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Showing papers by "Research Triangle Park published in 2005"


Journal ArticleDOI
TL;DR: To better delineate periods of peak prevalence and incidence for perinatal depression and identify high risk subpopulations, studies with larger and more representative samples are needed.

2,797 citations


Journal ArticleDOI
21 Apr 2005-Nature
TL;DR: The draft sequence of the M. grisea genome is reported, reflecting the clonal nature of this fungus imposed by widespread rice cultivation and analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease.
Abstract: Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.

1,520 citations


Journal ArticleDOI
29 Sep 2005-Nature
TL;DR: This mechanism provides an explanation for how an agonist-bound nuclear receptor can be converted from an activator of transcription to a promoter-specific repressor of NF-κB target genes that regulate immunity and homeostasis.
Abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has essential roles in adipogenesis and glucose homeostasis, and is a molecular target of insulin-sensitizing drugs. Although the ability of PPAR-gamma agonists to antagonize inflammatory responses by transrepression of nuclear factor kappa B (NF-kappaB) target genes is linked to antidiabetic and antiatherogenic actions, the mechanisms remain poorly understood. Here we report the identification of a molecular pathway by which PPAR-gamma represses the transcriptional activation of inflammatory response genes in mouse macrophages. The initial step of this pathway involves ligand-dependent SUMOylation of the PPAR-gamma ligand-binding domain, which targets PPAR-gamma to nuclear receptor corepressor (NCoR)-histone deacetylase-3 (HDAC3) complexes on inflammatory gene promoters. This in turn prevents recruitment of the ubiquitylation/19S proteosome machinery that normally mediates the signal-dependent removal of corepressor complexes required for gene activation. As a result, NCoR complexes are not cleared from the promoter and target genes are maintained in a repressed state. This mechanism provides an explanation for how an agonist-bound nuclear receptor can be converted from an activator of transcription to a promoter-specific repressor of NF-kappaB target genes that regulate immunity and homeostasis.

1,199 citations


Journal ArticleDOI
23 Dec 2005-Science
TL;DR: This work combined field research, synthesis of more than 600 observations, and climate and economic modeling to document substantial losses in stream flow, and increased soil salinization and acidification, with afforestation in tree plantations.
Abstract: Carbon sequestration strategies highlight tree plantations without considering their full environmental consequences. We combined field research, synthesis of more than 600 observations, and climate and economic modeling to document substantial losses in stream flow, and increased soil salinization and acidification, with afforestation. Plantations decreased stream flow by 227 millimeters per year globally (52%), with 13% of streams drying completely for at least 1 year. Regional modeling of U.S. plantation scenarios suggests that climate feedbacks are unlikely to offset such water losses and could exacerbate them. Plantations can help control groundwater recharge and upwelling but reduce stream flow and salinize and acidify some soils.

1,002 citations


Journal ArticleDOI
TL;DR: Novel vector design and cell engineering approaches will serve to further enhance the value of baculovirus technology.
Abstract: Today, many thousands of recombinant proteins, ranging from cytosolic enzymes to membrane-bound proteins, have been successfully produced in baculovirus-infected insect cells. Yet, in addition to its value in producing recombinant proteins in insect cells and larvae, this viral vector system continues to evolve in new and unexpected ways. This is exemplified by the development of engineered insect cell lines to mimic mammalian cell glycosylation of expressed proteins, baculovirus display strategies and the application of the virus as a mammalian-cell gene delivery vector. Novel vector design and cell engineering approaches will serve to further enhance the value of baculovirus technology.

954 citations


Journal ArticleDOI
TL;DR: Underlying economic causes behind the obesity epidemic are examined, such as technological advancements, and economic consequences of obesity, including increasing obesity-related medical expenditures are described, and the role of government in combating the epidemic is discussed.
Abstract: Obesity is not only a health but also an economic phenomenon. This chapter (a) examines underlying economic causes, such as technological advancements, behind the obesity epidemic; (b) describes economic consequences of obesity, including increasing obesity-related medical expenditures; and (c) discusses the role of government in combating the obesity epidemic. Because of the high costs of obesity, and the fact that the majority of these costs are financed by taxpayers, there is a clear motivation for government to try to reduce these costs. However, because obesity may result from poor information and addictive behavior and/or as a result of living in an increasingly obesogenic environment, interventions will need to be multifaceted to ensure the best chance of success.

786 citations


Journal ArticleDOI
TL;DR: When combined with an accurate clinical diagnosis, likelihood ratios from ancillary tests improve diagnostic accuracy in a synergistic manner.

718 citations


Journal ArticleDOI
TL;DR: Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001 and correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important.
Abstract: Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001. Emission factors were calculated from measurements of fine (PM2.5) and coarse (PM10) particulate matter at tunnel entrances and exits, and effects of fleet composition and season were investigated. Cascade impactors (MOUDI) were used to obtain size-resolved metal emission rates. Metals were quantified with inductively-coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence (XRF). PM10 emission rates ranged from 38.7 to 201 mg km(-1) and were composed mainly of organic carbon (OC, 30%), inorganic ions (sulfate, chloride, nitrate, ammonium, 20%), metals (19%), and elemental carbon (EC, 9.3%). PM10 metal emissions were dominated by crustal elements Si, Fe, Ca, Na, Mg, Al, and K, and elements associated with tailpipe emissions and brake and tire wear, including Cu, Zn, Sb, Ba, Pb, and S. Metals emitted in PM2.5 were lower (11.6% of mass). Resuspension of roadway dust was dependent on weather and road surface conditions, and increased emissions were related to higher traffic volumes and fractions of heavy trucks. Emission of noble metals from catalytic converters appeared to be impacted by the presence of older vehicles. Elements related to brake wear were impacted by enriched road dust resuspension, but correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important. A submicrometer particle mode was observed in the emissions of Pb, Ca, Fe, and Cu.

700 citations


Journal ArticleDOI
TL;DR: This research suggests that selected chemicals are useful as tracers of human wastewater discharge by determining the persistence of a chemically diverse suite of emerging contaminants in streams.
Abstract: The quality of drinking and recreational water is currently (2005) determined using indicator bacteria. However, the culture tests used to analyze forthese bacteria require a long time to complete and do not discriminate between human and animal fecal material sources. One complementary approach is to use chemicals found in human wastewater, which would have the advantages of (1) potentially shorter analysis times than the bacterial culture tests and (2) being selected for human-source specificity. At 10 locations, water samples were collected upstream and at two successive points downstream from a wastewaster treatment plant (WWTP); a treated effluent sample was also collected at each WWTP. This sampling plan was used to determine the persistence of a chemically diverse suite of emerging contaminants in streams. Samples were also collected at two reference locations assumed to have minimal human impacts. Of the 110 chemical analytes investigated in this project, 78 were detected at least once. The number of compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP effluent sample. The total analyte load at each location varied from 0.018 microg/L at the reference location to 97.7 microg/L in a separate WWTP effluent sample. Although most of the compound concentrations were in the range of 0.01-1.0 microg/L, in some samples, individual concentrations were in the range of 5-38 microg/L. The concentrations of the majority of the chemicals present in the samples generally followed the expected trend: they were either nonexistent or at trace levels in the upstream samples, had their maximum concentrations in the WWTP effluent samples, and then declined in the two downstream samples. This research suggests that selected chemicals are useful as tracers of human wastewater discharge.

670 citations


Journal ArticleDOI
TL;DR: It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress.

664 citations


Journal ArticleDOI
Jie Liu1
TL;DR: Oleanolic acid and ursolic acid are ubiquitous triterpenoids in plant kingdom, medicinal herbs, and are integral part of the human diet.

Journal ArticleDOI
TL;DR: The formulation of the American Meteorological Society (AMS) and U.S. Environmental Protection Agency (EPA) Regulatory Model (AERMOD) Improvement Committee's applied air dispersion model is described in this paper.
Abstract: The formulation of the American Meteorological Society (AMS) and U.S. Environmental Protection Agency (EPA) Regulatory Model (AERMOD) Improvement Committee’s applied air dispersion model is described. This is the first of two articles describing the model and its performance. Part I includes AERMOD’s characterization of the boundary layer with computation of the Monin–Obukhov length, surface friction velocity, surface roughness length, sensible heat flux, convective scaling velocity, and both the shear- and convection-driven mixing heights. These parameters are used in conjunction with meteorological measurements to characterize the vertical structure of the wind, temperature, and turbulence. AERMOD’s method for considering both the vertical inhomogeneity of the meteorological characteristics and the influence of terrain are explained. The model’s concentration estimates are based on a steady-state plume approach with significant improvements over commonly applied regulatory dispersion models. Co...

Journal ArticleDOI
TL;DR: A single target-site mutation in the AHAS gene may confer tolerance to AHAS-inhibiting herbicides, so that it is technically possible to develop the imidazolinone-tolerance trait in many crops.
Abstract: Imidazolinone herbicides, which include imazapyr, imazapic, imazethapyr, imazamox, imazamethabenz and imazaquin, control weeds by inhibiting the enzyme acetohydroxyacid synthase (AHAS), also called acetolactate synthase (ALS). AHAS is a critical enzyme for the biosynthesis of branched-chain amino acids in plants. Several variant AHAS genes conferring imidazolinone tolerance were discovered in plants through mutagenesis and selection, and were used to create imidazolinone-tolerant maize (Zea mays L), wheat (Triticum aestivum L), rice (Oryza sativa L), oilseed rape (Brassica napus L) and sunflower (Helianthus annuus L). These crops were developed using conventional breeding methods and commercialized as Clearfield* crops from 1992 to the present. Imidazolinone herbicides control a broad spectrum of grass and broadleaf weeds in imidazolinone-tolerant crops, including weeds that are closely related to the crop itself and some key parasitic weeds. Imidazolinone-tolerant crops may also prevent rotational crop injury and injury caused by interaction between AHAS-inhibiting herbicides and insecticides. A single target-site mutation in the AHAS gene may confer tolerance to AHAS-inhibiting herbicides, so that it is technically possible to develop the imidazolinone-tolerance trait in many crops. Activities are currently directed toward the continued improvement of imidazolinone tolerance and development of new Clearfield* crops. Management of herbicide-resistant weeds and gene flow from crops to weeds are issues that must be considered with the development of any herbicide-resistant crop. Thus extensive stewardship programs have been developed to address these issues for Clearfield* crops.

Journal ArticleDOI
TL;DR: This study found that smoking prevalence among all students declined from 25.3% to 18.0% between 1999 and 2002 and that the "truth" campaign accounted for approximately 22% of this decline.
Abstract: Objectives. In early 2000, the American Legacy Foundation launched the national “truth” campaign, the first national antismoking campaign to discourage tobacco use among youths. We studied the impact of the campaign on national smoking rates among US youths (students in grades 8, 10, and 12).Methods. We used data from the Monitoring the Future survey in a pre/post quasi-experimental design to relate trends in youth smoking prevalence to varied doses of the “truth” campaign in a national sample of approximately 50000 students in grades 8, 10, and 12, surveyed each spring from 1997 through 2002.Results. Findings indicate that the campaign accounted for a significant portion of the recent decline in youth smoking prevalence. We found that smoking prevalence among all students declined from 25.3% to 18.0% between 1999 and 2002 and that the campaign accounted for approximately 22% of this decline.Conclusions. This study showed that the campaign was associated with substantial declines in youth smoking and has ...

Journal ArticleDOI
TL;DR: The branding of trials as unethical on the basis of an imprecise sample size calculation process might be acceptable if investigators use methodological rigor to eliminate bias, properly report to avoid misinterpretation, and always publish results to avert publication bias.

Journal ArticleDOI
TL;DR: To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed.
Abstract: Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system.

Journal ArticleDOI
26 Sep 2005
TL;DR: The main goal of this paper is to consider some of the most promising THz S&I applications within the specific context of their particular science and technology challenges in an attempt to credibly judge (or speculate on) their future potential.
Abstract: In recent years, the field of terahertz (THz) science and technology has entered a completely new phase of unprecedented expansion that is generating ever growing levels of broad-based international attention. In particular,there have been important advances in state-of-the-art THz technology and very enthusiastic growth in research activities associated with related scientific and industrial applications. One can legitimately argue that the potential payoffs of THz sensing and imaging (THz S&I) to application areas such as defense, security, biology and medicine are the major drivers of this new phenomenon. However, there remain major science and technology "gaps" in the THz regime that must be reconciled before many of the perceived payoffs ever become realizable. Therefore, it is natural to ask the question "Is now the time for THz?" or rather, are these recent events just a repeat of previous cycles in THz overenthusiasm that have been witnessed during the last century? The main goal of this paper is to consider some of the most promising THz S&I applications within the specific context of their particular science and technology challenges in an attempt to credibly judge (or speculate on) their future potential.

Journal ArticleDOI
TL;DR: With the continual advancement of remote sensing technology and global data assimilation systems, AOT measurements derived from satellite remote sensors may provide a cost-effective approach as a supplemental source of information for determining ground-level particle concentrations.
Abstract: An empirical model based on the regression between daily PM2.5 (particles with aerodynamic diameters of less than 2.5 μm) concentrations and aerosol optical thickness (AOT) measurements from the multiangle imaging spectroradiometer (MISR) was developed and tested using data from the eastern United States during the period of 2001. Overall, the empirical model explained 48% of the variability in PM2.5 concentrations. The root-mean-square error of the model was 6.2 μg/m3 with a corresponding average PM2.5 concentration of 13.8 μg/m3. When PM2.5 concentrations greater than 40 μg/m3 were removed, model results were shown to be unbiased estimators of observations. Several factors, such as planetary boundary layer height, relative humidity, season, and other geographical attributes of monitoring sites, were found to influence the association between PM2.5 and AOT. The findings of this study illustrate the strong potential of satellite remote sensing in regional ambient air quality monitoring as an extension to ...

Journal ArticleDOI
TL;DR: The data suggest that BIK1 modulates the signaling of cellular factors required for defense responses to pathogen infection and normal root hair growth, linking defense response regulation with that of growth and development.
Abstract: Plant resistance to disease is controlled by the combination of defense response pathways that are activated depending on the nature of the pathogen. We identified the Arabidopsis thaliana BOTRYTIS-INDUCED KINASE1 (BIK1) gene that is transcriptionally regulated by Botrytis cinerea infection. Inactivation of BIK1 causes severe susceptibility to necrotrophic fungal pathogens but enhances resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae pv tomato. The response to an avirulent bacterial strain is unchanged, limiting the role of BIK1 to basal defense rather than race-specific resistance. The jasmonate- and ethylene-regulated defense response, generally associated with resistance to necrotrophic fungi, is attenuated in the bik1 mutant based on the expression of the plant defensin PDF1.2 gene. bik1 mutants show altered root growth, producing more and longer root hairs, demonstrating that BIK1 is also required for normal plant growth and development. Whereas the pathogen responses of bik1 are mostly dependent on salicylic acid (SA) levels, the nondefense responses are independent of SA. BIK1 is membrane-localized, suggesting possible involvement in early stages of the recognition or transduction of pathogen response. Our data suggest that BIK1 modulates the signaling of cellular factors required for defense responses to pathogen infection and normal root hair growth, linking defense response regulation with that of growth and development.

Journal ArticleDOI
TL;DR: Survival of extremely low birth weight infants improved between 1993 and 1998, and although some outcomes remained unchanged, the rates of low Bayley MDI scores and NDI improved.
Abstract: Objective. This study evaluated the impact of changes in perinatal management on neurodevelopmental impairment (NDI) at 18 to 22 months’ corrected age of low gestation (22–26 weeks) and higher gestation (27–32 weeks) extremely low birth weight infants (401–1000 g birth weight) who were cared for in the National Institute of Child Health and Human Development Neonatal Research Network during 3 epochs (1993–1994, 1995–1996, and 1997–1998). It was hypothesized that outcomes would improve over the 3 epochs. Methods. A multicenter cohort study was conducted of the outcomes of 3785 infants with assessments at 18 to 22 months’ corrected age. Regression analyses were completed to evaluate for epoch effects, gestational age effects, and time plus gestational age interaction. Regression analyses were also performed to identify the independent associations of epoch and 4 study perinatal interventions: antenatal steroids (yes, no), high-frequency ventilation (yes, no), number of days to regain birth weight as a marker of nutritional intake, and postnatal steroids for treatment of bronchopulmonary dysplasia (yes, no) with outcomes. Results. Survival improved for both the low (55%–61%) and higher (82%–86%) gestational age groups during the 3 epochs. Regression analyses indicated that the decreased risk for adverse outcome was significantly lower in epoch 2 compared with epoch 1 with decreased rates of low Bayley Mental Development Index (MDI) and neurodevelopmental impairment (NDI). Antenatal steroids were associated with decreased risk for moderate to severe cerebral palsy (CP) and low Bayley Psychomotor Development Index. High-frequency ventilation was associated with a low Bayley MDI and NDI, and postnatal steroids were associated with moderate to severe CP, any CP, low Bayley MDI, low Bayley Psychomotor Development Index, and increased NDI. Conclusion. Survival of extremely low birth weight infants improved between 1993 and 1998. Although some outcomes remained unchanged, the rates of low Bayley MDI scores and NDI improved. Antenatal steroid administration was the only study intervention associated with improved outcomes.

Journal ArticleDOI
TL;DR: In this paper, the impacts of organic matter removal and soil compaction are reported for the 26 oldest installations in the nation-wide network of long-term soil productivity sites, and the results show that complete removal of surface organic matter led to declines in soil C concentration to 20 cm depth and to reduced nutrient availability.

Journal ArticleDOI
11 Feb 2005-Cell
TL;DR: Structural and biochemical data for three NR5A members-mouse and human SF-1 and human LRH-1-which reveal that these receptors bind phosphatidyl inositol second messengers and that ligand binding is required for maximal activity are presented.

Journal ArticleDOI
TL;DR: Use of control (comparison) groups is a powerful research tool in case-control studies, but readers need to think carefully about how representative the controls are.

Journal ArticleDOI
TL;DR: The data on acrylamide levels in food including its formation and analytical methods, the determination of human consumption patterns, dietary intake of the general population, estimation of maximum intake levels and identification of groups of potentially high intakes are reviewed.

Journal ArticleDOI
TL;DR: The merits and limitations of several PFC techniques used in today's network-server and telecom power supplies to maximize their conversion efficiencies are discussed, and the effect of recent advancements in semiconductor technology on the performance and design considerations of PFC converters is discussed.
Abstract: A review of high-performance, state-of-the-art, active power-factor-correction (PFC) techniques for high-power, single-phase applications is presented. The merits and limitations of several PFC techniques that are used in today's network-server and telecom power supplies to maximize their conversion efficiencies are discussed. These techniques include various zero-voltage-switching and zero-current-switching, active-snubber approaches employed to reduce reverse-recovery-related switching losses, as well as techniques for the minimization of the conduction losses. Finally, the effect of recent advancements in semiconductor technology, primarily silicon-carbide technology, on the performance and design considerations of PFC converters is discussed.

Journal ArticleDOI
TL;DR: The key finding is that peer effects play a significant role in youth smoking decisions: moving a high-school student from a school where no children smoke to aSchool where one quarter of the youths smoke is found to increase the probability that the youth smokes by about 14.5 percentage points.

Journal ArticleDOI
TL;DR: Investigators should use adjustments when the clinical decision-making argument rests solely on one or more of the primary endpoints being significant, and in these cases, adjustments somewhat rescue scattershot analyses.

Journal ArticleDOI
TL;DR: Assessment of HER2 amplification by FISH is the preferred method to select patients for trastuzumab therapy, as determined by fluorescence in situ hybridization (FISH), in women with metastatic breast cancer treated with trastizumab in 3 clinical trials.


Journal ArticleDOI
TL;DR: The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.
Abstract: Background: Although it is widely believed tha the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine). Method: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared. Results: The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p <.001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth. Conclusion: Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.