bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposal of Criteria Characterizing Assembly Operations of Flexible Beam Parts for Virtual Reality Applications
Authors: Mikchevitch A. , Le´on J.-C. , Gouskov A.
Published: April 2009

Fast simulation of Assembly/Disassembly (A/D) operations is important to improve quickly the performance and quality of products. However, it is difficult to model accurately the A/D operations of products containing flexible parts given their complex mechanical behavior. To evaluate the A/D of flexible parts in order to provide better responses in terms of design, maintenance, ergonomics, a user needs criteria characterizing A/D operations. The aim of this work is to propose some of these criteria based on geometric and physical parameters. The realistic values of these parameters are coupled to an adequate behavior model of flexible parts and can be used in virtual A/D simulations. So, as an issue of current A/D approach problems, the requirements for integration of the Interactive Mechanical Model (IMM) into a virtual A/D system are discussed. An example of flexible beam IMM providing the realistic data is presented. The use of non-linear IMMs raises questions regarding the boundary conditions required to model a user’s action during a virtual A/D operation simulation. To this end, physical and numerical experiments have been performed using an optical tracking system. From these experiments, the necessary parameters can be extracted to characterize both real and virtual A/D operations.
Proactive Cost Impact Assessments of Design Alternatives
Authors: Falque Joseph P.
Published: April 2009

This paper discusses how a process-based parametric cost model, SEER-DFM, is used to facilitate the proactive real time cost impact assessment of composite and metallic design alternatives. The main purpose is to introduce the underlying methodology and demonstrate the flexibility of the cost model for developing trade studies. Readers are introduced to the model, its premise, and how engineers use it to obtain substantial cost savings through ‘real world’ cases.
Design for End-of-Life: Repair, Recondition, Remanufacture or Recycle?
Authors: King Andrew , Burgess Stuart , Ijomah Winnie , McMahon Chris
Published: April 2009

Between 1980 and 1997, municipal waste in OECD (Organisation for Economic Co-operation and Development) countries increased by around 40%. The European Union has responded by introducing legislation on extended producer responsibility (EPR). This paper further explains the context of this new legislation and describes, compares and then contrasts the four alternative strategies to reducing end-of-life waste: namely repairing, reconditioning, remanufacturing or recycling. It also introduces a more robust definition of remanufacturing, validated by earlier research, which differentiates it from repair and reconditioning. From a consideration of the different factors involved, it concludes that remanufacturing may often be a strong strategy. This is based on the fact that it preserves both the embodied energy of virgin production (thus reducing the environmental impact) and the intrinsic “value adding” process of the producer (thus increasing the manufacturer’s profitability). As a result, this new environmental policy is likely to lead to significant increases in remanufacturing as an end-of-life strategy in the European Union. However, effective end-of life strategies are dictated by product characteristics and therefore vary from product to product (Rose et al, 1998). Thus further research is required to compare and contrast the effectiveness of remanufacturing and alternative end-of-life strategy for particular product types.
Identifying Similar Parts for Assisting Cost Estimation of Prismatic Machined Parts
Authors: Cardone Antonio , Gupta Satyandra K. , Karnik Mukul
Published: April 2009

This paper presents a method for identifying those parts in a database that are similar to a given query part to be machined and hence can be potentially used as a basis for estimating the machining cost of the query part. We utilize projected feature vectors consisting of feature access directions, feature types, and feature volumes as a basis for assessing shape similarity. We have defined a distance function between two sets of projected feature vectors to assess the similarity between them from the cost estimation point of view. To assess similarity between the two parts, one set of projected feature vectors is transformed in space using rigid body transformations with respect to the other set such that the distance between them is minimized. The distance between the projected feature vectors is used as a measure of similarity between the two parts. The existing parts are rank ordered based on the value of the distance with respect to the new part. The cost of machining the new part can then be estimated by using the cost of previously machined parts that have a very small distance from the new part.
Surface Blemishes in 3D Offset Machining
Authors: Loftus Martin , Wang Da-Zhi
Published: April 2009

High-speed machining (HSM) provides a new dimension to machining parts in hard steel because it eliminates intermediate processes and minimizes hand-finishing operations. Lead times and overall manufacturing costs are reduced, but the potential benefits can only be realized when the high-speed processes are implemented correctly. Successful high-speed applications depend on the linkage between contributing factors (machine tool, control system, tooling system, CAM system, CAM operator and machine operator) working effectively. A weakness in one of these areas can jeopardize the geometric form and surface quality in a high-speed operation. Such weaknesses can raise the paradox that as the quality of a machined part is improved through HSM, there is an increasing awareness of smaller defects. This is an acute problem in the final stages of the manufacture of dies, molds, and prototype components, where finished parts are rejected on their overall appearance, even though they satisfy all the standard design quality criteria. Very small, localized surface marks produced during machining operations are perceived as serious blemishes to the eye. One of the most obvious, and frequent surface blemishes are the marks associated with the popular 3D offset machining strategy. These marks are produced every time the 3D offset strategy is used and the parts have to be finished in a manual benching operation. This manual process is indeterminate in terms of time and cost. There is also a great risk that the geometric shapes and tolerances are compromised by the uncontrolled manual operations. This paper reports the results of a series of machining trials to assess the effect of the 3D offset strategy on machined parts, and it considers two modified offset strategies that were designed to alleviate the marking process.
A Generic Framework for Automated Cost Evaluation of Product Variants and Fabrication Plants
Authors: Elgh Fredrik
Published: April 2009

Cost is one of the most important criteria for evaluation of product variants. In this paper a framework for building systems for cost evaluation of product variants and fabrication plants is presented and discussed. These systems have the purpose of governing the design work towards solutions with an optimal balance between product and production properties. The starting point of the proposed procedure is the cost structure of a manufactured product: identification of information needed for evaluation of different product variants, fabrication plants, or both; where the necessary information can be derived from; and how information accessibility and extraction can be supported. The creation of information models for product cost, plant resources, process plans and product geometry is introduced and the relationships between models are examined, supporting system development. Important guidelines for the creation of a parametric solid model that will serve as the foundation for an automated cost evaluation system are presented.
Estimation of Product Response: The Empirical Similitude Method and Technique of Conformal Mapping
Authors: Tadepalli Srikanth , Wood Kristin L. , Crawford Richard H. , Doud Brian L.
Published: April 2009

Functional testing of representative prototypes is an important phase in the evolution of most products. Layer Fabrication methods, importantly the Selective Laser Sintering (SLS) process allow for quick fabrication of test prototypes such that the experimental data derived from them can be used to predict the response of a hypothetical product for a desired variable of interest. Traditional Similitude Method (TSM) or Buckingham π theorem has been used conventionally for dimensional analysis to correlate the similarity between different structures. Some of its inherent limitations have prompted researchers to include the effects of non-linear material variations and geometric distortions during the scaling process. Thus, the development of the Empirical Similitude Method (ESM) is largely based on the hypothesis that these non-linear variations and distortions can be captured mathematically by using intermediate test specimens. In an effort to improve ESM, conformal mapping has been hypothesized to be an important technique for scaling and analysis. This paper explores the technique of Conformal Mapping as a potential equivalence procedure based on the principle of ESM. The methodology is elucidated along with a heat transfer example.
Design of Deposition Head Trajectory for Robotized Filament Winding of Complex Shape Parts
Authors: Polini W. , Sorrentino L.
Published: April 2009

When the roving is winding on the die, the tension value may move away the nominal one that has been optimized by considering the quality and the mechanical properties of the wound composite parts. The variance of the tension value during winding from the nominal one strongly depends on the deposition head trajectory. The present work focuses on the planning of the winding trajectory for winding complex shape parts in composite material by a robotized cell. The planning of the winding trajectory should be based on the structural constraints of the robotized cell and on the technological requirements of the process. In particular, this work aims to study the conditions by which the value of the roving tension verges on the nominal one during winding. The developed planning logics and implemented by a CAD/CAM software have been validated by experimental tests. This work represents the first step towards the optimization of the winding trajectory.
A Modular Design Approach to Support Sustainable Design
Authors: Bryant Cari R. , Sivaramakrishnan Karthik L. , Van Wie Michael , Stone Robert B. , McAdams Daniel A.
Published: April 2009

This paper presents a redesign method supporting sustainable design of products. The method correlates product modularity with various life cycle directions at the conceptual stage of design. In the case of product redesign, the modular design approach allows designers to focus on increasing the sustainability of a product in terms of recyclability, disassembly and reduction of resource usage at the conceptual stage. By stepping back to the conceptual design phase and analyzing the product free from its current embodiment solutions, the scope of redesign and the potential product improvement increases. At this stage of design, the comprehension of the relationship between the various life cycle aspects of the product and the product design is essential. The elimination preference index (EPI) metric, calculated by pair-wise comparison of various factors governing the product design, quantifies the effect of redesign alternatives on product sustainability. The method is applied to the redesign of twelve small-scale consumer products, of which one example is presented here. In all cases, the redesigned products exhibited enhancement in modularity and part count reduction.
Haptic-Based Function Analysis and Shape Modeling of Multi-Material Product: A Case Study
Authors: Yang Z. Y. , Chen Y. H.
Published: April 2009

In this paper, an intuitive interface of synthesized industrial design and engineering analysis of multi-material product is proposed. In a product design cycle, designers not only need to determine the geometry of a design, but also need to verify the design functions. Besides the concerns of function and geometry, other requirements like ergonomics, aesthetics, and types of visible surfaces also need to be considered. All these concerns are considered in this research through an investigation into multi-material product design. Multi-material product manufacturing processes allow designers to select different materials for different portions of objects in order to improve material-function compatibility for the overall object. Based on a haptic shape modeling system, a permutation method for multi-material product design is developed. A volumetric FEM-based function evaluation method is adopted for multi-material product analysis with the assumption of small displacements. The design and analysis are conducted on the same platform which is enhanced with a haptic device that can provide an intuitive correlation between the applied force and incurred displacement. The methodology is presented through a case study: the design of a toothbrush.
A “Mathematics Background Check”
Authors: Hubisz John
Published: April 2009

Early in my career someone else reported that the best indicator of success in calculus-based physics (CBP) at our school was whether students had taken mathematics in a certain region of New Brunswick. I sat down with a very longtime mathematics teacher and asked him what he thought students should know in mathematics after high school to succeed in college. He quickly gave me five areas that every student should know and pointedly indicated that it was best to give them the questions and watch how they attacked the problems. A solution was not even important; all one had to note was the immediate steps that the student took.
Approximation for the Rayleigh Resolution of a Circular Aperture
Authors: Mungan Carl E.
Published: April 2009

Rayleigh's criterion states that a pair of point sources are barely resolved by an optical instrument when the central maximum of the diffraction pattern due to one source coincides with the first minimum of the pattern of the other source. As derived in standard introductory physics textbooks,1 the first minimum for a rectangular slit of width a is located at angular position θ = sin−1 (λ/a) for light of wavelength λ. If the angular separation of the two sources is small, we can use the small-angle approximation sin θ ≈ θ to conclude that the resolution is θmin = λ/a for a rectangular aperture. On the other hand, for a circular aperture of diameter D, the limiting angle is shown in optics texts2 to be θmin = 1.22 λ/D. The derivation of the numerical prefactor of 1.22 involves finding the zero of a Bessel function and is beyond the reach of introductory physics students. Consequently, elementary texts simply pull that prefactor out of thin air. The purpose of the present paper is to briefly explain why we expect a prefactor larger than unity and to make simple estimates of its value, using only algebra.
Rubber Band Bohr Wave Functions
Authors: Graf Erlend H.
Published: April 2009

A simple apparatus for demonstrating circular standing-wave modes can be made inexpensively using rubber bands and other easily obtained materials.
Trapping Moving Targets with Small Molecules
Authors: Lee Gregory M. , Craik Charles S.
Published: April 2009

Structure-based drug design traditionally uses static protein models as inspirations for focusing on “active” site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.
Curved Plasma Channel Generation Using Ultraintense Airy Beams
Authors: Polynkin Pavel , Kolesik Miroslav , Moloney Jerome V. , Siviloglou Georgios A. , Christodoulides Demetrios N.
Published: April 2009

Plasma channel generation (or filamentation) using ultraintense laser pulses in dielectric media has a wide spectrum of applications, ranging from remote sensing to terahertz generation to lightning control. So far, laser filamentation has been triggered with the use of ultrafast pulses with axially symmetric spatial beam profiles, thereby generating straight filaments. We report the experimental observation of curved plasma channels generated in air using femtosecond Airy beams. In this unusual propagation regime, the tightly confined main intensity feature of the axially nonsymmetric laser beam propagates along a bent trajectory, leaving a curved plasma channel behind. Secondary channels bifurcate from the primary bent channel at several locations along the beam path. The broadband radiation emanating from different longitudinal sections of the curved filament propagates along angularly resolved trajectories.
Running Droplets of Gallium from Evaporation of Gallium Arsenide
Authors: Tersoff J. , Jesson D. E. , Tang W. X.
Published: April 2009

High-temperature annealing of gallium arsenide in vacuum causes excess evaporation of arsenic, with accumulation of gallium as liquid droplets on the surface. Using real-time in situ surface electron microscopy, we found that these droplets spontaneously run across the crystal surface. Running droplets have been seen in many systems, but they typically require special surface preparation or gradient forces. In contrast, we show that noncongruent evaporation automatically provides a driving force for running droplets. The motion is predicted and observed to slow and stop near a characteristic temperature, with the speed increasing both below and above this temperature. The same behavior is expected to occur during the evaporation of similar III-V semiconductors such as indium arsenide.
Social Selection
Authors: Franks Nigel R.
Published: April 2009

The Lives of Ants
.
By Laurent Keller and Élisabeth Gordon
. Oxford University Press, Oxford, 2009. 272 pp. $27.95, £14.99. ISBN 9780199541867.

This accessible introduction to the ecology, behavior, and evolution of ants also considers ways that findings from studies of ants apply to such topics as computer programming and swarm intelligence.
Development and Evaluation of an Enzyme-Linked Immunosorbent Assay To DetectHistoplasma capsulatumAntigenuria in Immunocompromised Patients
Authors: Scheel Christina M. , Samayoa Blanca , Herrera Alejandro , Lindsley Mark D. , Benjamin Lynette , Reed Yvonne , Hart John , Lima Sandra , Rivera Blanca E. , Raxcaco Gabriella , Chiller Tom , Arathoon Eduardo , Gómez Beatriz L.
Published: April 2009

Histoplasma capsulatuminfection causes significant morbidity and mortality in human immunodeficiency virus-infected individuals, particularly those in countries with limited access to rapid diagnostics or antiretroviral therapies. The fungus easily disseminates in persons with AIDS, resulting in progressive disseminated histoplasmosis (PDH), which can progress rapidly to death if undiagnosed. The availability of a simple, rapid method to detectH. capsulatuminfection in less developed countries where the infection is endemic would dramatically decrease the time to diagnosis and treatment of PDH. We have developed an antigen-capture enzyme-linked immunosorbent assay (ELISA) to detect PDH antigenuria in infected patients. The assay uses polyclonal antibodies againstH. capsulatumas both capture and detection reagents, and a standard reference curve is included to quantify antigenuria and ensure reproducibility. We evaluated this assay using specimens collected from patients with AIDS and culture-proven histoplasmosis in a Guatemalan clinic (n= 48), from healthy persons (n= 83), and from patients with other, nonhistoplasmosis diseases (n= 114). The ELISA demonstrated a sensitivity of 81% and a specificity of 95% in detectingH. capsulatumantigen in urine. This assay relies on simple technology that can be performed in institutions with limited resources. Use of this test will facilitate rapid diagnosis of PDH in countries where mortality is high, expediting treatment and likely reducing PDH-related mortality.
Effect of Porcine Circovirus Type 2 (PCV2) Vaccination of the Dam on PCV2 Replication In Utero
Authors: Madson D. M. , Patterson A. R. , Ramamoorthy S. , Pal N. , Meng X. J. , Opriessnig T.
Published: April 2009

The aims of this study were to determine if porcine circovirus type 2 (PCV2) vaccination of the dam is effective in preventing fetal PCV2 infection and reproductive failure. Twelve pregnant, PCV2-naïve sows were randomly divided into four groups, with three sows in each group. Group 1 sows served as noninoculated, nonvaccinated negative controls, group 2 sows were vaccinated with a commercially available PCV2 vaccine at 28 days of gestation and were not inoculated, group 3 sows were vaccinated at 28 days of gestation and inoculated with PCV2b at 56 days of gestation, and group 4 sows were inoculated with PCV2b but were not vaccinated. Serum samples from all sows were collected weekly throughout the gestation period, and sows were allowed to farrow naturally. At parturition, sow colostrum samples, presuckle serum samples, and tissues from the piglets were collected. Reproductive failure was not observed under the study conditions. PCV2 vaccination induced PCV2-specific immunoglobulin G and serum neutralizing antibodies in sows from groups 2 and 3 and prevented detectable PCV2 viremia in the dams after challenge. In group 3, PCV2 DNA was detected in colostrum samples, fetuses, and live-born pigs; however, microscopic lesions and PCV2-specific antigen were not present in any of the fetuses in this group. The results from this study indicate that vertical transmission of PCV2 can occur in PCV2-vaccinated dams.
Evaluation of Low-Colony-Number Counts of
Mycobacterium tuberculosis
on Solid Media as a Microbiological Marker of Cross-Contamination
Authors: Ribeiro F. K. C. , Lemos E. M. , Hadad D. J. , Leão S. C. , Viana-Niero C. , Dietze R. , Johnson J. L. , Eisenach K. D. , Palaci M.
Published: April 2009

Low-colony-number counts on solid media are considered characteristic of cross-contamination, although they are normally observed in true-positive cultures from some groups of patients. The aim of this study was to evaluate low-yield growth cultures as a microbiological marker for cross-contamination. We evaluated 106 cultures with <15 colonies from 94 patients, and the proportions of false-positive cultures were 0.9% per sample and 1.1% per patient, which indicates that low-yield growth is not a reliable marker of cross-contamination.
Probing Population Dynamics of
Trypanosoma cruzi
during Progression of the Chronic Phase in Chagasic Patients
Authors: D'Ávila Daniella Alchaar , Macedo Andréa Mara , Valadares Helder Magno Silva , Gontijo Eliane Dias , de Castro Ana Maria , Machado Carlos Renato , Chiari Egler , Galvão Lúcia Maria Cunha
Published: April 2009

Our research aimed to characterize the genetic profiles of 102
Trypanosoma cruzi
isolates recently obtained from 44 chronic chagasic patients from different regions of the states of Minas Gerais and Goiás in Brazil. At least two isolates were obtained from each patient at different times in order to study the parasite population dynamics during disease progression in the chronic phase. The isolates were characterized molecularly by genotyping the 3′ region of the 24Sα rRNA, the mitochondrial cytochrome oxidase subunit 2 (COII) gene, and the intergenic region of the spliced leader intergenic region (SL-IR) gene. Seventy-seven isolates were analyzed for nine microsatellite loci. The data presented here show a strong correlation between the
T. cruzi
lineage II (
T. cruzi
II) and human infection in these regions of Brazil. Interestingly, isolates from two patients were initially characterized (by rRNA genotyping) as
T. cruzi
I and hybrid strains, but subsequent analyses of the COII and SL-IR genes confirmed that those isolates belonged to
T. cruzi
III and a hybrid group, respectively. Our results confirm the risk of misclassifying
T. cruzi
isolates on the basis of analysis of a single molecular marker. The microsatellite profiles showed that different isolates obtained from the same patient were genetically identical and monoclonal. Exceptions were observed for
T. cruzi
isolates from two patients who presented differences for the SCLE11 locus and also from two other patients who showed amplification of three peaks for a microsatellite locus (TcAAAT6), implying that they were multiclonal. On the basis of the findings of the studies described here, we were not able to establish a correlation between the clinical forms of Chagas' disease and the genetic profiles of the
T. cruzi
isolates.
Correlation of Cefoxitin MICs with the Presence of
mecA
in
Staphylococcus
spp
Authors: Swenson Jana M. , Brasso William B. , Ferraro Mary Jane , Hardy Dwight J. , Knapp Cynthia C. , Lonsway David , McAllister Sigrid , Reller L. Barth , Sader Helio S. , Shortridge Dee , Skov Robert , Weinstein Melvin P. , Zimmer Barbara L. , Patel Jean B.
Published: April 2009

This report describes the results of an 11-laboratory study to determine if a cefoxitin broth microdilution MIC test could predict the presence of
mecA
in staphylococci. Using breakpoints of ≤4 μg/ml for
mecA
-negative and ≥6 or 8 μg/ml for
mecA
-positive isolates, sensitivity and specificity based on
mecA
or presumed
mecA
for
Staphylococcus aureus
at 18 h of incubation were 99.7 to 100% in three cation-adjusted Mueller-Hinton broths tested. For coagulase-negative strains at 24 h of incubation, breakpoints of ≤2 μg/ml for
mecA
-negative and ≥4 μg/ml for
mecA
-positive isolates gave sensitivity and specificity of 94 to 99% and 69 to 80%, respectively.
Canine Distemper Virus Selectively Inhibits Apoptosis Progression in Infected Immune Cells
Authors: Pillet Stéphane , von Messling Veronika
Published: April 2009

Morbillivirus infections are characterized by severe leukopenia and immune suppression that develop even before the onset of clinical signs. To characterize in more detail the fate of the immune cells during the critical first week, we evaluated the overall viability, level of apoptosis, cell cycle status, and extent of infection in different immune tissues of ferrets inoculated with a lethal canine distemper virus (CDV) strain. Initial experiments with MDCK cells, a canine epithelial cell line, revealed that CDV infection resulted in only a marginal increase in apoptosis at high infection levels and that infected cells were more resistant to chemically induced apoptosis. In ferrets, levels of viability and early and late apoptosis remained stable in thymus and lymph node, where more than 80% of cells were infected, whereas a gradual albeit small increase in apoptosis was observed in peripheral blood mononuclear cells and spleen. Furthermore, the progression of spontaneous apoptosis in infected cells was inhibited, while the proportion of apoptotic noninfected “bystander” cells increased. The distribution of cells in the different stages of the cell cycle in the bone marrow was not affected, but dividing cells in the thymus decreased by 50%, and a 10-fold increase in cell division was noted in the spleen. It is unlikely that the extent of infection-induced cell death and cell cycle alterations alone can account for the dramatic leukopenia observed in this model. The investigation of additional mechanisms is therefore warranted.
Acquisition of Polyfunctionality by Epstein-Barr Virus-Specific CD8
+
T Cells Correlates with Increased Resistance to Galectin-1-Mediated Suppression
Authors: Smith Corey , Beagley Leone , Khanna Rajiv
Published: April 2009

Latent membrane antigen 1 and -2 (LMP-1/2)-specific CD8
+
T cells from newly diagnosed and relapsed Hodgkin's lymphoma (HL) patients display a selective functional impairment. In contrast, CD8
+
T cells specific for Epstein-Barr virus (EBV) nuclear proteins and lytic antigens retain normal T-cell function. Reversion to a dysfunctional phenotype of LMP-1/2-specific T cells is coincident with the regression of HL. To delineate the potential basis for this differential susceptibility for the loss of function, we have carried out a comprehensive functional analysis of EBV-specific T cells using ex vivo multiparametric flow cytometry in combination with assessment of antigen-driven proliferative potential. This analysis revealed that LMP-1/2-specific T cells from healthy virus carriers display a deficient polyfunctional profile compared to that of T cells specific for epitopes derived from EBV nuclear proteins and lytic antigens. Furthermore, LMP-specific T-cells are highly susceptible to galectin-1-mediated immunosuppression and are less likely to degranulate following exposure to cognate peptide epitopes and poorly recognized endogenously processed epitopes from virus-infected B cells. More importantly, ex vivo stimulation of these T cells with an adenoviral vector encoding multiple minimal CD8
+
T-cell epitopes as a polyepitope, in combination with a γC cytokine, interleukin-2, restored polyfunctionality and shielded these cells from the inhibitory effects of galectin-1.
Polarization Restricts Hepatitis C Virus Entry into HepG2 Hepatoma Cells
Authors: Mee Christopher J. , Harris Helen J. , Farquhar Michelle J. , Wilson Garrick , Reynolds Gary , Davis Christopher , van IJzendoorn Sven C. D. , Balfe Peter , McKeating Jane A.
Published: April 2009

The primary reservoir for hepatitis C virus (HCV) replication is believed to be hepatocytes, which are highly polarized with tight junctions (TJ) separating their basolateral and apical domains. HepG2 cells develop polarity over time, resulting in the formation and remodeling of bile canalicular (BC) structures. HepG2 cells expressing CD81 provide a model system to study the effects of hepatic polarity on HCV infection. We found an inverse association between HepG2-CD81 polarization and HCV pseudoparticle entry. As HepG2 cells polarize, discrete pools of claudin-1 (CLDN1) at the TJ and basal/lateral membranes develop, consistent with the pattern of receptor staining observed in liver tissue. The TJ and nonjunctional pools of CLDN1 show an altered association with CD81 and localization in response to the PKA antagonist Rp-8-Br-cyclic AMPs (cAMPs). Rp-8-Br-cAMPs reduced CLDN1 expression at the basal membrane and inhibited HCV infection, supporting a model where the nonjunctional pools of CLDN1 have a role in HCV entry. Treatment of HepG2 cells with proinflammatory cytokines, tumor necrosis factor alpha and gamma interferon, perturbed TJ integrity but had minimal effect(s) on cellular polarity and HCV infection, suggesting that TJ integrity does not limit HCV entry into polarized HepG2 cells. In contrast, activation of PKC with phorbol ester reduced TJ integrity, ablated HepG2 polarity, and stimulated HCV entry. Overall, these data show that complex hepatocyte-like polarity alters CLDN1 localization and limits HCV entry, suggesting that agents which disrupt hepatocyte polarity may promote HCV infection and transmission within the liver.
Characterization of Imjin Virus, a Newly Isolated Hantavirus from the Ussuri White-Toothed Shrew (
Crocidura lasiura
)
Authors: Song Jin-Won , Kang Hae Ji , Gu Se Hun , Moon Sung Sil , Bennett Shannon N. , Song Ki-Joon , Baek Luck Ju , Kim Heung-Chul , O'Guinn Monica L. , Chong Sung-Tae , Klein Terry A. , Yanagihara Richard
Published: April 2009

Until recently, the single known exception to the rodent-hantavirus association was Thottapalayam virus (TPMV), a long-unclassified virus isolated from the Asian house shrew (
Suncus murinus
). Robust gene amplification techniques have now uncovered several genetically distinct hantaviruses from shrews in widely separated geographic regions. Here, we report the characterization of a newly identified hantavirus, designated Imjin virus (MJNV), isolated from the lung tissues of Ussuri white-toothed shrews of the species
Crocidura lasiura
(order Soricomorpha, family Soricidae, subfamily Crocidurinae) captured near the demilitarized zone in the Republic of Korea during 2004 and 2005. Seasonal trapping revealed the highest prevalence of MJNV infection during the autumn, with evidence of infected shrews' clustering in distinct foci. Also, marked male predominance among anti-MJNV immunoglobulin G antibody-positive Ussuri shrews was found, whereas the male-to-female ratio among seronegative Ussuri shrews was near 1. Plaque reduction neutralization tests showed no cross neutralization for MJNV and rodent-borne hantaviruses but one-way cross neutralization for MJNV and TPMV. The nucleotide and deduced amino acid sequences for the different MJNV genomic segments revealed nearly the same calculated distances from hantaviruses harbored by rodents in the subfamilies Murinae, Arvicolinae, Neotominae, and Sigmodontinae. Phylogenetic analyses of full-length S, M, and L segment sequences demonstrated that MJNV shared a common ancestry with TPMV and remained in a distinct out-group, suggesting early evolutionary divergence. Studies are in progress to determine if MJNV is pathogenic for humans.
The Orthopoxvirus 68-Kilodalton Ankyrin-Like Protein Is Essential for DNA Replication and Complete Gene Expression of Modified Vaccinia Virus Ankara in Nonpermissive Human and Murine Cells
Authors: Sperling Karin M. , Schwantes Astrid , Staib Caroline , Schnierle Barbara S. , Sutter Gerd
Published: April 2009

Modified vaccinia virus Ankara (MVA) is a highly attenuated and replication-deficient vaccinia virus (VACV) that is being evaluated as replacement smallpox vaccine and candidate viral vector. MVA lacks many genes associated with virulence and/or regulation of virus tropism. The 68-kDa ankyrin-like protein (68k-ank) is the only ankyrin repeat-containing protein that is encoded by the MVA genome and is highly conserved throughout the
Orthopoxvirus
genus. We showed previously that 68k-ank is composed of ankyrin repeats and an F-box-like domain and forms an SCF ubiquitin ligase complex together with the cellular proteins Skp1a and Cullin-1. We now report that 68k-ank (MVA open reading frame 186R) is an essential factor for completion of the MVA intracellular life cycle in nonpermissive human and murine cells. Infection of mouse NIH 3T3 and human HaCaT cells with MVA with a deletion of the 68k-ank gene (MVA-Δ68k-ank) was characterized by an extensive reduction of viral intermediate RNA and protein, as well as late transcripts and drastically impaired late protein synthesis. Furthermore, infections with MVA-Δ68k-ank failed to induce the host protein shutoff that is characteristic of VACV infections. Although we demonstrated that proteasome function in general is essential for the completion of the MVA molecular life cycle, we found that a mutant 68k-ank protein with a deletion of the F-box-like domain was able to fully complement the deficiency of MVA-Δ68k-ank to express all classes of viral genes. Thus, our data demonstrate that the 68k-ank protein contains another critical domain that may function independently of SCF ubiquitin ligase complex formation, suggesting multiple activities of this interesting regulatory protein.
Interferon-Induced ISG15 Conjugation Inhibits Influenza A Virus Gene Expression and Replication in Human Cells
Authors: Hsiang Tien-Ying , Zhao Chen , Krug Robert M.
Published: April 2009

The ubiquitin-like ISG15 protein, as well as its conjugating enzymes, is induced by type I interferons (IFNs). Experiments using ISG15 knockout (ISG15
−/−
) mice established that ISG15 and/or its conjugation inhibits the replication of influenza A virus. However, in contrast to the virus inhibition results for mice, the rates of virus replication in ISG15
+/+
and ISG15
−/−
mouse embryo fibroblasts in tissue culture were similar. Here we focus on human tissue culture cells and on the effect of ISG15 and/or its conjugation on influenza A virus gene expression and replication in such cells. We demonstrate that IFN-induced antiviral activity against influenza A virus in human cells is significantly alleviated by inhibiting ISG15 conjugation using small interfering RNAs directed against ISG15-conjugating enzymes. IFN-induced antiviral activity against influenza A virus protein synthesis was reduced 5- to 20-fold by suppressing ISG15 conjugation. The amounts of the viral proteins that were restored by these siRNA treatments were approximately 40 to 50% of the amounts produced in cells that were not pretreated with IFN. Further, we show that ISG15 conjugation inhibits influenza A virus replication 10- to 20-fold at early times after infection in human cells. These results show that ISG15 conjugation plays a substantial role in the antiviral state induced by IFN in human cells. In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression.
Regulation of
vif
mRNA Splicing by Human Immunodeficiency Virus Type 1 Requires 5′ Splice Site D2 and an Exonic Splicing Enhancer To Counteract Cellular Restriction Factor APOBEC3G
Authors: Mandal Dibyakanti , Exline Colin M. , Feng Zehua , Stoltzfus C. Martin
Published: April 2009

The human immunodeficiency virus type 1 (HIV-1) accessory protein Vif is encoded by an incompletely spliced mRNA resulting from splicing of the major splice donor in the HIV-1 genome, 5′ splice site (5′ss) D1, to the first splice acceptor, 3′ss A1. We have shown previously that splicing of HIV-1
vif
mRNA is tightly regulated by suboptimal 5′ss D2, which is 50 nucleotides downstream of 3′ss A1; a GGGG silencer motif proximal to 5′ss D2; and an SRp75-dependent exonic splicing enhancer (ESEVif). In agreement with the exon definition hypothesis, mutations within 5′ss D2 that are predicted to increase or decrease U1 snRNP binding affinity increase or decrease the usage of 3′ss A1 (D2-up and D2-down mutants, respectively). In this report, the importance of 5′ss D2 and ESEVif for avoiding restriction of HIV-1 by APOBEC3G (A3G) was determined by testing the infectivities of a panel of mutant viruses expressing different levels of Vif. The replication of D2-down and ESEVif mutants in permissive CEM-SS cells was not significantly different from that of wild-type HIV-1. Mutants that expressed Vif in 293T cells at levels greater than 10% of that of the wild type replicated similarly to the wild type in H9 cells, and Vif levels as low as 4% were affected only modestly in H9 cells. This is in contrast to Vif-deleted HIV-1, whose replication in H9 cells was completely inhibited. To test whether elevated levels of A3G inhibit replication of D2-down and ESEVif mutants relative to wild-type virus replication, a Tet-off Jurkat T-cell line that expressed approximately 15-fold-higher levels of A3G than control Tet-off cells was generated. Under these conditions, the fitness of all D2-down mutant viruses was reduced relative to that of wild-type HIV-1, and the extent of inhibition was correlated with the level of Vif expression. The replication of an ESEVif mutant was also inhibited only at higher levels of A3G. Thus, wild-type 5′ss D2 and ESEVif are required for production of sufficient Vif to allow efficient HIV-1 replication in cells expressing relatively high levels of A3G.
Particle Assembly and Ultrastructural Features Associated with Replication of the Lytic Archaeal Virus
Sulfolobus
Turreted Icosahedral Virus
Authors: Brumfield Susan K. , Ortmann Alice C. , Ruigrok Vincent , Suci Peter , Douglas Trevor , Young Mark J.
Published: April 2009

Little is known about the replication cycle of archaeal viruses. We have investigated the ultrastructural changes of
Sulfolobus solfataricus
P2 associated with infection by
Sulfolobus t
urreted
i
cosahedral
v
irus (STIV). A time course of a near synchronous STIV infection was analyzed using both scanning and transmission electron microscopy. Assembly of STIV particles, including particles lacking DNA, was observed within cells, and fully assembled STIV particles were visible by 30 h postinfection (hpi). STIV was determined to be a lytic virus, causing cell disruption beginning at 30 hpi. Prior to cell lysis, virus infection resulted in the formation of pyramid-like projections from the cell surface. These projections, which have not been documented in any other host-virus system, appeared to be caused by the protrusion of the cell membrane beyond the bordering S-layer. These structures are thought to be sites at which progeny virus particles are released from infected cells. Based on these observations of lysis, a plaque assay was developed for STIV. From these studies we propose an overall assembly model for STIV.
Treatment Recommendations Should Take Account of Individual Patient Variation Not Just Group Responses
Authors: Lundeberg Thomas , Lund Iréne
Published: April 2009

Recommendations for treatment are commonly based on results evaluating variation in systematic effects (group responses) from randomised controlled trials without taking the individual patient's variation into account. In the evaluation of acupuncture-related treatment effects, the trial design and statistical analysis used are a challenge since the assessed variables commonly have subjective properties and are based on the person's own self-report. Thus, the results that are seen are often varied, most likely due to inter-individual variation in rating of the actual variable such that the treatment effects are expressed more (or less) in some individuals than in others. The basis for the individual variation is probably multi-modal and could be related to the individuals’ expectation, gender, genetic polymorphisms and the aetiology of the condition. The assessment methods used should preferably have proven useful in controlled trials, and the methods for statistical analysis should consider the non-metric properties of the variable and the contribution of the individuals’ variation in the results. In order to evaluate the treatment effects more properly and increase the possibility of detecting any effectiveness, it is therefore important to assess the level of perceived dysfunction or symptom, taking into account the individual variation as well as the systematic effects (the effects of the group). In the evaluation of acupuncture effects, both systematic and individual variation should be reported allowing for the detection of subgroup effects and thereby leading to treatment recommendations that are more likely to be based on each individual's specific needs.
Egg Binding and Hind Limb Paralysis in An African Penguin – a Case Report
Authors: Crouch Monique Anamarie
Published: April 2009

This case report assesses the role acupuncture played in the rehabilitation therapy of an African penguin with bilateral hind limb paresis and paralysis following egg binding and a caesarean section. Egg binding is the failure of the oviduct to pass the egg down into the cloaca. In avian species the sciatic nerve runs through the middle of the kidney. Swelling of the kidney tissue due to the pressure exerted by the retained egg will cause pressure on the sciatic nerve which may lead to hind limb paresis/paralysis.

Acupuncture was used to relieve any muscle, joint or nerve pain and to attempt to stimulate recovery of the sciatic nerve. Acupuncture was incorporated into a fairly intensive physical rehabilitation programme to help the penguin to walk again so that it could be re-introduced back into the sanctuary's captive colony.
Modellvorhaben Akupunktur – a Summary of the Art, Arc and Gerac Trials
Authors: Cummings Mike
Published: April 2009

In October 2000 the German Federal Committee of Physicians and Health Insurers recommended that special Model Projects on Acupuncture (“ Modellvorhaben Akupunktur”) be developed in order to determine the evidence-based role of acupuncture in the treatment of certain illnesses. This paper presents a summary of the main randomised controlled trials performed as part of these projects, and the associated economic analyses.

Overall the results show that acupuncture is effective in practice for a range of chronic conditions, and it seems likely to have acceptable cost utility (at least at a rate of ¢35 per session). Sham acupuncture, in the form of minimal off-point needling in a therapeutic context, also appears to be effective, being no different to prophylactic medication in migraine, and superior to guideline-based standard care in chronic low back pain.

In patients recruited to acupuncture trials, the response to treatment does not differ between those that agree to be randomised and those that do not. This suggests that the results of the pragmatic Acupuncture in Routine Care studies are applicable to patients from the general population who express a preference for acupuncture.

In conclusion, acupuncture appears to be effective in a range of chronic conditions and it seems to have acceptable cost-effectiveness in Western health economic terms. These programmes of research do not confirm the hypothesis that needling at specific points is essential to achieve satisfactory clinical effects of acupuncture. Sham acupuncture, in the form of minimal off-point needling in a therapeutic context, is unlikely to be an inactive placebo.

In April 2006, the German health authorities decided that acupuncture would be included into routine reimbursement by social health insurance funds for chronic low back pain and chronic osteoarthritis of the knee.
Western Medical Acupuncture: A Definition
Authors: White Adrian
Published: April 2009

Western medical acupuncture is a therapeutic modality involving the insertion of fine needles; it is an adaptation of Chinese acupuncture using current knowledge of anatomy, physiology and pathology, and the principles of evidence based medicine. While Western medical acupuncture has evolved from Chinese acupuncture, its practitioners no longer adhere to concepts such as Yin/ Yang and circulation of qi, and regard acupuncture as part of conventional medicine rather than a complete “alternative medical system”. It acts mainly by stimulating the nervous system, and its known modes of action include local antidromic axon reflexes, segmental and extrasegmental neuromodulation, and other central nervous system effects. Western medical acupuncture is principally used by conventional healthcare practitioners, most commonly in primary care. It is mainly used to treat musculoskeletal pain, including myofascial trigger point pain. It is also effective for postoperative pain and nausea. Practitioners of Western medical acupuncture tend to pay less attention than classical acupuncturists to choosing one point over another, though they generally choose classical points as the best places to stimulate the nervous system. The design and interpretation of clinical studies is constrained by lack of knowledge of the appropriate dosage of acupuncture, and the likelihood that any form of needling used as a usual control procedure in “placebo controlled” studies may be active. Western medical acupuncture justifies an unbiased evaluation of its role in a modern health service.
NON-RIEMANNIAN GEOMETRIES AND HIGHER-DIMENSIONAL THEORIES OF SPACETIME
Authors: ROMERO C.
Published: April 2009

We discuss the role that non-Riemannian geometries might play in the formulation of modern higher-dimensional spacetime theories. Among the vast number of non-Riemannian geometries we consider the two simplest ones: Weyl geometry and Riemann-Cartan geometry. We approach the problem of classical confinement of particles in branes and show how this question may be investigated in the context of the two mentioned geometries. We show that there is a classical analogue of the confinement of fermions induced by a scalar field and the one that might be induced by a Weyl field. In similar fashion we show that the same role may be played by a torsion field.