bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Identification of
Mycobacterium tuberculosis
and Nontuberculous Mycobacteria by Multiplex, Real-Time PCR
Authors: Richardson E. T. , Samson D. , Banaei N.
Published: March 2009

The rapid identification of mycobacteria from culture is of primary importance for the administration of empirical antibiotic therapy and for the implementation of public health measures, yet there are few commercially available assays that can easily and accurately identify the mycobacteria in culture in a timely manner. Here we report on the development of a multiplex, real-time PCR assay that can identify 93% of the pathogenic mycobacteria in our laboratory in two parallel reactions. The mycobacteria identified by this assay include the
Mycobacterium tuberculosis
complex (MTC), the
M. avium
complex (MAC), the
M. chelonae
-
M
.
abscessus
group (MCAG), the
M. fortuitum
group (MFG), and
M. mucogenicum
. The primer targets included the 16S rRNA gene and the internal transcribed spacer. The assay was initially validated with a repository of reference strains and was subsequently tested with 314 clinical cultures identified by the AccuProbe assay or high-performance liquid chromatography. Of the 314 cultures tested, multiplex, real-time PCR produced congruent results for 99.8% of the 1,559 targets evaluated. The sensitivity and the specificity were each 99% or greater for MTC (
n
= 96), MAC (
n
= 97), MCAG (
n
= 68), and
M. mucogenicum
(
n
= 9) and 95% and 100%, respectively, for MFG (
n
= 19). We conclude that this multiplex, real-time PCR assay is a useful diagnostic tool for the rapid and accurate identification of MTC and clinically relevant nontuberculous mycobacteria.
Optimal Translation Initiation Enables Vif-Deficient Human Immunodeficiency Virus Type 1 To Escape Restriction by APOBEC3G
Authors: Haché Guylaine , Abbink Truus E. M. , Berkhout Ben , Harris Reuben S.
Published: March 2009

APOBEC3G restricts Vif-deficient human immunodeficiency virus type 1 (HIV-1) by deaminating viral cDNA cytosines to uracils. This promutagenic activity is counteracted by HIV-1 Vif, which is a natural APOBEC3G antagonist. However, we previously reported that Vif-deficient HIV-1 could evolve resistance to APOBEC3G by a novel mechanism requiring an A200-to-C/T transition mutation and Vpr inactivation. A pyrimidine at nucleotide 200 in the untranslated leader region contributed to resistance by increasing virus particle production, which resulted in fewer APOBEC3G molecules per particle. Here we show that the A200-to-C/T mutation functions posttranscriptionally by inactivating an upstream start codon, which in turn enables optimal viral mRNA translation from canonical start codons.
Effect of Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells on Mice Infected with Prions
Authors: Song Chang-Hyun , Honmou Osamu , Ohsawa Natsuo , Nakamura Kiminori , Hamada Hirofumi , Furuoka Hidefumi , Hasebe Rie , Horiuchi Motohiro
Published: March 2009

Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions in experimental models of ischemia, tumors, and neurodegenerative diseases and to ameliorate functional deficits. In this study, we attempted to evaluate the therapeutic potential of MSCs for treating prion diseases. Immortalized human MSCs (hMSCs) that express the
LacZ
gene were transplanted into the unilateral hippocampi or thalami of mice, and their distributions were monitored by the expression of β-galactosidase. In mice infected with prions, hMSCs transplanted at 120 days postinoculation (dpi) were detected on the contralateral side at 2 days after transplantation and existed there even at 3 weeks after transplantation. In contrast, few hMSCs were detected on the contralateral side for mock-infected mice. Interestingly, the migration of hMSCs appeared to correlate with the severity of neuropathological lesions, including disease-specific prion protein deposition. The hMSCs also migrated to a prion-specific lesion in the brain, even when intravenously injected. Although the effects were modest, intrahippocampal and intravenous transplantation of hMSCs prolonged the survival of mice infected with prions. A subpopulation of hMSCs in the brains of prion-infected mice produced various trophic factors and differentiated into cells of neuronal and glial lineages. These results suggest that MSCs have promise as a cellular vehicle for the delivery of therapeutic genes to brain lesions associated with prion diseases and, furthermore, that they may help to regenerate neuronal tissues damaged by prion propagation.
Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice
Authors: Szretter Kristy J. , Gangappa Shivaprakash , Belser Jessica A. , Zeng Hui , Chen Hualan , Matsuoka Yumiko , Sambhara Suryaprakash , Swayne David E. , Tumpey Terrence M. , Katz Jacqueline M.
Published: March 2009

Widespread distribution of highly pathogenic avian H5N1 influenza viruses in domesticated and wild birds continues to pose a threat to public health, as interspecies transmission of virus has resulted in increasing numbers of human disease cases. Although the pathogenic mechanism(s) of H5N1 influenza viruses has not been fully elucidated, it has been suggested that the ability to evade host innate responses, such as the type I interferon response, may contribute to the virulence of these viruses in mammals. We investigated the role that type I interferons (alpha/beta interferon [IFN-α/β]) might play in H5N1 pathogenicity in vivo, by comparing the kinetics and outcomes of H5N1 virus infection in IFN-α/β receptor (IFN-α/βR)-deficient and SvEv129 wild-type mice using two avian influenza A viruses isolated from humans, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486), which exhibit high and low lethality in mice, respectively. IFN-α/βR-deficient mice experienced significantly more weight loss and more rapid time to death than did wild-type mice. HK/486 virus caused a systemic infection similar to that with HK/483 virus in IFN-α/βR-deficient mice, suggesting a role for IFN-α/β in controlling the systemic spread of this H5N1 virus. HK/483 virus replicated more efficiently than HK/486 virus both in vivo and in vitro. However, replication of both viruses was significantly reduced following pretreatment with IFN-α/β. These results suggest a role for the IFN-α/β response in the control of H5N1 virus replication both in vivo and in vitro, and as such it may provide some degree of protection to the host in the early stages of infection.
Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
Authors: Yoshikawa Naoko , Yoshikawa Tomoki , Hill Terence , Huang Cheng , Watts Douglas M. , Makino Shinji , Milligan Gregg , Chan Tehsheng , Peters Clarence J. , Tseng Chien-Te K.
Published: March 2009

We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8+T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.
Herd Immunity to GII.4 Noroviruses Is Supported by Outbreak Patient Sera
Authors: Cannon Jennifer L. , Lindesmith Lisa C. , Donaldson Eric F. , Saxe Lauryn , Baric Ralph S. , Vinjé Jan
Published: March 2009

Noroviruses (NoVs) of genogroup II, cluster 4 (GII.4), are the most common cause of outbreaks of acute gastroenteritis worldwide. During the past 13 years, GII.4 NoVs caused four seasons of widespread activity globally, each associated with the emergence of a new strain. In this report, we characterized the most recent epidemic strain, GII.4-2006 Minerva, by comparing virus-like particle (VLP) antigenic relationships and histo-blood group antigen (HBGA) binding profiles with strains isolated earlier. We also investigated the seroprevalence and specificity of GII.4 antibody in the years prior to, during, and following the GII.4 pandemic of 1995 and 1996 using a large collection of acute- and convalescent-phase serum pairs (
n
= 298) collected from 34 outbreaks. In a surrogate neutralization assay, we measured the blockade of HBGA binding using a panel of GII.4 VLPs representing strains isolated in 1987, 1997, 2002, and 2006 and a GII.3 VLP representing a strain isolated in the mid-1990s. Serum titers required for 50% HBGA blockade were compared between populations. In general, blockade of GII.4 VLP-HBGA binding was greater with convalescent-phase outbreak sera collected near the time of origin of the VLP strain. Heterotypic genotypes did not contribute to herd immunity against GII.4 NoVs based on their inability to block GII.4 VLP binding to HBGA. However, previous exposure to GII.4 NoV followed by infection by GII.3 NoV appeared to evoke an immune response to GII.4 NoV. These results support the hypothesis that herd immunity is a driving force for GII.4 evolution in the U.S. population. The data also suggest that complex patterns of cross-protection may exist across NoV genotypes in humans.
Different Evolutionary Trajectories of European Avian-Like and Classical Swine H1N1 Influenza A Viruses
Authors: Dunham Eleca J. , Dugan Vivien G. , Kaser Emilee K. , Perkins Sarah E. , Brown Ian H. , Holmes Edward C. , Taubenberger Jeffery K.
Published: March 2009

In 1979, a lineage of avian-like H1N1 influenza A viruses emerged in European swine populations independently from the classical swine H1N1 virus lineage that had circulated in pigs since the Spanish influenza pandemic of 1918. To determine whether these two distinct lineages of swine-adapted A/H1N1 viruses evolved from avian-like A/H1N1 ancestors in similar ways, as might be expected given their common host species and origin, we compared patterns of nucleotide and amino acid change in whole genome sequences of both groups. An analysis of nucleotide compositional bias across all eight genomic segments for the two swine lineages showed a clear lineage-specific bias, although a segment-specific effect was also apparent. As such, there appears to be only a relatively weak host-specific selection pressure. Strikingly, despite each lineage evolving in the same species of host for decades, amino acid analysis revealed little evidence of either parallel or convergent changes. These findings suggest that although adaptation due to evolutionary lineages can be distinguished, there are functional and structural constraints on all gene segments and that the evolutionary trajectory of each lineage of swine A/H1N1 virus has a strong historical contingency. Thus, in the context of emergence of an influenza A virus strain via a host switch event, it is difficult to predict what specific polygenic changes are needed for mammalian adaptation.
Incorporating setup into load and resistance factor design of driven piles in sand
Authors: Yang Luo , Liang Robert
Published: March 2009

A comprehensive database is developed for the setup for piles driven into sand. Based on the compiled pile-testing data, pile setup is significant and continues to develop for a long time after pile installation. The statistical analysis shows that a logarithm-normal distribution can be used to describe the probabilistic characteristics of the predicted setup capacity using the Skov and Denver equation. The main objective of this paper is to incorporate the setup effect into a reliability-based load and resistance factor design (LRFD) of driven piles in sand. The first-order reliability method (FORM) is used to derive separate resistance factors that would account for different degrees of uncertainties associated with measured short-term capacity and predicted setup capacity. The incorporation of setup effects in the LRFD helps improve the prediction of total capacity of driven piles, resulting in more economical design. A practical design procedure within the LRFD framework to incorporate the pile setup effects is outlined.
25 years of movement monitoring on South Peak, Turtle Mountain: understanding the hazard
Authors: Froese Corey R. , Moreno Francisco , Jaboyedoff Michel , Cruden David M.
Published: March 2009

In 1981, an Alberta Government project upgraded the monitoring of South Peak, Turtle Mountain, on the south margin of the 1903 Frank Slide. The monitoring program aimed at understanding the rates of deformation over large, deep fractures encompassing South Peak and predicting a second large rock avalanche on the mountain. The monitoring program consisted of a complement of static ground points and remotely monitored targets measured periodically, and climatic, microseismic, and deformation data collected automatically on daily intervals and archived. In the late 1980s, developmental funding for the monitoring program ceased and some of the installations fell into disrepair. Between May 2004 and September 2006, readings from the remaining functional monitoring points were compiled and interpreted. In addition, readings compiled previously were re-interpreted based on a more recent understanding of short-term movement patterns and climatic influences. These observations were compared with recent observations from an airborne light detection and ranging (LiDAR) digital elevation model and field photographs to give more precise estimates of the overall rates, extent, and patterns of motion for the past 25 years.
Reduced thin filament length in nebulin-knockout skeletal muscle alters isometric contractile properties
Authors: Gokhin David S. , Bang Marie-Louise , Zhang Jianlin , Chen Ju , Lieber Richard L.
Published: March 2009

Nebulin (NEB) is a large, rod-like protein believed to dictate actin thin filament length in skeletal muscle. NEB gene defects are associated with congenital nemaline myopathy. The functional role of NEB was investigated in gastrocnemius muscles from neonatal wild-type (WT) and NEB knockout (NEB-KO) mice, whose thin filaments have uniformly shorter lengths compared with WT mice. Isometric stress production in NEB-KO skeletal muscle was reduced by 27% compared with WT skeletal muscle on postnatal day 1 and by 92% on postnatal day 7, consistent with functionally severe myopathy. NEB-KO muscle was also more susceptible to a decline in stress production during a bout of 10 cyclic isometric tetani. Length-tension properties in NEB-KO muscle were altered in a manner consistent with reduced thin filament length, with length-tension curves from NEB-KO muscle demonstrating a 7.4% narrower functional range and an optimal length reduced by 0.13 muscle lengths. Expression patterns of myosin heavy chain isoforms and total myosin content did not account for the functional differences between WT and NEB-KO muscle. These data indicate that NEB is essential for active stress production, maintenance of functional integrity during cyclic activation, and length-tension properties consistent with a role in specifying normal thin filament length. Continued analysis of NEB's functional properties will strengthen the understanding of force transmission and thin filament length regulation in skeletal muscle and may provide insights into the molecular processes that give rise to nemaline myopathy.
Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression
Authors: Legan Sandra J. , Donoghue Kathleen M. , Franklin Kathleen M. , Duncan Marilyn J.
Published: March 2009

The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression.
Biphasic regulation of ENaC by TGF-α and EGF in renal epithelial cells
Authors: Liu Lian , Duke Billie Jeanne , Malik Bela , Yue Qiang , Eaton Douglas C.
Published: March 2009

The epithelial sodium channel (ENaC) is regulated by epidermal growth factor (EGF). We investigate whether ENaC is regulated by another EGF receptor (EGFR) ligand, transforming growth factor-α (TGF-α). We show that chronic (24 h) treatment with TGF-α inhibits ENaC in Xenopus laevis kidney cells 20 times more strongly than EGF. By using single-channel measurements, we show that TGF-α significantly reduces the number of ENaC per patch. The open probability ( Po) is unchanged by 24-h treatment with TGF-α. α-, β-, and γ-ENaC mRNA levels are significantly reduced by TGF-α or EGF. TGF-α or EGF reduces α- and γ-ENaC proteins in the membrane; however, β-ENaC is unchanged. TGF-α or EGF inhibits ENaC by activating EGFR since the EGFR inhibitor AG1478 blocks the effects of both. The MAPK 1/2 inhibitor U0126 also blocks the effect of TGF-α or EGF on ENaC, indicating that the MAPK1/2 pathway is involved in the TGF-α- or EGF-induced inhibition of ENaC. Interestingly, acute treatment (<1 h) with TGF-α or EGF does not inhibit ENaC current; it enhances ENaC activity by increasing Po. Pretreatment of the cells with U0126 potentiates the acute TGF-α- or EGF-induced stimulation of ENaC. This TGF-α- or EGF-induced increase in sodium current is abolished by a phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor, LY294002, suggesting that PI-3 kinase is involved in the activation of sodium transport. In conclusion, chronic treatment with TGF-α or EGF inhibits ENaC by decreasing the number of channels in the membrane transcriptionally through MAPK1/2 pathways, but acute treatment with TGF-α or EGF activates ENaC by increasing Povia PI-3 kinase.
The effect of posture-induced changes in peripheral nitric oxide uptake on exhaled nitric oxide
Authors: Verbanck Sylvia , Kerckx Yannick , Schuermans Daniel , de Bisschop Claire , Guénard Hervé , Naeije Robert , Vincken Walter , Van Muylem Alain
Published: March 2009

Airway and alveolar NO contributions to exhaled NO are being extracted from exhaled NO measurements performed at different flow rates. To test the robustness of this method and the validity of the underlying model, we deliberately induced a change in NO uptake in the peripheral lung compartment by changing body posture between supine and prone. In 10 normal subjects, we measured exhaled NO at target flows ranging from 50 to 350 ml/s in supine and prone postures. Using two common methods, bronchial NO production [Jaw(NO)] and alveolar NO concentration (FANO) were extracted from exhaled NO concentration vs. flow or flow−1 curves. There was no significant Jaw(NO) difference between prone and supine but a significant FANO decrease from prone to supine ranging from 23 to 33% depending on the method used. Total lung capacity was 7% smaller supine than prone ( P = 0.03). Besides this purely volumetric effect, which would tend to increase FANO from prone to supine, the observed degree of FANO decrease from prone to supine suggests a greater opposing effect that could be explained by the increased lung capillary blood volume (Vc) supine vs. prone ( P = 0.002) observed in another set of 11 normal subjects. Taken together with the relative changes of NO and CO transfer factors, this Vc change can be attributed mainly to pulmonary capillary recruitment from prone to supine. Realistic models for exhaled NO simulation should include the possibility that a portion of the pulmonary capillary bed is unavailable for NO uptake, with a maximum capacity of the pulmonary capillary bed in the supine posture.
The Main Sequence of Human Optokinetic Afternystagmus (OKAN)
Authors: Kaminiarz Andre , Königs Kerstin , Bremmer Frank
Published: March 2009

Different types of fast eye movements, including saccades and fast phases of optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN), are coded by only partially overlapping neural networks. This is a likely cause for the differences that have been reported for the dynamic parameters of fast eye movements. The dependence of two of these parameters—peak velocity and duration—on saccadic amplitude has been termed “main sequence.” The main sequence of OKAN fast phases has not yet been analyzed. These eye movements are unique in that they are generated by purely subcortical control mechanisms and that they occur in complete darkness. In this study, we recorded fast phases of OKAN and OKN as well as visually guided and spontaneous saccades under identical background conditions because background characteristics have been reported to influence the main sequence of saccades. Our data clearly show that fast phases of OKAN and OKN differ with respect to their main sequence. OKAN fast phases were characterized by their lower peak velocities and longer durations compared with those of OKN fast phases. Furthermore we found that the main sequence of spontaneous saccades depends heavily on background characteristics, with saccades in darkness being slower and lasting longer. On the contrary, the main sequence of visually guided saccades depended on background characteristics only very slightly. This implies that the existence of a visual saccade target largely cancels out the effect of background luminance. Our data underline the critical role of environmental conditions (light vs. darkness), behavioral tasks (e.g., spontaneous vs. visually guided), and the underlying neural networks for the exact spatiotemporal characteristics of fast eye movements.
Cocaine-Induced LTP in the Ventral Tegmental Area: New Insights Into Mechanism and Time Course Illuminate the Cellular Substrates of Addiction
Authors: Heshmati Mitra
Published: March 2009

Previous work has shown that a single dose of cocaine can produce long-term potentiation (LTP) of the glutamatergic synapses received by dopamine neurons in the ventral tegmental area (VTA). This and other plastic changes in the brain's reward circuitry have been suggested to underlie addiction. A recent study has provided new insights into cocaine-induced LTP, showing that it begins 3–5 h after exposure, requires activation of a dopamine D5/NMDA receptor cascade, and can be evoked by cocaine application directly to the VTA.
Ocean Heat Transport, Sea Ice, and Multiple Climate States: Insights from Energy Balance Models
Authors: Rose Brian E. J. , Marshall John
Published: March 2009

Several extensions of energy balance models (EBMs) are explored in which (i) sea ice acts to insulate the atmosphere from the ocean and (ii) ocean heat transport is allowed to have some meridional structure controlled by the wind, with minima at which the ice edge can rest. These new models support multiple stable ice edges not found in the classical EBM and a hysteresis loop capable of generating abrupt warming as the ice edge “jumps” from mid- to high latitudes. The new equilibria are demonstrated in two classes of model, in which the wind stress is either specified externally or generated interactively. Wind stress is computed by introducing a dynamical constraint into the EBM to represent the simultaneous meridional transport of energy and angular momentum in the atmosphere. This wind stress is used to drive ocean gyres, with associated structure in their meridional heat transport, so that the atmosphere and ocean are coupled together both thermally and mechanically.
Acoustic Tomography for Scalar and Vector Fields: Theory and Application to Temperature and Wind Estimation
Authors: Jovanović Ivana , Sbaiz Luciano , Vetterli Martin
Published: March 2009

Acoustic tomography is a type of inverse problem. The idea of estimating physical quantities that influence sound propagation by measuring the parameters of propagation has proven to be successful in many practical domains, including temperature and wind estimation in the atmosphere. However, in most of the previous work in this area, the algorithms used have not been proven mathematically to provide the correct solution to the inverse problem.

This paper considers the problem of reconstructing 2D temperature and wind fields by using acoustic tomography setups. Primarily, it shows that the classical time-of-flight measurements are not sufficient to reconstruct wind fields. As a solution, an additional set of measurements related solely to the parameters of sound propagation—more precisely, to the angles of departure/arrival of sound waves—is suggested. To take the full benefit of this additional information, the bent-ray model of sound propagation is introduced. In this work, it is also shown that, when a temperature and a source-free 2D wind field are observed on bounded domains, the complete reconstruction is possible using only measurements of the time of flight. Conversely, the angles of departures/arrivals are sufficient to reconstruct a temperature and a curl-free 2D wind fields on bounded domains. Further, an iterative reconstruction algorithm is proposed and possible variations to the main scheme are discussed. Finally, the performed numerical simulations confirm the theoretical results, demonstrate fast convergence, and show the advantages of the adopted bent-ray model for sound propagation over the straight-ray model.
Quality Control of Meteorological Data for the Chemical Stockpile Emergency Preparedness Program
Authors: Liljegren James C. , Tschopp Stephen , Rogers Kevin , Wasmer Fred , Liljegren Lucia , Myirski Michael
Published: March 2009

The Chemical Stockpile Emergency Preparedness Program Meteorological Support Project ensures the accuracy and reliability of data acquired by meteorological monitoring stations located at seven U.S. Army chemical weapons depots where storage and weapons destruction (demilitarization) activities are ongoing. The data are delivered in real time to U.S. Army plume dispersion models, which are used to plan for and respond to a potential accidental release of a chemical weapons agent. The project provides maintenance, calibration, and audit services for the instrumentation; collection, automated screening, visual inspection, and analysis of the data; and problem reporting and tracking to carefully control the data quality. The resulting high-quality meteorological data enhance emergency response modeling and public safety.
AERONET-OC: A Network for the Validation of Ocean Color Primary Products
Authors: Zibordi Giuseppe , Mélin Frédéric , Berthon Jean-François , Holben Brent , Slutsker Ilya , Giles David , D’Alimonte Davide , Vandemark Doug , Feng Hui , Schuster Gregory , Fabbri Bryan E. , Kaitala Seppo , Seppälä Jukka
Published: March 2009

The ocean color component of the Aerosol Robotic Network (AERONET-OC) has been implemented to support long-term satellite ocean color investigations through cross-site consistent and accurate measurements collected by autonomous radiometer systems deployed on offshore fixed platforms. The AERONET-OC data products are the normalized water-leaving radiances determined at various center wavelengths in the visible and near-infrared spectral regions. These data complement atmospheric AERONET aerosol products, such as optical thickness, size distribution, single scattering albedo, and phase function. This work describes in detail this new AERONET component and its specific elements including measurement method, instrument calibration, processing scheme, quality assurance, uncertainties, data archive, and products accessibility. Additionally, the atmospheric and bio-optical features of the sites currently included in AERONET-OC are briefly summarized. After illustrating the application of AERONET-OC data to the validation of primary satellite products over a variety of complex coastal waters, recommendations are then provided for the identification of new deployment sites most suitable to support satellite ocean color missions.
China
Authors: Ching Kwan Lee  , Yuan Shen
Published: March 2009

This article examines the predicament and possibility for the development of a public sociology of labor in China. Labor studies that take seriously workers' class experience and capacity have been stymied by a Communist regime keen on censoring and domesticating sociology as a profession as well as fragmenting the interests, identities, and mobilization of the working class. Yet, in recent years, persistent struggles by Chinese workers themselves have created intense pressure on the Chinese state to redefine its position toward labor conflicts. At the same time, global labor and academic communities have infused ideas and resources that help expand the scope and linkages of labor civic activism.
Integrin-linked kinase associated with integrin activation
Authors: Honda Shigenori , Shirotani-Ikejima Hiroko , Tadokoro Seiji , Maeda Yusuke , Kinoshita Taroh , Tomiyama Yoshiaki , Miyata Toshiyuki
Published: March 2009

Platelet integrin αIIbβ3 activation is tightly controlled by intracellular signaling pathways, and several molecules, including talin, have been identified as critical for αIIbβ3 activation. However, the whole pathway associated with αIIbβ3 activation remains to be determined. To address this issue, we established a Chinese hamster ovary cell line (parental cells) that expresses constitutively activated chimeric integrin αIIbα6Bβ3, and then obtained mutant cells expressing inactivated αIIbα6Bβ3 by genome-wide mutagenesis. We have performed expression cloning to isolate signaling molecules responsible for integrin activation in the mutant cells. We show that integrin-linked kinase (ILK) complements defective integrin activation in the mutant cells. ILK mRNAs in the mutant cells contained 2 nonsense mutations, R317X and W383X, in a compound heterozygous state, resulting in a complete loss of ILK expression. Moreover, the mutant cells showed partially impaired activation of endogenous β1 integrins. Knockdown of ILK in parental cells significantly suppressed the activated state of αIIbα6Bβ3. However, ILK overexpression did not rescue the impaired integrin activation in talin knocked-down parental cells, whereas overexpression of talin-F3, a subdomain of the talin head domain, restored the function. Our present data suggest that ILK contributes to inside-out integrin activation.
Spatiotemporal association of DNAJB13 with the annulus during mouse sperm flagellum development
Authors: Guan Jikui , Kinoshita Makoto , Yuan Li
Published: March 2009

Background

The sperm annulus is a septin-based fibrous ring structure connecting the midpiece and the principal piece of the mammalian sperm flagellum. Although ultrastructural abnormalities and functional importance of the annulus have been addressed in Sept4-null mutant mice and a subset of human patients with asthenospermia syndrome, little is known about how the structure is assembled and positioned to the midpiece-principal piece junction during mammalian sperm flagellum development.

Results

By performing immunofluorescence and biochemical approaches with antibodies against DNAJB13 and an annulus constituent SEPT4, we report here a spatiotemporal association of DNAJB13 with sperm annulus during mouse sperm flagellum development. DNAJB13 co-localized with SEPT4 to the annulus, and both were first able to be detected in step 9 spermatids. As spermiogenesis proceeded, the annular DNAJB13 immunosignal increased until the annulus reached the midpiece-principal piece junction, and then gradually disappeared from it in late spermiogenesis. In contrast, the SEPT4 immunosignal was relatively unaltered, and still present on annulus of mature spermatozoa. In Sept4-null mouse spermatids lacking the annulus structure, the annulus-like DNAJB13 immunosignal was still able to be detected, albeit weaker, at the neck region of the flagella. In vitro DNAJB13 was co-localized and interacted with SEPT4 directly.

Conclusion

The direct interaction of DNAJB13 with SEPT4 in vitro and its spatiotemporal association with the annulus during sperm flagellum development, and even its annulus-like appearance in the annulus-deficient spermatids, suggest that DNAJB13 may be involved in assembling the annulus structure and positioning it towards the midpiece-principal piece junction.
Yeast Sgf73/Ataxin-7 serves to anchor the deubiquitination module into both SAGA and Slik(SALSA) HAT complexes
Authors: Lee Kenneth K , Swanson Selene K , Florens Laurence , Washburn Michael P , Workman Jerry L
Published: March 2009

Spinocerebellar ataxia (SCA) is a physically devastating, genetically inherited disorder characterized by abnormal brain function that results in the progressive loss of the ability to coordinate movements. There are many types of SCAs as there are various gene mutations that can cause this disease. SCA types 1–3, 6–10, 12, and 17 result from a trinucleotide repeat expansion in the DNA-coding sequence. Intriguingly, recent work has demonstrated that increased trinucleotde expansions in the SCA7 gene result in defect in the function of the SAGA histone acetyltransferase complex. The SCA7 gene encodes a subunit of the SAGA complex. This subunit is conserved in yeast as the SGF73 gene. We demonstrate that Sgf73 is required to recruit the histone deubiquitination module into both SAGA and the related SliK(SALSA) complex, and to maintain levels of histone ubiquitination, which is necessary for regulation of transcription at a number of genes.
DrosophilaTubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation
Authors: Jin Shan , Pan Luyuan , Liu Zhihua , Wang Qifu , Xu Zhiheng , Zhang Yong Q.
Published: March 2009

Hypoparathyroidism, mental retardation and facial dysmorphism (HRD) is a fatal developmental disease caused by mutations in tubulin-specific chaperone E (TBCE). A mouse Tbce mutation causes progressive motor neuronopathy. To dissect the functions of TBCE and the pathogenesis of HRD, we generated mutations in Drosophila tbce, and manipulated its expression in a tissue-specific manner. Drosophila tbce nulls are embryonic lethal. Tissue-specific knockdown and overexpression of tbce in neuromusculature resulted in disrupted and increased microtubules, respectively. Alterations in TBCE expression also affected neuromuscular synapses. Genetic analyses revealed an antagonistic interaction between TBCE and the microtubule-severing protein Spastin. Moreover, treatment of muscles with the microtubule-depolymerizing drug nocodazole implicated TBCE as a tubulin polymerizing protein. Taken together, our results demonstrate that TBCE is required for the normal development and function of neuromuscular synapses and that it promotes microtubule formation. As defective microtubules are implicated in many neurological and developmental diseases, our work on TBCE may offer novel insights into their basis.
On the Emergence of the Progressive and other Aspectual Formations in Irish and Celtic
Authors: Corráin Ailbhe Ó
Published: March 2009

This paper examines the evolution of aspectual formations in Insular Celtic. It is argued that the emergence of these formations and their unusual morphosyntactic structure have been determined by internal systemic factors. It is also suggested that the manner in which these formations developed is of importance for our understanding of the processes involved in the emergence of grammatical subsystems in general. It is demonstrated that the Celtic aspectual system evolves in a manner reminiscent of the concept of developmental stratification and, significantly, that it evolves in a remarkably coherent and ordered fashion. The inexorable and structured nature of this evolution would seem to provide evidence for the claim that there may exist within languages a certain teleological impulse; in other words, that rather than being simply random, language change is in some fundamental and meaningful sense goal-directed.
Defining User Access to the Romanian Online Dialect Atlas
Authors: Embleton Sheila , Uritescu Dorin , Wheeler Eric S.
Published: March 2009

The Romanian Online Dialect Atlas (RODA) provides a digitized version of an extensive hard-copy atlas of the Crişana region of Romania (Stan & Uritescu, Noul Atlas lingvistic român. Crişana Vol. I, 1996, Stan & Uritescu, Noul Atlas lingvistic român. Crişana Vol. II, 2003). The set of tools we are now developing permits us to access data on a range of questions that would have been difficult to answer otherwise, and to visualize the results with dynamically generated maps.
Latvian in Siberia: The Present and Prospects
Authors: Stafecka Anna
Published: March 2009

This paper deals with the language used in Latvian settlements in Siberia. It is based on the author's observations and on data gathered during three ethnolinguistic expeditions to Lejas Bulana, in the Krasnoyarsk District, in 1991 and 2004, as well as to Timofejevka, in the Novosibirsk District, in 2006.

An analysis was carried out to assess the extent of the Latvian language in these areas, which are separated from their ethnic territory. The study focussed on the language skills of different generations, depending on their education, religious identity and amount of communication with Latvia. The situation is better in Lejas Bulana, where in recent years teachers have been coming from Latvia. However, this community is losing its young generation to big cities, where their exposure to Latvian culture is lost, and thus little by little they begin to forget the Latvian language
A Critical Assessment of Global Mechanical Approaches to Creep Crack Initiation and Creep Crack Growth in 316L Steel
Authors: Bensussan P , Piques R , Pineau A
Published: March 2009

Both the initiation and propagation of macroscopic creep cracks have been studied in 316L stainless steel at 575 to 650C. This alloy was found to be creep ductile, which can be justified in terms of fracture mechanics concepts applied to creeping solids. Fracture mechanics is yet unable to provide unique correlations with global load-geometry parameters, such as K, J, or C*, for all the stages of both creep crack initiation and growth. Unique correlations nevertheless exist between C* and the time to initiation, and between C* and the Stage I to Stage II crack growth transition time. Time versus C* diagrams based on these latter correlations, in which creep crack initiation, slow creep crack growth, and fast creep crack growth regimes can be delimited, are the only global approach data which can be safely used for life prediction purposes in engineering applications.
Growth of Macroscopic Cracks by Void Coalescence Under Extensive Creeping Conditions
Authors: Hui C-Y , Wu K-C
Published: March 2009

The growth history of a macroscopic crack at high temperatures is studied using a crack growth criterion based on void growth and coalescence. Two models of crack growth are considered: a discrete model in which the crack advances by discrete jumps, each with a length equal to the void spacing, and a continuous model in which the crack advances continuously because of the accumulation of damage ahead of the crack tip. The resulting crack growth histories based on the two models are compared. Our results indicate that, irrespective of the void growth mechanisms, the continuous and discrete models give practically the same results. The effect of void nucleation is included in the analysis by the requirement that no void growth occur below a critical void nucleation stress. For the continuous crack growth model, an exact solution for the entire crack growth history is obtained as a function of the path-independent integral C* for a wide variety of void growth mechanisms. Both discrete and continuous models show that crack growth exhibits stop, and go, behavior before approaching steady state. The amplitude of these stop and go episodes is shown to decrease exponentially to zero with a characteristic distance R, where R is the nucleation distance. It was found that the steady-state crack growth rate is approximately proportional to C* and independent of the void growth mechanisms. The authors also show that the presence of a breakpoint commonly observed in the experimental crack extension rate versus C* curves can be explained by examining the entire crack growth history predicted by the models.
An Anisotropic, Damage-Coupled Viscoplastic Model for Creep-Dominated Cyclic Loading
Authors: McDowell DL , Ho K-I , Stalley J
Published: March 2009

There are many practical applications in the power and propulsion industries that involve sustained periods of loading at high temperatures with periodic unloading-reloading sequences. Such histories may often be regarded as creep-dominated when only a small number of unloading-reloading events occurs over the life of the component. Typically, thermal constraint additionally results in rotation of the principal stress axes with respect to fixed material axes in regions of stress and temperature gradients, such as nozzle inlets. This rotation may produce anisotropic states of both creep damage and inelastic deformation. Such rotations also occur in the creep zone for an advancing creep crack or if far-field tractions change nonproportionally. In this paper, a continuum creep damage approach is coupled with a rate-dependent bounding surface theory to correlate nonproportional, axial-torsional experiments conducted on thin-walled tubular specimens of Type 304 stainless steel at 593C. A directionally dependent scalar damage distribution evolves as a second-order, symmetric tensor for each unique set of principal stress axes for this material, based on quantitative metallographic assessment of the damage distribution. A general higher order symmetric damage growth law is also introduced.
Influence of Loading Rate on the Deformation and Ductile Fracture of A533B Steel at 70C
Authors: Smith DJ , Garwood SJ
Published: March 2009

Many engineering materials exhibit rate- or time-dependent inelastic deformation. This phenomenon is generally associated with the strain rate sensitivity of the flow stress. The main objective of the work described in this paper is to examine the influence of loading rate on the deformation and ductile fracture of a reactor pressure vessel steel, A533B Class 1, at 70C.

The reported experimental work is in three parts, examining the behavior of (1) uniaxial specimens, (2) small-scale notched bend specimens, and (3) large-scale notched plate specimens (wide plates). The tests on the notched bend and the plate specimens were part of an earlier test program conducted at The Welding Institute. To complement the previous experimental work, the rate dependence of plastic deformation was examined using uniaxial specimens. The observed rate dependence of the flow stress is shown to agree with collated data from the literature. The amount of creep deformation under sustained loading is shown to be large.

A detailed examination of earlier small-scale notched bend experiments shows that there is an influence of applied loading rate on the material's resistance to continuing ductile fracture in terms of J and crack-tip opening displacement. However, the data obtained are of a limited nature. A distinction is drawn between locally controlled displacement rates and globally controlled loading conditions. For the latter case, the resistance curve obtained is considered to be a locus through a series of resistance curves obtained from locally controlled bend tests.

The wide-plate tests have also been examined in detail. The plate deformations during sustained loading are shown to be extensive. Furthermore, clear evidence of crack growth during the load hold periods has been found. The resistance curves for the large-scale specimens are shown to be significantly influenced by the creep deformation.

The effect of loading rate on the resistance curves for A533B steel at 70C is shown to be marginal and in agreement with the weak strain-rate sensitivity of the flow stress. However, the wide-plate specimens, which exhibit less constraint than bend specimens, are more likely to creep under uncontained yielding conditions than to exhibit continuing ductile crack growth.
Measurement of the J-Integral with Caustics: An Experimental and Numerical Investigation
Authors: Zehnder AT , Rosakis AJ , Narasimhan R
Published: March 2009

The optical method of caustics as applied to the measurement of the J-integral in plastically deforming materials was studied numerically and experimentally. The numerical calculations modeled a cracked body loaded under Mode I, plane-stress, small-scale yielding conditions. The results were used to generate simulated optical patterns for caustics obtained from both inside and outside the crack-tip plastic zone. These caustics were compared with corresponding caustics observed experimentally. In addition, the region of dominance of the plane-stress, Hutchinson-Rice-Rosengren (HRR) field was investigated, and the effect of plasticity on the accuracy of caustics from the elastic region outside the plastic zone was determined. The extent of the region of three dimensionality near the crack tip and its effect on the method of caustics were also investigated.