bluuebunny/crossref_metadata_2025 huggingface dataset:
Tamavidins – novel avidin‐like biotin‐binding proteins from the Tamogitake mushroom
Authors: Takakura Yoshimitsu , Tsunashima Masako , Suzuki Junko , Usami Satoru , Kakuta Yoshimitsu , Okino Nozomu , Ito Makoto , Yamamoto Takeshi
Published: January 2009

Novel biotin‐binding proteins, referred to herein as tamavidin 1 and tamavidin 2, were found in a basidiomycete fungus, Pleurotus cornucopiae, known as the Tamogitake mushroom. These are the first avidin‐like proteins to be discovered in organisms other than birds and bacteria. Tamavidin 1 and tamavidin 2 have amino acid sequences with 31% and 36% identity, respectively, to avidin, and 47% and 48% identity, respectively, to streptavidin. Unlike any other biotin‐binding proteins, tamavidin 1 and tamavidin 2 are expressed as soluble proteins at a high level in Escherichia coli. Recombinant tamavidin 2 was purified as a tetrameric protein in a single step by 2‐iminobiotin affinity chromatography, with a yield of 5 mg per 100 mL culture of E. coli. The kinetic parameters measured by a BIAcore biosensor indicated that recombinant tamavidin 2 binds biotin with high affinity, in a similar manner to binding by avidin and streptavidin. The overall crystal structure of recombinant tamavidin 2 is similar to that of avidin and streptavidin. However, recombinant tamavidin 2 is immunologically distinct from avidin and streptavidin. Tamavidin 2 and streptavidin are very similar in terms of the arrangement of the residues interacting with biotin, but different with regard to the number of hydrogen bonds to biotin carboxylate. Recombinant tamavidin 2 is more stable than avidin and streptavidin at high temperature, and nonspecific binding to DNA and human serum by recombinant tamavidin 2 is lower than that for avidin. These findings highlight tamavidin 2 as a probable powerful tool, in addition to avidin and streptavidin, in numerous applications of biotin‐binding proteins.
Do Terrestrial Tank Bromeliads in Brazil Create Safe Sites for Palm Establishment or Act as Natural Traps for Its Dispersed Seeds?
Authors: Brancalion Pedro H. S. , Gabriel Vagner de A. , Gómez José M.
Published: January 2009

This study shows for the first time that terrestrial tank bromeliads from Brazilian restinga can act as natural traps for dispersed palm Euterpe edulis seeds. Such bromeliads, which are shade intolerant, gain benefits by limiting palm recruitment since they hinder canopy formation and, consequently, increase luminosity over its aggregates.
Appropriateness of Cholesterol Management in Primary Care by Sex and Level of Cardiovascular Risk
Authors: Barham Ann Hiott , Goff Jr David C , Chen Haiying , Balasubramanyam Aarthi , Rosenberger Erica , Bonds Denise E. , Bertoni Alain G.
Published: January 2009

A study was undertaken to ascertain the appropriateness of lipid screening and management per the Third Report of the Adult Treatment Panel National Cholesterol Education Program (ATP III) guideline in a sample of North Carolina primary care practices. Demographics, cholesterol values, and comorbid conditions were abstracted from the medical records from 60 community practices participating in a randomized practice‐based trial (Guideline Adherence for Heart Health). Eligible patients were aged 21 to 84 years, seen during the baseline period of June 1, 2001, through May 31, 2003, and who were not taking lipid‐lowering therapy. Multivariable logistic regression was utilized to assess whether age, sex, race/ethnicity, diabetes, cardiovascular disease, ATP III risk category, or pretreatment low‐density lipoprotein (LDL) influenced treatment. Among 5031 eligible patients, 1711 (34.5%) received screening lipid profiles. Screening rates were higher with older age, diabetes, and cardiovascular disease. No large differences were seen by sex. Among patients screened (mean age, 51.6 years; 57.9% female), 76.6% were appropriately managed within 4 months. In adjusted analyses, older age was associated with less appropriate treatment (odds ratio [OR] per 5 years, 0.91; P=.01), and patients with LDL cholesterol ≤130 mg/dL (OR, 18.8; P<.001) and the low‐risk group (OR, 27.5; P<.001) were more likely to be managed appropriately compared with patients with LDL ≥190 mg/dL and those at high risk. Among 375 patients eligible for drug treatment, those with LDL levels between 131 and 159 mg/dL were much less likely to be treated (OR, 0.15; P<.001) compared with those with LDL >190 mg/dL, whereas risk category did not influence treatment. The challenge facing implementation of ATP III guidelines is much greater for intermediate‐ and high‐risk patients than for low‐risk patients.
Microsatellite markers isolated from Drosophila hydei
Authors: PETERS MAUREEN B. , HAGEN CRIS , SNYDER BRIAN , GLENN TRAVIS C. , GOWATY PATRICIA ADAIR
Published: January 2009

We isolated and characterized 10 polymorphic microsatellite loci in Drosophila hydei. The number of alleles per locus ranged from 3 to 8 (N = 23 individuals). Polymorphic information content ranged from 0.316 to 0.750 and observed heterozygosity from 0.261 to 0.913. These markers will be valuable in studies of sexual selection and parental investment in D. hydei.
Chloroplast simple sequence repeats (cpSSRs): technical resources and recommendations for expanding cpSSR discovery and applications to a wide array of plant species
Authors: EBERT DANIEL , PEAKALL ROD
Published: January 2009

Chloroplast microsatellites, or simple sequence repeats (cpSSRs), are typically mononucleotide tandem repeats. When located in the noncoding regions of the chloroplast genome (cpDNA), they commonly show intraspecific variation in repeat number. Despite the growing number of studies applying cpSSRs, studies of economically important plants and their relatives remain over‐represented. Thus, the potential of cpSSRs to offer unique insights into ecological and evolutionary processes in wild plant species has yet to be fully realized. This review provides an overview of the technical resources available to aid cpSSR discovery including a list of cpSSR primer sets available and cpDNA sequencing resources. Our updated analysis of 99 whole chloroplast genomes downloaded from GenBank confirms that potentially variable cpSSRs are abundant in the noncoding cpDNA of plants. Overall variation in the frequency of cpSSRs was extreme, ranging from one to 700 per genome (median = 93), while in 81 vascular plants, between 35 and 160 cpSSRs were detected per genome (median = 86). We offer five recommendations to aid wider development and application of cpSSRs: (i) When genus‐specific cpSSR primers are available, cross‐species amplification can often be fruitful. (ii) While potentially useful, universal cpSSR primers at best provide access to only a small number of variable markers. (iii) De novo sequencing of noncoding cpDNA is the most effective and efficient way to develop cpSSR markers in wild species. (iv) DNA sequencing of cpSSR alleles is essential, given the complex nature of the genetic variation associated with hypervariable cpDNA regions. (v) The reliability of cpSSR length based genetic assays need to be validated in all studies.
Posterior pedicle screws combined with shortening and release techniques for lumbar and thoracolumbar adolescent idiopathic scoliosis
Authors: Gu Su‐xi , Li Ming , Zhu Xiao‐dong , Wang Chuan‐feng , Wu Da‐jiang , Zhao Ying‐chuan
Published: January 2009

Objective:  To prospectively evaluate the clinical and radiographic effects of posterior surgery with wide posterior shortening release and segmental pedicle screws techniques in a consecutive group of patients with thoracolumbar /lumbar adolescent idiopathic scoliosis.

Methods:  Between April 2002 and July 2005, 114 patients (86 women and 28 men) were enrolled in this study. There were 72 Lenke type 5, 32 Lenke type 6, and 10 Lenke type 3C curves. Radiographic parameters such as coronal plane Cobb angle; lordosis angle; lowest instrumented vertebrae (LIV) angulation; and the distances from the central sacral vertical line (CSVL) to the LIV, to the apical vertebra and to the C7 plumb line, were analyzed. Complication rates were also recorded during follow‐up.

Results:  The average coronal correction was from 61° to 13° (78.6%). In the sagittal plane, lumbar lordosis was normalized from 36° with a wide range (23°–67°) to 42° with a normal range (34°–55°). The LIV had 79% correction of coronal angulations. The center sacral line to LIV was improved from 2.3 cm to 0.5 cm, apex to center sacral line from 5.0 cm to 1.6 cm, and CSVL from 2.7 cm to 0.8 cm. A total of 1460 pedicle screws were placed safely, average 9.6 levels (5–14) were fused. The patients were followed up for an average of 30 months (range, 12–50). There was excellent maintenance of correction at final follow‐up.

Conclusion:  Wide posterior release and segmental pedicle screw instrumentation has excellent radiographic and clinical results with minimal complications.
A Receptor-Like Protein That Promotes Polarization of an Asymmetric Cell Division in Maize
Authors: Cartwright Heather N. , Humphries John A. , Smith Laurie G.
Published: January 2009

Polarization of cell division is essential for eukaryotic development, but little is known about how this is accomplished in plants. The formation of stomatal complexes in maize involves the polarization of asymmetric subsidiary mother cell (SMC) divisions toward the adjacent guard mother cell (GMC), apparently under the influence of a GMC-derived signal. We found that the maize
pan1
gene promotes the premitotic polarization of SMCs and encodes a leucine-rich repeat receptor-like protein that becomes localized in SMCs at sites of GMC contact. PAN1 has an inactive kinase domain but is required for the accumulation of a membrane-associated phosphoprotein, suggesting a function for PAN1 in signal transduction. Our findings implicate PAN1 in the transmission of an extrinsic signal that polarizes asymmetric SMC divisions toward GMCs.
Comment on "Arsenic (III) Fuels Anoxygenic Photosynthesis in Hot Spring Biofilms from Mono Lake, California"
Authors: Schoepp-Cothenet B. , Duval S. , Santini J. M. , Nitschke W.
Published: January 2009

Kulp
et al
. (Reports, 15 August 2008, p. 967) described a bacterium able to photosynthetically oxidize arsenite [As(III)] via arsenate [As(V)] reductase functioning in reverse. Based on their phylogenetic analysis of As(V) reductase, they proposed that this enzyme was responsible for the anaerobic oxidation of As(III) in the Archean. We challenge this proposition based on paleogeochemical, bioenergetic, and phylogenetic arguments.
A Human Telomerase Holoenzyme Protein Required for Cajal Body Localization and Telomere Synthesis
Authors: Venteicher Andrew S. , Abreu Eladio B. , Meng Zhaojing , McCann Kelly E. , Terns Rebecca M. , Veenstra Timothy D. , Terns Michael P. , Artandi Steven E.
Published: January 2009

Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomere repeats in tissue progenitor cells and cancer cells. Active human telomerase consists of at least three principal subunits, including the telomerase reverse transcriptase, the telomerase RNA (TERC), and dyskerin. Here, we identify a holoenzyme subunit, TCAB1 (telomerase Cajal body protein 1), that is notably enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. TCAB1 associates with active telomerase enzyme, established telomerase components, and small Cajal body RNAs that are involved in modifying splicing RNAs. Depletion of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase-telomere association, and abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase trafficking and is required for telomere synthesis in human cancer cells.
Divergent Evolution of Duplicate Genes Leads to Genetic Incompatibilities Within
A. thaliana
Authors: Bikard David , Patel Dhaval , Le Metté Claire , Giorgi Veronica , Camilleri Christine , Bennett Malcolm J. , Loudet Olivier
Published: January 2009

Genetic incompatibilities resulting from interactions between two loci represent a potential source of postzygotic barriers and may be an important factor in evolution when they impair the outcome of interspecific crosses. We show that, in crosses between strains of the plant
Arabidopsis thaliana
, loci interact epistatically, controlling a recessive embryo lethality. This interaction is explained by divergent evolution occurring among paralogs of an essential duplicate gene, for which the functional copy is not located at the same locus in different accessions. These paralogs demonstrate genetic heterogeneity in their respective evolutionary trajectories, which results in widespread incompatibility among strains. Our data suggest that these passive mechanisms, gene duplication and extinction, could represent an important source of genetic incompatibilities across all taxa.
Serotonin Mediates Behavioral Gregarization Underlying Swarm Formation in Desert Locusts
Authors: Anstey Michael L. , Rogers Stephen M. , Ott Swidbert R. , Burrows Malcolm , Simpson Stephen J.
Published: January 2009

Desert locusts,
Schistocerca gregaria
, show extreme phenotypic plasticity, transforming between a little-seen solitarious phase and the notorious swarming gregarious phase depending on population density. An essential tipping point in the process of swarm formation is the initial switch from strong mutual aversion in solitarious locusts to coherent group formation and greater activity in gregarious locusts. We show here that serotonin, an evolutionarily conserved mediator of neuronal plasticity, is responsible for this behavioral transformation, being both necessary if behavioral gregarization is to occur and sufficient to induce it. Our data demonstrate a neurochemical mechanism linking interactions between individuals to large-scale changes in population structure and the onset of mass migration.
Survival from Hypoxia in
C. elegans
by Inactivation of Aminoacyl-tRNA Synthetases
Authors: Anderson Lori L. , Mao Xianrong , Scott Barbara A. , Crowder C. Michael
Published: January 2009

Hypoxia is important in a wide range of biological processes, such as animal hibernation and cell survival, and is particularly relevant in many diseases. The sensitivity of cells and organisms to hypoxic injury varies widely, but the molecular basis for this variation is incompletely understood. Using forward genetic screens in
Caenorhabditis elegans
, we isolated a hypoxia-resistant reduction-of-function mutant of
rrt-1
that encodes an arginyl–transfer RNA (tRNA) synthetase, an enzyme essential for protein translation. Knockdown of
rrt-1
, and of most other genes encoding aminoacyl-tRNA synthetases, rescued animals from hypoxia-induced death, and the level of hypoxia resistance was inversely correlated with translation rate. The unfolded protein response was induced by hypoxia and was required for the hypoxia resistance of the reduction-of-function mutant of
rrt-1
. Thus, translational suppression produces hypoxia resistance, in part by reducing unfolded protein toxicity.
Ligand-Dependent Equilibrium Fluctuations of Single Calmodulin Molecules
Authors: Junker Jan Philipp , Ziegler Fabian , Rief Matthias
Published: January 2009

Single-molecule force spectroscopy allows superb mechanical control of protein conformation. We used a custom-built low-drift atomic force microscope to observe mechanically induced conformational equilibrium fluctuations of single molecules of the eukaryotic calcium-dependent signal transducer calmodulin (CaM). From this data, the ligand dependence of the full energy landscape can be reconstructed. We find that calcium ions affect the folding kinetics of the individual CaM domains, whereas target peptides stabilize the already folded structure. Single-molecule data of full length CaM reveal that a wasp venom peptide binds noncooperatively to CaM with 2:1 stoichiometry, whereas a target enzyme peptide binds cooperatively with 1:1 stoichiometry. If mechanical load is applied directly to the target peptide, real-time binding/unbinding transitions can be observed.
Dynamical Quorum Sensing and Synchronization in Large Populations of Chemical Oscillators
Authors: Taylor Annette F. , Tinsley Mark R. , Wang Fang , Huang Zhaoyang , Showalter Kenneth
Published: January 2009

Populations of certain unicellular organisms, such as suspensions of yeast in nutrient solutions, undergo transitions to coordinated activity with increasing cell density. The collective behavior is believed to arise through communication by chemical signaling via the extracellular solution. We studied large, heterogeneous populations of discrete chemical oscillators (∼100,000) with well-defined kinetics to characterize two different types of density-dependent transitions to synchronized oscillatory behavior. For different chemical exchange rates between the oscillators and the surrounding solution, increasing oscillator density led to (i) the gradual synchronization of oscillatory activity, or (ii) the sudden “switching on” of synchronized oscillatory activity. We analyze the roles of oscillator density and exchange rate of signaling species in these transitions with a mathematical model of the interacting chemical oscillators.
Calcineurin/NFAT Signaling Is Required for Neuregulin-Regulated Schwann Cell Differentiation
Authors: Kao Shih-Chu , Wu Hai , Xie Jianming , Chang Ching-Pin , Ranish Jeffrey A. , Graef Isabella A. , Crabtree Gerald R.
Published: January 2009

Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking
calcineurin B1
in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca
2+
, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate
Krox20
, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.
Facile Synthesis of AsP
3
Authors: Cossairt Brandi M. , Diawara Mariam-Céline , Cummins Christopher C.
Published: January 2009

The elements phosphorus and arsenic form tetrahedral P4 and As4 molecules, of which the former is a commodity chemical and the latter unstable. Previously, information on molecules of intermediate composition was limited to a spectroscopic study involving hot gas-phase mixtures of phosphorus and arsenic. The AsP3 molecule has yielded to chemical synthesis and was isolated in solid form as a pure substance with a melting point from 71° to 73°C. Physical properties and spectroscopic characterization data for AsP3 are described, and its structure was determined as a ligand in a coordination complex. Soluble in organic solvents, AsP3 represents an attractive starting point for any synthesis in which the target molecule or material contains an exact 1:3 ratio of arsenic to phosphorus.
Mechanically Activated Integrin Switch Controls α
5
β
1
Function
Authors: Friedland Julie C. , Lee Mark H. , Boettiger David
Published: January 2009

The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that α
5
β
1
integrin switches between relaxed and tensioned states in response to myosin II–generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the α
5
β
1
-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.
Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy
Authors: Savitt Anne G. , Mena-Taboada Patricio , Monsalve Gloria , Benach Jorge L.
Published: January 2009

Francisella tularensisis the causative agent of tularemia and a potential agent of biowarfare. As an easily transmissible infectious agent, rapid detection and treatment are necessary to provide a positive clinical outcome. As an agent of biowarfare, there is an additional need to prevent infection. We made monoclonal antibodies to theF. tularensissubsp.holarcticalive vaccine strain (F. tularensisLVS) by infecting mice with a sublethal dose of bacteria and, following recovery, by boosting the mice with sonicated organisms. The response to the initial and primary infection was restricted to immunoglobulin M antibody directed solely against lipopolysaccharide (LPS). After boosting with sonicated organisms, the specificity repertoire broadened against protein antigens, including DnaK, LpnA, FopA, bacterioferritin, the 50S ribosomal protein L7/L12, and metabolic enzymes. These monoclonal antibodies detectF. tularensisLVS by routine immunoassays, including enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence. The ability of the antibodies to protect mice from intradermal infection, both prophylactically and therapeutically, was examined. An antibody to LPS which provides complete protection from infection withF. tularensisLVS and partial protection from infection withF. tularensissubsp.tularensisstrain SchuS4 was identified. There was no bacteremia and reduced organ burden within the first 24 h when mice were protected fromF. tularensisLVS infection with the anti-LPS antibody. No antibody that provided complete protection when administered therapeutically was identified; however, passive transfer of antibodies against LPS, FopA, and LpnA resulted in 40 to 50% survival of mice infected withF. tularensisLVS.
Herpes Simplex Virus Utilizes the Large Secretory Vesicle Pathway for Anterograde Transport of Tegument and Envelope Proteins and for Viral Exocytosis from Growth Cones of Human Fetal Axons
Authors: Miranda-Saksena Monica , Boadle Ross A. , Aggarwal Anupriya , Tijono Bibing , Rixon Frazer J. , Diefenbach Russell J. , Cunningham Anthony L.
Published: January 2009

Axonal transport of herpes simplex virus (HSV-1) is essential for viral infection and spread in the peripheral nervous system of the host. Therefore, the virus probably utilizes existing active transport and targeting mechanisms in neurons for virus assembly and spread from neurons to skin. In the present study, we used transmission immnunoelectron microscopy to investigate the nature and origin of vesicles involved in the anterograde axonal transport of HSV-1 tegument and envelope proteins and of vesicles surrounding partially and fully enveloped capsids in growth cones. This study aimed to elucidate the mechanism of virus assembly and exit from axons of human fetal dorsal root ganglia neurons. We demonstrated that viral tegument and envelope proteins can travel in axons independently of viral capsids and were transported to the axon terminus in two types of transport vesicles, tubulovesicular membrane structures and large dense-cored vesicles. These vesicles and membrane carriers were derived from the
trans
-Golgi network (TGN) and contained key proteins, such as Rab3A, SNAP-25, GAP-43, and kinesin-1, involved in the secretory and exocytic pathways in axons. These proteins were also observed on fully and partially enveloped capsids in growth cones and on extracellular virions. Our findings provide further evidence to the subassembly model of separate transport in axons of unenveloped capsids from envelope and tegument proteins with final virus assembly occurring at the axon terminus. We postulate that HSV-1 capsids invaginate tegument- and envelope-bearing TGN-derived vesicles and utilize the large secretory vesicle pathway of exocytosis for exit from axons.
Alphavirus-Adjuvanted Norovirus-Like Particle Vaccines: Heterologous, Humoral, and Mucosal Immune Responses Protect against Murine Norovirus Challenge
Authors: LoBue Anna D. , Thompson Joseph M. , Lindesmith Lisa , Johnston Robert E. , Baric Ralph S.
Published: January 2009

The development of an effective norovirus vaccine likely requires the capacity to protect against infection with multiple norovirus strains. Advanced recombinant genetic systems and the recent discovery of a mouse-tropic norovirus strain (MNV) provide robust model systems for vaccine efficacy studies. We coadministered multivalent norovirus-like particle (VLP) vaccines with alphavirus adjuvant particles to mice and evaluated homotypic and heterotypic humoral and protective immunity to human and murine norovirus strains. Multivalent VLP vaccines induced robust receptor-blocking antibody responses to heterologous human strains not included in the vaccine composition. Inclusion of alphavirus adjuvants in the inoculum significantly augmented VLP-induced systemic and mucosal immunity compared to the responses induced by low-dose CpG DNA, validating the utility of such adjuvants with VLP antigens. Furthermore, multivalent vaccination, either including or excluding MNV VLP, resulted in significantly reduced viral loads following MNV challenge. Passive transfer of sera from mice monovalently vaccinated with MNV VLP to immunodeficient or immunocompetent mice protected against MNV infection; however, adoptive transfer of purified CD4
+
or CD8
+
cells did not influence viral loads in murine tissues. Together, these data suggest that humoral immunity induced by multivalent norovirus vaccines may protect against heterologous norovirus challenge.
Usage of Integrin and Heparan Sulfate as Receptors for Mouse Adenovirus Type 1
Authors: Raman Sharmila , Hsu Tien-Huei , Ashley Shanna L. , Spindler Katherine R.
Published: January 2009

Adenovirus fiber knobs are the capsid components that interact with binding receptors on cells, while an Arg-Gly-Asp (RGD) sequence usually found in the penton base protein is important for the interaction of most adenoviruses with integrin entry receptors. Mouse adenovirus type 1 (MAV-1) lacks an RGD sequence in the virion penton base protein. We tested whether an RGD sequence found in the MAV-1 fiber knob plays a role in infection. Treatment of cells with a competitor RGD peptide or a purified recombinant RGD-containing fiber knob prior to infection resulted in reduced virus yields compared to those of controls, indicating the importance of the RGD sequence for infection. An investigation of the role of integrins as possible receptors showed that MAV-1 yields were reduced in the presence of EDTA, an inhibitor of integrin binding, and in the presence of anti-α
v
integrin antibody. Moreover, mouse embryo fibroblasts that were genetically deficient in α
v
integrin yielded less virus, supporting the hypothesis that α
v
integrin is a likely receptor for MAV-1. We also investigated whether glycosaminoglycans play a role in MAV-1 infection. Preincubation of MAV-1 with heparin, a heparan sulfate glycosaminoglycan analog, resulted in a decrease in MAV-1 virus yields. Reduced MAV-1 infectivity was also found with cells that genetically lack heparan sulfate or cells that were treated with heparinase I. Cumulatively, our data demonstrate that the RGD sequence in the MAV-1 fiber knob plays a role in infection by MAV-1, α
v
integrin acts as a receptor for the virus, and cell surface heparin sulfate glycosaminoglycans are important in MAV-1 infection.
Nonintegrating Lentivector Vaccines Stimulate Prolonged T-Cell and Antibody Responses and Are Effective in Tumor Therapy
Authors: Karwacz Katarzyna , Mukherjee Sayandip , Apolonia Luis , Blundell Michael P. , Bouma Gerben , Escors David , Collins Mary K. , Thrasher Adrian J.
Published: January 2009

Lentiviral vectors (lentivectors) are effective for stimulation of cell-mediated and humoral immunity following subcutaneous and intramuscular immunization. However, lentivector genome integration carries a risk of perturbation of host gene expression. Here, we demonstrate that lentivectors with multiple mutations that prevent integration are also effective immunogens. First, systemic CD8+T-cell responses to the model antigen ovalbumin were detected following subcutaneous injection of nonintegrating lentivectors. Transfer of transgenic OT1 T cells demonstrated that antigen presentation persisted for at least 30 days. Furthermore, an enhanced CD8+T-cell response, peaking at 7 days, was stimulated by coexpression of p38 MAP kinase or an NF-κB activator from the same vector. Second, we demonstrated systemic CD8+T-cell and antibody responses to the secreted hepatitis B virus (HBV) surface antigen expressed from a nonintegrating lentivector injected intramuscularly. The induction, specificity, and kinetics of antibody production closely mimicked those of natural HBV infection. In this case, both the vector genome and the immune response were maintained for at least 2 months. Together, our data indicate that nonintegrating lentivectors can be employed to generate effective vaccines.
CoMPSoC
Authors: Hansson Andreas , Goossens Kees , Bekooij Marco , Huisken Jos
Published: January 2009

A growing number of applications, often with firm or soft real-time requirements, are integrated on the same System on Chip, in the form of either hardware or software intellectual property. The applications are started and stopped at run time, creating different use-cases. Resources, such as interconnects and memories, are shared between different applications, both within and between use-cases, to reduce silicon cost and power consumption.

The functional and temporal behaviour of the applications is verified by simulation and formal methods. Traditionally, designers resort to monolithic verification of the system as whole, since the applications interfere in shared resources, and thus affect each other's behaviour. Due to interference between applications, the integration and verification complexity grows exponentially in the number of applications, and the task to verify correct behaviour of concurrent applications is on the system designer rather than the application designers.

In this work, we propose a Composable and Predictable Multi-Processor System on Chip (CoMPSoC) platform template. This scalable hardware and software template removes all interference between applications through resource reservations. We demonstrate how this enables a divide-and-conquer design strategy, where all applications, potentially using different programming models and communication paradigms, are developed and verified independently of one another. Performance is analyzed per application, using state-of-the-art dataflow techniques or simulation, depending on the requirements of the application. These results still apply when the applications are integrated onto the platform, thus separating system-level design and application design.
An energy-efficient I/O request mechanism for multi-bank flash-memory storage systems
Authors: Wu Chin-Hsien
Published: January 2009

Emerging critical issues for flash-memory storage systems, especially with regard to implementation within many embedded systems, are the programmed I/O nature of data transfers and their energy-efficient nature. We propose an I/O request mechanism in the Memory-Technology-Device (MTD) layer to exploit the programmed I/O-based data transfers for flash-memory storage systems. We propose to revise the waiting function in the Memory-Technology-Device (MTD) layer to relieve the microprocessor from busy-waiting, in order to make more CPU cycles available for other tasks. An energy-efficient mechanism based on the I/O request mechanism is also presented for multi-bank flash-memory storage systems, which particularly focuses on switching the power state of each flash-memory bank. We demonstrate that the energy-efficient I/O request mechanism not only saves more CPU cycles to execute other tasks, but also reduces the energy consumption of flash-memory, based on experiments incorporating realistic system workloads.
Design intent coverage revisited
Authors: Sinha Arnab , Dasgupta Pallab , Pal Bhaskar , Das Sayantan , Basu Prasenjit , Chakrabarti P. P.
Published: January 2009

Design intent coverage
is a formal methodology for analyzing the gap between a formal architectural specification of a design and the formal functional specifications of the component RTL blocks of the design. In this article we extend the design intent coverage methodology to hybrid specifications containing both state-machines and formal properties. We demonstrate the benefits of this extension in two domains of considerable recent interest, namely (a) the use of auxiliary state-machines in formal specifications, and (b) the use of modest sized RTL blocks in the design intent coverage analysis.
Congestion prediction in early stages of physical design
Authors: Sham Chiu-Wing , Young Evangeline F. Y. , Lu Jingwei
Published: January 2009

Routability optimization has become a major concern in physical design of VLSI circuits. Due to the recent advances in VLSI technology, interconnect has become a dominant factor of the overall performance of a circuit. In order to optimize interconnect cost, we need a good congestion estimation method to predict routability in the early designing stages. Many congestion models have been proposed but there's still a lot of room for improvement. Besides, routers will perform rip-up and reroute operations to prevent overflow, but most models do not consider this case. The outcome is that the existing models will usually underestimate the routability. In this paper, we have a comprehensive study on our proposed congestion models. Results show that the estimation results of our approaches are always more accurate than the previous congestion models.
Lens aberration aware placement for timing yield
Authors: Kahng Andrew B. , Park Chul-Hong , Sharma Puneet , Wang Qinke
Published: January 2009

Process variations due to lens aberrations are to a large extent systematic, and can be modeled for purposes of analyses and optimizations in the design phase. Traditionally, variations induced by lens aberrations have been considered random due to their small extent. However, as process margins reduce, and as improvements in reticle enhancement techniques control variations due to other sources with increased efficacy, lens aberration-induced variations gain importance. For example, our experiments indicate that delays of most cells in the Artisan TSMC 90nm library are affected by 2--8% due to lens aberration. Aberration-induced variations are systematic and depend on the location in the lens field. In this article, we first propose an aberration-aware timing analysis flow that accounts for aberration-induced cell delay variations. We then propose an aberration-aware timing-driven analytical placement approach that utilizes the predictable slow and fast regions created on the chip due to aberration to improve cycle time. We study the dependence of our improvement on chip size, as well as use of the technique along with field blading which allows partial reticle exposure. We evaluate our technique on two testcases,
AES
and
JPEG
implemented in 90
nm
technology. The proposed technique reduces cycle time by 4.322% (80ps) at the cost of 1.587% increase in trial-routed wirelength for AES. On JPEG, we observe a cycle time reduction of 5.182% (132ps) at the cost of 1.095% increase in trial-routed wirelength.
The SmartFrog configuration management framework
Authors: Goldsack Patrick , Guijarro Julio , Loughran Steve , Coles Alistair , Farrell Andrew , Lain Antonio , Murray Paul , Toft Peter
Published: January 2009

SmartFrog is a framework for creating configuration-driven systems. It has been designed with the express purpose of making the design, deployment and management of distributed component-based systems simpler and more robust. Over the last decade it has been the focus for ongoing research into aspects of configuration management and large-scale distributed systems, providing a platform for experimentation. The paper covers the rationale for the design of the framework, details of its design, plus a description of the further research that is in progress.
COTSon
Authors: Argollo Eduardo , Falcón Ayose , Faraboschi Paolo , Monchiero Matteo , Ortega Daniel
Published: January 2009

Simulation has historically been the primary technique used for evaluating the performance of new proposals in computer architecture. Speed and complexity considerations have traditionally limited its applicability to single-thread processors running application-level code. This is no longer sufficient to model modern multicore systems running the complex workloads of commercial interest today.

COTSon is a simulator framework jointly developed by HP Labs and AMD. The goal of COTSon is to provide fast and accurate evaluation of current and future computing systems, covering the full software stack and complete hardware models. It targets cluster-level systems composed of hundreds of commodity multicore nodes and their associated devices connected through a standard communication network. COTSon adopts a functional-directed philosophy, where fast functional emulators and timing models cooperate to improve the simulation accuracy at a speed sufficient to simulate the full stack of applications, middleware and OSs.

This paper describes the changes in simulation philosophy we embraced in COTSon to address these new challenges. We base functional emulation on established, fast and validated tools that support commodity OSs and complex multitier applications. Through a robust interface between the functional and timing domain, we can leverage other existing simulators for individual sub-components, such as disks or networks. We abandon the idea of "always-on" cycle-based simulation in favor of statistical sampling approaches that can trade accuracy for speed.

COTSon opens up a new dimension in the speed/accuracy space, allowing simulation of a cluster of nodes several orders of magnitude faster with a minimal accuracy loss.
The influence of information sensitivity compensation on privacy concern and behavioral intention
Authors: Yang Shu , Wang Kanliang
Published: January 2009

The drawbacks of information privacy in online marketing result in scholars' research concern for privacy. Following the current research trends and further extending the limitations from one specific context, this study examines the effects of information sensitivity and compensation on privacy concern and behavioral intention, where behavioral intention has three dimensions including information disclosure, protection intention and transaction intention. In order to simulate the phenomenon in the online environment, a 2x3 experimental design (low or high level of information sensitivity; 5%, 30%, 60% sale discount) and a 2x2 experimental design (low or high level of information sensitivity; low or high level of job-hunting compensation) were implemented and assessed. The results show that privacy concern has a negative effect on information disclosure, but a positive effect on protection intention. The interactions of information sensitivity and compensation have significant effects on information disclosure and transaction intention. Additionally, information sensitivity has a negative effect on information disclosure and transaction intention. In the online purchasing environment, a 30% sales discount performs better than either a 5% or a 60% discount. However, across contexts, services provided in the job hunting environment are more prized by customers than the 30% sale discount. These outcomes imply that marketers should beware of designing at the cost-benefit level to eliminate information privacy concern that reduces behavioral intention.
Phenotype of neurons in the nucleus of the solitary tract that express CCK-induced activation of the ERK signaling pathway
Authors: Babic Tanja , Townsend R. Leigh , Patterson Laurel M. , Sutton Gregory M. , Zheng Huiyuan , Berthoud Hans-Rudolf
Published: January 2009

The satiating potency of CCK has been well characterized, including its mediation by capsaicin-sensitive vagal primary afferents. We have previously shown that peripherally administered CCK activates the MAPK-signaling cascade in a population of nucleus of the solitary tract (NTS) neurons and that preventing ERK1/2 phosphorylation partly attenuates CCK's satiating potency. The aim of this study was to identify the neurochemical phenotypes of the NTS neurons that exhibit CCK-induced activation of ERK1/2. Using confocal microscopy, we demonstrate that intraperitoneal CCK administration increases the number of neurons that express phosphorylated ERK1/2 (pERK1/2) in the medial and commissural subnuclei of the NTS and that CCK-induced expression of ERK1/2 is increased in tyrosine hydroxylase-immunoreactive neurons. Using Western blot analysis, we show that the robust increase in tyrosine hydroxylase phosphorylation obtained with intraperitoneal CCK is significantly attenuated in rats pretreated with the ERK-pathway blocker U0126 injected into the 4th ventricle. In addition, CCK injections increased pERK1/2 expression in POMC neurons in the NTS. In contrast, only the rare GAD67, neuronal nitric oxide synthase, and leptin-responsive neuron exhibited CCK-induced pERK immunoreactivity. We conclude that activation of POMC-immunoreactive neurons and tyrosine hydroxylase activity via the ERK-signaling pathway in the NTS likely contributes to CCK's satiating effects.
Responses of the trout cardiac natriuretic peptide system to manipulation of salt and water balance
Authors: Johnson Keven R. , Olson Kenneth R.
Published: January 2009

Natriuretic peptides (NPs) are evolutionarily conserved hormones that affect blood pressure and fluid volume through membrane-bound guanylate cyclase (GC)-linked natriuretic peptide receptors-A and -B (NPR-A and NPR-B, respectively) in a variety of vascular, renal, and other tissues. The principal physiological stimulus for cardiac NPs in fish is somewhat debated between two prominent theories: regulation of salt balance (osmoregulatory hypothesis) or prevention of volume expansion (cardioprotective hypothesis). In the present study, we examined atrial and ventricular expression of trout NPs, atrial (ANP), brain (BNP), and ventricular (VNP) using Northern (mRNA), Western (NP pro-hormone), and qPCR (GC-NPR-A and -B mRNA) blot analysis following independent manipulation of plasma salt and volume levels after chronic exposure to freshwater (FW; volume loaded, salt depleted), saltwater (SW; volume depleted, salt loaded), or freshwater trout fed a high-salt diet (FW-HSD; volume and salt loaded). We also measured NP transcriptional response to acute (2 h) volume expansion with dialyzed plasma (VE; 80% blood vol) or volume depletion by hemorrhage (VD, 20% blood volume every 30 min for 2 h) with real-time PCR. In essentially all instances, increased expression of the NP system was associated with FW-HSD or plasma expansion. There were no differences in NP expression between chronically adapted FW and SW fish, and hemorrhage decreased atrial ANP and VNP mRNA. These results indicate that rainbow trout cardiac NPs and cardiovascular GC-NPRs respond principally to volume, not salt overload, and this suggests that the primary function of trout cardiac NP system is to protect the heart.
Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains
Authors: Packard Matthew , Saad Yasser , Gunning William T. , Gupta Shalini , Shapiro Joseph , Garrett Michael R.
Published: January 2009

An earlier linkage analysis conducted on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) identified 10 genomic regions linked to several renal and/or cardiovascular traits. In particular, loci on rat chromosomes (RNO) 8 and 13 were linked to proteinuria, albuminuria, and renal damage. At both loci, the S allele was associated with increased proteinuria and renal damage. The current study aimed to confirm the linkage analysis and to evaluate the effect of genetic background on the ability of each locus (either RNO8 or RNO13) to exert a phenotypic difference when placed on a genetic background either susceptible (S rat) or resistant (SHR) to the development of renal disease. Congenic strains developed to transfer genomic segments from either RNO8 or RNO13 from the SHR onto the S genetic background [S.SHR( 8 ) or S.SHR( 13 )] demonstrated significantly reduced proteinuria and improved renal function. Both congenic strains demonstrated significantly reduced glomerular and tubular injury, with renal interstitial fibrosis as the predominant pathological difference compared with the S. In contrast, transfer of RNO8 or RNO13 genomic regions from the S onto the resistant SHR genetic background [SHR.S( 8 ) or SHR.S( 13 )] yielded no significant difference in proteinuria or glomerular, tubular, or interstitial injury compared with SHR. These findings demonstrate that genetic context plays a significant and important role in the phenotypic expression of genes influencing proteinuria on RNO8 and RNO13.
Perfluorocarbon emulsions as a promising technology: a review of tissue and vascular gas dynamics
Authors: Spiess Bruce D.
Published: January 2009

Perfluorocarbon (PFC) emulsions are halogen-substituted carbon nonpolar oils with resultant enhanced dissolved respiratory gas (O2, N2, CO2, nitric oxide) capabilities. In the first demonstration of enhanced O2 solubility, inhaled PFC could sustain rat metabolism. Intravenous emulsions were then trialed as “blood substitutes.” In the last 10 yr, biocomputational modeling has enhanced our mechanistic understanding of PFCs. Contemporary research is now taking advantage of these physiological discoveries and applying PFCs as “oxygen therapeutics,” as well as ways to enhance other gas movements. One particularly promising area of research is the treatment of gas embolism (arterial and venous emboli/decompression sickness). An expansive understanding of PFC-enhanced diffusive gas movements through tissue and vasculature may have analogous applications for O2 or other respiratory gases and should provide a revolution in medicine. This review will stress the fundamental knowledge we now have regarding how respiratory gas movements are changed when intravenous PFC is present.