bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematics of a Special 3-DOF 3-UPU Parallel Manipulator
Authors: Li Shihua , Huang Zhen , Zuo Rongguo
Published: October 2012

This paper discusses kinematic of a special 3-UPU parallel pyramid manipulator by using two different principal, in every branch two middle revolute pairs are perpendicular to each other. This mechanism has three instantaneous translational degrees of freedom, but it is not a three-dimension translational mechanism like the general 3-UPU mechanism with two middle revolute pairs parallel to each other in every branch. By analyzed in depth this special mechanism, we discovers some interesting and special characteristics of the mechanism. All of the results are useful for enriching the mechanism theory and should be applied in mechanism design.
Singularity-Free Fully-Isotropic Translational Parallel Manipulators
Authors: Carricato Marco , Parenti-Castelli Vincenzo
Published: October 2012

This paper focuses on translational parallel manipulators (TPMs), that is on parallel manipulators whose output link (platform) is provided with a pure translational motion with respect to the frame. It deals with the general problem of the topological synthesis and classification of TPMs and investigates both their constraint and direct singularities. In particular, it identifies for the first time special families of fully-isotropic mechanisms. Such manipulators exhibit outstanding properties, as they are free from singularities and show a constant orthogonal Jacobian matrix throughout their workspace. As a consequence, both the direct and the inverse position problems are linear and the kinematic analysis proves straightforward.
Displacement Analysis of Spherical Mechanisms Having Three or Fewer Loops
Authors: Wampler Charles W.
Published: October 2012

Spherical linkages, having rotational joints whose axes coincide in a common centerpoint, are sometimes used in multi-degree-of-freedom robot manipulators and in one-degree-of-freedom mechanisms. The forward kinematics of parallel-link robots, the inverse kinematics of serial-link robots and the in-put/output motion of single-degree-of-freedom mechanisms are all problems in displacement analysis. In this article, loop equations are formulated and solved for the displacement analysis of all spherical mechanisms up to three loops. We show how to solve each mechanism type using either a formulation in terms of rotation matrices or quaternions. In either formulation, the solution method is a modification of Sylvester’s elimination method, leading directly to numerical calculation via standard eigenvalue routines.
A Different Kinematic Model of the Tricept Robot
Authors: Sinatra Rosario
Published: October 2012

This paper presents an alternative architecture for the Tricept robot to that designed by Neos Robotics (Taby, Sweden). First, a complete kinematic of a new model is introduced. The model is then used to derive the kinematic relations of the robot at the displacement, velocity and acceleration levels. These equations are implemented in an algorithm and a numerical example which simulates the kinematic behavior of the manipulator while following a sample trajectory is illustrated. Numerical and other considerations comparing the two architectures of the Tricept robot are presented.
Experimental and Theoretical Analysis of a Uni-Drive Modular Robot: Design and Modeling
Authors: Karbasi Hamidreza , Huissoon Jan , Khajepour Amir
Published: October 2012

In this paper, the fundamental principals of design and modeling of so-called uni-drive modular robots are introduced. Lightweight modules are significantly important in the design and application of modular robots. This is achieved in this new class of modular robots by using a single base-mounted drive from which all joints tap power via a central rotating shaft using clutches. The clutches in the uni-drive modular robot are controlled using the pulse width modulation (PWM) technique. The position and velocity of the joints are regulated by controlling the engagement time of the clutches. The design of the mechanical drive unit is presented, with which this new design concept is implemented. The unit consists of two clutches to provide each joint with a bi-directional output while its input is uni-directional. For simulation purposes, a lumped parameter model for the selected type of clutch (spring wrap clutch) is developed. Finally, the experimental and simulation results for the fabricated and modeled mechanical drive unit are presented to show the feasibility of the uni-drive modular robot concept.
Force Sensor Based Calibration of Robot Grinding
Authors: Zhang Yue , Sun Yunquan , Kazerounian Kazem , Gan Zhongxue
Published: October 2012

Industry is now seeing a dramatic increase in robot simulation and off-line programming. In order to use off-line programming effectively, the variance between the simulation system and the real world has to be identified. This requires a more efficient and accurate method for robot calibration. Unlike measuring the position variation, this paper introduces a technique to calibrate the robot paths by using force and torque sensor. Based on the difference of the contact forces between each path, both the system geometric distortion and positioning errors are calibrated and compensated by updating the workpiece coordinate system and tool coordinate system. Finally, the proper and even force distribution is achieved in the grinding process. The experimental result demonstrates the effectiveness of proposed calibration approach.
Solving the Burmester Problem Using Kinematic Mapping
Authors: Hayes M. J. D. , Zsombor-Murray P. J.
Published: October 2012

Planar kinematic mapping is applied to the five-position Burmester problem for planar four-bar mechanism synthesis. The problem formulation takes the five distinct rigid body poses directly as inputs to generate five quadratic constraint equations. The five poses are on the fourth order curve of intersection of up to four hyperboloids of one sheet in the image space. Moreover, the five poses uniquely specify these two hyperboloids. So, given five positions of any reference point on the coupler and five corresponding orientations, we get the fixed revolute centres, the link lengths, crank angles, and the locations of the coupler attachment points by solving a system of five quadratics in five variables that always factor in such a way as to give two pairs of solutions for the five variables (when they exist).
Inverse Kinematic Solution for Universal-Jointed Hyper-Redundant Robots
Authors: Fahimi Farbod , Ashrafiuon Hashem , Nataraj C.
Published: October 2012

A new and efficient kinematic position and velocity solution scheme for spatial hyper-redundant manipulators is presented. The manipulator’s arm has discrete links and universal joints. Backbone curve concepts and a modal approach are used to resolve the manipulator’s redundancy. The effects of the mode shapes and the slope of backbone curve at the starting point on the workspace are studied. It is shown that the usage of conventional mode shapes limits the workspace of the hyper-redundant arm. By introducing new mode shapes, an improved workspace is obtained. A simple and efficient recursive fitting method is introduced to avoid complications involved with solving systems of nonlinear algebraic equations. This method also guarantees the existence of solutions for the inverse kinematic problem at the velocity level. Velocity properties of the backbone curve are investigated and the inverse velocity propagation is solved for the spatial hyper-redundant arm. The velocity propagation scheme is recursive and is efficiently applicable to any number of links.
A pencil beam algorithm for helium ion beam therapy
Authors: Fuchs Hermann , Ströbele Julia , Schreiner Thomas , Hirtl Albert , Georg Dietmar
Published: October 2012

Purpose:

To develop a flexible pencil beam algorithm for helium ion beam therapy. Dose distributions were calculated using the newly developed pencil beam algorithm and validated using Monte Carlo (MC) methods.

Methods:

The algorithm was based on the established theory of fluence weighted elemental pencil beam (PB) kernels. Using a new real‐time splitting approach, a minimization routine selects the optimal shape for each sub‐beam. Dose depositions along the beam path were determined using a look‐up table (LUT). Data for LUT generation were derived from MC simulations in water using GATE 6.1. For materials other than water, dose depositions were calculated by the algorithm using water‐equivalent depth scaling. Lateral beam spreading caused by multiple scattering has been accounted for by implementing a non‐local scattering formula developed by Gottschalk. A new nuclear correction was modelled using a Voigt function and implemented by a LUT approach. Validation simulations have been performed using a phantom filled with homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were incident perpendicular to the phantoms surface with initial particle energies ranging from 50 to 250 MeV/A with a total number of 107 ions per beam. For comparison a special evaluation software was developed calculating the gamma indices for dose distributions.

Results:

In homogeneous phantoms, maximum range deviations between PB and MC of less than 1.1% and differences in the width of the distal energy falloff of the Bragg‐Peak from 80% to 20% of less than 0.1 mm were found. Heterogeneous phantoms using layered slabs satisfied a γ‐index criterion of 2%/2mm of the local value except for some single voxels. For more complex phantoms using laterally arranged bone‐air slabs, the γ‐index criterion was exceeded in some areas giving a maximum γ‐index of 1.75 and 4.9% of the voxels showed γ‐index values larger than one. The calculation precision of the presented algorithm was considered to be sufficient for clinical practice. Although only data for helium beams was presented, the performance of the pencil beam algorithm for proton beams was comparable.

Conclusions:

The pencil beam algorithm developed for helium ions presents a suitable tool for dose calculations. Its calculation speed was evaluated to be similar to other published pencil beam algorithms. The flexible design allows easy customization of measured depth‐dose distributions and use of varying beam profiles, thus making it a promising candidate for integration into future treatment planning systems. Current work in progress deals with RBE effects of helium ions to complete the model.
A real‐time in vivo dosimetric verification method for high‐dose rate intracavitary brachytherapy of nasopharyngeal carcinoma
Authors: Qi Zhen‐Yu , Deng Xiao‐Wu , Cao Xin‐ping , Huang Shao‐Min , Lerch Michael , Rosenfeld Anatoly
Published: October 2012

Purpose:

A real‐timein vivo dosimetric verification method using metal‐oxide‐semiconductor field effect transistor (MOSFET) dosimeters has been developed for patient dosimetry in high‐dose rate (HDR) intracavitary brachytherapy of nasopharyngeal carcinoma (NPC).

Methods:

The necessary calibration and correction factors for MOSFET measurements in192Iridium source were determined in a water phantom. With the detector placed inside a custom‐made nasopharyngeal applicator, the actual dose delivered to the tumor was measured in vivo and compared to the calculated values using a commercial brachytherapy planning system.

Results:

Five MOSFETs were independently calibrated with the HDR source, yielding calibration factors of 0.48 ± 0.007 cGy/mV. The maximum sensitivity variation was no more than 7% in the clinically relevant distance range of 1–5 cm from the source. A total of 70in vivo measurements in 11 NPC patients demonstrated good agreement with the treatment planning. The mean differences between the planned and the actually delivered dose within a single treatment fraction were −0.1% ± 3.8% and −0.1% ± 3.7%, respectively, for right and left side assessments. The maximum dose deviation was less than 8.5%.

Conclusions:

In vivo measurement using the real‐time MOSFET dosimetry system is possible to evaluate the actual dose to the tumor received by the patient during a treatment fraction and thus can offer another line of security to detect and prevent large errors.
Preparing tutorial and recitation instructors: A pedagogical approach to focusing attention on content and student reasoning
Authors: Spike Benjamin T. , Finkelstein Noah D.
Published: October 2012

Instructors in transformed educational environments face an increased demand to anticipate, engage with, and build upon student ideas in the classroom. Consequently, there is a need to augment traditional forms of preparation to accommodate the expanding role of instructors in these environments. We document a model of weekly preparation designed to engage graduate teaching assistants (TAs) and undergraduate learning assistants (LAs) in developing broader teaching skills through the weekly discussion of student difficulties. In this paper, we describe this model and present evidence of success at focusing instructor attention on student difficulties, accomplished within existing institutional structures and without adding significantly to instructor preparation time.
Why do stars twinkle, and do they twinkle on Mars?
Authors: Whitehead Lorne , Huizinga John , Mossman Michele
Published: October 2012

The question “Why do stars twinkle?” is typically given a superficial answer that satisfies most people. However, as is often the case for physics-related questions about everyday phenomena, a more complete explanation is surprisingly rich and somewhat subtle.
Methylation Subtypes and Large-Scale Epigenetic Alterations in Gastric Cancer
Authors: Zouridis Hermioni , Deng Niantao , Ivanova Tatiana , Zhu Yansong , Wong Bernice , Huang Dan , Wu Yong Hui , Wu Yingting , Tan Iain Beehuat , Liem Natalia , Gopalakrishnan Veena , Luo Qin , Wu Jeanie , Lee Minghui , Yong Wei Peng , Goh Liang Kee , Teh Bin Tean , Rozen Steve , Tan Patrick
Published: October 2012

A large-scale genomic survey of epigenetic alterations in gastric cancer identifies clinically relevant molecular subgroups.
A Warning Bell Tolls for Type 1 Diabetes
Authors: Nakamura Takahisa
Published: October 2012

Toll-like receptor induces dysregulated interleukin-1β and interleukin-6 responses in subjects at risk for the development of type 1 diabetes.
Science Translational Medicine
Podcast: 17 October 2012
Authors: Saluja Ashok K. , Colmone Angela
Published: October 2012

In this podcast, Ashok Saluja discusses Minnelide, a potential new treatment for pancreatic cancer.
In VivoEfficacy of a Chimeric Peptide Derived from the Conserved Region of the M Protein against Group C and G Streptococci
Authors: Nordström Therese , Malcolm Jessica , Magor Graham , Good Michael F. , Batzloff Michael R.
Published: October 2012

The J8 peptide from the conserved region of the M protein protects against group A streptococcus infections. In this study, we demonstrate that vaccination with a J8-containing formulation induces IgG that recognizes and binds group C and G streptococci. Moreover, this formulation has the potential to provide protection against infections caused by these organisms.
False Daptomycin-Nonsusceptible MIC Results by Microscan Panel PC 29 Relative to Etest Results for Staphylococcus aureus and Enterococci
Authors: Palavecino Elizabeth L. , Burnell Jacqueline M.
Published: October 2012

This study correlated the daptomycin MIC results obtained by Microscan and by Etest in
Staphylococcus aureus
and enterococci and found that the Microscan panel GP 29 had a high rate of false nonsusceptible results. Of the isolates interpreted as nonsusceptible by Microscan, 87% of
Staphylococcus aureus
, 90% of
Enterococcus faecalis
, and 88% of
Enterococcus faecium
isolates were interpreted as susceptible by Etest. In turn, Etest also has false nonsusceptible results compared to reference methods.
Comparison of Ahlstrom Grade 226, Munktell TFN, and Whatman 903 Filter Papers for Dried Blood Spot Specimen Collection and Subsequent HIV-1 Load and Drug Resistance Genotyping Analysis
Authors: Rottinghaus Erin , Bile Ebi , Modukanele Mosetsanagape , Maruping Maruping , Mine Madisa , Nkengasong John , Yang Chunfu
Published: October 2012

Dried blood spots (DBS) collected onto filter paper have eased the difficulty of blood collection in resource-limited settings. Currently, Whatman 903 (W-903) filter paper is the only filter paper that has been used for HIV load and HIV drug resistance (HIVDR) testing. We therefore evaluated two additional commercially available filter papers, Ahlstrom grade 226 (A-226) and Munktell TFN (M-TFN), for viral load (VL) testing and HIVDR genotyping using W-903 filter paper as a comparison group. DBS specimens were generated from 344 adult patients on antiretroviral therapy (ART) in Botswana. The VL was measured with NucliSENS EasyQ HIV-1 v2.0, and genotyping was performed for those specimens with a detectable VL (≥2.90 log10copies/ml) using an in-house method. Bland-Altman analysis revealed a strong concordance in quantitative VL analysis between W-903 and A-226 (bias = −0.034 ± 0.246 log10copies/ml [mean difference ± standard deviation]) and W-903 and M-TFN (bias = −0.028 ± 0.186 log10copies/ml) filter papers, while qualitative VL analysis for virological failure determination, defined as a VL of ≥3.00 log10copies/ml, showed low sensitivities for A-266 (71.54%) and M-TFN (65.71%) filter papers compared to W-903 filter paper. DBS collected on M-TFN filter paper had the highest genotyping efficiency (100%) compared to W-903 and A-226 filter papers (91.7%) and appeared more sensitive in detecting major HIVDR mutations. DBS collected on A-226 and M-TFN filter papers performed similarly to DBS collected on W-903 filter paper for quantitative VL analysis and HIVDR detection. Together, the encouraging genotyping results and the variability observed in determining virological failure from this small pilot study warrant further investigation of A-226 and M-TFN filter papers as specimen collection devices for HIVDR monitoring surveys.
Neutralizing DNA Aptamers against Swine Influenza H3N2 Viruses
Authors: Wongphatcharachai Manoosak , Wang Ping , Enomoto Shinichiro , Webby Richard J. , Gramer Marie R. , Amonsin Alongkorn , Sreevatsan Srinand
Published: October 2012

Triple reassortant influenza A viruses (IAVs) of swine, particularly the North American H3N2 subtype, circulate in swine herds and may reassort and result in the emergence of novel zoonotic strains. Current diagnostic tools rely on isolation of the viruses, followed by serotyping by hemagglutination or genome sequencing, both of which can be expensive and time-consuming. Thus, novel subtype-specific ligands and methods are needed for rapid testing and subtyping of IAVs in the field. To address this need, we selected DNA aptamers against the recombinant HA protein from swine IAV H3 cluster IV using systematic evolution of ligands by exponential enrichment (SELEX). Four candidate aptamers (HA68, HA7, HA2a, and HA2b) were identified and characterized. The dissociation constants (
K

d

) of aptamers HA68, HA7, HA2a, and HA2b against recombinant H3 protein were 7.1, 22.3, 16.0, and 3.7 nM, respectively. The binding site of HA68 to H3 was identified to be between nucleotide residues 8 and 40. All aptamers inhibited H3 hemagglutination. HA68 was highly specific to all four lineages within the North American H3N2 subtype. Further, the other three aptamers specifically identified live viruses belonging to the phylogenetic clusters I, II/III, and IV especially the virus that closely related to the recent H3N2 variant (H3N2v). Aptamer HA68 was also able to bind and detect H3N2v isolated from recent human cases. In conclusion, we provide subtype-specific aptamers against H3N2 IAVs of swine that can now be used in rapid detection and typing protocols for field applications.
Rapid Detection and Statistical Differentiation of KPC Gene Variants in Gram-Negative Pathogens by Use of High-Resolution Melting and ScreenClust Analyses
Authors: Roth Amanda L. , Hanson Nancy D.
Published: October 2012

In the United States, the production of the
Klebsiella pneumoniae
carbapenemase (KPC) is an important mechanism of carbapenem resistance in Gram-negative pathogens. Infections with KPC-producing organisms are associated with increased morbidity and mortality; therefore, the rapid detection of KPC-producing pathogens is critical in patient care and infection control. We developed a real-time PCR assay complemented with traditional high-resolution melting (HRM) analysis, as well as statistically based genotyping, using the Rotor-Gene ScreenClust HRM software to both detect the presence of
bla
KPC
and differentiate between KPC-2-like and KPC-3-like alleles. A total of 166 clinical isolates of
Enterobacteriaceae
,
Pseudomonas aeruginosa
, and
Acinetobacter baumannii
with various β-lactamase susceptibility patterns were tested in the validation of this assay; 66 of these organisms were known to produce the KPC β-lactamase. The real-time PCR assay was able to detect the presence of
bla
KPC
in all 66 of these clinical isolates (100% sensitivity and specificity). HRM analysis demonstrated that 26 had KPC-2-like melting peak temperatures, while 40 had KPC-3-like melting peak temperatures. Sequencing of 21 amplified products confirmed the melting peak results, with 9 isolates carrying
bla
KPC-2
and 12 isolates carrying
bla
KPC-3
. This PCR/HRM assay can identify KPC-producing Gram-negative pathogens in as little as 3 h after isolation of pure colonies and does not require post-PCR sample manipulation for HRM analysis, and ScreenClust analysis easily distinguishes
bla
KPC-2-like
and
bla
KPC-3-like
alleles. Therefore, this assay is a rapid method to identify the presence of
bla
KPC
enzymes in Gram-negative pathogens that can be easily integrated into busy clinical microbiology laboratories.
Interplay between Polyadenylate-Binding Protein 1 and Kaposi's Sarcoma-Associated Herpesvirus ORF57 in Accumulation of Polyadenylated Nuclear RNA, a Viral Long Noncoding RNA
Authors: Massimelli Maria J. , Majerciak Vladimir , Kruhlak Michael , Zheng Zhi-Ming
Published: October 2012

Polyadenylate-binding protein cytoplasmic 1 (PABPC1) is a cytoplasmic-nuclear shuttling protein important for protein translation initiation and both RNA processing and stability. We report that PABPC1 forms a complex with the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein, which allows ORF57 to interact with a 9-nucleotide (nt) core element of KSHV
p
oly
a
denylated
n
uclear (PAN) RNA, a viral long noncoding RNA (lncRNA), and increase PAN stability. The N-terminal RNA recognition motifs (RRMs) of PABPC1 are necessary for the direct interaction with ORF57. During KSHV lytic infection, the expression of viral ORF57 leads to a substantial decrease in overall PABPC1 expression, along with a shift in the cellular distribution of the remaining PABPC1 to the nucleus. Interestingly, PABPC1 and ORF57 have opposing functions in modulating PAN steady-state accumulation. The suppressive effect of PABPC1 specific to PAN expression is alleviated by small interfering RNA knockdown of PABPC1 or by overexpression of ORF57. Conversely, ectopic PABPC1 reduces ORF57 steady-state protein levels and induces aberrant polyadenylation of PAN and thereby indirectly inhibits ORF57-mediated PAN accumulation. However, E1B-AP5 (heterogeneous nuclear ribonucleoprotein U-like 1), which interacts with a region outside the 9-nt core to stimulate PAN expression, does not interact or even colocalize with ORF57. Unlike PABPC1, the nuclear distribution of E1B-AP5 remains unchanged by viral lytic infection or overexpression of ORF57. Together, these data indicate that PABPC1 is an important cellular target of viral ORF57 to directly upregulate PAN accumulation during viral lytic infection, and the ability of host PABPC1 to disrupt ORF57 expression is a strategic host counterbalancing mechanism.
TRIM Protein-Mediated Regulation of Inflammatory and Innate Immune Signaling and Its Association with Antiretroviral Activity
Authors: Uchil Pradeep D. , Hinz Angelika , Siegel Steven , Coenen-Stass Anna , Pertel Thomas , Luban Jeremy , Mothes Walther
Published: October 2012

Members of the
tri
partite interaction
m
otif (TRIM) family of E3 ligases are emerging as critical regulators of innate immunity. To identify new regulators, we carried out a screen of 43 human TRIM proteins for the ability to activate NF-κB, AP-1, and interferon, hallmarks of many innate immune signaling pathways. We identified 16 TRIM proteins that induced NF-κB and/or AP-1. We found that one of these, TRIM62, functions in the TRIF branch of the TLR4 signaling pathway. Knockdown of TRIM62 in primary macrophages led to a defect in TRIF-mediated late NF-κB, AP-1, and interferon production after lipopolysaccharide challenge. We also discovered a role for TRIM15 in the RIG-I-mediated interferon pathway upstream of MAVS. Knockdown of TRIM15 limited virus/RIG-I ligand-induced interferon production and enhanced vesicular stomatitis virus replication. In addition, most TRIM proteins previously identified to inhibit murine leukemia virus (MLV) demonstrated an ability to induce NF-κB/AP-1. Interfering with the NF-κB and AP-1 signaling induced by the antiretroviral TRIM1 and TRIM62 proteins rescued MLV release. In contrast, human immunodeficiency virus type 1 (HIV-1) gene expression was increased by TRIM proteins that induce NF-κB. HIV-1 resistance to inflammatory TRIM proteins mapped to the NF-κB sites in the HIV-1 long terminal repeat (LTR) U3 and could be transferred to MLV. Thus, our work identifies new TRIM proteins involved in innate immune signaling and reinforces the striking ability of HIV-1 to exploit innate immune signaling for the purpose of viral replication.
Dissection of Functional Sites in Herpesvirus Saimiri Complement Control Protein Homolog
Authors: Reza Malik Johid , Kamble Ashish , Ahmad Muzammil , Krishnasastry Musti V. , Sahu Arvind
Published: October 2012

Herpesvirus saimiri is known to encode a homolog of human complement regulators named complement control protein homolog (CCPH). We have previously reported that this virally encoded inhibitor effectively inactivates complement by supporting factor I-mediated inactivation of complement proteins C3b and C4b (termed cofactor activity), as well as by accelerating the irreversible decay of the classical/lectin and alternative pathway C3 convertases (termed decay-accelerating activity). To fine map its functional sites, in the present study, we have generated a homology model of CCPH and performed substitution mutagenesis of its conserved residues. Functional analyses of 24 substitution mutants of CCPH indicated that (i) amino acids R118 and F144 play a critical role in imparting C3b and C4b cofactor activities, (ii) amino acids R35, K142, and K191 are required for efficient decay of the C3 convertases, (iii) positively charged amino acids of the linker regions, which are dubbed to be critical for functioning in other complement regulators, are not crucial for its function, and (iv) S100K and G110D mutations substantially enhance its decay-accelerating activities without affecting the cofactor activities. Overall, our data point out that ionic interactions form a major component of the binding interface between CCPH and its interacting partners.
The Compensatory G88R Change Is Essential in Restoring the Normal Functions of Influenza A/WSN/33 Virus Matrix Protein 1 with a Disrupted Nuclear Localization Signal
Authors: Xie Hang , Lin Zhengshi , Mosier Philip D. , Desai Umesh R. , Gao Yamei
Published: October 2012

G88R emerged as a compensatory mutation in matrix protein 1 (M1) of influenza virus A/WSN/33 when its nuclear localization signal (NLS) was disrupted by R101S and R105S substitutions. The resultant M1 triple mutant M(NLS-88R) regained replication efficiency
in vitro
while remaining attenuated
in vivo
with the potential of being a live vaccine candidate. To understand why G88R was favored by the virus as a compensatory change for the NLS loss and resultant replication deficiency, three more M1 triple mutants with an alternative G88K, G88V, or G88E change in addition to R101S and R105S substitutions in the NLS were generated. Unlike the other M1 triple mutants, M(NLS-88R) replicated more efficiently
in vitro
and
in vivo
. The G88R compensatory mutation not only restored normal functions of M1 in the presence of a disrupted NLS but also resulted in a strong association of M1 with viral ribonucleoprotein. Under a transmission electron microscope, only the M1 layer of the M(NLS-88R) virion exhibited discontinuous fingerprint-like patterns with average thicknesses close to that of wild-type A/WSN/33. Computational modeling suggested that the compensatory G88R change could reestablish the integrity of the M1 layer through new salt bridges between adjacent M1 subunits when the original interactions were interrupted by simultaneous R101S and R105S replacements in the NLS. Our results suggested that restoring the normal functions of M1 was crucial for efficient virus replication.
Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop
Authors: Costin Joshua M. , Zaitseva Elena , Kahle Kristen M. , Nicholson Cindo O. , Rowe Dawne K. , Graham Amanda S. , Bazzone Lindsey E. , Hogancamp Greg , Figueroa Sierra Marielys , Fong Rachel H. , Yang Sung-Tae , Lin Li , Robinson James E. , Doranz Benjamin J. , Chernomordik Leonid V. , Michael Scott F. , Schieffelin John S. , Isern Sharon
Published: October 2012

There are no available vaccines for dengue, the most important mosquito-transmitted viral disease. Mechanistic studies with anti-dengue virus (DENV) human monoclonal antibodies (hMAbs) provide a rational approach to identify and characterize neutralizing epitopes on DENV structural proteins that can serve to inform vaccine strategies. Here, we report a class of hMAbs that is likely to be an important determinant in the human humoral response to DENV infection. In this study, we identified and characterized three broadly neutralizing anti-DENV hMAbs: 4.8A, D11C, and 1.6D. These antibodies were isolated from three different convalescent patients with distinct histories of DENV infection yet demonstrated remarkable similarities. All three hMAbs recognized the E glycoprotein with high affinity, neutralized all four serotypes of DENV, and mediated antibody-dependent enhancement of infection in Fc receptor-bearing cells at subneutralizing concentrations. The neutralization activities of these hMAbs correlated with a strong inhibition of virus-liposome and intracellular fusion, not virus-cell binding. We mapped epitopes of these antibodies to the highly conserved fusion loop region of E domain II. Mutations at fusion loop residues W101, L107, and/or G109 significantly reduced the binding of the hMAbs to E protein. The results show that hMAbs directed against the highly conserved E protein fusion loop block viral entry downstream of virus-cell binding by inhibiting E protein-mediated fusion. Characterization of hMAbs targeting this region may provide new insights into DENV vaccine and therapeutic strategies.
Recombinant Parainfluenza Virus 5 Vaccine Encoding the Influenza Virus Hemagglutinin Protects against H5N1 Highly Pathogenic Avian Influenza Virus Infection following Intranasal or Intramuscular Vaccination of BALB/c Mice
Authors: Mooney Alaina J. , Li Zhuo , Gabbard Jon D. , He Biao , Tompkins S. Mark
Published: October 2012

New approaches for vaccination to prevent influenza virus infection are needed. Emerging viruses, such as the H5N1 highly pathogenic avian influenza (HPAI) virus, pose not only pandemic threats but also challenges in vaccine development and production. Parainfluenza virus 5 (PIV5) is an appealing vector for vaccine development, and we have previously shown that intranasal immunization with PIV5 expressing the hemagglutinin from influenza virus was protective against influenza virus challenge (S. M. Tompkins, Y. Lin, G. P. Leser, K. A. Kramer, D. L. Haas, E. W. Howerth, J. Xu, M. J. Kennett, J. E. Durbin, R. A. Tripp, R. A. Lamb, and B. He, Virology362:139–150, 2007). While intranasal immunization is an appealing approach, PIV5 may have the potential to be utilized in other formats, prompting us to test the efficacy of rPIV5-H5, which encodes the HA from H5N1 HPAI virus, in different vaccination schemes. In the BALB/c mouse model, a single intramuscular or intranasal immunization with a live rPIV5-H5 (ZL46) rapidly induced robust neutralizing serum antibody responses and protected against HPAI challenge, although mucosal IgA responses primed by intranasal immunization more effectively controlled virus replication in the lung. The rPIV5-H5 vaccine incorporated the H5 HA into the virion, so we tested the efficacy of an inactivated form of the vaccine. Inactivated rPIV5-H5 primed neutralizing serum antibody responses and controlled H5N1 virus replication; however, similar to other H5 antigen vaccines, it required a booster immunization to prime protective immune responses. Taken together, these results suggest that rPIV5-HA vaccines and H5-specific vaccines in particular can be utilized in multiple formats and by multiple routes of administration. This could avoid potential contraindications based on intranasal administration alone and provide opportunities for broader applications with the use of a single vaccine vector.
Exceptional Simian Hemorrhagic Fever Virus Diversity in a Wild African Primate Community
Authors: Lauck Michael , Sibley Samuel D. , Hyeroba David , Tumukunde Alex , Weny Geoffrey , Chapman Colin A. , Ting Nelson , Switzer William M. , Kuhn Jens H. , Friedrich Thomas C. , O'Connor David H. , Goldberg Tony L.
Published: October 2012

Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (
Cercopithecus ascanius
). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (
Procolobus rufomitratus
). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification.
Herpes Simplex Virus Membrane Proteins gE/gI and US9 Act Cooperatively To Promote Transport of Capsids and Glycoproteins from Neuron Cell Bodies into Initial Axon Segments
Authors: Howard Paul W. , Howard Tiffani L. , Johnson David C.
Published: October 2012

Herpes simplex virus (HSV) and other alphaherpesviruses must move from sites of latency in ganglia to peripheral epithelial cells. How HSV navigates in neuronal axons is not well understood. Two HSV membrane proteins, gE/gI and US9, are key to understanding the processes by which viral glycoproteins, unenveloped capsids, and enveloped virions are transported toward axon tips. Whether gE/gI and US9 function to promote the loading of viral proteins onto microtubule motors in neuron cell bodies or to tether viral proteins onto microtubule motors within axons is not clear. One impediment to understanding how HSV gE/gI and US9 function in axonal transport relates to observations that gE
−
, gI
−
, or US9
−
mutants are not absolutely blocked in axonal transport. Mutants are significantly reduced in numbers of capsids and glycoproteins in distal axons, but there are less extensive effects in proximal axons. We constructed HSV recombinants lacking both gE and US9 that transported no detectable capsids and glycoproteins to distal axons and failed to spread from axon tips to adjacent cells. Live-cell imaging of a gE
−
/US9
−
double mutant that expressed fluorescent capsids and gB demonstrated >90% diminished capsids and gB in medial axons and no evidence for decreased rates of transport, stalling, or increased retrograde transport. Instead, capsids, gB, and enveloped virions failed to enter proximal axons. We concluded that gE/gI and US9 function in neuron cell bodies, in a cooperative fashion, to promote the loading of HSV capsids and vesicles containing glycoproteins and enveloped virions onto microtubule motors or their transport into proximal axons.
The Adeno-Associated Virus Type 5 Small Rep Proteins Expressed via Internal Translation Initiation Are Functional
Authors: Fasina Olufemi , Pintel David J.
Published: October 2012

Although precluded from using splicing to produce multiple small Rep proteins, adeno-associated virus type 5 (AAV5) generates a Rep40-like protein by alternative translation initiation at an internal AUG. A defined region upstream of the internal AUG was both required and sufficient to program internal initiation within AAV5 and may act similarly in heterologous contexts. The internally initiated AAV5 Rep40-like protein was functional and had helicase activity similar to that of AAV2 Rep40. Surprisingly, both the AAV5 Rep40-like protein and Rep52 were able to be translated from the AAV5 upstream P7-generated RNAs; however, the relative level of small to large Rep proteins was reduced compared to that of the wild type. A P19 mutant AAV5 infectious clone generated near-wild-type levels of the double-stranded monomer replicative form (mRF) replicative intermediate but reduced levels of virus, consistent with the previously defined role of Rep40-like proteins in genome encapsidation. Levels of mutant virus were dramatically reduced upon amplification.
Diagnostic accuracy of scapular physical examination tests for shoulder disorders: a systematic review
Authors: Wright Alexis A , Wassinger Craig A , Frank Mason , Michener Lori A , Hegedus Eric J
Published: October 2012

Objective

To systematically review and critique the evidence regarding the diagnostic accuracy of physical examination tests for the scapula in patients with shoulder disorders.

Methods

A systematic, computerised literature search of PubMED, EMBASE, CINAHL and the Cochrane Library databases (from database inception through January 2012) using keywords related to diagnostic accuracy of physical examination tests of the scapula. The Quality Assessment of Diagnostic Accuracy Studies tool was used to critique the quality of each paper.

Results

Eight articles met the inclusion criteria; three were considered to be of high quality. Of the three high-quality studies, two were in reference to a ‘diagnosis’ of shoulder pain. Only one high-quality article referenced specific shoulder pathology of acromioclavicular dislocation with reported sensitivity of 71% and 41% for the scapular dyskinesis and SICK scapula test, respectively.

Conclusions

Overall, no physical examination test of the scapula was found to be useful in differentially diagnosing pathologies of the shoulder.
COMPUTER SIMULATION FOR THE CROSSING TIME IN A DIPLOID, ASYMMETRIC, SHARPLY-PEAKED LANDSCAPE IN THE INFINITE POPULATION LIMIT
Authors: GILL WONPYONG
Published: October 2012

This study calculated the crossing time in the diploid mutation–selection model in an infinite population limit for various dominance parameters, h, and selective advantages, by switching on a diploid, asymmetric, sharply-peaked landscape, from an initial state which is the steady state in a diploid, sharply-peaked landscape. The crossing time for h < 1 was found to diverge at the critical fitness parameter, which increased with increasing selective advantage and decreased with increasing sequence length. When the sequence length was increased with a fixed extension parameter, there was no crossing time for h < 1 when the sequence length was longer than the critical sequence length, which increased with increasing selective advantage. The crossing time for h ≤ 1 was found to be an exponentially increasing function of the sequence length, and the crossing time for h > 1 became saturated at a long sequence length. The crossing time decreased with increasing selective advantage, mainly because the larger selective advantage caused the increase in relative density of the reversal allele to grow exponentially at an earlier time.
DYNAMICS DETERMINES GEOMETRY
Authors: HOJMAN SERGIO A. , GAMBOA J. , MÉNDEZ F.
Published: October 2012

The inverse problem of calculus of variations and s-equivalence are re-examined by using results obtained from non-commutative geometry ideas. The role played by the structure of the modified Poisson brackets is discussed in a general context and it is argued that classical s-equivalent systems may be non-equivalent at the quantum mechanical level. This last fact is explicitly discussed comparing different approaches to deal with the Nair–Polychronakos oscillator.
EMERGENT UNIVERSE WITH EXOTIC MATTER IN LOOP QUANTUM COSMOLOGY, DGP BRANE-WORLD AND KALUZA–KLEIN COSMOLOGY
Authors: RUDRA PRABIR
Published: October 2012

In this work we have investigated the emergent scenario of the Universe described by loop quantum cosmology model, DGP brane model and Kaluza–Klein cosmology. Scalar field along with barotropic fluid as normal matter is considered as the matter content of the Universe. In loop quantum cosmology it is found that the emergent scenario is realized with the imposition of some conditions on the value of the density of normal matter in case of normal and phantom scalar field. This is a surprising result indeed considering the fact that scalar field is the dominating matter component! In case of tachyonic field, emergent scenario is realized with some constraints on the value of ρ1 for both normal and phantom tachyon. In case of DGP brane-world realization of an emergent scenario is possible almost unconditionally for normal and phantom fields. Plots and table have been generated to testify this fact. In case of tachyonic field emergent scenario is realized with some constraints on [Formula: see text]. In Kaluza–Klein cosmology emergent scenario is possible only for a closed Universe in case of normal and phantom scalar field. For a tachyonic field, realization of emergent Universe is possible for all models (closed, open and flat).
QUANTUM MECHANICS OF A CHARGED PARTICLE IN A BACKGROUND MAGNETIC FIELD INTERACTING WITH LINEARIZED GRAVITATIONAL WAVES
Authors: GANGOPADHYAY SUNANDAN , SAHA ANIRBAN
Published: October 2012

We present the quantum dynamics of a charged particle interacting simultaneously with background electromagnetic field and linearized gravitational waves in the long wave-length and low-velocity limit. We start from the geodesic deviation equation, considering its close association with the proper detector frame, rather than the usual geodesic equation which is solved classically in the existing literature. The Hamiltonian is obtained, quantized and solved by using algebraic iterative methods. The solution shows conformity with the classical analysis by exhibiting the same resonance condition.
COSMOLOGICAL ANALYTIC SOLUTIONS WITH REDUCED RELATIVISTIC GAS
Authors: MEDEIROS L. G.
Published: October 2012

In this paper one examines analytical solutions for flat and non-flat universes composed by four components namely hot matter (ultra-relativistic), warm matter (WM) (relativistic), cold matter (CM) (non-relativistic) and cosmological constant. The WM is treated as a reduced relativistic gas (RRG) and the other three components are treated in the usual way. The solutions achieved contains one, two or three components of which one component is of WM type. A solution involving all the four components was not found.
RISK ASSESSMENT AND ADAPTIVE GROUP TESTING OF SEMANTIC WEB SERVICES
Authors: BAI XIAOYING , KENETT RON S. , YU WEI
Published: October 2012

Testing is necessary to ensure the quality of web services that are loosely coupled, dynamic bound and integrated through standard protocols. Exhaustive testing of web services is usually impossible due to unavailable source code, diversified user requirements and large number of possible service combinations delivered by the open platform. This paper proposes a risk-based approach for selecting and prioritizing test cases for testing service-based systems. We specially address the problem in the context of semantic web services. Semantic web services introduce semantics to service integration and interoperation using ontology models and specifications. Semantic errors are considered more difficult to detect than syntactic errors. Due to the complexity of conceptual uniformity, it is hard to ensure the completeness, consistency and unified quality of ontology model. A failure of the semantic service-based software may result from many factors such as misused data, unsuccessful service binding, and unexpected usage scenarios. This work analyzes the two factors of risk estimation: failure probability and importance, from three aspects: ontology data, service and composite service. With this approach, test cases are associated to semantic features, and are scheduled based on the risks of their target features. Risk assessment is used to control the process of Web Services progressive group testing, including test case ranking, test case selection and service ruling out. This paper discusses the control architecture and adaptive measurement mechanism for adaptive group testing. As a statistical testing technique, the proposed approach aims to detect, as early as possible, the problems with highest impact on the users.
INTEGRATED FRAMEWORK FOR SEAMLESS MODELING OF BUSINESS AND TECHNICAL ASPECTS IN PROCESS-ORIENTED ENTERPRISE APPLICATIONS
Authors: DRAHEIM DIRK , GEIST VERENA , NATSCHLÄGER CHRISTINE
Published: October 2012

The different views and modeling techniques of both the business analysts and software developers are a common problem in business process modeling. Various modeling approaches result in communication problems, as well as redundancies and inconsistencies in system documentation. Thus, when modeling process-oriented enterprise applications seamless support of both expert groups is necessary. However, current business process management and workflow technologies are not fully integrated with user interaction, nor do they offer an appropriate data model. Based on the requirements of two industrial projects, we developed an integrated framework that combines the best practices from process-oriented and form-based approaches to overcome these shortcomings. The described framework supports the submit/response-style interaction paradigm and is independent of modeling languages and tools. In this work, we will present a detailed description of the proposed framework, its application to an industrial project and a discussion of related work.
HOW TO DETECT AN ANTI-SPACETIME
Authors: CHRISTODOULOU MARIOS , RIELLO ALDO , ROVELLI CARLO
Published: October 2012

Is it possible, in principle, to measure the sign of the Lapse? We show that fermion dynamics distinguishes spacetimes having the same metric but different tetrads, for instance a Lapse with opposite sign. This sign might be a physical quantity not captured by the metric. We discuss its possible role in quantum gravity.
SUPERLUMINAL GROUP VELOCITY OF NEUTRINOS: REVIEW, DEVELOPMENT AND PROBLEMS
Authors: FUJII KAZUYUKI
Published: October 2012

The purpose of this paper is both to provide mathematical reinforcements to the paper [Mecozzi and Bellini, Superluminal group velocity of neutrinos, arXiv: 1110.1253 [hep-ph]] by taking decoherence into consideration and to present some important related problems.

We claim that neutrinos have superluminality as a latent possibility.
THE LONG WAVELENGTH ARRAY SOFTWARE LIBRARY
Authors: DOWELL JAYCE , WOOD DANIEL , STOVALL KEVIN , RAY PAUL S. , CLARKE TRACY , TAYLOR GREGORY
Published: October 2012

The Long Wavelength Array Software Library (LSL) is a Python module that provides a collection of utilities to analyze and export data collected at the first station of the Long Wavelength Array, LWA1. Due to the nature of the data format and large-N (≳100 inputs) challenges faced by the LWA, currently available software packages are not suited to process the data. Using tools provided by LSL, observers can read in the raw LWA1 data, synthesize a filter bank, and apply incoherent de-dispersion to the data. The extensible nature of LSL also makes it an ideal tool for building data analysis pipelines and applying the methods to other low frequency arrays.