bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Recombination of Human Immunodeficiency Virus Type 1 in One Round of Viral Replication: Effects of Genetic Distance, Target Cells, Accessory Genes, and Lack of High Negative Interference in Crossover Events
Authors: Rhodes Terence D. , Nikolaitchik Olga , Chen Jianbo , Powell Douglas , Hu Wei-Shau
Published: January 2005

Recombination is a major mechanism that generates variation in populations of human immunodeficiency virus type 1 (HIV-1). Mutations that confer replication advantages, such as drug resistance, often cluster within regions of the HIV-1 genome. To explore how efficiently HIV-1 can assort markers separated by short distances, we developed a flow cytometry-based system to study recombination. Two HIV-1-based vectors were generated, one encoding the mouse heat-stable antigen gene and green fluorescent protein gene (
GFP
), and the other encoding the mouse
Thy-1
gene and
GFP
. We generated derivatives of both vectors that contained nonfunctional
GFP
inactivated by different mutations. Recombination in the region between the two inactivating mutations during reverse transcription could yield a functional
GFP
. With this system, we determined that the recombination rates of markers separated by 588, 300, 288, and 103 bp in one round of viral replication are 56, 38, 31, and 12%, respectively, of the theoretical maximum measurable recombination rate. Statistical analyses revealed that at these intervals, recombination rates and marker distances have a near-linear relationship that is part of an overall quadratic fit. Additionally, we examined the segregation of three markers within 600 bp and concluded that HIV-1 crossover events do not exhibit high negative interference. We also examined the effects of target cells and viral accessory proteins on recombination rate. Similar recombination rates were observed when human primary CD4
+
T cells and a human T-cell line were used as target cells. We also found equivalent recombination rates in the presence and absence of accessory genes
vif
,
vpr
,
vpu
, and
nef
. These results illustrate the power of recombination in generating viral population variation and predict the rapid assortment of mutations in the HIV-1 genome in infected individuals.
The Fusion-Controlling Disulfide Bond Isomerase in Retrovirus Env Is Triggered by Protein Destabilization
Authors: Wallin Michael , Ekström Maria , Garoff Henrik
Published: January 2005

The membrane fusion function of murine leukemia virus (MLV) is carried by the Env protein. This protein is composed of three SU-TM subunit complexes. The fusion activity is loaded into the transmembrane TM subunit and controlled by the peripheral, receptor-binding SU subunit. It is assumed that TM adopts a metastable conformation in the native Env and that fusion activation involves the folding of TM into a stable form. Activation is suppressed by the associated SU and triggered by its dissociation, which follows receptor binding. Recently we showed that the two subunits are disulfide linked and that SU dissociation and triggering of the fusion function are caused by a switch of the intersubunit disulfide into an intrasubunit disulfide isomer using an isomerization-active CWLC motif in SU (M. Wallin, M. Ekstrom, and H. Garoff, EMBO J.
23:
54-65, 2004). In the present work we address how the SU disulfide isomerase is activated. Using Moloney MLV, we show that isomerization of the SU-TM disulfide bond can be triggered by heat, urea, or guanidinium hydrochloride. Such protein perturbation treatments also significantly increase the kinetics and efficiency of viral fusion. The threshold conditions for the effects on isomerization and fusion are virtually the same. This finding indicates that destabilization of interactions in the SU oligomer induces the disulfide bond isomerase and the subsequent activation of the fusion function in TM.
CCR5, GPR15, and CXCR6 Are Major Coreceptors of Human Immunodeficiency Virus Type 2 Variants Isolated from Individuals with and without Plasma Viremia
Authors: Blaak H. , Boers P. H. M. , Gruters R. A. , Schuitemaker H. , van der Ende M. E. , Osterhaus A. D. M. E.
Published: January 2005

Human immunodeficiency virus type 2 (HIV-2) is generally considered capable of using a broad range of coreceptors. Since HIV-2 variants from individuals with nonprogressive infection were not studied previously, the possibility that broad coreceptor usage is a property of variants associated with progressive infection could not be excluded. To test this, we determined the coreceptor usage of 43 HIV-2 variants isolated from six long-term-infected individuals with undetectable plasma viremia. Using GHOST indicator cells, we showed for the first time that the only coreceptors efficiently used by low-pathogenic HIV-2 variants are CCR5, GPR15 (BOB), and CXCR6 (BONZO). Surprisingly, control HIV-2 variants (
n
= 45) isolated from seven viremic individuals also mainly used these three coreceptors, whereas use of CCR1, CCR2b, or CCR3 was rare. Nearly a quarter of all HIV-2 variants tested could infect the parental GHOST cells, which could be partially explained by CXCR4 usage. Use of CXCR4 was observed only for HIV-2 variants from viremic individuals. Thirty-eight variants from aviremic and viremic HIV-2-infected individuals were additionally tested in U87 cells. All except one were capable of infecting the parental U87 cells, often with high efficiency. When virus production in parental cells was regarded as background in the coreceptor-transduced cell lines, the results in U87 cells were largely in agreement with the findings in GHOST cells. HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells. Broad coreceptor usage, therefore, does not appear to be associated with pathogenicity of HIV-2.
Mutation of the SP1 Sequence Impairs both Multimerization and Membrane-Binding Activities of Human Immunodeficiency Virus Type 1 Gag
Authors: Guo Xiaofeng , Roldan Ariel , Hu Jing , Wainberg Mark A. , Liang Chen
Published: January 2005

The Gag protein of human immunodeficiency virus type 1 contains a 14-amino-acid region, termed SP1, between the capsid and downstream nucleocapsid sequences. Although SP1 is known to be indispensable for virus production, the mechanisms involved are mostly unclear. In this study, we demonstrate that an M368A mutation within SP1 severely diminished the ability of Gag to associate with cellular membranes. Although wild-type levels of membrane binding were restored to the M368A Gag by a second-site L20K mutation within matrix, the resultant Gag mutant L20K-M368A remained defective in virus production. This latter deficit was partially consequent to the binding of L20K-M368A Gag to nonraft membranes as opposed to raft association seen for wild-type Gag. Further analysis revealed that the majority of membrane-bound M368A Gag proteins were small oligomers, indicating a multimerization defect. In support of this observation, purified recombinant Gag derivatives containing the M368A mutation formed much lower amounts of high-molecular-weight complexes that were pelletable at 21,000 ×
g
than did wild-type Gag. Based on the myristyl switch model, we propose that the M368A mutation inhibits Gag multimerization and, as a result, restricts the binding of Gag to cellular membranes.
Evaluation of Transcriptional Efficiency of Hepatitis B Virus Covalently Closed Circular DNA by Reverse Transcription-PCR Combined with the Restriction Enzyme Digestion Method
Authors: Chou Yu-Chi , Jeng King-Song , Chen Mong-Liang , Liu Hsiao-Hui , Liu Tzu-Ling , Chen Ya-Ling , Liu Yu-Chih , Hu Cheng-po , Chang Chungming
Published: January 2005

Virus persistence in chronic hepatitis B patients is due to the sustaining level of covalently closed circular DNA (cccDNA) within the nuclei of infected hepatocytes. In this study, we used a modified 1.3-fold hepatitis B virus (HBV) genome, with a BclI genetic marker embedded in the redundancy region, to examine the transcriptional activity of cccDNA and the effect of the HBx protein on transcriptional regulation. After harvesting total RNA from transfected cells or stable lines, we specifically identified and monitored the transcripts from cccDNA by using reverse transcription-PCR (RT-PCR) combined with the restriction enzyme digestion method. In this approach, we have found that (i) RT-PCR combined with detection of the BclI marker is a highly specific method for distinguishing cccDNA-derived transcripts from the original integrated viral genome, (ii) the transcriptional ability of cccDNA was less efficient than that from the integrated viral genome, and (iii) the transcriptional activity of cccDNA was significantly regulated by the HBx protein, a potential transcription activator. In conclusion, we provided a tool with which to elucidate the transcriptional regulation of cccDNA and clarified the transcriptional regulation mechanism of HBx on cccDNA. The results obtained may be helpful in the development of a clinical intervention for patients with chronic HBV infections.
The Hantavirus Nucleocapsid Protein Recognizes Specific Features of the Viral RNA Panhandle and Is Altered in Conformation upon RNA Binding
Authors: Mir M. A. , Panganiban A. T.
Published: January 2005

Hantaviruses are tripartite negative-sense RNA viruses and members of the
Bunyaviridae
family. The nucleocapsid (N) protein is the principal structural component of the viral capsid. N forms a stable trimer that specifically recognizes the panhandle structure formed by the viral RNA termini. We used trimeric glutathione
S
-transferase (GST)-N protein and small RNA panhandles to examine the requirements for specific recognition by Sin Nombre hantavirus N. Trimeric GST-N recognizes the panhandles of the three viral RNAs (S, M, and L) with high affinity, whereas the corresponding plus-strand panhandles of the complementary RNA are recognized with lower affinity. Based on analysis of nucleotide substitutions that alter either the higher-order structure of the panhandle or the primary sequence of the panhandle, both secondary structure and primary sequence are necessary for stable interaction with N. A panhandle 23 nucleotides long is necessary and sufficient for high-affinity binding by N, and stoichiometry calculations indicate that a single N trimer interacts with a single panhandle. Surprisingly, displacement of the panhandle structure away from the terminus does not eliminate recognition by N. The binding of N to the panhandle is an entropy-driven process resulting in initial stable N-RNA interaction followed by a conformational change in N. Taken together, these data provide insight into the molecular events that take place during interaction of N with the panhandle and suggest that specific high-affinity interaction between an RNA binding domain of trimeric N and the panhandle is required for encapsidation of the three viral RNAs.
Glc1.8 fromMicroplitis demolitorBracovirus Induces a Loss of Adhesion and Phagocytosis in Insect High Five and S2 Cells
Authors: Beck Markus , Strand Michael R.
Published: January 2005

Polydnaviridaeis a unique family of DNA viruses that are symbiotically associated with parasitoid wasps. Upon oviposition, wasps inject these viruses into their hosts, where they cause several physiological alterations, including suppression of the cellular immune response. Here we report that expression of theglc1.8gene fromMicroplitis demolitorbracovirus (MdBV) causes a loss of adhesion by two hemocyte-like cell lines, namely, High Five cells from the lepidopteranTrichoplusia niand S2 cells from the dipteranDrosophila melanogaster. The expression of recombinant Glc1.8 also greatly reduced the ability of these cells to phagocytize foreign targets. Glc1.8 is characterized by a signal peptide at its N terminus, an extracellular domain comprised of five nearly perfect tandem repeats of 78 amino acids, and a C-terminal hydrophobic domain that encodes a putative membrane anchor sequence. The expression of a Glc1.8 mutant lacking the anchor sequence resulted in a secreted protein that had no effect on adhesion or phagocytosis. In contrast, sequential deletion of the repeats in the extracellular domain resulted in a progressive reduction in immunosuppressive activity. Since each repeat and its associated glycosylation sites are nearly identical, these results suggested that adhesion-blocking activity depends more on the overall number of repeats in the extracellular domain than on the specific determinants within each repeat. While it severely compromised adhesion and phagocytic functions, Glc1.8 did not cause cell death. Collectively, these results indicate that Glc1.8 is a major pathogenic determinant of MdBV that is involved in suppression of the insect cellular immune response.
Exposure of RNA Templates and Encapsidation of Spliced Viral RNA Are Influenced by the Arginine-Rich Domain of Human Hepatitis B Virus Core Antigen (HBcAg 165-173)
Authors: Le Pogam Sophie , Chua Pong Kian , Newman Margaret , Shih Chiaho
Published: January 2005

Previously, human hepatitis B virus
(
HBV) mutant 164, which has a truncation at the C terminus of the HBV core antigen (HBcAg), was speculated to secrete immature genomes. For this study, we further characterized mutant 164 by different approaches. In addition to the 3.5-kb pregenomic RNA (pgRNA), the mutant preferentially encapsidated the 2.2-kb or shorter species of spliced RNA, which can be reverse transcribed into double-stranded DNA before virion secretion. We observed that mutant 164 produced less 2.2-kb spliced RNA than the wild type. Furthermore, it appeared to produce at least two different populations of capsids: one encapsidated a nuclease-sensitive 3.5-kb pgRNA while the other encapsidated a nuclease-resistant 2.2-kb spliced RNA. In contrast, the wild-type core-associated RNA appeared to be resistant to nuclease. When arginines and serines were systematically restored at the truncated C terminus, the core-associated DNA and nuclease-resistant RNA gradually increased in both size and signal intensity. Full protection of encapsidated pgRNA from nuclease was observed for HBcAg 1-171. A full-length positive-strand DNA phenotype requires positive charges at amino acids 172 and 173. Phosphorylation at serine 170 is required for optimal RNA encapsidation and a full-length positive-strand DNA phenotype. RNAs encapsidated in
Escherichia coli
by capsids of HBcAg 154, 164, and 167, but not HBcAg 183, exhibited nuclease sensitivity; however, capsid instability after nuclease treatment was observed only for HBcAg 164 and 167. A new hypothesis is proposed here to highlight the importance of a balanced charge density for capsid stability and intracapsid anchoring of RNA templates.
Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells
Authors: Mohan Joanne , Bruce Moira E. , Mabbott Neil A.
Published: January 2005

Many natural transmissible spongiform encephalopathy (TSE) infections are likely to be acquired peripherally, and studies in mice show that skin scarification is an effective means of scrapie transmission. After peripheral exposure, TSE agents usually accumulate in lymphoid tissues before spreading to the brain. The mechanisms of TSE transport to lymphoid tissues are not known. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen. To investigate the potential role of LCs in scrapie transportation from the skin, we utilized mouse models in which their migration was blocked either due to CD40 ligand deficiency (CD40L−/−mice) or after caspase-1 inhibition. We show that the early accumulation of scrapie infectivity in the draining lymph node and subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus, LCs are not involved in TSE transport from the skin. After intracerebral inoculation with scrapie, wild-type mice and CD40L−/−mice develop clinical disease with similar incubation periods. However, after inoculation via skin scarification CD40L−/−mice develop disease significantly earlier than do wild-type mice. The shorter incubation period in CD40L−/−mice is unexpected and suggests that a CD40L-dependent mechanism is involved in impeding scrapie pathogenesis. In vitro studies demonstrated that LCs have the potential to acquire and degrade protease-resistant prion protein, which is thought to be a component of the infectious agent. Taken together, these data suggest that LCs are not involved in scrapie transport to draining lymphoid tissues but might have the potential to degrade scrapie in the skin.
Attenuating Mutations of the Matrix Gene of Influenza A/WSN/33 Virus
Authors: Liu Teresa , Ye Zhiping
Published: January 2005

The matrix protein (M1) of influenza virus plays an essential role in viral replication. Our previous studies have shown that basic amino acids 101RKLKR105 of M1 are involved in RNP binding and nuclear localization. For the present work, the functions of 101RKLKR105 were studied by introducing mutations into the M gene of influenza virus A/WSN/33 by reverse genetic methods. Individual substitution, R101S or R105S, had a minimal effect on viral replication. In contrast, the double mutation R101S-R105S was synergistic and resulted in temperature sensitivity reflected by reduced viral replication at a restrictive temperature. To investigate the in vivo effect on infection, BALB/c mice were infected with either A/WSN/33 wild-type (Wt) or mutant viruses and assessed for signs of illness, viral replication in the lungs, and survival rates. The results from mouse studies indicated that the R101S-R105S double mutant virus was strongly attenuated, while single mutant viruses R101S and R105S were minimally attenuated compared to A/WSN33 Wt under the same conditions. In challenge studies, mice immunized by infection with R101S-R105S were fully protected from lethal challenge with A/WSN/33. The replication and attenuating properties of R101S-R105S suggest its potential in development of live influenza virus vaccines.
Inhibition of Interferon Signaling by the New York 99 Strain and Kunjin Subtype of West Nile Virus Involves Blockage of STAT1 and STAT2 Activation by Nonstructural Proteins
Authors: Liu Wen Jun , Wang Xiang Ju , Mokhonov Vladislav V. , Shi Pei-Yong , Randall Richard , Khromykh Alexander A.
Published: January 2005

The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-α/β) and gamma IFN (IFN-γ) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-α. IFN-α signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins responsible for this inhibition.
Transcriptional Activity of Baculovirus Very Late Factor 1
Authors: Mistretta Toni-Ann , Guarino Linda A.
Published: January 2005

The product of the
vlf-1
(very late factor 1) gene is required for expression of very late genes during the final phase of infection. To determine whether VLF-1 functions as a transcriptional activator, VLF-1 was overexpressed and purified by affinity and cation exchange chromatography. The addition of purified protein to transcription assays containing baculovirus RNA polymerase stimulated transcription of the very late polyhedrin promoter but not the late
39k
promoter. Furthermore, construction and analysis of chimeric templates identified sequences within the polyhedrin promoter that were necessary for enhancement.
Human Herpesvirus 6B Induces Cell Cycle Arrest Concomitant with p53 Phosphorylation and Accumulation in T Cells
Authors: Øster Bodil , Bundgaard Bettina , Höllsberg Per
Published: January 2005

We studied the interactions between human herpesvirus 6B (HHV-6B) and its host cell. Productive infections of T-cell lines led to G
1
/S- and G
2
/M-phase arrest in the cell cycle concomitant with an increased level and enhanced DNA-binding activity of p53. More than 70% of HHV-6B-infected cells did not bind annexin V, indicating that the majority of cells were not undergoing apoptosis. HHV-6B infection induced Ser20 and Ser15 phosphorylation on p53, and the latter was inhibited by caffeine, an ataxia telangiectasia mutated kinase inhibitor. Thus, a productive HHV-6B infection suppresses T-cell proliferation concomitant with the phosphorylation and accumulation of p53.
Atomic Force Microscopy Investigation of Isolated Virions of Murine Leukemia Virus
Authors: Kuznetsov Y. G. , Low A. , Fan H. , McPherson A.
Published: January 2005

Virions of mouse leukemia virus spread on glass substrates were visualized by atomic force microscopy. The size distribution mode was 145 nm, significantly larger than that for human immunodeficiency virus particles. The distribution of particle sizes is broad, indicating that no two particles are likely identical in content or surface features. Virions possess knoblike protrusions, which may represent vestiges of budding from cell membranes. Particles which split open allowed imaging of intact cores with diameters of 65 nm. They also permitted estimation of viral shell thickness (35 to 40 nm) and showed the presence of a distinct trough between the shell and the core surface.
Is the rate of biological aging, as measured by age at diagnosis of cancer, socioeconomically patterned?
Authors: Adams Jean , White Martin , Forman David
Published: January 2005

Study objective:To investigate the hypothesis that biological aging, as measured by age at diagnosis of some common cancers, is socioeconomically patterned.

Design:A cross sectional analysis of the association between an area based measure of material deprivation and age at diagnosis of four common cancers (breast, prostate, colorectal, and lung cancers). A further analysis, restricted to breast and colorectal cancer, adjusted for stage and grade of cancer at diagnosis.

Setting:The Northern and Yorkshire cancer registry and information service, Northern and Yorkshire region, UK.

Participants:All people living in the Northern and Yorkshire region diagnosed with breast, prostate, colorectal, or lung cancer in 1986–1995. All people living in the Northern and Yorkshire region diagnosed with breast or colorectal cancer in 1998–2000 with data on stage and grade of cancer at diagnosis.

Main results:There was evidence that greater material deprivation was associated with younger age at diagnosis of cancer in prostate (β coefficient −0.073), colorectal (women: −0.042; men: −0.063), and lung cancer (women: −0.214; men: −0.161). The opposite association was found in women with breast cancer (0.149). Adjusting for stage and grade at incidence, where possible, had little effect on the magnitude of the β coefficients.

Conclusions:Age at diagnosis of some common cancers seems to be socioeconomically patterned with people from more deprived areas being diagnosed with prostate, colorectal, and lung cancers earlier in life. The opposite was seen in women with breast cancer. Further work is required to investigate the socioeconomic distribution of more accurate measures of biological aging.
Childhood cancers and atmospheric carcinogens
Authors: Knox E G
Published: January 2005

Study objectives:To retest previous findings that childhood cancers are probably initiated by prenatal exposures to combustion process gases and to volatile organic compounds (VOCs); and to identify specific chemical hazards.

Design:Birth and death addresses of fatal child cancers in Great Britain between 1966 and 1980, were linked with high local atmospheric emissions of different chemical species. Among migrant children, distances from each address to the nearest emissions “hotspot” were compared. Excesses of outward over inward migrations show an increased prenatal or early infancy risk.

Setting and subjects:Maps of emissions of many different substances were published on the internet by the National Atmospheric Emissions Inventory and “hotspots” for 2001 were translated to map coordinates. Child cancer addresses were extracted from an earlier inquiry into the carcinogenic effects of obstetric radiographs; and their postcodes translated to map references.

Main results:Significant birth proximity relative risks were found within 1.0 km of hotspots for carbon monoxide, PM10 particles, VOCs, nitrogen oxides, benzene, dioxins, 1,3-butadiene, and benz(a)pyrene. Calculated attributable risks showed that most child cancers and leukaemias are probably initiated by such exposures.

Conclusions:Reported associations of cancer birth places with sites of industrial combustion, VOCs uses, and associated engine exhausts, are confirmed. Newly identified specific hazards include the known carcinogens 1,3-butadiene, dioxins, and benz(a)pyrene. The mother probably inhales these or related materials and passes them to the fetus across the placenta.
The pioneering use of a questionnaire to investigate a food borne disease outbreak in early 20th century Britain: Table 1
Authors: Morabia Alfredo , Hardy Anne
Published: January 2005

This paper describes the investigation by a British local government board inspector in 1902, H Timbrell Bulstrode, into the cause of an outbreak of enteric fever after a mayoral banquet given at Winchester. This investigation helped to confirm the role of oysters as an agent of transmission of typhoid fever. The data are also reanalysed using a modern approach, which confirmed the role of oysters (odds ratio  = 11.2, 95% CI 2.5 to 50.1). This episode is illustrative of the role of British public health inspectors at the turn of the 20th century as well as of the conditions in which the technique of investigating outbreaks of food borne diseases using a standardised menu was developed. Current methods of outbreak investigations that differ from Bulstrode’s pioneering work are also discussed.
Compression and strength of dense sand at high pressures and elevated temperatures
Authors: Graham James , Alfaro Marolo , Ferris Gerald
Published: January 2005

The paper examines the stressstrain behaviour of densely compacted sand tested at pressures up to 80 MPa in one-dimensional compression and 7.2 MPa confining pressure in triaxial tests. Tests were performed at temperatures up to 100 °C. The testing relates to a proposal by Atomic Energy of Canada Limited to fill containers of waste nuclear fuel with a crushed quartz sand to provide additional stiffness. No significant effects of temperature were encountered in either isotropic compression or triaxial shear.Key words: sand, compression, shear strength, temperature, pressure.
A large landslide in Zigui County, Three Gorges area
Authors: Dai F C , Deng J H , Tham L G , Law K T , Lee C F
Published: January 2005

On 13 July 2003, a landslide with a volume of approximately 20 × 106 m3 occurred on the left bank of the Qinggan River, Zigui County, Hubei Province, China. As a result, 14 people died and 10 people are missing. A landslide dam was formed, blocking the Qinggan River. A channelized diversion was constructed for prevention of upstream flooding and damage downstream caused by dam breaching. The landslide was a typical translational rockslide in weathered shale and sandstone, a block of which slipped down along the bedding plane. It is estimated that the landslide was caused by the combined effect of the following factors: (i) a bedding plane between incompetent weathered shale and competent sandstone that daylights at or is shallowly buried at the bottom of the Qinggan River; (ii) a thin layer of clayey soil acting as the slip plane that is likely a preexisting shear surface; (iii) excavation of the shale as raw material for brick fabricating on the slope; and (iv) a combination of prolonged rainfall and reservoir impounding.Key words: landslide, landslide dam, rainfall, impounding, Three Gorges area.
Detecting heavy metal contamination in soil using complex permittivity and artificial neural networks
Authors: Shang J Q , Ding W , Rowe R K , Josic L
Published: January 2005

The use of the complex permittivity, an intrinsic electrical property of materials, to detect the presence and type of heavy metals in soil is investigated. The soil specimens are prepared by mixing the soil with distilled and deionized water, NaCl solutions, and copper and zinc salt solutions and compacting at known water contents. The complex permittivities of the soil specimens are measured in the laboratory using a custom-developed apparatus. A database, which includes both contaminated and uncontaminated soil specimens, is developed, with the soil water content, density, and pore-fluid salinity varying over a relatively wide range. Two artificial neural network (ANN) models are developed to (i) identify whether the heavy metals are present in the soil; and, if so, (ii) distinguish the metal type, based on the complex permittivities measured on the soil specimens. The first ANN model (identification) can correctly identify the presence of heavy metals in 90% of cases. The second ANN model (classification) can correctly classify the type of the heavy metal in 95% of cases. Better performance can be achieved if more complex permittivity data are available for the training of the networks.Key words: heavy metals, soil contamination, contamination detection, complex permittivity, artificial neural networks.
A model for the analysis of rapid landslide motion across three-dimensional terrain
Authors: McDougall Scott , Hungr Oldrich
Published: January 2005

A new numerical model for the dynamic analysis of rapid flow slides, debris flows, and avalanches has been developed. The model is an extension of an earlier algorithm and is implemented using a numerical method adapted from smoothed particle hydrodynamics. Its features include (i) the ability to simulate flow across complex three-dimensional terrain; (ii) the ability to allow nonhydrostatic and anisotropic internal stress distributions, coupled with strain changes through frictional relationships; (iii) the ability to simulate material entrainment; (iv) a choice of different rheological kernels, including frictional, plastic, viscous, Bingham, and Voellmy; (v) a meshless solution, which eliminates problems with mesh distortion during long displacements; and (vi) highly efficient and simple operation. The model has been tested by analysing a series of laboratory flume experiments with granular materials, both on straight and curved paths. The model is capable of accurately predicting the margins of various curving flows using a single set of input parameters. A preliminary analysis of a real rock avalanche case history is also included.Key words: landslides, debris flows, rock avalanches, runout analysis, dynamic modelling, numerical methods.
An assessment procedure for glacial hazards in the Swiss Alps
Authors: Huggel Christian , Haeberli Wilfried , Kääb Andreas , Bieri Daniel , Richardson Shaun
Published: January 2005

Glacial hazards such as ice avalanches, glacial lake outburst floods, and debris flows have caused severe damage in populated mountain regions such as the Swiss Alps. Assessment of such hazards must consider basic glaciological, geomorphological, and hydraulic principles together with experience gained from previous events. An approach is presented here to assess the maximum event magnitude and probability of occurrence of glacial hazards. Analysis of magnitude is based on empirical relationships derived from published case histories from the Swiss Alps and other mountain regions. Probability of occurrence is difficult to estimate because of rapid changes in the nature of glacial systems, the low frequency of events, and the high complexity of the involved processes. Here, the probability is specified in qualitative and systematic terms based on indicators such as dam type, geometry, and freeboard height (for glacial lakes) and tendency of avalanche repetition, precursor events, and increased water supply to the glacier bed (for ice avalanche events). The assessment procedures are applied to a recent lake outburst with subsequent debris flow and to an ice avalanche in the Swiss Alps. The results yield reasonable event maxima that were not exceeded by actual events. The methods provide first-order assessments and may be applied in dynamic mountain environments where population and infrastructure growth require continuous evaluation of hazards.Key words: glacial hazards, lake outburst, debris flow, ice avalanche, hazard assessment procedure, probability of occurrence.
Numerical modeling of vacuum preloading and field applications
Authors: Indraratna Buddhima , Bamunawita Chamari , Khabbaz Hadi
Published: January 2005

This study describes the effect of unsaturation at a drain boundary on the behaviour of a single prefabricated vertical drain subjected to vacuum preloading based on a two-dimensional plane strain finite element model incorporating the modified CamClay model. Unsaturation of soil adjacent to the drain can occur due to mandrel withdrawal or application of vacuum pressure through prefabricated vertical band drains (PVDs). Following initial laboratory simulation in a large-scale radial drainage consolidometer, the authors have attempted to explain the observed retardation of pore pressure dissipation through a series of models, which consider the effect of unsaturation at the drain-soil interface. The results indicate that the introduction of an unsaturated soil layer adjacent to a PVD improves the accuracy of numerical predictions. Lastly, a multidrain analysis is conducted to study the behaviour of an embankment stabilized with vertical drains subjected to vacuum preloading, and the field measurements are compared with a series of numerical model predictions.Key words: consolidation, embankment, finite element method, settlement, soft clay, vacuum preloading, vertical drains.
Empirical correlations of compression index for marine clay from regression analysis
Authors: Yoon Gil Lim , Kim Byung Tak , Jeon Sang Soo
Published: January 2005

Single and multiple regression models to estimate the compression index of marine clay in coastal areas in Korea were investigated based on soil property data from more than 1200 consolidation tests on undisturbed samples. Site-specific empirical correlations were proposed to estimate the compression index in terms of both single and multiple soil properties. The proposed regression equations were then compared with the existing empirical equations. It was found that the compression index predicted by a simple linear regression model involving the natural water content, natural void ratio, and liquid limit can reasonably evaluate the real soil compression index. These regression equations may allow a preliminary estimation of the ground settlement for marine clay. It was also recognized that the applications of empirical equations suggested in previous studies result in large uncertainties in estimating the compression index of marine clayey soil in the coastal zone in Korea.Key words: settlement, compression index, regression, statistical analysis, consolidation.
Effects of near-surface environmental conditions on instability of an unsaturated soil slope
Authors: Blatz James A , Ferreira Nelson J , Graham James
Published: January 2005

In 1999, after a period of extensive rainfall, two shallow slope failures developed in the right-of-way of Provincial Road 259 near Virden, Manitoba. The rainfall caused dissipation of soil suction in the near-surface soil, thereby reducing shear resistance and triggering failure. A research project was initiated between the Geotechnical Group at the University of Manitoba and the Manitoba Department of Highways and Transportation to assess the mechanism of failure. The project included a field investigation program, laboratory testing program, and advanced numerical modeling to identify the cause of failure. The results demonstrate that the rainfall resulted in dissipation of the suction in the soil slope, resulting in a reduction in the soil shear strength that triggered shallow failures. The dissipation of the soil suction has been modeled using a time-dependent seepage model that accounts for the flux boundary condition that existed at the ground surface.Key words: slope stability, unsaturated soils, laboratory tests, soil suction, seepage modeling, flux boundary.
Clay mineral characterization through the methylene blue test: comparison with other experimental techniques and applications of the method
Authors: Chiappone Antonella , Marello Stefania , Scavia Claudio , Setti Massimo
Published: January 2005

This article illustrates an experimental study of clay mineral characterization conducted with the aid of the methylene blue "stain" test, which yields a semiquantitative evaluation of the activity of a geomaterial based on the type and quantity of clay minerals contained in it. The properties of clay minerals are described briefly, with special regard to their swelling behaviour in the presence of water. The testing method is described with reference to the procedures and interpretation criteria specified in the Association française de Normalization (AFNOR) and American Society for Testing and Materials (ASTM) standards. The results are then presented of a testing campaign conducted to assess the applicability of the methylene blue test for the characterization of geomaterials through a comparison with other testing methods. Additional tests were performed on stratigraphic sequences to identify the levels containing higher proportions of active clay minerals, based on their tendency to swell on coming into contact with water. This characterization technique was applied to marlyarenaceous formations of the Langhe region (Piedmont, Italy), where planar sliding instability phenomena have often been observed following abundant rainfall, and marlyarenaceous formations of Monferrato (another region in southeast Piedmont, Italy), where studies of a geologicalstructural nature have often revealed traces of postsedimentary tectonic phenomena.Key words: methylene blue stain test, marl, clay mineral, swelling phenomenon, planar sliding instability.
A bounding surface plasticity model for sands exhibiting particle crushing
Authors: Russell Adrian R , Khalili Nasser
Published: January 2005

A new bounding surface constitutive model for sands is presented and is suited to a wide range of stresses, including those sufficient to cause particle crushing. The basic concepts of critical state soil mechanics are shown to be valid, and a uniquely shaped critical state line is defined to capture the three modes of plastic deformation observed across a wide range of stresses, including particle rearrangement, particle crushing, and pseudoelastic deformation. A limiting isotropic compression line is separated from the critical state line in the υ  In p′ plane by a constant shift along an elastic unloadreload line. In the deviator stress  mean effective stress (qp′) plane, the loading and bounding surfaces are homologous about the origin and defined by a simple and versatile function. Isotropic hardening and softening of the loading and bounding surfaces are controlled by plastic volumetric strains. A commonly used non associative flow rule is adopted. Experimental results of monotonically loaded drained and undrained triaxial tests, isotropic compression tests, and oedometric compression tests are presented for a quartz sand and used to calibrate the model. Membrane penetration is accounted for in the model simulations of the test results. A single set of material parameters is introduced enabling rigorous and accurate predictions of stressstrain behaviour in sands.Key words: sand, bounding surface, plasticity, particle crushing.
QED CORRECTIONS TO ISOSPIN-RELATED DECAY RATES OF CHARGED AND NEUTRAL B MESONS
Authors: NAM SOO-HYEON
Published: January 2005

We estimate the isospin-violating QED radiative corrections to the charged-to-neutral ratios of the decay rates for B+ and B0 in non-leptonic B meson decays. In particular, these corrections are potentially important for precision measurement of the charged-to-neutral production ratio of B meson in e+e- annihilation. We calculate explicitly the QED corrections to the ratios of two different types of decay rates Γ(B+→J/ψK+)/Γ(B0→J/ψK0) and [Formula: see text] taking into account the form factors of the mesons based on the vector meson dominance model, and compare them with the results obtained for the point-like mesons.
DODD PARAMETERS AND λ-INDEXING OF EXTENDERS
Authors: ZEMAN MARTIN
Published: January 2005

We study generalizations of Dodd parameters and establish their fine structural properties in Jensen extender models with λ-indexing. These properties are one of the key tools in various combinatorial constructions, such as constructions of square sequences and morasses.
APPLICATIONS OF DNA MICROARRAYS IN BIOLOGY
Authors: Stoughton Roland B.
Published: January 2005

▪ Abstract  DNA microarrays have enabled biology researchers to conduct large-scale quantitative experiments. This capacity has produced qualitative changes in the breadth of hypotheses that can be explored. In what has become the dominant mode of use, changes in the transcription rate of nearly all the genes in a genome, taking place in a particular tissue or cell type, can be measured in disease states, during development, and in response to intentional experimental perturbations, such as gene disruptions and drug treatments. The response patterns have helped illuminate mechanisms of disease and identify disease subphenotypes, predict disease progression, assign function to previously unannotated genes, group genes into functional pathways, and predict activities of new compounds. Directed at the genome sequence itself, microarrays have been used to identify novel genes, binding sites of transcription factors, changes in DNA copy number, and variations from a baseline sequence, such as in emerging strains of pathogens or complex mutations in disease-causing human genes. They also serve as a general demultiplexing tool to sort spatially the sequence-tagged products of highly parallel reactions performed in solution. A brief review of microarray platform technology options, and of the process steps involved in complete experiment workflows, is included.
Antimitogenic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways
Authors: Hung Pei-Fang , Wu Bo-Tsung , Chen Hui-Chian , Chen Yen-Hang , Chen Chia-Lin , Wu Ming-Hua , Liu Hsien-Chun , Lee Meng-Jung , Kao Yung-Hsi
Published: January 2005

Green tea catechins, especially (−)-epigallocatechin gallate (EGCG), have been proposed as a chemopreventative for obesity, diabetes, cancer, and cardiovascular diseases. However, relatively little is known about the mechanism of the action of EGCG on fat cell function. This study was designed to investigate the pathways of EGCG's modulation of the mitogenesis of 3T3-L1 preadipocytes. Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU) was inhibited by EGCG in dose-, time-, and growth phase-dependent manners. Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D1 proteins, reduced Cdk2 activity, and increased levels of G0/G1 growth arrest, p21waf/cip, and p27kip1, but not p18ink, proteins and their associations to Cdk2. However, neither MEK1, ERK1/2, p38 MAPK, phospho-p38, JNK, nor phospho-JNK was changed. Increased phospho-ERK1/2 content and Cdk2 activity, respectively, via the transfection of MEK1 and Cdk2 cDNA into preadipocytes prevented EGCG from reducing cell numbers. These data demonstrate the ERK- and Cdk2-dependent antimitogenic effects of EGCG. Moreover, EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in changing the mitogenic signals. The signal of EGCG in reducing growth of 3T3-L1 preadipocytes differed from that of 3T3 fibroblasts. Results of this study may relate to the mechanism by which EGCG modulates body weight.
Inhibition of complex I of the electron transport chain causes O2−·-mediated mitochondrial outgrowth
Authors: Koopman Werner J. H. , Verkaart Sjoerd , Visch Henk-Jan , van der Westhuizen Francois H. , Murphy Michael P. , van den Heuvel Lambertus W. P. J. , Smeitink Jan A. M. , Willems Peter H. G. M.
Published: January 2005

Recent evidence indicates that oxidative stress is central to the pathogenesis of a wide variety of degenerative diseases, aging, and cancer. Oxidative stress occurs when the delicate balance between production and detoxification of reactive oxygen species is disturbed. Mammalian cells respond to this condition in several ways, among which is a change in mitochondrial morphology. In the present study, we have used rotenone, an inhibitor of complex I of the respiratory chain, which is thought to increase mitochondrial O2−· production, and mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to investigate the relationship between mitochondrial O2−· production and morphology in human skin fibroblasts. Video-rate confocal microscopy of cells pulse loaded with the mitochondria-specific cation rhodamine 123, followed by automated analysis of mitochondrial morphology, revealed that chronic rotenone treatment (100 nM, 72 h) significantly increased mitochondrial length and branching without changing the number of mitochondria per cell. In addition, this treatment caused a twofold increase in lipid peroxidation as determined with C11-BODIPY581/591. Finally, digital imaging microscopy of cells loaded with hydroethidine, which is oxidized by O2−· to yield fluorescent ethidium, revealed that chronic rotenone treatment caused a twofold increase in the rate of O2−· production. MitoQ (10 nM, 72 h) did not interfere with rotenone-induced ethidium formation but abolished rotenone-induced outgrowth and lipid peroxidation. These findings show that increased mitochondrial O2−· production as a consequence of, for instance, complex I inhibition leads to mitochondrial outgrowth and that MitoQ acts downstream of this O2−· to prevent alterations in mitochondrial morphology.