bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulation of the Transient Flow in a Centrifugal Pump During Starting Period
Authors: Li Zhifeng , Wu Dazhuan , Wang Leqin , Huang Bin
Published: August 2010

Computational fluid dynamics were used to study the three-dimensional unsteady incompressible viscous flows in a centrifugal pump during rapid starting period (≈0.12 s). The rotational speed variation of the field around the impeller was realized by a dynamic slip region method, which combines the dynamic mesh method with nonconformal grid boundaries. In order to avoid introducing errors brought by the externally specified unsteady inlet and outlet boundary conditions, a physical model composed of a pipe system and pump was developed for numerical self-coupling computation. The proposed method makes the computation processes more close to the real conditions. Relations between the instantaneous flow evolutions and the corresponding transient flow-rate, head, efficiency and power were analyzed. Relative velocity comparisons between the transient and the corresponding quasisteady results were discussed. Observations of the formations and evolutions of the primary vortices filled between the startup blades illustrate the features of the transient internal flow. The computational transient performances qualitatively agree with published data, indicating that the present method is capable of solving unsteady flow in a centrifugal pump under transient operations.
A Level Set Method Coupled With a Volume of Fluid Method for Modeling of Gas-Liquid Interface in Bubbly Flow
Authors: Nichita Bogdan A. , Zun Iztok , Thome John R.
Published: August 2010

This paper describes the implementation of a 3D parallel and Cartesian level set (LS) method coupled with a volume of fluid (VOF) method into the commercial CFD code FLUENT for modeling the gas-liquid interface in bubbly flow. Both level set and volume of fluid methods belong to the so called “one” fluid methods, where a single set of conservation equations is solved and the interface is captured via a scalar function. Since both LS and VOF have advantages and disadvantages, our aim is to couple these two methods to obtain a method, which is superior to both standalone LS and VOF and verify it versus a selection of test cases. VOF is already available in FLUENT, so we implemented an LS method into FLUENT via user defined functions. The level set function is used to compute the surface tension contribution to the momentum equations, via curvature and its normal to the interface, using the Brackbill method while the volume of fluid function is used to capture the interface itself. A re-initialization equation is implemented and solved at every time step using a fifth-order weighted essentially nonoscillatory scheme for the spatial derivative, and a first-order Euler method for time integration. The coupling effect is introduced by solving at the end of each time step an equation, which connects the volume fractions with the level set function. The verification of parasitic currents and interfacial deformation due to numerical error is assessed in comparison to original VOF scheme. Validation is presented for free rising bubbles of different diameters for Morton numbers ranging from 102 to 10−11.
Microscale Falling Cylinder Viscometer With Slip Boundary
Authors: Bataineh Khaled M. , Al-Nimr Moh’d A. , Batayneh Wafa
Published: August 2010

This paper theoretically investigates the hydrodynamic behavior of a falling microcylinder viscometer. The Navier slip conditions are applied to all fluid/solid interfacial boundary conditions of the device. Previous investigations focused on the behavior at the macroscale level and did not consider the slip conditions. The slip coefficients for typical devices and operating conditions are found to be major parameters that affect the behavior of the microscale viscometer. Formulas for determining the viscosity coefficients using a microscale viscometer without considering slip conditions give inaccurate results. The theoretical model has been verified by comparing its predictions with that of the macroviscometer after neglecting the slip conditions.
The Peak Overpressure Field Resulting From Shocks Emerging From Circular Shock Tubes
Authors: Newman A. J. , Mollendorf J. C.
Published: August 2010

A simple semi-empirical model for predicting the peak overpressure field that results when a shock emerges from a circular shock tube is presented and validated. By assuming that the shape of the expanding shock remains geometrically similar after an initial development period, an equation that describes the peak overpressure field in the horizontal plane containing the shock tube’s centerline was developed. The accuracy of this equation was evaluated experimentally by collecting peak overpressure field measurements along radials from the shock tube exit at 0 deg, 45 deg, and 90 deg over a range of shock Mach numbers from 1.15 to 1.45. It was found that the equation became more accurate at higher Mach numbers with percent differences between experimental measurements and theoretical predictions ranging from 1.1% to 3.6% over the range of Mach numbers considered. (1) Shocks do propagate in a geometrically similar manner after some initial development length over the range of Mach numbers considered here. (2) The model developed here gives reasonable predictions for the overpressure field from a shock emerging from a circular shock tube. (3) Shocks are expected to be completely symmetric with respect to the shock tube’s centerline, and hence, a three dimensional overpressure field may be predicted by the model developed here. (4) While there is a range of polar angle at which the shock shape may be described as being spherical with respect to the shock tube’s exit, this range does not encompass the entirety of the half space in front of the shock tube, and the model developed here is needed to accurately describe the entire peak overpressure field.
An Adaptable Peptide-Based Porous Material
Authors: Rabone J. , Yue Y.-F. , Chong S. Y. , Stylianou K. C. , Bacsa J. , Bradshaw D. , Darling G. R. , Berry N. G. , Khimyak Y. Z. , Ganin A. Y. , Wiper P. , Claridge J. B. , Rosseinsky M. J.
Published: August 2010

Swelling Pores

Porosity is a key parameter when selecting materials for catalysts, chemical separations, gas storage, host-guest interactions, and related chemical processes. In most cases the porosity of a material is fixed.

Rabone
et al.

(p.
1053
; see the Perspective by

Wright

) have described a molecular material in which the size of the pores changed during the sorption process. The porosity increased because a dipeptide linker between metal centers reoriented during uptake of some gases, thus improving the capacity of the material to adsorb.
Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism
Authors: Young Barry P. , Shin John J. H. , Orij Rick , Chao Jesse T. , Li Shu Chen , Guan Xue Li , Khong Anthony , Jan Eric , Wenk Markus R. , Prinz William A. , Smits Gertien J. , Loewen Christopher J. R.
Published: August 2010

Intracellular pH and Lipid Metabolism

Intracellular pH regulates metabolism by poorly understood mechanisms, but biosensors are likely to be important in this process.

Young
et al.

(p.
1085
) took a systems-biology approach in yeast to identify in excess of 200 genes that regulate phospholipid metabolism. They found that the signaling lipid, phosphatidic acid, appeared to act as a cytosolic biosensor via the pH-dependent binding of protein effectors to phosphatidic acid. This pH-dependent mechanism directly affects gene expression and is involved in a pathway in which nutrient availability regulates phospholipid metabolism to control production of membranes.
CoRoT Reveals a Magnetic Activity Cycle in a Sun-Like Star
Authors: García Rafael A. , Mathur Savita , Salabert David , Ballot Jérôme , Régulo Clara , Metcalfe Travis S. , Baglin Annie
Published: August 2010

Observations of a distant star reveal a magnetic activity cycle similar to that of the Sun.
Dynamical Instability Produces Transform Faults at Mid-Ocean Ridges
Authors: Gerya Taras
Published: August 2010

Cracking Up

Transform faults perpendicular to mid-ocean ridges are some of the most prominently visual features on the sea floor. Because they form slowly over thousands of years, the lack of observational data means their mechanism of formation has remained controversial. Taking a numerical modeling approach,
Gerya
(p.
1047
) suggests that due to asymmetric growth of the plate boundary, sections of the mid-ocean ridge become unstable and eventually rotate 90°. As the ridge continues to grow, the transform faults continue to develop long after their initiation. This mechanism also explains how offsets of these transform faults occur discontinuously as a result of new fractures at the ridge.
Seeing and Thinking in the Mist
The Invisible Gorilla
And Other Ways Our Intuitions Deceive Us

by Christopher Chabris and Daniel Simons

Crown, New York, 2010. 320 pp. $27, C$32. ISBN 9780307459657.
Authors: Oliva Aude
Published: August 2010

Writing for nonspecialists, Chabris and Simons draw from research on attention, perception, memory, and reasoning to discuss how everyday illusions can lead us astray.
Learning from the Natural World
Teaching Children Science
Hands-On Nature Study in North America, 1890–1930

by Sally Gregory Kohlstedt

University of Chicago Press, Chicago, 2010. 379 pp. $45, £29. ISBN 9780226449906.
Authors: Barrow Mark V.
Published: August 2010

Kohlstedt examines the nature study movement in early-20th-century America and considers the impact of its efforts to introduce science into primary education.
Trapping a Diradical Transition State by Mechanochemical Polymer Extension
Authors: Lenhardt Jeremy M. , Ong Mitchell T. , Choe Robert , Evenhuis Christian R. , Martinez Todd J. , Craig Stephen L.
Published: August 2010

Forced Open

Traditionally, the study of reaction chemistry has relied on random encounters between molecules to initiate the proceedings. Heating and stirring increase the power and frequency of such encounters but provide little finer control. Very recently, chemists have learned how to initiate reactions more directly by embedding precursors in the backbone of a polymer large enough to manipulate with shear forces.

Lenhardt
et al.

(p.
1057
) applied this technique to a cyclopropyl ring-opening reaction. When the strained triangular carbon rings were embedded within a polymer, shear force applied by sonication ruptured their bonds as the polymer backbone stretched. The taut polymer then redirected the ring-opened intermediates toward a product differently arranged from that generated by simple heating.
Prime, Boost, and Broaden
Authors: Doms Robert W.
Published: August 2010

A combined immunization approach represents a possible strategy for developing a “universal” flu vaccine.
Scenario-Building for the Deepwater Horizon Oil Spill
Authors: Machlis Gary E. , McNutt Marcia K.
Published: August 2010

Interdisciplinary science-based scenarios can assist responses to the Gulf oil spill and similar environmental crises.
Serological Evidence of Human Klassevirus Infection
Authors: Greninger Alexander L. , Holtz Lori , Kang Gagandeep , Ganem Donald , Wang David , DeRisi Joseph L.
Published: August 2010

Klassevirus is a proposed new genus of picornavirus that has been associated with pediatric diarrhea. In this study, we used recombinant klassevirus 3C protease as the capture antigen for an indirect serological enzyme-linked immunosorbent assay (ELISA). Four of six klassevirus reverse transcription (RT)-PCR-positive individuals demonstrated seroconversion against the 3C protease, suggesting that klassevirus infection and replication occur in humans. Additional screening of 353 samples from an age-banded serological cohort from two St. Louis hospitals indicated a seroprevalence of 6.8%.
Spoligotypes of
Mycobacterium tuberculosis
from Different Provinces of China
Authors: Dong Haiyan , Liu Zhiguang , Lv Bing , Zhang Yuanyuan , Liu Jie , Zhao Xiuqin , Liu Jinghua , Wan Kanglin
Published: August 2010

A total of 2,346
Mycobacterium tuberculosis
isolates from 13 provinces in China were genotyped by spoligotyping. Two hundred seventy-eight spoligotypes were identified: 2,153 isolates were grouped into 85 clusters, and the remaining 193 isolates were orphans. Comparison with the SpolDB4.0 database revealed that 118 spoligotypes had shared international type numbers in the database and the other 160 were novel. These 160 novel spoligotypes were assigned to families and subfamilies using the
SpotClust
program. The most prevalent family was the Beijing family (74.08%), followed by the T family (14.11%). CAS family strains were found only in the Xinjiang and Tibet regions, while EAI family strains were found only in Fujian Province. In conclusion, the present study of the
M. tuberculosis
population in China demonstrated that Beijing family isolates are the most prevalent strains in China and that they exhibit geographical variation. Furthermore, many new spoligotypes were found in this study.
Improved Safety for Molecular Diagnosis of Classical Rabies Viruses by Use of a TaqMan Real-Time Reverse Transcription-PCR “Double Check” Strategy
Authors: Hoffmann B. , Freuling C. M. , Wakeley P. R. , Rasmussen T. B. , Leech S. , Fooks A. R. , Beer M. , Müller T.
Published: August 2010

To improve the diagnosis of classical rabies virus with molecular methods, a validated, ready-to-use, real-time reverse transcription-PCR (RT-PCR) assay was developed. In a first step, primers and 6-carboxyfluorescien-labeled TaqMan probes specific for rabies virus were selected from the consensus sequence of the nucleoprotein gene of 203 different rabies virus sequences derived from GenBank. The selected primer-probe combination was highly specific and sensitive. During validation using a sample set of rabies virus strains from the virus archives of the Friedrich-Loeffler-Institut (FLI; Germany), the Veterinary Laboratories Agency (VLA; United Kingdom), and the DTU National Veterinary Institute (Lindholm, Denmark), covering the global diversity of rabies virus lineages, it was shown that both the newly developed assay and a previously described one had some detection failures. This was overcome by a combined assay that detected all samples as positive. In addition, the introduction of labeled positive controls (LPC) increased the diagnostic safety of the single as well as the combined assay. Based on the newly developed, alternative assay for the detection of rabies virus and the application of LPCs, an improved diagnostic sensitivity and reliability can be ascertained for postmortem andintra vitamreal-time RT-PCR analyses in rabies reference laboratories.
Ureaplasma urealyticum
Continuous Ambulatory Peritoneal Dialysis-Associated Peritonitis Diagnosed by 16S rRNA Gene PCR
Authors: Yager Jessica E. , Ford Emily S. , Boas Zachary P. , Haseley Leah A. , Cookson Brad T. , SenGupta Dhruba J. , Fang Ferric C. , Gottlieb Geoffrey S.
Published: August 2010

In some patients with peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD), a causative organism is never identified. We report a case of
Ureaplasma urealyticum
CAPD-associated peritonitis diagnosed by 16S rRNA gene PCR.
Ureaplasma
may be an underrecognized cause of peritonitis because it cannot be recovered using routine culture methods.
The Coronavirus Nucleocapsid Protein Is Dynamically Associated with the Replication-Transcription Complexes
Authors: Verheije Monique H. , Hagemeijer Marne C. , Ulasli Mustafa , Reggiori Fulvio , Rottier Peter J. M. , Masters Paul S. , Haan Cornelis A. M. de
Published: August 2010

The coronavirus nucleocapsid (N) protein is a virion structural protein. It also functions, however, in an unknown way in viral replication and localizes to the viral replication-transcription complexes (RTCs). Here we investigated, using recombinant murine coronaviruses expressing green fluorescent protein (GFP)-tagged versions of the N protein, the dynamics of its interactions with the RTCs and the domain(s) involved. Using fluorescent recovery after photobleaching, we showed that the N protein, unlike the nonstructural protein 2, is dynamically associated with the RTCs. Recruitment of the N protein to the RTCs requires the C-terminal N2b domain, which interacts with other N proteins in an RNA-independent manner.
A Determinant of Sindbis Virus Neurovirulence Enables Efficient Disruption of Jak/STAT Signaling
Authors: Simmons Jason D. , Wollish Amy C. , Heise Mark T.
Published: August 2010

Previous studies with Venezuelan equine encephalitis virus and Sindbis virus (SINV) indicate that alphaviruses are capable of suppressing the cellular response to type I and type II interferons (IFNs) by disrupting Jak/STAT signaling; however, the relevance of this signaling inhibition toward pathogenesis has not been investigated. The relative abilities of neurovirulent and nonneurovirulent SINV strains to downregulate Jak/STAT signaling were compared to determine whether the ability to inhibit IFN signaling correlates with virulence potential. The adult mouse neurovirulent strain AR86 was found to rapidly and robustly inhibit tyrosine phosphorylation of STAT1 and STAT2 in response to IFN-γ and/or IFN-β. In contrast, the closely related SINV strains Girdwood and TR339, which do not cause detectable disease in adult mice, were relatively inefficient inhibitors of STAT1/2 activation. Decreased STAT activation in AR86-infected cells was associated with decreased activation of the IFN receptor-associated tyrosine kinases Tyk2, Jak1, and Jak2. To identify the viral factor(s) involved, we infected cells with several panels of AR86/Girdwood chimeric viruses. Surprisingly, we found that a single amino acid determinant, threonine at nsP1 position 538, which is required for AR86 virulence, was also required for efficient disruption of STAT1 activation, and this determinant fully restored STAT1 inhibition when it was introduced into the avirulent Girdwood background. These data indicate that a key virulence determinant plays a critical role in downregulating the response to type I and type II IFNs, which suggests that the ability of alphaviruses to inhibit Jak/STAT signaling relates to their
in vivo
virulence potential.
Hepatitis C Virus Egress and Release Depend on Endosomal Trafficking of Core Protein
Authors: Lai Chao-Kuen , Jeng King-Song , Machida Keigo , Lai Michael M. C.
Published: August 2010

Hepatitis C virus (HCV) assembly is known to occur in juxtaposition to lipid droplets, but the mechanisms of nascent virion transport and release remain poorly understood. Here we demonstrate that HCV core protein targets to early and late endosomes but not to mitochondria or peroxisomes. Further, by employing inhibitors of early and late endosome motility in HCV-infected cells, we demonstrate that the movement of core protein to the early and late endosomes and virus production require an endosome-based secretory pathway. We also observed that this way is independent of that of the internalization of endocytosed virus particles during virus entry.
Diverging Affinity of Tospovirus RNA Silencing Suppressor Proteins, NSs, for Various RNA Duplex Molecules
Authors: Schnettler Esther , Hemmes Hans , Huismann Rik , Goldbach Rob , Prins Marcel , Kormelink Richard
Published: August 2010

The tospovirus NSs protein was previously shown to suppress the antiviral RNA silencing mechanism in plants. Here the biochemical analysis of NSs proteins from different tospoviruses, using purified NSs or NSs containing cell extracts, is described. The results showed that all tospoviral NSs proteins analyzed exhibited affinity to small double-stranded RNA molecules, i.e., small interfering RNAs (siRNAs) and micro-RNA (miRNA)/miRNA* duplexes. Interestingly, the NSs proteins from tomato spotted wilt virus (TSWV), impatiens necrotic spot virus (INSV), and groundnut ringspot virus (GRSV) also showed affinity to long double-stranded RNA (dsRNA), whereas tomato yellow ring virus (TYRV) NSs did not. The TSWV NSs protein was shown to be capable of inhibiting Dicer-mediated cleavage of long dsRNA
in vitro
. In addition, it suppressed the accumulation of green fluorescent protein (GFP)-specific siRNAs during coinfiltration with an inverted-repeat-GFP RNA construct in
Nicotiana benthamiana
.
In vivo
interference of TSWV NSs in the miRNA pathway was shown by suppression of an enhanced GFP (eGFP) miRNA sensor construct. The ability to stabilize miRNA/miRNA* by different tospovirus NSs proteins
in vivo
was demonstrated by increased accumulation and detection of both miRNA171c and miRNA171c* in tospovirus-infected
N. benthamiana
. All together, these data suggest that tospoviruses interfere in the RNA silencing pathway by sequestering siRNA and miRNA/miRNA* molecules before they are uploaded into their respective RNA-induced silencing complexes. The observed affinity to long dsRNA for only a subset of the tospoviruses studied is discussed in light of evolutional divergence and their ancestral relation to the animal-infecting members of the
Bunyaviridae.
The Noncanonical Gag Domains p8 and n Are Critical for Assembly and Release of Mouse Mammary Tumor Virus
Authors: Zábranský Aleš , Hoboth Peter , Hadravová Romana , Štokrová Jitka , Sakalian Michael , Pichová Iva
Published: August 2010

The mouse mammary tumor virus (MMTV) Gag contains the unique domains pp21, p3, p8, and n. We investigated the contribution of these domains to particle assembly and found that the region spanning the p8 and n domains is critical for shape determination and assembly. Deletion of pp21 and p3 reduced the number of released particles, but deletion of the n domain resulted in frequent formation of aberrant particles, while deletion of p8 severely impaired assembly. Further investigation of p8 revealed that both the basic and the proline-rich motifs within p8 contribute to MMTV assembly.
Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Signaling by Blocking STAT1/STAT2 Nuclear Translocation
Authors: Patel Deendayal , Nan Yuchen , Shen Meiyan , Ritthipichai Krit , Zhu Xiaoping , Zhang Yan-Jin
Published: August 2010

Type I interferons (IFNs) IFN-α/β play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type I IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In the present study, we found that PRRSV interferes with the IFN signaling pathway. The transcript levels of IFN-stimulated genes ISG15 and ISG56 and protein level of signal transducer and activator of transcription 2 (STAT2) in PRRSV VR2385-infected MARC-145 cells were significantly lower than those in mock-infected cells after IFN-α treatment. IFN-induced phosphorylation of both STAT1 and STAT2 and their heterodimer formation in the PRRSV-infected cells were not affected. However, the majority of the STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained in the cytoplasm of PRRSV-infected cells, which indicates that the nuclear translocation of the heterotrimers was blocked. Overexpression of NSP1β of PRRSV VR2385 inhibited expression of ISG15 and ISG56 and blocked nuclear translocation of STAT1, which suggests that NSP1β might be the viral protein responsible for the inhibition of IFN signaling. PRRSV infection in primary porcine pulmonary alveolar macrophages (PAMs) also inhibited IFN-α-stimulated expression of the ISGs and the STAT2 protein. In contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live virus (MLV), activated expression of IFN-inducible genes, including those of chemokines and antiviral proteins, in PAMs without the addition of external IFN and had no detectable effect on IFN signaling. These findings suggest that PRRSV interferes with the activation and signaling pathway of type I IFNs by blocking ISG factor 3 (ISGF3) nuclear translocation.
An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA by the Host Nuclease XRN1
Authors: Silva Patrícia A. G. C. , Pereira Carina F. , Dalebout Tim J. , Spaan Willy J. M. , Bredenbeek Peter J.
Published: August 2010

Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3′-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5′-3′ exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced
in vitro
by incubation with purified XRN1. These two YFV sfRNAs formed a 5′-nested set. The 5′ ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production.
Early Innate Recognition of Herpes Simplex Virus in Human Primary Macrophages Is Mediated via the MDA5/MAVS-Dependent and MDA5/MAVS/RNA Polymerase III-Independent Pathways
Authors: Melchjorsen Jesper , Rintahaka Johanna , Søby Stine , Horan Kristy A. , Poltajainen Alina , Østergaard Lars , Paludan Søren R. , Matikainen Sampsa
Published: August 2010

Innate recognition of viruses is mediated by pattern recognition receptors (PRRs) triggering expression of antiviral interferons (IFNs) and proinflammatory cytokines. In mice, Toll-like receptor 2 (TLR2) and TLR9 as well as intracellular nucleotide-sensing pathways have been shown to recognize herpes simplex virus (HSV). Here, we describe how human primary macrophages recognize early HSV infection via intracellular pathways. A number of inflammatory cytokines, IFNs, and IFN-stimulated genes were upregulated after HSV infection. We show that early recognition of HSV and induction of IFNs and inflammatory cytokines are independent of TLR2 and TLR9, since inhibition of TLR2 using TLR2 neutralizing antibodies did not affect virus-induced responses and the macrophages were unresponsive to TLR9 stimulation. Instead, HSV recognition involves intracellular recognition systems, since induction of tumor necrosis factor alpha (TNF-α) and IFNs was dependent on virus entry and replication. Importantly, expression of IFNs was strongly inhibited by small interfering RNA (siRNA) knockdown of MAVS, but this MAVS-dependent IFN induction occurred independently of the recently discovered polymerase III (Pol III)/RIG-I DNA sensing system. In contrast, induction of TNF-α was largely independent of MAVS, suggesting that induction of inflammatory cytokines during HSV infection proceeds via a novel pathway. Transfection with ODN2006, a broad inhibitor of intracellular nucleotide recognition, revealed that nucleotide-sensing systems are employed to induce both IFNs and TNF-α. Finally, using siRNA knockdown, we found that MDA5, but not RIG-I, was the primary mediator of HSV recognition. Thus, innate recognition of HSV by human primary macrophages occurs via two distinct intracellular nucleotide-sensing pathways responsible for induction of IFNs and inflammatory cytokine expression, respectively.
Pathogenesis of Hepatitis E Virus and Hepatitis C Virus in Chimpanzees: Similarities and Differences
Authors: Yu Claro , Boon Denali , McDonald Shannon L. , Myers Timothy G. , Tomioka Keiko , Nguyen Hanh , Engle Ronald E. , Govindarajan Sugantha , Emerson Suzanne U. , Purcell Robert H.
Published: August 2010

The chimpanzee is the only animal model for investigating the pathogenesis of viral hepatitis types A through E in humans. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host responses to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), were compared in multiple experimentally infected chimpanzees. Affymetrix U133 + 2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. Respecting the limitations of microarray probes designed for human target transcripts to effectively assay chimpanzee transcripts, we conducted probe-level analysis of the microarray data in conjunction with a custom mapping of the probe sequences to the most recent human and chimpanzee genome sequences. Time points for statistical comparison were chosen based on independently measured viremia levels. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust in the magnitude and number of differentially expressed genes compared to HEV infection.
Modification of Human Papillomavirus Minor Capsid Protein L2 by Sumoylation
Authors: Marušič Martina Bergant , Mencin Nina , Ličen Mia , Banks Lawrence , Grm Helena Šterlinko
Published: August 2010

The human papillomavirus (HPV) minor capsid protein L2 plays important roles in the generation of infectious viral particles and in the initial steps of infection. Here we show that HPV-16 L2 protein is sumoylated at lysine 35 and that sumoylation affects its stability. Interestingly, the sumoylated form of L2 cannot bind to the major capsid protein L1, suggesting a mechanism by which capsid assembly may be modulated in an infected cell. Additionally, L2 appears to modulate the overall sumoylation status of the host cell. These observations indicate a complex interplay between the HPV L2 protein and the host sumoylation machinery.
Host Insect Inhibitor-of-Apoptosis SfIAP Functionally Replaces Baculovirus IAP but Is Differentially Regulated by Its N-Terminal Leader
Authors: Cerio Rebecca J. , Vandergaast Rianna , Friesen Paul D.
Published: August 2010

The inhibitor-of-apoptosis (IAP) proteins encoded by baculoviruses bear a striking resemblance to the cellular IAP homologs of their invertebrate hosts. By virtue of the acquired selective advantage of blocking virus-induced apoptosis, baculoviruses may have captured cellular IAP genes that subsequently evolved for virus-specific objectives. To compare viral and host IAPs, we defined antiapoptotic properties of SfIAP, the principal cellular IAP of the lepidopteran host
Spodoptera frugiperda
. We report here that SfIAP prevented virus-induced apoptosis as well as viral Op-IAP3 (which is encoded by the
Orgyia pseudotsugata
nucleopolyhedrovirus) when overexpressed from the baculovirus genome. Like Op-IAP3, SfIAP blocked apoptosis at a step prior to caspase activation. Both of the baculovirus IAP repeats (BIRs) were required for SfIAP function. Moreover, deletion of the C-terminal RING motif generated a loss-of-function SfIAP that interacted and dominantly interfered with wild-type SfIAP. Like Op-IAP3, wild-type SfIAP formed intracellular homodimers, suggesting that oligomerization is a functional requirement for both cellular and viral IAPs. SfIAP possesses a ∼100-residue N-terminal leader domain, which is absent among all viral IAPs. Remarkably, deletion of the leader yielded a fully functional SfIAP with dramatically increased protein stability. Thus, the SfIAP leader contains an instability motif that may confer regulatory options for cellular IAPs that baculovirus IAPs have evolved to bypass for maximal stability and antiapoptotic potency. Our findings that SfIAP and viral IAPs have common motifs, share multiple biochemical properties including oligomerization, and act at the same step to block apoptosis support the hypothesis that baculoviral IAPs were derived by acquisition of host insect IAPs.
Identification of a Previously Unrecognized Promoter That Drives Expression of the UXP Transcription Unit in the Human Adenovirus Type 5 Genome
Authors: Ying Baoling , Tollefson Ann E. , Wold William S. M.
Published: August 2010

We previously identified an adenovirus (Ad) protein named U exon protein (UXP) encoded by a leftward-strand (
l
-strand) transcription unit. Here we identify and characterize the UXP promoter. Primer extension and RNase protection assays mapped the transcription initiation site at 32 nucleotides upstream of the UXP gene initiation codon. A series of viral mutants with mutations at two putative inverted CCAAT (I-CCAAT) boxes and two E2F sites were generated. With mutants lacking the proximal I-CCAAT box, the UXP mRNA level decreased significantly to 30% of the Ad type 5 (Ad5) mRNA level as measured by quantitative reverse transcription-PCR. Decreased UXP was also observed by immunoblotting and immunofluorescence. UXP mRNA and protein levels were similar to those of Ad5 for mutants lacking the distal I-CCAAT box or both putative E2F sites. Ad DNA levels were similar in mutant- and wild-type Ad5-infected cells during the late stage of infection, strongly suggesting that the decreased UXP mRNA and protein from mutants lacking the proximal I-CCAAT box was due to decreased promoter activity. Electrophoretic mobility shift assays (EMSA) indicated that a cellular factor binds specifically to the proximal I-CCAAT box of the UXP promoter. An
in vitro
luciferase reporter assay demonstrated that basal promoter activity lies between bp −158 and +30 of the transcription initiation site. No E1A-mediated promoter transactivation was observed in 293 cells compared with A549 cells. Thus, we propose that there is a previously unidentified Ad5 promoter that drives expression of the UXP transcription unit. This promoter is embedded within the gene for fiber, and it contains a proximal I-CCAAT box critical for UXP mRNA transcription.
Hepatitis C Virus RNA Replication Requires a Conserved Structural Motif within the Transmembrane Domain of the NS5B RNA-Dependent RNA Polymerase
Authors: Brass Volker , Gouttenoire Jérôme , Wahl Anja , Pal Zsuzsanna , Blum Hubert E. , Penin François , Moradpour Darius
Published: August 2010

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.
The role of doctors' religious faith and ethnicity in taking ethically controversial decisions during end-of-life care
Authors: Seale Clive
Published: August 2010

Background and Aims

The prevalence of religious faith among doctors and its relationship with decision-making in end-of-life care is not well documented. The impact of ethnic differences on this is also poorly understood. This study compares ethnicity and religious faith in the medical and general UK populations, and reports on their associations with ethically controversial decisions taken when providing care to dying patients.

Method

A postal survey of 3733 UK medical practitioners, of whom 2923 reported on the care of their last patient who died.

Findings

Specialists in care of the elderly were somewhat more likely to be Hindu or Muslim than other doctors; palliative care specialists were somewhat more likely to be Christian, religious and ‘white’ than others. Ethnicity was largely unrelated to rates of reporting ethically controversial decisions. Independently of speciality, doctors who described themselves as non-religious were more likely than others to report having given continuous deep sedation until death, having taken decisions they expected or partly intended to end life, and to have discussed these decisions with patients judged to have the capacity to participate in discussions. Speciality was independently related to wide variations in the reporting of decisions taken with some intent to end life, with doctors in ‘other hospital’ specialities being almost 10 times as likely to report this when compared with palliative medicine specialists, regardless of religious faith.

Conclusions

Greater acknowledgement of the relationship of doctors' values with clinical decision-making is advocated.
Intraorbital access using fluoroscopic flat panel detector CT navigation and three-dimensional MRI overlay
Authors: Cooke Daniel L , Levitt Michael , Kim Louis J , Hallam Danial K , Ghodke Basavaraj
Published: August 2010

Background

Flat panel detector CT (FD-CT), three-dimensional image overlay and navigation software on contemporary fluoroscopic units generate less radiation dose while performing imaging of comparable quality to conventional CT. They can superimpose MR and CT datasets and can accurately guide percutaneous procedures providing live instrument visualization and the capability of re-imaging without patient transfer. These techniques, however, have been minimally used for accessing the head.

Materials and methods

Using an Allura Xper FD20 unit (Philips Healthcare Andover, Massachusetts, USA), three-dimensional image overlay and FD-CT navigation were used for percutaneous n-butyl cyanoacrylate (nBCA) embolization of an intraorbital mass in a 69-year-old man.

Results

Three-dimensional image overlay provides accurate anatomical relationships between the optic nerve and vascular portions of the mass. Percutaneous nBCA was technically successful without non-target embolization and with no significant bleeding encountered during operative resection.

Conclusion

FD-CT navigation and three-dimensional image overlay provide accurate instrument guidance and spatial resolution comparable with current neuro-navigation systems while also providing real time instrument position and the ability to re-image without moving the patient. These are features not available with other types of neuro-navigation.
Economic evaluation of a workplace intervention for sick-listed employees with distress
Authors: van Oostrom Sandra H , Heymans Martijn W , de Vet Henrica C W , van Tulder Maurits W , van Mechelen Willem , Anema Johannes R
Published: August 2010

Objectives

To evaluate the cost effectiveness, cost utility and cost benefit of a workplace intervention compared with usual care for sick-listed employees with distress.

Methods

An economic evaluation was conducted alongside a randomised controlled trial. Employees with distress and who were sick-listed for 2–8 weeks were randomised to a workplace intervention (n=73) or to usual care (n=72). The workplace intervention is a stepwise process involving the sick-listed employee and their supervisor, aimed at formulating a consensus-based plan for return to work (RTW). The effect outcomes were lasting RTW and quality-adjusted life years (QALYs). Healthcare utilisation was measured over 12 months. Cost effectiveness analyses (CEA) and cost utility analyses (CUA) were conducted from the societal perspective and cost benefit analyses (CBA) from the employer perspective. Bootstrapping techniques were used to estimate cost and effect differences, related CIs, and cost effectiveness and cost utility ratios. Cost effectiveness planes were presented and subgroup analyses were performed.

Results

CEA and CUA revealed no statistically significant differences in lasting RTW, QALYs or costs. The CBA indicated a statistically significant higher cost of occupational health services in the workplace intervention group. The workplace intervention was not cost effective according to the CEA, CUA and CBA.

Conclusions

Widespread implementation of the workplace intervention for sick-listed employees with distress is not recommended because there was no economic benefit compared with usual care. Future trials should confirm if the workplace intervention is cost effective for the subgroup employees who intended to return to work despite symptoms.

This trial has been registered at the Dutch National Trial Register

ISRCTN92307123.
A graphical tool to evaluate temporal coverage of occupational history by exposure measurements: Figure 1
Authors: Vlaanderen Jelle , Fransman Wouter , Miller Brian , Burstyn Igor , Heederik Dick , Hurley Fintan , Vermeulen Roel , Kromhout Hans
Published: August 2010

Introduction

In occupational epidemiology, differences in the temporal coverage of the exposure history by available exposure measurement data may affect the uncertainty of exposure estimates. In the reporting of results of studies, greater attention should be paid to the extent to which exposure assessments require extrapolation outside the timeframe for which exposure measurements are available. We propose a simple graphical method that can be used to visualise the temporal coverage of exposure history with exposure measurements and the extent of temporal extrapolation needed.

Methods

We construct a graph that displays the accumulated work history years for which exposure had to be assessed in each calendar year. Years for which exposure measurements were available are shaded. The proportion of work history years covered by exposure measurements and the proportion of work history years accrued before the first measurements are summarised. When available, the actual number of measurements available in each calendar year is shown.

Results

We demonstrate the application of the graphical tool in three nested case–control studies that reported on leukaemia in relation to low-level benzene exposures in the petroleum industry. Considerable differences in temporal coverage between the studies were illustrated, which may have resulted in differences in the reliability of the retrospective exposure estimates derived for these studies.

Conclusion

We introduce a graphical tool for visualising the temporal coverage by available exposure measurement data in epidemiological studies and encourage others to use similar graphs to derive and share better qualitative insights into the uncertainty in exposure assessment.
ELASTIC AND SLIP COMPONENTS OF THEDEFORMATION OF SAND
Authors: Barden L. , Khayatt A. J. , Wightman A.
Published: August 2010

The significance of a separation into elastic and slip components is considered for the case of particulate material. Tests on sand, including a variety of stress paths in a triaxial and a plane strain apparatus, indicate that for a majority of first-loading paths the total strains are closely given by the slip strains alone. The stress dilatancy theory is seen to provide a simple and accurate flow rule for predicting the slip strains.
ON THE EFFECTIVENESS OF SAND DRAINS
Authors: Casagrande L. , Poulos S.
Published: August 2010

The detrimental effects of driving sand drains in sensitive soils are discussed. Several case records of the behavior of embankments on such soils are analyzed. It is concluded that if a careful foundation investigation indicates the desirability of increasing the rate of primary consolidation, non-displacement sand drains should be used. It is also shown that sand drains of any type are of little or no value in soils that exhibit substantial secondary settlements.
ADFREEZING OF LEDA CLAY TO ANCHORED FOOTING COLUMNS
Authors: Penner E. , Irwin W. W.
Published: August 2010

The heaving force transmitted to [Formula: see text] (7.6-cm) diameter steel pipes by adfreezing in Leda clay was measured in the field for two consecutive winters. The maximum uplift force was approximately 6000 lb (2700 kg), which corresponds to an apparent adfreeze strength of about 12.5 p.s.i. (≈ 0.9 kg/cm2). It developed gradually during prolonged periods of cold weather, but dropped off rapidly during warming trends, although the whole soil profile remained below 0 °C. Adfreezing did not retard frost heave in the soil in the vicinity of the steel pipes.Agreement between experimental values for maximum uplift forces by adfreezing and values predicted by Dalmotov's equation suggests that such predictions can be used as a guide for design purposes if no other information is available.
COMPARISON OF PILE LOAD-TEST – SKIN-FRICTION VALUES AND LABORATORY STRENGTH TESTS
Authors: Watt W. G. , Kurfurst P J , Zeman Z. P.
Published: August 2010

Three full-scale bored cast-in-place concrete piles constructed to give no tip resistance were loaded to failure using the equilibrium method of loading. Each pile was 24 inches (61 cm) in diameter, but of different length, stopping in turn in strata of partly saturated highly plastic clay, saturated silty clay, and till. Ultimate skin friction values were calculated and compared to direct shear tests, and laboratory and field vane tests giving values of undrained shear strength.There were large variations in shear strength results even at the same depth in adjacent holes. Comparison of vane tests on soil samples and on the surface of the bored hole showed disturbance caused by drilling to be negligible for these soils.Results from an interfacial friction de-vice lowered into the hole indicated that the skin friction increased with lateral stress and that the lateral pressure on the concreted piles at the time of testing was less than 10 psi (.7 kg/cm2).
A LATERAL DEFORMATION TRANSDUCER FOR TRIAXIAL TESTING: RESEARCH NOTE
Authors: Holubec I. , Finn P. J.
Published: August 2010

As research is expanding into more detailed study of stress–strain behavior of soils in the triaxial test, it is necessary to develop new techniques for measuring more accurately loads and deformations. However, the necessary measuring equipment is not always available commercially. The writers have developed a transducerized apparatus to measure the diameter of triaxial samples, and information on the design and characteristics are presented in this research note.
THE GROUND-STATE PHASE DIAGRAMS OF SPIN-3/2 ISING MODEL ON A FM/AFM TWO-LAYER LATTICE WITH CRYSTAL FIELD
Authors: ALBAYRAK ERHAN , YIGIT ALI , CENGIZ TUNC
Published: August 2010

The ground-state (GS) phase diagrams of spin-3/2 Ising model for ferromagnetic/antiferromagnetic (FM/AFM) interactions on a two-layer lattice are studied under a constant magnetic field by varying the crystal field values for general coordination number q in detail. Thus, it is found that the system exhibits twenty-nine topologically different GS configurations according to their GS phase diagrams obtained in the (J2/J1, J3/qJ1) planes. As the crystal field becomes more and more negative, the remaining phase configurations in the phase diagrams include only spin ±1/2 values as expected.