensitivity for the three sampling methods was found when influenza viruses, coronaviruses, and rhinoviruses were analyzed separately. The three sampling methods yielded equal sensitivity rates for respiratory syncytial virus. We conclude that nasopharyngeal sampling has a higher rate of sensitivity than oropharyngeal sampling and that the use of NPW has a higher rate of sensitivity than the use of NPS with a rigid cotton swab for the identification of respiratory viruses in adults. Sampling by all three methods is required for the maximal detection of respiratory viruses.
Comparison of the EntericBio Multiplex PCR System with Routine Culture for Detection of Bacterial Enteric Pathogens
Authors: O'Leary James , Corcoran Daniel , Lucey Brigid
Published: September 2009

The EntericBio system uses a multiplex PCR assay for the simultaneous detection of
Campylobacter
spp.,
Salmonella enterica
,
Shigella
spp., and
Escherichia coli
O157 from feces. It combines overnight broth enrichment with PCR amplification and detection by hybridization. An evaluation of this system was conducted by comparing the results obtained with the system with those obtained by routine culture, supplemented with alternative PCR detection methods. In a study of 773 samples, routine culture and the EntericBio system yielded 94.6 and 92.4% negative results, respectively. Forty-two samples had positive results by culture, and all of these were positive with the EntericBio system. This system detected an additional 17 positive samples (
Campylobacter
spp.,
n
= 12;
Shigella
spp.,
n
= 1;
E. coli
O157,
n
= 4), but the results for 5 samples (
Campylobacter
spp.,
n
= 2;
Shigella
spp.,
n
= 1;
E. coli
O157,
n
= 2) could not be confirmed. The target for
Shigella
spp. detected by the EntericBio system is the
ipaH
gene, and the molecular indication of the presence of
Shigella
spp. was investigated by sequence analysis, which confirmed that the
ipaH
gene was present in a
Klebsiella pneumoniae
isolate from the patient. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 99.3%, 91.5%, and 100%, respectively. Turnaround times were significantly reduced with the EntericBio system, and a result was available between 24 and 32 h after receipt of the sample in the laboratory. In addition, the amount of laboratory waste was significantly reduced by use of this system. In summary, the EntericBio system proved convenient to use, more sensitive than the conventional culture used in this study, and highly specific; and it generated results significantly faster than routine culture for the pathogens tested.
Arginine Methylation Increases the Stability of Human Immunodeficiency Virus Type 1 Tat
Authors: Sivakumaran Haran , van der Horst Armando , Fulcher Alex J. , Apolloni Ann , Lin Min-Hsuan , Jans David A. , Harrich David
Published: September 2009

Arginine methylation of human immunodeficiency virus type 1 (HIV-1) Tat protein downregulates its key function in viral-gene transactivation. The fate of methylated Tat is unknown, so it is unclear whether methylated Tat is degraded or persists in the cell for additional functions. Here we show that the arginine methyltransferase PRMT6 increases Tat protein half-life by 4.7-fold. Tat stabilization depends on the catalytic activity of PRMT6 and requires arginine methylation within the Tat basic domain. In contrast, HIV-1 Rev, which is also methylated by PRMT6, is completely refractory to the stabilizing effect. Proteasome inhibition and silencing experiments demonstrated that Tat can be degraded by a REGγ-independent proteasome, against which PRMT6 appears to act to increase Tat half-life. Our data reveal a proteasome-dependent Tat degradation pathway that is inhibited by arginine methylation. The stabilizing action of PRMT6 could allow Tat to persist within the cell and the extracellular environment and thereby enable functions implicated in AIDS-related cancer, neurodegeneration, and T-cell death.
Simian Immunodeficiency Virus SIV
agm
from African Green Monkeys Does Not Antagonize Endogenous Levels of African Green Monkey Tetherin/BST-2
Authors: Lim Efrem S. , Emerman Michael
Published: September 2009

The Vpu accessory gene that originated in the primate lentiviral lineage leading to human immunodeficiency virus type 1 is an antagonist of human tetherin/BST-2 restriction. Most other primate lentivirus lineages, including the lineage represented by simian immunodeficiency virus SIV
agm
from African green monkeys (AGMs), do not encode Vpu. While some primate lineages encode gene products other than Vpu that overcome tetherin/BST-2, we find that SIV
agm
does not antagonize physiologically relevant levels of AGM tetherin/BST-2. AGM tetherin/BST-2 can be induced by low levels of type I interferon and can potently restrict two independent strains of SIV
agm
. Although SIV
agm
Nef had an effect at low levels of AGM tetherin/BST-2, simian immunodeficiency virus SIV
mus
Vpu, from a virus that infects the related monkey
Cercopithecus
c
ephus
, is able to antagonize even at high levels of AGM tetherin/BST-2 restriction. We propose that since the replication of SIV
agm
does not induce interferon production in vivo, tetherin/BST-2 is not induced, and therefore, SIV
agm
does not need Vpu. This suggests that primate lentiviruses evolve tetherin antagonists such as Vpu or Nef only if they encounter tetherin during the typical course of natural infection.
Quaranfil, Johnston Atoll, and Lake Chad Viruses Are Novel Members of the Family
Orthomyxoviridae
Authors: Presti Rachel M. , Zhao Guoyan , Beatty Wandy L. , Mihindukulasuriya Kathie A. , Travassos da Rosa Amelia P. A. , Popov Vsevolod L. , Tesh Robert B. , Virgin Herbert W. , Wang David
Published: September 2009

Arboviral infections are an important cause of emerging infections due to the movements of humans, animals, and hematophagous arthropods. Quaranfil virus (QRFV) is an unclassified arbovirus originally isolated from children with mild febrile illness in Quaranfil, Egypt, in 1953. It has subsequently been isolated in multiple geographic areas from ticks and birds. We used high-throughput sequencing to classify QRFV as a novel orthomyxovirus. The genome of this virus is comprised of multiple RNA segments; five were completely sequenced. Proteins with limited amino acid similarity to conserved domains in polymerase (PA, PB1, and PB2) and hemagglutinin (HA) genes from known orthomyxoviruses were predicted to be present in four of the segments. The fifth sequenced segment shared no detectable similarity to any protein and is of uncertain function. The end-terminal sequences of QRFV are conserved between segments and are different from those of the known orthomyxovirus genera. QRFV is known to cross-react serologically with two other unclassified viruses, Johnston Atoll virus (JAV) and Lake Chad virus (LKCV). The complete open reading frames of PB1 and HA were sequenced for JAV, while a fragment of PB1 of LKCV was identified by mass sequencing. QRFV and JAV PB1 and HA shared 80% and 70% amino acid identity to each other, respectively; the LKCV PB1 fragment shared 83% amino acid identity with the corresponding region of QRFV PB1. Based on phylogenetic analyses, virion ultrastructural features, and the unique end-terminal sequences identified, we propose that QRFV, JAV, and LKCV comprise a novel genus of the family
Orthomyxoviridae
.
Characterization of Determinants Important for Hepatitis C Virus p7 Function in Morphogenesis by Using
trans
-Complementation
Authors: Brohm Christiane , Steinmann Eike , Friesland Martina , Lorenz Ivo C. , Patel Arvind , Penin Francois , Bartenschlager Ralf , Pietschmann Thomas
Published: September 2009

Hepatitis C virus (HCV) p7 is an integral membrane protein that forms ion channels in vitro and that is crucial for the efficient assembly and release of infectious virions. Due to these properties, p7 was included in the family of viroporins that comprises proteins like influenza A virus M2 and human immunodeficiency virus type 1 (HIV-1) vpu, which alter membrane permeability and facilitate the release of infectious viruses. p7 from different HCV isolates sustains virus production with variable efficiency. Moreover, p7 determinants modulate processing at the E2/p7 and the p7/NS2 signal peptidase cleavage sites, and E2/p7 cleavage is incomplete. Consequently, it was unclear if a differential ability to sustain virus production was due to variable ion channel activity or due to alternate processing at these sites. Therefore, we developed a
trans
-complementation assay permitting the analysis of p7 outside of the HCV polyprotein and thus independently of processing. The rescue of p7-defective HCV genomes was accomplished by providing E2, p7, and NS2, or, in some cases, by p7 alone both in a transient complementation assay as well as in stable cell lines. In contrast, neither influenza A virus M2 nor HIV-1 vpu compensated for defective p7 in HCV morphogenesis. Thus, p7 is absolutely essential for the production of infectious HCV particles. Moreover, our data indicate that p7 can operate independently of an upstream signal sequence, and that a tyrosine residue close to the conserved dibasic motif of p7 is important for optimal virus production in the context of genotype 2a viruses. The experimental system described here should be helpful to investigate further key determinants of p7 that are essential for its structure and function in the absence of secondary effects caused by altered polyprotein processing.
Truncation of the Membrane-Spanning Domain of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Defines Elements Required for Fusion, Incorporation, and Infectivity
Authors: Yue Ling , Shang Liang , Hunter Eric
Published: September 2009

The membrane-spanning domain (MSD) of the envelope (Env) glycoprotein from human (HIV) and simian immunodeficiency viruses plays a key role in anchoring the Env complex into the viral membrane but also contributes to its biological function in fusion and virus entry. In HIV type 1 (HIV-1), it has been predicted to span 27 amino acids, from lysine residue 681 to arginine 707, and encompasses an internal arginine at residue 694. By examining a series of C-terminal-truncation mutants of the HIV-1 gp41 glycoprotein that substituted termination codons for amino acids 682 to 708, we show that this entire region is required for efficient viral infection of target cells. Truncation to the arginine at residue 694 resulted in an Env complex that was secreted from the cells. In contrast, a region from residues 681 to 698, which contains highly conserved hydrophobic residues and glycine motifs and extends 4 amino acids beyond 694R, can effectively anchor the protein in the membrane, allow efficient transport to the plasma membrane, and mediate wild-type levels of cell-cell fusion. However, these fusogenic truncated Env mutants are inefficiently incorporated into budding virions. Based on the analysis of these mutants, a “snorkeling” model, in which the flanking charged amino acid residues at 681 and 694 are buried in the lipid while their side chains interact with polar head groups, is proposed for the HIV-1 MSD.
Cidofovir Inhibits Genome Encapsidation and Affects Morphogenesis during the Replication of Vaccinia Virus
Authors: Jesus Desyreé Murta , Costa Lilian T. , Gonçalves Daniela L. , Achete Carlos Alberto , Attias Marcia , Moussatché Nissin , Damaso Clarissa R.
Published: September 2009

Cidofovir (CDV) is one of the most effective antiorthopoxvirus drugs, and it is widely accepted that viral DNA replication is the main target of its activity. In the present study, we report a detailed analysis of CDV effects on the replicative cycles of distinct vaccinia virus (VACV) strains: Cantagalo virus, VACV-IOC, and VACV-WR. We show that despite the approximately 90% inhibition of production of virus progeny, virus DNA accumulation was reduced only 30%, and late gene expression and genome resolution were unaltered. The level of proteolytic cleavage of the major core proteins was diminished in CDV-treated cells. Electron microscopic analysis of virus-infected cells in the presence of CDV revealed reductions as great as 3.5-fold in the number of mature forms of virus particles, along with a 3.2-fold increase in the number of spherical immature particles. A detailed analysis of purified virions recovered from CDV-treated cells demonstrated the accumulation of unprocessed p4a and p4b and nearly 67% inhibition of DNA encapsidation. However, these effects of CDV on virus morphogenesis resulted from a primary effect on virus DNA synthesis, which led to later defects in genome encapsidation and virus assembly. Analysis of virus DNA by atomic force microscopy revealed that viral cytoplasmic DNA synthesized in the presence of CDV had an altered structure, forming aggregates with increased strand overlapping not observed in the absence of the drug. These aberrant DNA aggregations were not encapsidated into virus particles.
Contribution of Matrix, Fusion, Hemagglutinin, and Large Protein Genes of the CAM-70 Measles Virus Vaccine Strain to Efficient Growth in Chicken Embryonic Fibroblasts
Authors: Sharma Luna Bhatta , Ohgimoto Shinji , Kato Seiichi , Kurazono Sekiko , Ayata Minoru , Takeuchi Kaoru , Ihara Toshiaki , Ogura Hisashi
Published: September 2009

Attenuated live vaccines of measles virus (MV) have been developed from clinical isolates by serial propagation in heterologous cells, mainly chicken embryonic cells. The safety and effectiveness of these vaccines have been well established. However, the molecular mechanism of their attenuation remains a subject of investigation. The CAM-70 MV vaccine strain was developed from the Tanabe strain by serial propagation in chicken embryonic cells. In the present study, we assessed the contribution of each gene in the CAM-70 strain to efficient growth in chicken embryonic fibroblasts (CEF). We used a cloned MV IC323 based on the wild-type IC-B strain and generated a series of IC323s that possess one or more of the CAM-70 genes. Then, we examined the infection of CEF and CEF expressing human signaling lymphocyte activation molecule with the recombinant MVs. Our results demonstrated that MV needs to adapt to CEF at both the entry and postentry steps and that the CAM-70 matrix protein gene plays an important role in adaptation to CEF at the early stage of the virus replication cycle. The CAM-70 large protein gene was responsible for the efficient transcription and replication in CEF, and the CAM-70 hemagglutinin and fusion protein genes were responsible for efficient entry. Investigations focusing on these genes might elucidate unknown molecular mechanisms underlying the attenuation of MV.
Exclusion of West Nile Virus Superinfection through RNA Replication
Authors: Zou Gang , Zhang Bo , Lim Pei-Yin , Yuan Zhiming , Bernard Kristen A. , Shi Pei-Yong
Published: September 2009

Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Using West Nile virus (WNV) as a model, we show that replicating replicons in BHK-21 cells suppress subsequent WNV infection. The WNV replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. Mode-of-action analysis indicates that the exclusion of WNV superinfection occurs at the step of RNA synthesis. The continuous culturing of WNV in the replicon-containing cells generated variants that could overcome the superinfection exclusion. The sequencing of the selected viruses revealed mutations in structural (prM S90R or envelope E138K) and nonstructural genes (NS4a K124R and peptide 2K V9M). Mutagenesis analysis showed that the mutations in structural genes nonselectively enhance viral infection in both naïve and replicon-containing BHK-21 cells; in contrast, the mutations in nonstructural genes more selectively enhance viral replication in the replicon-containing cells than in the naïve cells. Mechanistic analysis showed that the envelope mutation functions through the enhancement of virion attachment to BHK-21 cells, whereas the 2K mutation (and, to a lesser extent, the NS4a mutation) functions through the enhancement of viral RNA synthesis. Furthermore, we show that WNV superinfection exclusion is reversible by the treatment of the replicon cells with a flavivirus inhibitor. The preestablished replication of the replicon could be suppressed by infecting the cells with the 2K mutant WNV but not with the wild-type virus. These results suggest that WNV superinfection exclusion is a result of competition for intracellular host factors that are required for viral RNA synthesis.
5-Azacytidine Can Induce Lethal Mutagenesis in Human Immunodeficiency Virus Type 1
Authors: Dapp Michael J. , Clouser Christine L. , Patterson Steven , Mansky Louis M.
Published: September 2009

Ribonucleosides inhibit human immunodeficiency virus type 1 (HIV-1) replication by mechanisms that have not been fully elucidated. Here, we report the antiviral mechanism for the ribonucleoside analog 5-azacytidine (5-AZC). We hypothesized that the anti-HIV-1 activity of 5-AZC was due to an increase in the HIV-1 mutation rate following its incorporation into viral RNA during transcription. However, we demonstrate that 5-AZC's primary antiviral activity can be attributed to its effect on the early phase of HIV-1 replication. Furthermore, the antiviral activity was associated with an increase in the frequency of viral mutants, suggesting that 5-AZC's primary target is reverse transcription. Sequencing analysis showed an enrichment in G-to-C transversion mutations and further supports the idea that reverse transcription is an antiviral target of 5-AZC. These results indicate that 5-AZC is incorporated into viral DNA following reduction to 5-aza-2′-deoxycytidine. Incorporation into the viral DNA leads to an increase in mutant frequency that is consistent with lethal mutagenesis during reverse transcription as the primary antiviral mechanism of 5-AZC. Antiviral activity and increased mutation frequency were also associated with the late phase of HIV-1 replication; however, 5-AZC's effect on the late phase was less robust. These results reveal that the primary antiviral mechanism of 5-AZC can be attributed to its ability to increase the HIV-1 mutation frequency through viral-DNA incorporation during reverse transcription. Our observations indicate that 5-AZC can affect two steps in HIV-1 replication (i.e., transcription and reverse transcription) but that its primary antiviral activity is due to incorporation during reverse transcription.
Inhibition of T-Cell Receptor-Induced Actin Remodeling and Relocalization of Lck Are Evolutionarily Conserved Activities of Lentiviral Nef Proteins
Authors: Rudolph Jochen M. , Eickel Nina , Haller Claudia , Schindler Michael , Fackler Oliver T.
Published: September 2009

Nef, an important pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), elevates virus replication in vivo. Among other activities, Nef affects T-cell receptor (TCR) signaling via several mechanisms. For HIV-1 Nef these include alteration of the organization and function of the immunological synapse (IS) such as relocalization of the Lck kinase, as well as early inhibition of TCR/CD3 complex (TCR-CD3)-mediated actin rearrangements and tyrosine phosphorylation. Although most SIV and HIV-2 Nef alleles (group 2) potently downregulate cell surface TCR-CD3, this activity was lost in the viral lineage that gave rise to HIV-1 and its SIV counterparts (group 1). To address the contribution of TCR-CD3 downregulation to Nef effects on TCR signal initiation, we compared the activities of 18 group 1 and group 2 Nef proteins, as well as SIV Nef mutants with defects in TCR-CD3 downmodulation. We found that alteration of Lck's subcellular localization is largely conserved and occurs independently of actin remodeling inhibition or TCR-CD3 downregulation. Surprisingly, Nef proteins of both groups also strongly reduced TCR-induced actin remodeling and tyrosine phosphorylation on TCR-stimulatory surfaces and TCR-CD3 downmodulation competence by group 2 Nef proteins only slightly elevated these effects. Furthermore, Nef proteins from HIV-1 and SIV reduced conjugation between infected primary human T lymphocytes and Raji B cells and potently prevented F-actin polarization at the IS independently of their ability to downmodulate TCR-CD3. These results establish alterations of early TCR signaling events at the IS, including F-actin remodeling and relocalization of Lck, as evolutionary conserved activities of highly divergent lentiviral Nef proteins.
Prediction of monomer reactivity ratios in radical copolymerization of vinyl monomers
Authors: Yu Xinliang , Yu Wenhao , Yi Bing , Wang Xueye
Published: September 2009

Quantitative structure-property relationship (QSPR) models are developed to predict monomer reactivity ratios (log r12) in radical copolymerization with monomers M1 (styrene, methyl methacrylate and acrylonitrile) and M2 (vinyl monomers). The quantum chemical descriptors are calculated by the density functional theory (DFT) at B3LYP level of theory with 6-31G(d) basis set. Stepwise multiple linear regression analysis and artificial neural network (ANN) were used to generate Model S (monomer 1: styrene), Model MM (monomer 1: methyl methacrylate) and Model A (monomer 1: acrylonitrile). Simulation results show that the predicted log r12 values are in good agreement with the experimental data, with the test sets possessing correlation coefficients of 0.972 for Model S, 0.933 for Model MM and 0.946 for Model A.
THE RELAXATION TIME OF A SINGLE-MODE LASER SYSTEM DRIVEN BY PUMP AND QUANTUM NOISES WITH REAL AND IMAGINARY PARTS CORRELATED
Authors: WANG BING , TANG YONG-XIN , YAN SHAO-PING , ZHANG JIAN-QIU
Published: September 2009

Based on the Fokker–Planck description of a single-mode laser system and the projection operator method, the mean relaxation time T of a single-mode laser system with correlations between the real and imaginary parts of the quantum noise as well as the pump noise is studied. It is found that the mean relaxation time T increases with the increasing net gain a0 and decreases with the increasing self-saturation coefficient A. T increases with the increasing pump noise strength Q but decreases with the increasing quantum noise strength D. The mean relaxation time T increases (decreases) with the increasing pump noise self-correlation time τ if a0 > 0 (a0 < 0). T decreases with the increasing |λ| (λ is the coefficient of cross-correlation between the real and imaginary parts of the quantum noise).
THE INFLUENCES OF COOLING HEIGHT ON THE LEVITATION FORCE OF SINGLE-DOMAIN YBCO BULK
Authors: ZHOU JUN , ZHANG XING-YI , ZHOU YOU-HE
Published: September 2009

The levitation force characteristics in a superconducting levitation device are determined not only by the geometry and electromagnetic properties of its components, but also by the initial cooling process of the superconductor. In this paper we present the experimental results of effects of the different initial cooling heights between a superconductor and magnet on the levitation force characteristics including maximum levitation force, relaxation of the levitation force and drift of the levitation force caused by the magnet vibration. It was found that the different cooling heights have large influences on the levitation force characteristics of YBCO bulk.
QUANTUM STATISTICAL PROPERTIES OF THE EVEN AND ODD NEGATIVE BINOMIAL STATES
Authors: ZHANG XIAO-YAN , WANG JI-SUO , MENG XIANG-GUO , SU JIE
Published: September 2009

The properties of the even and odd negative binomial states are investigated. Mainly we concentrate on the statistical properties for such states and we consider the squeezing phenomenon by examining the variation in the quadrature variances. Using the Pegg–Barnett formalism of phase operator, the phase probability distributions of the states are discussed, and also the phase and number squeezing with different parameters are studied. The numerical computation results show that the phase probability distributions for the even and odd NBSs can clearly exhibit the different features of quantum effects.
PREPARATION AND PHOTOLUMINESCENCE PROPERTIES OFNdVO4NANOTUBES IN AAO TEMPLATE
Authors: PENG XIAO-NIU , ZHANG XIAN , YU LIAO , ZHOU LI
Published: September 2009

Porous anodized aluminum oxide (AAO) template was combined with sol-gel method in this work for the fabrication of high-ordered NdVO4nanotube arrays. The diameter, length, and wall thickness of the nanotubes can be adjusted conveniently. The sample was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), absorption spectra, and photoluminescence spectra. The results show that these uniformly distributed, high-ordered, and parallel nanotubes have great light emission in both the visible region and near-infrared region due to their corresponding energy level transitions. With this method, future application of rare-earth hollow nanostructures will be widely extended.
PHYSICAL AND OPTICAL POLARIZABILITY AND TRANSPORT PROPERTIES OF BISMUTHATE GLASSES
Authors: BALE SHASHIDHAR , RAHMAN SYED
Published: September 2009

Bismuth-based glasses containing ZnO , B 2 O 3 and Li 2 O are investigated through different physical, polarizability and transport properties. Raman spectroscopy reveals that these glasses are built from [ BiO 3] and [ BiO 6] units. Zinc in tetrahedral form is also observed. Density and glass transition temperature increase with the bismuth content. The refractive index, oxide ion polarizability and optical basicity also increase with the Bi 2 O 3 content, whereas the interaction parameter decreases. The DC electrical conductivity increases and the activation energy decreases with the increase in the Li 2 O content.
SQUEEZING AND PHOTON STATISTICS IN FIVE-WAVE MIXING PROCESS
Authors: RANI SUNIL , LAL JAWAHAR , SINGH NAFA
Published: September 2009

We investigate theoretically the generation of squeezed states in spontaneous and stimulated five-wave mixing process. It has been found that squeezing occurs in field amplitude, amplitude-squared, amplitude-cubed and fourth-order amplitude states of the fundamental mode in the process. It is found to be dependent on coupling parameter g and phase values of the field amplitude of the fundamental mode. The process involves the absorption of two pump photons each having frequency ω1, emission of two probe photons of same frequency ω2 and a signal photon of frequency ω3. It is shown that squeezing is greater in a stimulated interaction than the corresponding squeezing in the spontaneous process. It is found that the degree of squeezing depends on the photon number in the first and higher orders. We study the statistical behaviour of quantum field in the fundamental mode. It has been found that the field shows sub-Poissonian behavior in this mode.
TWO-DIMENSIONAL ATOMISTIC SIMULATION OF METALLIC NANOPARTICLES PUSHING
Authors: MAHBOOBI SEYED HANIF , MEGHDARI ALI , JALILI NADER , AMIRI FARSHID
Published: September 2009

Nanomanipulation as a new emerging area enables precise manipulation, interaction and control at the nanoscale. Currently, the modeling schemes are based on continuum mechanics approaches. A main consideration in the nanomanipulation process is the fact that surface attraction forces are greater than gravitational forces at the nanoscale. In other words, surface area properties dominate volume properties. Especially at the nanoscale (i.e. the manipulation of fine nanoparticles with size of about 5 nm) the physical phenomena have not been completely understood. Along this line of reasoning, the aim of this paper is to conduct an atomistic investigation of physical interaction analysis of particle–substrate system for manipulation and positioning purposes. In the present paper, 2D molecular dynamics have been conducted to simulate metallic nanoparticle behavior during the pushing process. Dependency of the aforementioned behavior on size, matter, temperature, etc. is investigated.