bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost Effectiveness of Natural Health Products: A Systematic Review of Randomized Clinical Trials
Authors: Kennedy Deborah A. , Hart Jason , Seely Dugald
Published: December 2007

Health care spending in North America is consuming an ever‐increasing share of Gross Domestic Product (GDP). A large proportion of alternative health care is consumed in the form of natural health products (NHPs). The question of whether or not NHPs may provide a cost‐effective choice in the treatment of disease is important for patients, physicians and policy makers. The objective of this study was to conduct a systematic review of the literature in order to find, appraise and summarize high‐quality studies that explore the cost effectiveness of NHPs as compared to conventional medicine. The following databases were searched independently in duplicate from inception to January 1, 2006: EMBASE, MEDLINE, CINAHL, BioethicsLine, Wilson General Science abstracts, EconLit, Cochrane Library, ABI/Inform and SciSearch. To be included in the review, trials had to be randomized, assessed for some measure of cost effectiveness and include the use of NHPs as defined by the Natural Health Products Directorate. Studies dealing with diseases due to malnutrition were excluded from appraisal. The pooled searches unveiled nine articles that fit the inclusion/exclusion criteria. The conditions assessed by the studies included three on postoperative complications, two on cardiovascular disease, two on gastrointestinal disorders, one on critically ill patients and one on urinary tract infections. Heterogeneity between the studies was too great to allow for meta‐analysis of the results. The use of NHPs shows evidence of cost effectiveness in relation to postoperative surgery but not with respect to the other conditions assessed. In conclusion, NHPs may be of use in preventing complications associated with surgery. The cost effectiveness of some NHPs is encouraging in certain areas but needs confirmation from further research.
The x‐ray light valve: A low‐cost digital radiographic imaging system
Authors: Koprinarov Ivaylo , Webster Christie Ann , MacDougall Robert D. , Rowlands J. A.
Published: December 2007

In recent years new digital x‐ray radiographic and fluoroscopic systems based on large‐area flat‐panel technology have revolutionized our capability of producing x‐ray images. However, such imagers are extraordinarily expensive and their rapid image acquisition capability is not required for many applications such as radiography. Here we report a novel approach to achieve a high‐quality digital radiographic system at a cost which is only a small fraction of competitive digital technologies. The results demonstrate that our proposed x‐ray light valve system has excellent spatial resolution and adequate sensitivity compared to existing technologies.
Segmentation of pulmonary nodules in three‐dimensional CT images by use of a spiral‐scanning technique
Authors: Wang Jiahui , Engelmann Roger , Li Qiang
Published: December 2007

Accurate segmentation of pulmonary nodules in computed tomography (CT) is an important and difficult task for computer‐aided diagnosis of lung cancer. Therefore, the authors developed a novel automated method for accurate segmentation of nodules in three‐dimensional (3D) CT. First, a volume of interest (VOI) was determined at the location of a nodule. To simplify nodule segmentation, the 3D VOI was transformed into a two‐dimensional (2D) image by use of a key “spiral‐scanning” technique, in which a number of radial lines originating from the center of the VOI spirally scanned the VOI from the “north pole” to the “south pole.” The voxels scanned by the radial lines provided a transformed 2D image. Because the surface of a nodule in the 3D image became a curve in the transformed 2D image, the spiral‐scanning technique considerably simplified the segmentation method and enabled reliable segmentation results to be obtained. A dynamic programming technique was employed to delineate the “optimal” outline of a nodule in the 2D image, which corresponded to the surface of the nodule in the 3D image. The optimal outline was then transformed back into 3D image space to provide the surface of the nodule. An overlap between nodule regions provided by computer and by the radiologists was employed as a performance metric for evaluating the segmentation method. The database included two Lung Imaging Database Consortium (LIDC) data sets that contained 23 and 86 CT scans, respectively, with 23 and 73 nodules that were 3 mm or larger in diameter. For the two data sets, six and four radiologists manually delineated the outlines of the nodules as reference standards in a performance evaluation for nodule segmentation. The segmentation method was trained on the first and was tested on the second LIDC data sets. The mean overlap values were and for the nodules in the first and second LIDC data sets, respectively, which represented a higher performance level than those of two existing segmentation methods that were also evaluated by use of the LIDC data sets. The segmentation method provided relatively reliable results for pulmonary nodule segmentation and would be useful for lung cancer quantification, detection, and diagnosis.
Daily targeting of liver tumors: Screening patients with a mock treatment and using a combination of internal and external fiducials for image‐guided respiratory‐gated radiotherapya)
Authors: Krishnan Sunil , Briere Tina Marie , Dong Lei , Murthy Ravi , Ng Chaan , Balter Peter , Mohan Radhe , Gillin Michael T. , Beddar A. Sam
Published: December 2007

The feasibility and accuracy of using a mock treatment to screen suitable patients for respiratory‐gated image‐guided radiotherapy was investigated. Radio‐opaque fiducials implanted adjacent to the liver tumor were used for online positioning to minimize the systematic error in patient positioning. The consistency in the degree of correlation between the external and internal fiducials was analyzed during a mock treatment. This technique could screen patients for gated therapy, reduce setup inaccuracy, and possibly individualize treatment margins.
Empirical electro‐optical and x‐ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x‐ray medical imaging
Authors: Arvanitis C. D. , Bohndiek S. E. , Royle G. , Blue A. , Liang H. X. , Clark A. , Prydderch M. , Turchetta R. , Speller R.
Published: December 2007

Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x‐ray medical imaging is required, critical electro‐optical and physical x‐ray performance evaluation was determined. The electro‐optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x‐ray performance, including x‐ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a standard three transistor CMOS active pixel sensor array with more than 75% fill factor and pitch. Reading at , it is found that the sensor has 114 electrons total additive noise, electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at . Two different structured CsI:Tl phosphors with thickness 95 and , respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x‐ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution and charge coupled device based x‐ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled to structured CsI:Tl can be used for conventional and advanced digital mammography due to their low noise, high resolution performance.
Target motion tracking with a scanned particle beam
Authors: Bert Christoph , Saito Nami , Schmidt Alexander , Chaudhri Naved , Schardt Dieter , Rietzel Eike
Published: December 2007

Treatment of moving targets with scanned particle beams results in local over‐ and under‐dosage due to interplay of beam and target motion. To mitigate the impact of respiratory motion, a motion tracking system has been developed and integrated in the therapy control system at Gesellschaft für Schwerionenforschung. The system adapts pencil beam positions as well as the beam energy according to target motion to irradiate the planned position. Motion compensation performance of the tracking system was assessed by measurements with radiographic films and a 3D array of 24 ionization chambers. Measurements were performed for stationary detectors and moving detectors using the tracking system. Film measurements showed comparable homogeneity inside the target area. Relative differences of 3D dose distributions within the target volume were with a maximum of . Dose gradients and dose to surrounding areas were in good agreement. The motion tracking system successfully preserved dose distributions delivered to moving targets and maintained target conformity.
Genetically Determined Differences in Learning from Errors
Authors: Klein Tilmann A. , Neumann Jane , Reuter Martin , Hennig Jürgen , von Cramon D. Yves , Ullsperger Markus
Published: December 2007

The role of dopamine in monitoring negative action outcomes and feedback-based learning was tested in a neuroimaging study in humans grouped according to the dopamine D2 receptor gene polymorphism DRD2-TAQ-IA. In a probabilistic learning task, A1-allele carriers with reduced dopamine D2 receptor densities learned to avoid actions with negative consequences less efficiently. Their posterior medial frontal cortex (pMFC), involved in feedback monitoring, responded less to negative feedback than others' did. Dynamically changing interactions between pMFC and hippocampus found to underlie feedback-based learning were reduced in A1-allele carriers. This demonstrates that learning from errors requires dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease sensitivity to negative action consequences, which may explain an increased risk of developing addictive behaviors in A1-allele carriers.
Evidence for Alfvén Waves in Solar X-ray Jets
Authors: Cirtain J. W. , Golub L. , Lundquist L. , van Ballegooijen A. , Savcheva A. , Shimojo M. , DeLuca E. , Tsuneta S. , Sakao T. , Reeves K. , Weber M. , Kano R. , Narukage N. , Shibasaki K.
Published: December 2007

Coronal magnetic fields are dynamic, and field lines may misalign, reassemble, and release energy by means of magnetic reconnection. Giant releases may generate solar flares and coronal mass ejections and, on a smaller scale, produce x-ray jets. Hinode observations of polar coronal holes reveal that x-ray jets have two distinct velocities: one near the Alfvén speed (∼800 kilometers per second) and another near the sound speed (200 kilometers per second). Many more jets were seen than have been reported previously; we detected an average of 10 events per hour up to these speeds, whereas previous observations documented only a handful per day with lower average speeds of 200 kilometers per second. The x-ray jets are about 2 × 10
3
to 2 × 10
4
kilometers wide and 1 × 10
5
kilometers long and last from 100 to 2500 seconds. The large number of events, coupled with the high velocities of the apparent outflows, indicates that the jets may contribute to the high-speed solar wind.
Structure of a Site-2 Protease Family Intramembrane Metalloprotease
Authors: Feng Liang , Yan Hanchi , Wu Zhuoru , Yan Nieng , Wang Zhe , Jeffrey Philip D. , Shi Yigong
Published: December 2007

Regulated intramembrane proteolysis by members of the site-2 protease (S2P) family is an important signaling mechanism conserved from bacteria to humans. Here we report the crystal structure of the transmembrane core domain of an S2P metalloprotease from
Methanocaldococcus jannaschii
. The protease consists of six transmembrane segments, with the catalytic zinc atom coordinated by two histidine residues and one aspartate residue ∼14 angstroms into the lipid membrane surface. The protease exhibits two distinct conformations in the crystals. In the closed conformation, the active site is surrounded by transmembrane helices and is impermeable to substrate peptide; water molecules gain access to zinc through a polar, central channel that opens to the cytosolic side. In the open conformation, transmembrane helices α1 and α6 separate from each other by 10 to 12 angstroms, exposing the active site to substrate entry. The structure reveals how zinc embedded in an integral membrane protein can catalyze peptide cleavage.
A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine
Authors: Bielinska Anna U. , Chepurnov Alexander A. , Landers Jeffrey J. , Janczak Katarzyna W. , Chepurnova Tatiana S. , Luker Gary D. , Baker James R.
Published: December 2007

Live-virus vaccines for smallpox are effective but have risks that are no longer acceptable for routine use in populations at minimal risk of infection. We have developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for at least 60 min causes the complete disruption and inactivation of VV. Simple mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE vaccine produced protection against lethal infection equal to vaccination by scarification, with 100% survival after challenge with 77 times the 50% lethal dose of live VV. However, animals protected with VV/NE immunization did after virus challenge have clinical symptoms more extensive than animals vaccinated by scarification. VV/NE-based vaccines are highly immunogenic and induce protective mucosal and systemic immunity without the need for an inflammatory adjuvant or infection with live virus.
Development of a Microtiter Plate Hybridization-Based PCR-Enzyme-Linked Immunosorbent Assay for Identification of Clinically Relevant Human Group A Rotavirus G and P Genotypes
Authors: Santos Norma , Honma Shinjiro , Timenetsky Maria do Carmo S. T. , Linhares Alexandre C. , Ushijima Hiroshi , Armah George E. , Gentsch Jon R. , Hoshino Yasutaka
Published: December 2007

A microtiter plate hybridization-based PCR-enzyme-linked immunosorbent assay (PCR-ELISA) has been used for the detection and identification of a variety of microorganisms. Here, we report the development of a PCR-ELISA for the identification of clinically relevant human rotavirus VP7 (G1 to G6, G8 to G10, and G12) and VP4 (P[4], P[6], P[8], P[9], and P[14]) genotypes. The G and P types of reference human and animal rotavirus strains for which specific probes were available were correctly identified by the PCR-ELISA. In addition, reference strains bearing G or P genotypes for which specific probes were unavailable, such as G11, G14, P[3], P[10], and P[11], did not display any cross-reactivity to the probes. The usefulness of the assay was further evaluated by analyzing a total of 396 rotavirus-positive stool samples collected in four countries: Brazil, Ghana, Japan, and the United States. The results of this study showed that the PCR-ELISA was sensitive and easy to perform without the use of any expensive and sophisticated equipment, the reagents used are easy to obtain commercially and advantageous over multiplex PCR since more than one type-specific probe is used and the selection of probes is more flexible.
Virulence Factors in Urinary
Escherichia coli
Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance
Authors: Piatti Gabriella , Mannini Alessandro , Balistreri Maria , Schito Anna Maria
Published: December 2007

Quinolone- and fluoroquinolone-resistant
Escherichia coli
strains harbor fewer virulence factors than susceptible strains. The reasons underlying this correlation are incompletely understood. We investigated the phylogenetic background, the presence of the
papC, hlyA
, and
cnf1
(pathogenicity island II
J96
-associated),
fimA, iss
, and
iutA
genes, and the presence of type 1 fimbriae, P fimbriae, and hemolysin in 243 urinary
E. coli
isolates resistant only to quinolones (8%), resistant to both quinolones and fluoroquinolones (51%), or susceptible to both drugs (41%). Group B2 accounted for 56% of the isolates, showing a significantly higher prevalence among fluoroquinolone-susceptible strains than among resistant strains (65% versus 50% [
P
= 0.03]).
hly
and
cnf1
were significantly more associated with susceptibility (
P
< 0.001) and with group B2 (
P
< 0.001 for group B2 versus groups A and D). However, within group B2, fluoroquinolone-resistant strains showed lower prevalences of
papC, hlyA
, and
cnf1
than their susceptible counterparts (
P
< 0.001). In contrast, the incidence of
iutA
appeared higher for refractory isolates, including group B2, than for susceptible isolates (
P
< 0.001). Only in group B2 did fluoroquinolone-resistant strains reveal a lesser ability to agglutinate
Saccharomyces cerevisiae
(7%) than quinolone-resistant (87%) and susceptible (80%) isolates, despite uniform possession of
fimA
genes. No similar contrast emerged for expression of hemolysin and P fimbriae. Mutations conferring quinolone and fluoroquinolone resistance may thus require a particular genetic background, not strictly correlated with phylogenetic groups. More interestingly, the mutational event itself can affect the expression of type 1 fimbriae, at least in the prevalent and complex B2 strains.
Molecular Characterization of Three New Virulent Newcastle Disease Virus Variants Isolated in China
Authors: Tan Lei-Tao , Xu Huai-Ying , Wang You-Ling , Qin Zhuo-Ming , Sun Lei , Liu Wen-Jun , Cui Zhi-Zhong
Published: December 2007

Three cases of Newcastle disease virus (NDV) found in nature had the lentogenic motif
112
G-R-Q-G-R-L
117
in their fusion protein cleavage sites. However, both intracerebral pathogenicity and intravenous pathogenicity indexes showed that these NDV isolates were virulent. In comparison with the LaSota live virus vaccine, these viruses had significant genetic variations in the hemagglutinin-neuraminidase gene.
Comparison of the BD GeneOhm Methicillin-Resistant
Staphylococcus aureus
(MRSA) PCR Assay to Culture by Use of BBL CHROMagar MRSA for Detection of MRSA in Nasal Surveillance Cultures from an At-Risk Community Population
Authors: Farley Jason E. , Stamper Paul D. , Ross Tracy , Cai Mian , Speser Sharon , Carroll Karen C.
Published: December 2007

We compared the BD GeneOhm methicillin-resistant
Staphylococcus aureus
(MRSA) PCR assay to culture with BBL CHROMagar MRSA for nasal surveillance among 602 arrestees from the Baltimore City Jail. The sensitivity and specificity were 88.5% and 91.0%, respectively, and after secondary analysis using enrichment broth, they were 89.0% and 91.7%, respectively. Twenty-three of 42 false-positive PCR lysates contained methicillin-susceptible
S. aureus
.
Cooperative Binding of the Class I Major Histocompatibility Complex Cytoplasmic Domain and Human Immunodeficiency Virus Type 1 Nef to the Endosomal AP-1 Complex via Its μ Subunit
Authors: Noviello Colleen M. , Benichou Serge , Guatelli John C.
Published: December 2007

Human immunodeficiency virus type 1 Nef provides immune evasion by decreasing the expression of major histocompatibility complex class I (MHC-I) at the surfaces of infected cells. The endosomal clathrin adaptor protein complex AP-1 is a key cellular cofactor for this activity, and it is recruited to the MHC-I cytoplasmic domain (CD) in the presence of Nef by an uncharacterized mechanism. To determine the molecular basis of this recruitment, we used an MHC-I CD-Nef fusion protein to represent the MHC-I CD/Nef complex during protein interaction assays. The MHC-I CD had no intrinsic ability to bind AP-1, but it conferred binding activity when fused to Nef. This activity was independent of the canonical leucine-based AP-binding motif in Nef; it required residue Y320 in the MHC-I CD and residues E62-65 and P78 in Nef, and it involved the μ but not the γ/σ subunits of AP-1. The impaired binding of mutants encoding substitutions of E62-65 or P78 in Nef was rescued by replacing the Y320SQA sequence in the MHC-I CD with YSQL, suggesting that Nef allows the YSQA sequence to act as if it were a canonical μ-binding motif. These data identify the μ subunit of AP-1 (μ1) as the key target of the MHC-I CD/Nef complex, and they indicate that both Y320 in the MHC-I CD and E62-65 in Nef interact directly with μ1. The data support a cooperative binding model in which Nef functions as a clathrin-associated sorting protein that allows recognition of an incomplete, tyrosine-based μ-binding signal in the MHC-I CD by AP-1.
Transgene Expression Facilitated by the v-
src
Splice Acceptor Can Impair Replication Kinetics and Lead to Genomic Instability of Rous Sarcoma Virus-Based Vectors
Authors: Portsmouth Daniel , Deitermann Daria , Salmons Brian , Günzburg Walter H. , Renner Matthias
Published: December 2007

Rous sarcoma virus (RSV) can be used for the simple generation of high-titer replication-competent retroviral (RCR) vectors. Retroviruses undergo frequent genomic recombination, however, and vectors with reduced replication kinetics are rapidly overgrown by mutant forms. Vector design is hence critical to vector efficacy. In this study, two different designs of RSV-based RCR vectors were evaluated. Vectors in which transgene expression was facilitated by the v-
src
splice acceptor were revealed to have greatly reduced replication kinetics and genomic stability in comparison to vectors in which transgene expression was mediated by an internal ribosome entry site in the 3′ untranslated region.
Hepatitis A Virus Mutant Spectra under the Selective Pressure of Monoclonal Antibodies: Codon Usage Constraints Limit Capsid Variability
Authors: Aragonès Lluís , Bosch Albert , Pintó Rosa M.
Published: December 2007

Severe structural constraints in the hepatitis A virus (HAV) capsid have been suggested as the reason for the lack of emergence of new serotypes in spite of the occurrence of complex distributions of mutants or quasispecies. Analysis of the HAV mutant spectra under immune pressure by the monoclonal antibodies (MAbs) K34C8 (immunodominant site) and H7C27 (glycophorin binding site) has revealed different evolutionary dynamics. Populations composed of complex ensembles of mutants with very low fitness or single dominant mutants with high fitness permit the acquisition of resistance to each of the MAbs, respectively. Deletion mutants were detected as components of the mutant spectra: up to 61 residues, with an average of 19, and up to 83 residues, with an average of 45, in VP3 and VP1 proteins, respectively. A clear negative selection of those replacements affecting the residues encoded by rare codons of the capsid surface has been detected through the present quasispecies analysis, confirming a certain beneficial role of such clusters. Since these clusters are located near or at the epitope regions, the need to maintain such clusters might prevent the emergence of new serotypes.
Noncanonical TATA Sequence in the UL44 Late Promoter of Human Cytomegalovirus Is Required for the Accumulation of Late Viral Transcripts
Authors: Isomura Hiroki , Stinski Mark F. , Kudoh Ayumi , Murata Takayuki , Nakayama Sanae , Sato Yoshitaka , Iwahori Satoko , Tsurumi Tatsuya
Published: December 2007

During productive infection, human cytomegalovirus (HCMV) UL44 transcription initiates at three distinct start sites that are differentially regulated. Two of the start sites, the distal and the proximal, are active at early times, whereas the middle start site is active only at late times after infection. The UL44 early viral gene product is essential for viral DNA synthesis. The UL44 gene product from the late viral promoter affects primarily viral gene expression at late times after infection rather than viral DNA synthesis (H. Isomura, M. F. Stinski, A. Kudoh, S. Nakayama, S. Iwahori, Y. Sato, and T. Tsurumi, J. Virol.
81
:6197, 2007). The UL44 early viral promoters have a canonical TATA sequence, “TATAA.” In contrast, the UL44 late viral promoter has a noncanonical TATA sequence. Using recombinant viruses, we found that the noncanonical TATA sequence is required for the accumulation of late viral transcripts. The GC boxes that surround the middle TATA element did not affect the kinetics or the start site of UL44 late transcription. Replacement of the distal TATA element with a noncanonical TATA sequence did not affect the kinetics of transcription or the transcription start site, but it did induce an alternative transcript at late times after infection. The data indicate that a noncanonical TATA box is used at late times after HCMV infection.
Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection
Authors: Williams Brent L. , Hornig Mady , Yaddanapudi Kavitha , Lipkin W. Ian
Published: December 2007

Infection of neonatal rats with Borna disease virus results in a characteristic behavioral syndrome and apoptosis of subsets of neurons in the hippocampus, cerebellum, and cortex (neonatal Borna disease [NBD]). In the NBD rat hippocampus, dentate gyrus granule cells progressively degenerate. Apoptotic loss of granule cells in NBD is associated with accumulation of zinc in degenerating neurons and reduced zinc in granule cell mossy fibers. Excess zinc can trigger poly(ADP-ribose) polymerase 1 (PARP-1) activation, and PARP-1 activation can mediate neuronal death. Here, we evaluate hippocampal PARP-1 mRNA and protein expression levels, activation, and cleavage, as well as apoptosis-inducing factor (AIF) nuclear translocation and executioner caspase 3 activation, in NBD rats. PARP-1 mRNA and protein levels were increased in NBD hippocampi. PARP-1 expression and activity were increased in granule cell neurons and glia with enhanced ribosylation of proteins, including PARP-1 itself. In contrast, levels of poly(ADP-ribose) glycohydrolase mRNA were decreased in NBD hippocampi. PARP-1 cleavage and AIF expression were also increased in astrocytes in NBD hippocampi. Levels of activated caspase 3 protein were increased in NBD hippocampi and localized to nuclei, mossy fibers, and dendrites of granule cell neurons. These results implicate aberrant zinc homeostasis, PARP-1, and caspase 3 activation as contributing factors in hippocampal neurodegeneration in NBD.
The Heat Shock Protein 70 Cochaperone
YDJ1
Is Required for Efficient Membrane-Specific Flock House Virus RNA Replication Complex Assembly and Function in
Saccharomyces cerevisiae
Authors: Weeks Spencer A. , Miller David J.
Published: December 2007

The assembly of RNA replication complexes on intracellular membranes is an essential step in the life cycle of positive-sense RNA viruses. We have previously shown that Hsp90 chaperone complex activity is essential for efficient Flock House virus (FHV) RNA replication in
Drosophila melanogaster
S2 cells. To further explore the role of cellular chaperones in viral RNA replication, we used both pharmacologic and genetic approaches to examine the role of the Hsp90 and Hsp70 chaperone systems in FHV RNA replication complex assembly and function in
Saccharomyces cerevisiae
. In contrast to results with insect cells, yeast deficient in Hsp90 chaperone complex activity showed no significant decrease in FHV RNA replication. However, yeast with a deletion of the Hsp70 cochaperone
YDJ1
showed a dramatic reduction in FHV RNA replication that was due in part to reduced viral RNA polymerase accumulation. Furthermore, the absence of
YDJ1
did not reduce FHV RNA replication when the viral RNA polymerase and replication complexes were retargeted from the mitochondria to the endoplasmic reticulum. These results identify
YDJ1
as an essential membrane-specific host factor for FHV RNA replication complex assembly and function in
S. cerevisiae
and are consistent with known differences in the role of distinct chaperone complexes in organelle-specific protein targeting between yeast and higher eukaryotes.
Translocation and Colocalization of ICP4 and ICP0 in Cells Infected with Herpes Simplex Virus 1 Mutants Lacking Glycoprotein E, Glycoprotein I, or the Virion Host Shutoff Product of the UL41 Gene
Authors: Kalamvoki Maria , Qu Jianguo , Roizman Bernard
Published: December 2007

In wild-type herpes simplex virus 1-infected cells, the major regulatory protein ICP4 resides in the nucleus whereas ICP0 becomes dynamically associated with proteasomes and late in infection is translocated and dispersed in the cytoplasm. Inhibition of proteasomal function results in retention or transport of ICP0 to the nucleus. We report that in cells infected with mutants lacking glycoprotein E (gE), glycoprotein I (gI), or the product of the UL41 gene, both ICP4 and ICP0 are translocated to the cytoplasm and coaggregate in small dense structures that, in the presence of proteasomal inhibitor MG132, also contain proteasomal components. Gold particle-conjugated antibody to ICP0 reacted in thin sections with dense protein aggregates in the cytoplasm of mutant virus-infected cells. Similar aggregates were present in the nuclei but not in the cytoplasm of wild-type virus-infected cells. Exposure of cells early in infection to MG132 does not result in retention of ICP0 as in wild-type virus-infected cells. The results suggest that the retention of ICP4 and ICP0 in the nucleus is a dynamic process that involves the function of other viral proteins that may include the Fc receptor formed by the gE/gI complex and is not merely the consequence of expression of a nuclear localization signal. It is noteworthy that in ΔUL41-infected cells gE is retained in thetrans-Golgi network and is not widely dispersed in cellular membranes.
Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial
Authors: Santin Alessandro D. , Bellone Stefania , Palmieri Michela , Zanolini Alessandro , Ravaggi Antonella , Siegel Eric R. , Roman Juan J. , Pecorelli Sergio , Cannon Martin J.
Published: December 2007

The safety and immunogenicity of the human papillomavirus type 16 (HPV16) or HPV18 (HPV16/18) E7 antigen-pulsed mature dendritic cell (DC) vaccination were evaluated for patients with stage IB or IIA cervical cancer. Escalating doses of autologous DC (5, 10, and 15 × 10
6
cells for injection) were pulsed with recombinant HPV16/18 E7 antigens and keyhole limpet hemocyanin (KLH; an immunological tracer molecule) and delivered in five subcutaneous injections at 21-day intervals to 10 cervical cancer patients with no evidence of disease after they underwent radical surgery. Safety, toxicity, delayed-type hypersensitivity (DTH) reaction, and induction of serological and cellular immunity against HPV16/18 E7 and KLH were monitored. DC vaccination was well tolerated, and no significant toxicities were recorded. All patients developed CD4
+
T-cell and antibody responses to DC vaccination, as detected by enzyme-linked immunosorbent spot (ELISpot) and enzyme-linked immunosorbent assays (ELISA), respectively, and 8 out of 10 patients demonstrated levels of E7-specific CD8
+
T-cell counts, detected by ELISpot during or immediately after immunization, that were increased compared to prevaccination baseline levels. The vaccine dose did not predict the magnitude of the antibody or T-cell response or the time to detection of HPV16/18 E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen and KLH were detected for all patients after vaccination. We conclude that HPV E7-loaded DC vaccination is safe and immunogenic for stage IB or IIA cervical cancer patients. Phase II E7-pulsed DC-based vaccination trials with cervical cancer patients harboring a limited tumor burden, or who are at significant risk of tumor recurrence, are warranted.
The Autodisplay Story, from Discovery to Biotechnical and Biomedical Applications
Authors: Jose Joachim , Meyer Thomas F.
Published: December 2007

Among the pathways used by gram-negative bacteria for protein secretion, the autotransporter pathway represents a solution of impressive simplicity. Proteins are transported, independent of their nature as recombinant or native passengers, as long as the coding nucleotide sequence is inserted in frame between those of an N-terminal signal peptide and a C-terminal domain, referred to as the β-barrel of the outer membrane translocation unit. The immunoglobulin A1 (IgA1) protease fromNeisseria gonorrhoeaewas the first identified member of the autotransporter family of secreted proteins. The IgA1 protease was employed in initial experiments investigating autotransporter-mediated surface display of recombinant proteins and to investigate structural and functional requirements. Various other autotransporter proteins have since been described, and the autodisplay system was developed on the basis of the naturalEscherichia coliautotransporter protein AIDA-I (adhesin involved in diffuse adherence). Autodisplay has been used for the surface display of random peptide libraries to successfully screen for novel enzyme inhibitors. The autodisplay system was also used for the surface display of functional enzymes, including esterases, oxidoreductases, and electron transfer proteins. WholeE. colicells displaying enzymes have been utilized to efficiently synthesize industrially important rare organic compounds with specific chirality. Autodisplay of epitopes on the surface of attenuatedSalmonellacarriers has also provided a novel way to induce immune protection after oral vaccination. This review summarizes the structural and functional features of the autodisplay system, illustrating its discovery and most recent applications. Autodisplay facilitates the export of more than 100,000 recombinant molecules per single cell and permits the oligomerization of subunits on the cell surface as well as the incorporation of inorganic prosthetic groups after transport of apoproteins onto the bacterial surface without disturbing bacterial integrity or viability. We discuss future biotechnical and biomedical applications in the light of these achievements.
Function, Structure, and Evolution of the RubisCO-Like Proteins and Their RubisCO Homologs
Authors: Tabita F. Robert , Hanson Thomas E. , Li Huiying , Satagopan Sriram , Singh Jaya , Chan Sum
Published: December 2007

About 30 years have now passed since it was discovered that microbes synthesize RubisCO molecules that differ from the typical plant paradigm. RubisCOs of forms I, II, and III catalyze CO2fixation reactions, albeit for potentially different physiological purposes, while the RubisCO-like protein (RLP) (form IV RubisCO) has evolved, thus far at least, to catalyze reactions that are important for sulfur metabolism. RubisCO is the major global CO2fixation catalyst, and RLP is a somewhat related protein, exemplified by the fact that some of the latter proteins, along with RubisCO, catalyze similar enolization reactions as a part of their respective catalytic mechanisms. RLP in some organisms catalyzes a key reaction of a methionine salvage pathway, while in green sulfur bacteria, RLP plays a role in oxidative thiosulfate metabolism. In many organisms, the function of RLP is unknown. Indeed, there now appear to be at least six different clades of RLP molecules found in nature. Consideration of the many RubisCO (forms I, II, and III) and RLP (form IV) sequences in the database has subsequently led to a coherent picture of how these proteins may have evolved, with a form III RubisCO arising from theMethanomicrobiaas the most likely ultimate source of all RubisCO and RLP lineages. In addition, structure-function analyses of RLP and RubisCO have provided information as to how the active sites of these proteins have evolved for their specific functions.
Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes
Authors: Kerr J R , Burke B , Petty R , Gough J , Fear D , Mattey D L , Axford J S , Dalgleish A G , Nutt D J
Published: December 2007

Aim:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity.

Methods:

In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype.

Results:

Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression).

Conclusion:

It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.
Inter-relationships between inflammatory markers in patients with stable COPD with bronchitis: intra-patient and inter-patient variability
Authors: Sapey E , Bayley D , Ahmad A , Newbold P , Snell N , Stockley R A
Published: December 2007

Background:

Measurements of pulmonary biomarkers can be used to monitor airway inflammation in chronic obstructive pulmonary disease (COPD), but the variability of sampled biomarkers and their inter-relationships are poorly understood. A study was undertaken to examine the intra- and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationship between biomarkers, cell counts and markers of disease.

Methods:

Sputum interleukin-1β, tumour necrosis factor α, interleukin 8, myeloperoxidase, leucotriene B4, growth-related oncogene α and differential cell counts were measured in patients with moderate to severe stable COPD (n = 14) on 11 occasions over a 1-month period.

Results:

There was significant variability in all inflammatory indices (median intra-patient coefficient of variation (CV) 35% (IQR 22–69), median inter-patient CV 102% (IQR 61–145)). Variability could be reduced by using a rolling mean of individual patient data points. Sample size calculations were undertaken to determine the number of patients required to detect a 50% reduction in neutrophil count. Using a crossover design of a putative effective treatment, the number needed using one data point per patient was 72, reducing to 23 when a mean of three data points was used. Significant correlations were demonstrated both between the inflammatory biomarkers themselves and between inflammatory biomarkers and markers of disease. Some relationships were not apparent when results from a single sample were used. The reliability of inter-relationships improved as more data points were used for each patient.

Conclusions:

Clear relationships exist between inflammatory biomarkers in patients with stable COPD. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.
DYNAMIC LIGHT SCATTERING STUDY OF REVERSE MICELLAR SYSTEMS FOR THE SYNTHESIS OF IRON-BASED NANOFLUIDS
Authors: GRAEVE OLIVIA A. , SINHA KAUSTAV
Published: December 2007

Iron nanoparticles dispersed in hydraulic oil were prepared by mixing two microemulsions containing iron (II) sulfate and sodium borohydride at a temperature of 60°C. Six values of ω 0 = [water]/[surfactant] were used, namely 5, 10, 15, 20, 25, and 30. Dynamic light scattering measurements of the hydrodynamic radius of the reverse micelles showed that the average size, surfactant shell thickness and water core radius, increased with ω0. The micelle size distribution for ω0 values of 5, 10, and 15, was in the nanometer regime, while for ω0 values of 20, 25, and 30 it was in the micrometer regime. Scanning electron microscopy showed that the nanoparticle diameters were around 30 nm for the powders prepared using an ω 0 = 10. In addition, a comparison between the particle size distribution of the iron nanoparticles dispersed in isopropyl alcohol and the iron nanoparticles in the reverse micellar solution was made. It was shown that once the particles are cleaned and separated from the micellar solution, they agglomerate into particles that are about 1 μm in size.
ELECTRORHEOLOGICAL AND DIELECTRIC PROPERTIES OF UREA/SIO2 NANOCOMPOSITE SUSPENSIONS MODIFIED BY N, N-DIMETHYLFORMAMIDE
Authors: BELZA TOMAS , PAVLINEK VLADIMIR , KURITKA IVO , SAHA PETR , QUADRAT OTAKAR
Published: December 2007

In this study, electrorheological (ER) behaviour of silica nanocomposite suspensions treated with urea and N , N – dimethylformamide (DMF) in DC electric field has been investigated. While the ER effect of the neat silica itself was very low, the modification of silica nanoparticles improved compatibility of the solid and liquid phase and increased considerably ER activity of the system. In contrast to maximum possible concentration about 5 wt.% of neat silica due to particle aggregation 20 wt.% suspension of treated particles with low field-off viscosity could be prepared. The dielectric measurements showed that with increasing amount of urea deposited on the silica particles both the difference between the limit values of the relative permittivities and the relaxation frequency increased. This indicates a great influence of both particle polarizability and the rate of rearrangement of the ER structure in the electric field on the ER intensity. After DMF addition the changes in dielectric properties reflected the higher ER activity. At higher particle loading (25 wt.%) mutual particle interaction increased and field-off viscosity steeply rose. The comparison of the behavior of 20 and 25 wt.% suspensions of modified particles showed that even if high yield stress at higher particle content under electric field application sets in, its relative increase indicating the ER efficiency due to high field-off value may be much lower than at lower suspension loading.
YIELD STRESS IN FERROFLUIDS?
Authors: SHAHNAZIAN HAMID , ODENBACH STEFAN
Published: December 2007

Recent experimental as well as theoretical investigations have shown that the formation of structures of magnetic nanoparticles has significant influence on the behaviour of ferrofluids. The dependence of this structure formation on the magnetic field strength and shear stress applied to the fluid leads to strong changes of the viscosity and to the appearance of viscoelastic effects in the fluids. The actual approaches for a description of the effects vary in the basic modeling of the fluid and its behaviour. Some models base on microscopic assumptions, other model the fluid on a mesoscale and even macroscopic descriptions abstaining from microscopic assumptions have been suggested. A point in which the predictions of the models differ is the question of an appearance of a magnetic field dependent yield stress in ferrofluids. For investigations concerning the appearance and field dependence of a yield stress a special stress controlled rheometer for ferrofluids has been designed. The preliminary results presented here, show a dependence of the yield stress on magnetic field strength for different kind of ferrofluids and magnetorheological fluids.
EVALUATION OF YIELD STRESS MEASUREMENT TECHNIQUES ON A PARALLEL PLATE MAGNETIC RHEOMETER
Authors: ULICNY JOHN C. , GOLDEN MARK A.
Published: December 2007

The on-state yield stress is the primary design parameter for an MR actuator. We have evaluated several methods for measuring yield stress on a number of MR fluids of varying composition using a commercial parallel plate magnetic rheometer. The data obtained by these methods is evaluated for reproducibility and sensitivity to sample size variation and is compared against data obtained with a concentric cylinder magnetic rheometer and literature results. Based on these evaluations and comparisons, we selected two tests for further evaluation.
MAGNETORHEOLOGY OF CARBONYL-IRON SUSPENSION WITH IRON/MCM-41 ADDITIVE
Authors: FANG F. F. , PARK B. J. , CHOI H. J. , AHN W. S.
Published: December 2007

Iron containg hexagonal mesoporous silica particle ( Fe - MCM -41) was prepared and adopted into carbonyl-iron ( CI ) based magnetorheological (MR) suspension as an additive to improve the sedimentation problem of the CI based MR fluid. Structural properties and morphology of the synthesized Fe - MCM -41 particles were observed using SEM. Their MR properties such as oscillation characteristics and flow response (shear stress and shear viscosity) were examined via a rotational rheometer in parallel plate geometry equipped with a magnetic field supplier under external magnetic field strengths ranging from 0 to 257 kA/m. The addition of Fe -containing mesoporous particles into CI suspension was found to improve not only MR behaviors but also sedimentation problem of the CI based MR fluid.
ER EFFECT OF LOW MOLECULAR LIQUID CRYSTAL ON ONE-SIDED PATTERNED ELECTRODES
Authors: KIKUCHI TAKEHITO , INOUE AKIO , FURUSHO JUNJI , KAWAMUKI RYOHEI
Published: December 2007

Several kinds of ER fluids (ERF) have been developed and have been applied to some mechatronics devices and processing technologies. In many conventional applications of ERFs, these devices consist of bilateral electrodes to apply electric field in ERF. However, the electric field of several kV/mm may be necessary to generate an ER effect sufficiently for practical purposes. The gap between a pair of electrodes should be, therefore, maintained narrowly and exactly for fears of short-circuit. At the same time, this electrode system also requires an interconnection on driving parts. To improve these disadvantages, we proposed "one-sided patterned electrode" (OSPE) systems in previous works. In this report, we confirmed the flow characteristics of low molecular liquid crystal (LMLC) on OSPE. Next, we also confirmed the different characteristics depending on the pattern type. Depending on results of electro-static analysis, we conclude that such a difference may results from the directors of LC molecules derived by electric field.
PHYSICAL PROPERTIES OF TOLMAN–BAYIN SOLUTIONS: SOME CASES OF STATIC CHARGED FLUID SPHERES IN GENERAL RELATIVITY
Authors: RAY SAIBAL , DAS BASANTI , RAHAMAN FAROOK , RAY SUBHARTHI
Published: December 2007

In this article, Einstein–Maxwell space–time is considered in connection with some of the astrophysical solutions previously obtained by Tolman (1939) and Bayin (1978). The effect of inclusion of charge in these solutions is investigated thoroughly and the nature of fluid pressure and mass density throughout the sphere is discussed. Mass–radius and mass–charge relations are derived for various cases of the charged matter distribution. Two cases are obtained where perfect fluid with positive pressures gives rise to electromagnetic mass models such that gravitational mass is of purely electromagnetic origin.