Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

Energy Technology Data Exchange (ETDEWEB)

Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

2017-06-12

Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

Science.gov (United States)

Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

2015-10-26

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Retroviral DNA integration: viral and cellular determinants of target-site selection.

Directory of Open Access Journals (Sweden)

Mary K Lewinski

2006-06-01

Full Text Available Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV integrates preferentially within active transcription units, whereas murine leukemia virus (MLV integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN coding region into HIV (to make HIVmIN caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb, and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.

Crops with target-site herbicide resistance for Orobanche and Striga control.

Science.gov (United States)

Gressel, Jonathan

2009-05-01

It is necessary to control root parasitic weeds before or as they attach to the crop. This can only be easily achieved chemically with herbicides that are systemic, or with herbicides that are active in soil. Long-term control can only be attained if the crops do not metabolise the herbicide, i.e. have target-site resistance. Such target-site resistances have allowed foliar applications of herbicides inhibiting enol-pyruvylshikimate phosphate synthase (EPSPS) (glyphosate), acetolactate synthase (ALS) (e.g. chlorsulfuron, imazapyr) and dihydropteroate synthase (asulam) for Orobanche control in experimental conditions with various crops. Large-scale use of imazapyr as a seed dressing of imidazolinone-resistant maize has been commercialised for Striga control. Crops with two target-site resistances will be more resilient to the evolution of resistance in the parasite, if well managed.

ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms

Directory of Open Access Journals (Sweden)

Voytas Daniel F

2011-01-01

Full Text Available Abstract Background Zinc Finger Nucleases (ZFNs have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms. Description ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; S. cerevisiae, C. reinhardtii, A. thaliana, D. melanogaster, D. rerio, C. elegans, and H. sapiens and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s. Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence. Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter "confidence" scores that estimate the likelihood that a chosen ZFN target site will function in vivo. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the

A new thermodynamic model for shaftwork targeting on total sites

Energy Technology Data Exchange (ETDEWEB)

Sorin, M.; Hammache, A. [CANMET Energy Technology Centre-Varennes, Quebec (Canada)

2005-05-01

The purpose of the paper is to introduce a targeting model based on a new thermodynamic insight on cogeneration in general and Rankine cycle in particular. The insight permits to express the ideal shaftwork of a cogeneration unit through the outlet heat load and the difference in Carnot factors between the heat source and heat sink for the given inlet temperature of the heat source. The deviation from the ideal shaftwork to the real one is assessed by using the traditionally turbine isentropic efficiency. Finally the new model allows targeting fuel consumption, cooling requirement and shaftwork production with high accuracy and visualizing then directly as special segments on the T-H diagram. A modified Site Utility Grand Composite Curve (SUGCC) diagram is proposed and compared to the original SUGCC. The shape of the right hand side of the diagram above site pinch is the same, however, below site pinch it is shifted to the left by an amount equal to shaftwork production below site pinch. Above site pinch VHP consumption is also corrected to account for shaftwork production above site pinch that is represented by segments rather than areas on the left hand side of the T-H diagram. (author)

Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

Science.gov (United States)

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

New emissions targeting strategy for site utility of process industries

International Nuclear Information System (INIS)

Manesh, Mohamamd Hasan Khoshgoftar; Amidpour, Majid; Hamedi, Mohammad Hosein; Abadi, Sajad Khamis; Ghalami, Hooman

2013-01-01

A new procedure for environmental targeting of co-generation system is presented. The proposed method is based on the concepts of pinch technology for total site targeting of fuel, power, steam, environmental impacts and total annualized cost with considering emissions taxes. This approach provides a consistent, general procedure for determining mass flow rates and efficiencies of the applied turbines. This algorithm utilizes the relationship of entropy with enthalpy and isentropic efficiency. Also, the life cycle assessment (LCA) as a well-known tool for analyzing environmental impacts on a wide perspective with reference to a product system and the related environmental and economic impacts have been applied. In this regard, a damage-oriented impact analysis method based on Eco-indicator 99 and footprints analysis was considered. In addition, the present work demonstrates the effect of including both sensible and latent heating of steam in the extended Site Utility Grand Composite Curve (ESUGCC). It is shown that including sensible heating allows for better thermal matching between the processes. Furthermore, the other representation YSUGCC as the other form of Site Utility Grand Composite has been proposed. Two case studies were used to illustrate the usefulness of the new environmental targeting method

Effects of Target Attributes on Children's Patterns of Referential Under- and Overspecification

Science.gov (United States)

Charest, Monique; Johnston, Judith R.

2016-01-01

We examined the effects of object attributes on children's descriptive patterns in a referential communication task. Thirty preschoolers described object pairs that were selected by the experimenter. The targets were defined by shared size or colour, and differed on the non-target dimension in half of the trials. The children also completed a…

A Quarter Century of TV Food Advertising Targeted at Children.

Science.gov (United States)

Gamble, Margaret; Cotugna, Nancy

1999-01-01

Analyzed current trends in television advertising targeting children, comparing results to the historical perspective of the last quarter century. Researchers evaluated 16 hours of Saturday morning children's programming on four network channels for commercial content based on Food Guide Pyramid and USDA Child Nutrition criteria. Overall,…

The impact of distracter-target similarity on contextual cueing effects of children and adults.

Science.gov (United States)

Yang, Yingying; Merrill, Edward C

2014-05-01

Contextual cueing reflects a memory-based attentional guidance process that develops through repeated exposure to displays in which a target location has been consistently paired with a specific context. In two experiments, we compared 20 younger children's (6-7 years old), 20 older children's (9-10 years old), and 20 young adults' (18-21 years old) abilities to acquire contextual cueing effects from displays in which half of the distracters predicted the location of the target and half did not. Across experiments, we varied the similarity between the predictive and nonpredictive distracters and the target. In Experiment 1, the predictive distracters were visually similar to the target and dissimilar from the nonpredictive distracters. In Experiment 2, the nonpredictive distracters were also similar to the target and predictive distracters. All three age groups exhibited contextual cueing in Experiment 1, although the effect was not as strong for the younger children relative to older children and adults. All participants exhibited weaker contextual cueing effects in Experiment 2, with the younger children not exhibiting significant contextual cueing at all. Apparently, when search processes could not be guided to the predictive distracters on the basis of salient stimulus features, younger children in particular experienced difficulty in implicitly identifying and using aspects of the context to facilitate with the acquisition of contextual cueing effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Caught in the Web: How Online Advertising Exploits Children.

Science.gov (United States)

Pasnik, Shelley

1997-01-01

Principals should be aware of Internet advertising targeted at children. According to a recent Center for Media Education study, many companies design online sites for children as a way to bypass adult authority and prey on children's vulnerabilities. Some companies use their online sites to develop brand loyalties or collect market-segment data…

Web Sites for Young Children: Gateway to Online Social Networking?

Science.gov (United States)

Bauman, Sheri; Tatum, Tanisha

2009-01-01

Traffic on Web sites for young children (ages 3-12) has increased exponentially in recent years. Advocates proclaim that they are safe introductions to the Internet and online social networking and teach essential 21st-century skills. Critics note developmental concerns. In this article, we provide basic information about Web sites for young…

Alarming Default Rates in South African Children with Moderate Malnutrition on Targeted Supplementary Feeding Programmes

International Nuclear Information System (INIS)

Steenkamp, Juliana; Lategan, Ronette

2014-01-01

statistically significant. The mean age of the sample of 226 children was 29.3 months (±13.5SD) which consisted of 50.2% males. Both parents were alive in >90% of children. With five visits possible, the mean number of clinic visits was 3.7. There was no correlation between time traveled to the clinic or age of the child and number of follow-up visits; and no association between age, gender or perceived food security of the child and defaulting. Of five possible visits, 51.3% attended all follow-up visits, with 30.5% attending only once or twice. Alarming default rates were found in this targeted supplementary feeding programme for children. It was expected that parents would be more diligent bringing younger children to the clinic, especially in cases of shorter traveling distances to the clinic. However, no association was found between age, gender or traveling distance and defaulting. Furthermore no association was found between breastfeeding, meal frequency or food security and default rates. Targeted food supplementation programmes only succeed if default rates are low and supplements are consumed. As defaulting was significantly associated with the site, research into the attitudes of parents and health professionals and content of nutrition information provided, should receive priority. (author)

Multimedia approach to estimating target cleanup levels for soils at hazardous waste sites

International Nuclear Information System (INIS)

Hwang, S.T.

1990-04-01

Contaminated soils at hazardous and nuclear waste sites pose a potential threat to human health via transport through environmental media and subsequent human intake. To minimize health risks, it is necessary to identify those risks and ensure that appropriate actions are taken to protect public health. The regulatory process may typically include identification of target cleanup levels and evaluation of the effectiveness of remedial alternatives and the corresponding reduction in risks at a site. The US Environmental Protection Agency (EPA) recommends that exposure assessments be combined with toxicity information to quantify the health risk posed by a specific site. This recommendation then forms the basis for establishing target cleanup levels. An exposure assessment must first identify the chemical concentration in a specific medium (soil, water, air, or food), estimate the exposure potential based on human intake from that media, and then combined with health criteria to estimate the upperbound health risks for noncarcinogens and carcinogens. Estimation of target cleanup levels involves the use of these same principles but can occur in reverse order. The procedure starts from establishing a permissible health effect level and ends with an estimated target cleanup level through an exposure assessment process. 17 refs

Does targeting children with hygiene promotion messages work? The effect of handwashing promotion targeted at children, on diarrhoea, soil-transmitted helminth infections and behaviour change, in low- and middle-income countries.

Science.gov (United States)

Watson, Julie A; Ensink, Jeroen H J; Ramos, Monica; Benelli, Prisca; Holdsworth, Elizabeth; Dreibelbis, Robert; Cumming, Oliver

2017-05-01

To synthesise evidence on the effect of handwashing promotion interventions targeting children, on diarrhoea, soil-transmitted helminth infection and handwashing behaviour, in low- and middle-income country settings. A systematic review of the literature was performed by searching eight databases, and reference lists were hand-searched for additional articles. Studies were reviewed for inclusion according to pre-defined inclusion criteria and the quality of all studies was assessed. Eight studies were included in this review: seven cluster-randomised controlled trials and one cluster non-randomised controlled trial. All eight studies targeted children aged 5-12 attending primary school but were heterogeneous for both the type of intervention and the reported outcomes so results were synthesised qualitatively. None of the studies were of high quality and the large majority were at high risk of bias. The reported effect of child-targeted handwashing interventions on our outcomes of interest varied between studies. Of the different interventions reported, no one approach to promoting handwashing among children appeared most effective. Our review found very few studies that evaluated handwashing interventions targeting children and all had various methodological limitations. It is plausible that interventions which succeed in changing children's handwashing practices will lead to significant health impacts given that much of the attributable disease burden is concentrated in that age group. The current paucity of evidence in this area, however, does not permit any recommendations to be made as to the most effective route to increasing handwashing with soap practice among children in LMIC. © 2017 John Wiley & Sons Ltd.

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

Science.gov (United States)

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel and viable acetylcholinesterase target site for developing effective and environmentally safe insecticides.

Science.gov (United States)

Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-04-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

Renton's Quendall Terminals on List of EPA Superfund Sites Targeted for Immediate, Intense Attention

Science.gov (United States)

EPA released the list of Superfund sites that Administrator Pruitt has targeted for intense and immediate attention, including the Quendall Terminals Site, a former creosote facility on the shore of Lake Washington in Renton, Washington.

What's on Malaysian television? - A survey on food advertising targeting children.

Science.gov (United States)

Karupaiah, Tilakavati; Chinna, Karuthan; Mee, Loi Huei; Mei, Lim Siau; Noor, Mohd Ismail

2008-01-01

The Malaysian government recently introduced a ban on fast food advertisements targeting children on television. This study reports on data covering 6 months of television food advertising targeting children. Six out of seven of the Nation's commercial television networks participated (response rate = 85.7%). Based on reported timings of children's programmes, prime time significantly differed ( p food advertisements appearing per month varied greatly between television stations (C = 1104; D = 643; F = 407; B = 327; A = 59; E = 47). Food advertising also increased the most in September (n = 3158), followed by July (n = 2770), August (n = 2431), October (n = 2291), November (n = 2245) and June (n = 2211). Content analysis of advertisements indicated snacks were the highest (34.5%), followed by dairy products (20.3%), sugars and candies (13.4%), biscuits (11.2%), fast food (6.7%), breakfast cereal (6.4%), beverages (4.1%), supplements (0.9%), rice (0.6%), noodles (0.5%), bread (0.3%), miscellaneous and processed foods (0.2%). Paradoxically, we found that the frequency of snack food advertised during children's prime time was 5 times more than fast foods. The sodium content (mean = 620 mg per 100g) of these snack foods was found to be highest.

INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

Science.gov (United States)

Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

2012-04-01

Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

Toddler foods, children's foods: assessing sodium in packaged supermarket foods targeted at children.

Science.gov (United States)

Elliott, Charlene D; Conlon, Martin J

2011-03-01

To critically examine child-oriented packaged food products sold in Canada for their sodium content, and to assess them light of intake recommendations, the current policy context and suggested targets. Baby/toddler foods (n 186) and child-oriented packaged foods (n 354) were coded for various attributes (including sodium). Summary statistics were created for sodium, then the children's food products were compared with the UK Food Standards Agency (FSA) 'targets' for sodium in packaged foods. Also assessed were the products' per-serving sodium levels were assessed in light of the US Institute of Medicine's dietary reference intakes and Canada's Food Guide. Calgary, Alberta, Canada. None. Twenty per cent of products could be classified as having high sodium levels. Certain sub-categories of food (i.e. toddler entrées, children's packaged lunches, soups and canned pastas) were problematic. Significantly, when scaled in according to Schedule M or viewed in light of the serving sizes on the Nutrition Facts table, the sodium level in various dry goods products generally fell within, and below, the Adequate Intake (AI)/Tolerable Upper Intake Level (UL) band for sodium. When scaled in accordance with the UK FSA targets, however, none of the (same) products met the targets. In light of AI/UL thresholds based on age and per-serving cut-offs, packaged foodstuffs for youngsters fare relatively well, with the exception of some problematic areas. 'Stealth sodium' and 'subtle sodium' are important considerations; so is use of the FSA's scaling method to evaluate sodium content, because it is highly sensitive to the difference between the reference amount and the actual real-world serving size for the product being considered.

Does Head Start differentially benefit children with risks targeted by the program's service model?

Science.gov (United States)

Miller, Elizabeth B; Farkas, George; Duncan, Greg J

Data from the Head Start Impact Study ( N = 3540) were used to test for differential benefits of Head Start after one program year and after kindergarten on pre-academic and behavior outcomes for children at risk in the domains targeted by the program's comprehensive services. Although random assignment to Head Start produced positive treatment main effects on children's pre-academic skills and behavior problems, residualized growth models showed that random assignment to Head Start did not differentially benefit the pre-academic skills of children with risk factors targeted by the Head Start service model. The models showed detrimental impacts of Head Start for maternal-reported behavior problems of high-risk children, but slightly more positive impacts for teacher-reported behavior. Policy implications for Head Start are discussed.

Prevalence and predictors of the sub-target Hb level in children on dialysis

DEFF Research Database (Denmark)

van Stralen, Karlijn J; Krischock, Leah; Schaefer, Franz

2012-01-01

Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.......Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level....

Children of mothers being released from incarceration : Characteristics and potential targets for intervention

NARCIS (Netherlands)

Menting, Ankie T A; Orobio de Castro, Bram; Matthys, Walter

2016-01-01

Incarcerated mothers and their children may face a multitude of problems. To identify possible targets for intervention, more clarity is needed about characteristics of these children and their mothers. This study examined children’s life events, behaviour problems and social cognitions and mothers’

Information site for parents of young children

OpenAIRE

Heggedal, Eivind

2005-01-01

For parents of small children and lay people it can be difficult to navigate specialist literature when trying to access paediatric problems on their own. Although information targeted at this group already exists, both on the Internet and in different brochures, pamphlets and books, it is of varying quality and is not always easily accessible. With this in mind, there is a need to collect and simplify the literature on this subject, and make it available to lay people and parents of smal...

Online Advertising: Examining the Content and Messages within Websites Targeted at Children

Science.gov (United States)

Kervin, Lisa; Jones, Sandra C.; Mantei, Jessica

2012-01-01

It is recognised that from a young age children spend considerable portions of their leisure time on the Internet. In Australia a number of child-targeted magazines have associated websites, which have high and ever-increasing readership. We do not yet know the impact of this medium upon children. Overt advertising is evident on webpages, but so…

Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.

Directory of Open Access Journals (Sweden)

Rick S Mitchell

2004-08-01

Full Text Available The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral vectors derived from human immunodeficiency virus (HIV, avian sarcoma-leukosis virus (ASLV, and murine leukemia virus (MLV. Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells. Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV integration, but these regions were found to be interleaved with unfavorable regions at CpG islands. MLV vectors showed a strong bias in favor of integration near transcription start sites, as reported previously. ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection.

Novel acetylcholinesterase target site for malaria mosquito control.

Directory of Open Access Journals (Sweden)

Yuan-Ping Pang

2006-12-01

Full Text Available Current anticholinesterase pesticides were developed during World War II and are toxic to mammals because they target a catalytic serine residue of acetylcholinesterases (AChEs in insects and in mammals. A sequence analysis of AChEs from 73 species and a three-dimensional model of a malaria-carrying mosquito (Anopheles gambiae AChE (AgAChE reported here show that C286 and R339 of AgAChE are conserved at the opening of the active site of AChEs in 17 invertebrate and four insect species, respectively. Both residues are absent in the active site of AChEs of human, monkey, dog, cat, cattle, rabbit, rat, and mouse. The 17 invertebrates include house mosquito, Japanese encephalitis mosquito, African malaria mosquito, German cockroach, Florida lancelet, rice leaf beetle, African bollworm, beet armyworm, codling moth, diamondback moth, domestic silkworm, honey bee, oat or wheat aphid, the greenbug, melon or cotton aphid, green peach aphid, and English grain aphid. The four insects are house mosquito, Japanese encephalitis mosquito, African malaria mosquito, and German cockroach. The discovery of the two invertebrate-specific residues enables the development of effective and safer pesticides that target the residues present only in mosquito AChEs rather than the ubiquitous serine residue, thus potentially offering an effective control of mosquito-borne malaria. Anti-AgAChE pesticides can be designed to interact with R339 and subsequently covalently bond to C286. Such pesticides would be toxic to mosquitoes but not to mammals.

Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

Directory of Open Access Journals (Sweden)

Paul S. Rennie

2013-06-01

Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

Asthma, respiratory symptoms and lung function in children living near a petrochemical site.

NARCIS (Netherlands)

Rovira, E.; Cuadras, A.; Aguilar, X.; Esteban, L.; Borràs-Santos, A.; Zock, J.P.; Sunyer, J.

2014-01-01

Residential proximity to environmental hazards has been related to adverse health outcomes. Respiratory health and allergies in children living near petrochemical sites have not been extensively studied. We evaluated the association between residential proximity to the petrochemical site of

A mathematical model of single target site location by Brownian movement in subcellular compartments.

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Kuthan, Hartmut

2003-03-07

The location of distinct sites is mandatory for many cellular processes. In the subcompartments of the cell nucleus, only very small numbers of diffusing macromolecules and specific target sites of some types may be present. In this case, we are faced with the Brownian movement of individual macromolecules and their "random search" for single/few specific target sites, rather than bulk-averaged diffusion and multiple sites. In this article, I consider the location of a distant central target site, e.g. a globular protein, by individual macromolecules executing unbiased (i.e. drift-free) random walks in a spherical compartment. For this walk-and-capture model, the closed-form analytic solution of the first passage time probability density function (p.d.f.) has been obtained as well as the first and second moment. In the limit of a large ratio of the radii of the spherical diffusion space and central target, well-known relations for the variance and the first two moments for the exponential p.d.f. were found to hold with high accuracy. These calculations reinforce earlier numerical results and Monte Carlo simulations. A major implication derivable from the model is that non-directed random movement is an effective means for locating single sites in submicron-sized compartments, even when the diffusion coefficients are comparatively small and the diffusing species are present in one copy only. These theoretical conclusions are underscored numerically for effective diffusion constants ranging from 0.5 to 10.0 microm(2) s(-1), which have been reported for a couple of nuclear proteins in their physiological environment. Spherical compartments of submicron size are, for example, the Cajal bodies (size: 0.1-1.0 microm), which are present in 1-5 copies in the cell nucleus. Within a small Cajal body of radius 0.1 microm a single diffusing protein molecule (with D=0.5 microm(2) s(-1)) would encounter a medium-sized protein of radius 2.5 nm within 1 s with a probability near

Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites.

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Qudrat, Anam; Mosabbir, Abdullah Al; Truong, Kevin

2017-06-22

Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Centredale Manor Superfund Site in Rhode Island included on EPA List of Targeted for Immediate Attention

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Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The Centredale Manor Restoration Project superfund site is one of the 21 sites on the list.

Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection

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Marius Rutkauskas

2015-03-01

Full Text Available CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by a large ribonucleoprotein surveillance complex called Cascade. The crRNA component of Cascade is used to recognize target sites in foreign DNA (protospacers by formation of an R-loop driven by base-pairing complementarity. Using single-molecule supercoiling experiments with near base-pair resolution, we probe here the mechanism of R-loop formation and detect short-lived R-loop intermediates on off-target sites bearing single mismatches. We show that R-loops propagate directionally starting from the protospacer-adjacent motif (PAM. Upon reaching a mismatch, R-loop propagation stalls and collapses in a length-dependent manner. This unambiguously demonstrates that directional zipping of the R-loop accomplishes efficient target recognition by rapidly rejecting binding to off-target sites with PAM-proximal mutations. R-loops that reach the protospacer end become locked to license DNA degradation by the auxiliary Cas3 nuclease/helicase without further target verification.

Not Just Fun and Games: Toy Advertising on Television Targeting Children Promotes Sedentary Play.

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Potvin Kent, Monique; Velkers, Clive

2017-10-01

To examine the volume of television toy advertising targeting Canadian children and to determine if it promotes active or sedentary play, targets males or females more frequently, and has changed over time. Data for toy/game advertising from 27 television stations in Toronto for the month of May in 2006 and 2013 were licensed from Neilsen Media Research (Montreal, Quebec, Canada). A content analysis was performed on all ads to determine what age group and gender were targeted and whether physical or sedentary activity was being promoted. Comparisons were made between 2006 and 2013. There were 3.35 toy ads/h/children's specialty station in 2013 (a 15% increase from 2006). About 88% of toy ads promoted sedentary play in 2013, a 27% increase from 2006 levels, while toy ads promoting active play decreased by 33%. In both 2006 and 2013, a greater number of sedentary toy ads targeted males (n = 1519, May 2006; n = 2030, May 2013) compared with females (n = 914, May 2006; n = 1619, May 2013), and between 2006 and 2013, these ads increased significantly for both males and females. Future research should explore whether such advertising influences children's preferences for activities and levels of physical activity.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

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Datis Kharrazian

2017-01-01

Full Text Available Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease.

Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay.

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Giménez, Ana; Saldamando, Luis de; Curutchet, María Rosa; Ares, Gastón

2017-06-12

Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children's eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children's attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products' sensory and hedonic characteristics. The study's findings provide additional evidence on the need to regulate packaging of products targeted at children.

Effects of surgical side and site on mood and behavior outcome in children with pharmacoresistant epilepsy

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Elizabeth N Andresen

2014-02-01

Full Text Available Children with epilepsy have a high rate of mood and behavior problems yet few studies consider the emotional and behavioral impact of surgery. No study to date has been sufficiently powered to investigate effects of both side (left/right and site (temporal/frontal of surgery. One hundred patients (aged 6-16 and their families completed measures of depression, anxiety and behavioral function as part of neuropsychological evaluations before and after surgery for pharmacoresistant epilepsy. Among children who had left-sided surgeries (frontal=16; temporal=38, there were significant interactions between time (pre to postoperative neuropsychological assessment and resection site (frontal/temporal on Anhedonia, Social Anxiety, and Withdrawn/Depressed scales. Patients with frontal lobe epilepsy (FLE endorsed greater presurgical anhedonia and social anxiety than patients with temporal lobe epilepsy (TLE, with scores normalizing following surgery. While scores on the Withdrawn/Depressed scale were similar between groups before surgery, the FLE group showed greater symptom improvement after surgery. In children who underwent right-sided surgeries (FLE=20; TLE=26 main effects of time (patients in both groups improved and resection site (caregivers of FLE patients endorsed greater symptoms than those with TLE were observed primarily on behavior scales. Individual data revealed that a greater proportion of children with left FLE demonstrated clinically significant improvements in Anhedonia, Social Anxiety, and Aggressive Behavior than children with TLE. This is the first study to demonstrate differential effects of both side and site of surgery in children with epilepsy at group and individual levels. Results suggest that children with FLE have greater emotional and behavioral dysfunction before surgery, but show marked improvement after surgery. Overall, most children had good emotional and behavioral outcomes, with most scores remaining stable or improving.

Protecting important sites for biodiversity contributes to meeting global conservation targets.

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Stuart H M Butchart

Full Text Available Protected areas (PAs are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs (referred to collectively hereafter as 'important sites'. Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites. Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs. While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45-1.14% annually since 1950 for IBAs and 0.79-1.49% annually for AZEs. Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends.

The dragnet of children's feeding programs in Atlantic Canada.

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Dayle, J B; McIntyre, L; Raine-Travers, K D

2000-12-01

Ivan Illich's 1976 prediction that medical dragnets will continue was correct. Now quasi-health dragnets are being established ostensibly to feed children perceived to be hungry. Our qualitative, multi-site case study found that programs justify their expansion to non-target group children as a means of reducing stigmatization, while reaching only an estimated one-third of targeted children. The dragnet continues as new services are added and franchising is proposed while the purpose of the program feeding healthy foods to children ultimately succumbs to drives for efficiency and the desire to maintain the program itself. In this field of social power relations, children become commodified through dialectical interplays among fundamental needs, manipulated needs, benevolence, and domination.

The influence of participation in target-shooting sport for children with inattentive, hyperactive and impulsive symptoms - A controlled study of best practice.

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Månsson, Annegrete Gohr; Elmose, Mette; Dalsgaard, Søren; Roessler, Kirsten K

2017-03-28

Practising target-shooting sport requires focused attention and motoric steadiness. A previous non-controlled pilot study suggests that children with impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) benefit from participating in target-shooting sport in local shooting associations, as rated by parents and teachers. This study aims at examining if, and to which extent, target-shooting sport reduces parent- and teacher-reported severity of inattentiveness, hyperactivity, and impulsivity in children with attention difficulties, and if, and to which extend, target-shooting sport improves the children's wellbeing and quality of life. A mixed method approach is applied. A non-blinded, waiting list controlled study is combined with a case study, consisting of interviews and observations. The intervention consists of children practising target-shooting sport, by attending a local shooting association, once a week for six months, during regular school hours. Data from questionnaires (ADHD-RS, SDQ, Kidscreen-27), as well as a computerized continued performance test (Qb test), measure the children's activity and attention. The study includes 50 children in an intervention group and 50 children in a waiting list control group. The Qb test collects data from at least 20 children from the intervention group and at least 20 children from the waiting list control group. Data from the questionnaires and Qb-test is collected at baseline, and six months post intervention. In addition, a case study is carried out, consisting of interviews of at least five children from the intervention group, their parents, teachers and shooting instructors. Observations are carried out, when children are in school and while they are attending the local shooting association. The case study adds to an in-depth understanding of children's participation in target-shooting sports. At present, little is known about the effects and influence of practising target-shooting sport for

School programs targeting stress management in children and adolescence: a meta-analysis

NARCIS (Netherlands)

Kraag, G.C; Zeegers, M.P.; Kok, G.J.; Hosman, C.M.H.; Huijer Abu-Saad, H.

2006-01-01

Introduction This meta-analysis evaluates the effect of school programs targeting stress management or coping skills in school children. Methods Articles were selected through a systematic literature search. Only randomized controlled trials or quasi-experimental studies were included. The

A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA

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Robert J Scarborough

2014-01-01

Full Text Available Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

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Butchart, Stuart H. M.; Scharlemann, Jörn P. W.; Evans, Mike I.; Quader, Suhel; Aricò, Salvatore; Arinaitwe, Julius; Balman, Mark; Bennun, Leon A.; Bertzky, Bastian; Besançon, Charles; Boucher, Timothy M.; Brooks, Thomas M.; Burfield, Ian J.; Burgess, Neil D.; Chan, Simba; Clay, Rob P.; Crosby, Mike J.; Davidson, Nicholas C.; De Silva, Naamal; Devenish, Christian; Dutson, Guy C. L.; Fernández, David F. Día z; Fishpool, Lincoln D. C.; Fitzgerald, Claire; Foster, Matt; Heath, Melanie F.; Hockings, Marc; Hoffmann, Michael; Knox, David; Larsen, Frank W.; Lamoreux, John F.; Loucks, Colby; May, Ian; Millett, James; Molloy, Dominic; Morling, Paul; Parr, Mike; Ricketts, Taylor H.; Seddon, Nathalie; Skolnik, Benjamin; Stuart, Simon N.; Upgren, Amy; Woodley, Stephen

2012-01-01

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends. PMID:22457717

Empirical estimation of school siting parameter towards improving children's safety

Science.gov (United States)

Aziz, I. S.; Yusoff, Z. M.; Rasam, A. R. A.; Rahman, A. N. N. A.; Omar, D.

2014-02-01

Distance from school to home is a key determination in ensuring the safety of hildren. School siting parameters are made to make sure that a particular school is located in a safe environment. School siting parameters are made by Department of Town and Country Planning Malaysia (DTCP) and latest review was on June 2012. These school siting parameters are crucially important as they can affect the safety, school reputation, and not to mention the perception of the pupil and parents of the school. There have been many studies to review school siting parameters since these change in conjunction with this ever-changing world. In this study, the focus is the impact of school siting parameter on people with low income that live in the urban area, specifically in Johor Bahru, Malaysia. In achieving that, this study will use two methods which are on site and off site. The on site method is to give questionnaires to people and off site is to use Geographic Information System (GIS) and Statistical Product and Service Solutions (SPSS), to analyse the results obtained from the questionnaire. The output is a maps of suitable safe distance from school to house. The results of this study will be useful to people with low income as their children tend to walk to school rather than use transportation.

Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression.

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Denzler, Rémy; McGeary, Sean E; Title, Alexandra C; Agarwal, Vikram; Bartel, David P; Stoffel, Markus

2016-11-03

Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent of repression, they have little effect on the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ∼20% of that observed for canonical 8-nt sites. In aggregate, low-affinity/background sites also contribute to competition. Sites with extensive additional complementarity can appear as more potent, but only because they induce miRNA degradation. Cooperative binding of proximal sites for the same or different miRNAs does increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNAs and target abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene regulation, and the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Targeted screening strategies to detect Trypanosoma cruzi infection in children.

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Michael Z Levy

2007-12-01

Full Text Available Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy.We performed a serological survey in children 2-18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4-7.9] children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children.We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

Food and Beverage Brands that Market to Children and Adolescents on the Internet: A Content Analysis of Branded Web Sites

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Henry, Anna E.; Story, Mary

2009-01-01

Objective: To identify food and beverage brand Web sites featuring designated children's areas, assess marketing techniques present on those industry Web sites, and determine nutritional quality of branded food items marketed to children. Design: Systematic content analysis of food and beverage brand Web sites and nutrient analysis of food and…

Exceptional preservation of children's footprints from a Holocene footprint site in Namibia

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Bennett, Matthew R.; Morse, Sarita A.; Liutkus-Pierce, Cynthia; McClymont, Juliet; Evans, Mary; Crompton, Robin H.; Francis Thackeray, J.

2014-09-01

Here we report on a Holocene inter-dune site close to Walvis Bay (Namibia) which contains exceptionally well-preserved children's footprints. The footprint surface is dated using Optically Stimulated Luminescence (OSL) methods to approximately 1.5 ka. These dates are compared to those obtained at nearby footprint sites and used to verify a model of diachronous footprint surfaces and also add to the archaeological data available for the communities that occupied these near-coastal areas during the Holocene. This model of diachronous footprint surfaces has implications for other soft-sediment footprint sites such as the 1.5 Ma old footprints at Ileret (Kenya). The distribution of both human and animal tracks, is consistent with the passage of small flock of small ungulates (probably sheep/goats) followed by a group of approximately 9 ± 2 individuals (children or young adults). Age estimates from the tracks suggest that some of the individuals may have been as young as five years old. Variation in track topology across this sedimentologically uniform surface is explained in terms of variations in gait and weight/stature of the individual print makers and is used to corroborate a model of footprint morphology developed at a nearby site. The significance of the site within the literature on human footprints lies in the quality of the track preservation, their topological variability despite a potentially uniform substrate, and the small size of the tracks, and therefore the inferred young age of the track-makers. The site provides an emotive insight into the life of the track-makers.

Achieving target voriconazole concentrations more accurately in children and adolescents.

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Neely, Michael; Margol, Ashley; Fu, Xiaowei; van Guilder, Michael; Bayard, David; Schumitzky, Alan; Orbach, Regina; Liu, Siyu; Louie, Stan; Hope, William

2015-01-01

Despite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled children and adults. We then used it in our multiple-model Bayesian adaptive control algorithm to predict measured concentrations and doses in a separate cohort of 33 pediatric patients aged 8 months to 17 years who were receiving voriconazole and enrolled in a pharmacokinetic study. Using all available samples to estimate the individual Bayesian posterior parameter values, the median percent prediction bias relative to a measured target trough concentration in the patients was 1.1% (interquartile range, -17.1 to 10%). Compared to the actual dose that resulted in the target concentration, the percent bias of the predicted dose was -0.7% (interquartile range, -7 to 20%). Using only trough concentrations to generate the Bayesian posterior parameter values, the target bias was 6.4% (interquartile range, -1.4 to 14.7%; P = 0.16 versus the full posterior parameter value) and the dose bias was -6.7% (interquartile range, -18.7 to 2.4%; P = 0.15). Use of a sample collected at an optimal time of 4 h after a dose, in addition to the trough concentration, resulted in a nonsignificantly improved target bias of 3.8% (interquartile range, -13.1 to 18%; P = 0.32) and a dose bias of -3.5% (interquartile range, -18 to 14%; P = 0.33). With the nonparametric population model and trough concentrations, our control algorithm can accurately manage voriconazole therapy in children independently of steady-state conditions, and it is generalizable to any drug with a nonparametric pharmacokinetic model. (This study has been registered at ClinicalTrials.gov under registration no. NCT01976078.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Morbidity among children living around clinical waste treatment and disposal site in the Northwest region of Cameroon

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Peter I. K. Mochungong

2011-03-01

Full Text Available Clinical waste is ineffectively treated and disposed in Cameroon. Disposal sites have unrestricted access and are located within communities. We hypothesize that vector proliferation and exposure to chronic low-level emissions will increase morbidity in children living around such sites. Self-reported disease frequency questionnaires were used to estimate the frequency of new episodes of intestinal, respiratory and skin infections among exposed children less than 10 years. Data was simultaneously collected for unexposed children of the same age, using the same questionnaire. Data reporting by the parents was done in the first week in each of the 6 months study period. The risk ratios were 3.54 (95% CI, 2.19-5.73, 3.20 (95% CI, 1.34-7.60 and 1.35 (95% CI, 0.75-2.44 for respiratory, intestinal and skin infections respectively. Their respective risk differences were 0.47 (47%, 0.18 (18% and 0.08 (8%. The study revealed that poor treatment and disposal of clinical waste sites enhance morbidity in children living close to such areas. Simple health promotion and intervention programs such as relocating such sites can significantly reduce morbidity.

Do On-Site Mental Health Professionals Change Pediatricians' Responses to Children's Mental Health Problems?

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McCue Horwitz, Sarah; Storfer-Isser, Amy; Kerker, Bonnie D; Szilagyi, Moira; Garner, Andrew S; O'Connor, Karen G; Hoagwood, Kimberly E; Green, Cori M; Foy, Jane M; Stein, Ruth E K

2016-01-01

To assess the availability of on-site mental health professionals (MHPs) in primary care; to examine practice/pediatrician characteristics associated with on-site MHPs; and to determine whether the presence of on-site MHPs is related to pediatricians' comanaging or more frequently identifying, treating/managing, or referring mental health (MH) problems. Analyses included American Academy of Pediatrics (AAP) members who participated in an AAP Periodic Survey in 2013 and who practiced general pediatrics (n = 321). Measures included sociodemographics, practice characteristics, questions about on-site MHPs, comanagement of MH problems, and pediatricians' behaviors in response to 5 prevalent MH problems. Weighted univariate, bivariate, and multivariable analyses were performed. Thirty-five percent reported on-site MHPs. Practice characteristics (medical schools, universities, health maintenance organizations, managed, or referred 5 common child MH problems. Among the subset of pediatricians who reported comanaging, there was an association with comanagement when the on-site MHP was a child psychiatrist, substance abuse counselor, or social worker. On-site MHPs are more frequent in settings where low-income children are served and where pediatricians train. Pediatricians who comanage MH problems are more likely to do so when the on-site MHP is a child psychiatrist, substance abuse counselor, or social worker. Overall, on-site MHPs were not associated with comanagement or increased likelihood of pediatricians identifying, treating/managing, or referring children with 5 common child MH problems. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Outreach for Outreach: Targeting social media audiences to promote a NASA kids’ web site

Science.gov (United States)

Pham, C. C.

2009-12-01

The Space Place is a successful NASA web site that benefits upper elementary school students and educators by providing games, activities, and resources to stimulate interest in science, technology, engineering, and mathematics, as well as to inform the audience of NASA’s contributions. As online social networking grows to be a central component of modern communication, The Space Place has explored the benefits of integrating social networks with the web site to increase awareness of materials the web site offers. This study analyzes the capabilities of social networks, and specifically the demographics of Twitter and Facebook. It then compares these results with the content, audience, and perceived demographics of The Space Place web site. Based upon the demographic results, we identified a target constituency that would benefit from the integration of social networks into The Space Place web site. As a result of this study, a Twitter feed has been established that releases a daily tweet from The Space Place. In addition, a Facebook page has been created to showcase new content and prompt interaction among fans of The Space Place. Currently, plans are under way to populate the Space Place Facebook page. Each social network has been utilized in an effort to spark excitement about the content on The Space Place, as well as to attract followers to the main NASA Space Place web site. To pursue this idea further, a plan has been developed to promote NASA Space Place’s social media tools among the target audience.

Molecular characterization of monoclonal antibodies that inhibit acetylcholinesterase by targeting the peripheral site and backdoor region.

Directory of Open Access Journals (Sweden)

Yves Bourne

Full Text Available The inhibition properties and target sites of monoclonal antibodies (mAbs Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE, have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis.

A genome-wide analysis of lentivector integration sites using targeted sequence capture and next generation sequencing technology.

Science.gov (United States)

Ustek, Duran; Sirma, Sema; Gumus, Ergun; Arikan, Muzaffer; Cakiris, Aris; Abaci, Neslihan; Mathew, Jaicy; Emrence, Zeliha; Azakli, Hulya; Cosan, Fulya; Cakar, Atilla; Parlak, Mahmut; Kursun, Olcay

2012-10-01

One application of next-generation sequencing (NGS) is the targeted resequencing of interested genes which has not been used in viral integration site analysis of gene therapy applications. Here, we combined targeted sequence capture array and next generation sequencing to address the whole genome profiling of viral integration sites. Human 293T and K562 cells were transduced with a HIV-1 derived vector. A custom made DNA probe sets targeted pLVTHM vector used to capture lentiviral vector/human genome junctions. The captured DNA was sequenced using GS FLX platform. Seven thousand four hundred and eighty four human genome sequences flanking the long terminal repeats (LTR) of pLVTHM fragment sequences matched with an identity of at least 98% and minimum 50 bp criteria in both cells. In total, 203 unique integration sites were identified. The integrations in both cell lines were totally distant from the CpG islands and from the transcription start sites and preferentially located in introns. A comparison between the two cell lines showed that the lentiviral-transduced DNA does not have the same preferred regions in the two different cell lines. Copyright © 2012 Elsevier B.V. All rights reserved.

Determining Antifungal Target Sites in the Sterol Pathway of the Yeast Candida and Saccharomyces

National Research Council Canada - National Science Library

Bard, Martin

1998-01-01

... as in topical infections which lead to significant losses in work-place productivity. The work reported here seeks to identify new target sites in the sterol biosynthetic pathway against which new antifungal compounds might be developed...

Occurrence Prospect of HDR and Target Site Selection Study in Southeastern of China

Science.gov (United States)

Lin, W.; Gan, H.

2017-12-01

Hot dry rock (HDR) geothermal resource is one of the most important clean energy in future. Site selection a HDR resource is a fundamental work to explore the HDR resources. This paper compiled all the HDR development projects domestic and abroad, and summarized the location of HDR geothermal geological index. After comparing the geological background of HDR in the southeast coastal area of China, Yangjiang Xinzhou in Guangdong province, Leizhou Peninsula area, Lingshui in Hainan province and Huangshadong in Guangzhou were selected from some key potential target area along the southeast coast of China. Deep geothermal field model of the study area is established based on the comprehensive analysis of the target area of deep geothermal geological background and deep thermal anomalies. This paper also compared the hot dry rock resources target locations, and proposed suggestions for the priority exploration target area and exploration scheme.

Child-targeted fast-food television advertising exposure is linked with fast-food intake among pre-school children.

Science.gov (United States)

Dalton, Madeline A; Longacre, Meghan R; Drake, Keith M; Cleveland, Lauren P; Harris, Jennifer L; Hendricks, Kristy; Titus, Linda J

2017-06-01

To determine whether exposure to child-targeted fast-food (FF) television (TV) advertising is associated with children's FF intake in a non-experimental setting. Cross-sectional survey conducted April-December 2013. Parents reported their pre-school child's TV viewing time, channels watched and past-week FF consumption. Responses were combined with a list of FF commercials (ads) aired on children's TV channels during the same period to calculate children's exposure to child-targeted TV ads for the following chain FF restaurants: McDonald's, Subway and Wendy's (MSW). Paediatric and Women, Infants, and Children (WIC) clinics in New Hampshire, USA. Parents (n 548) with a child of pre-school age. Children's mean age was 4·4 years; 43·2 % ate MSW in the past week. Among the 40·8 % exposed to MSW ads, 23·3 % had low, 34·2 % moderate and 42·5 % high exposure. McDonald's accounted for over 70 % of children's MSW ad exposure and consumption. Children's MSW consumption was significantly associated with their ad exposure, but not overall TV viewing time. After adjusting for demographics, socio-economic status and other screen time, moderate MSW ad exposure was associated with a 31 % (95 % CI 1·12, 1·53) increase and high MSW ad exposure with a 26 % (95 % CI 1·13, 1·41) increase in the likelihood of consuming MSW in the past week. Further adjustment for parent FF consumption did not change the findings substantially. Exposure to child-targeted FF TV advertising is positively associated with FF consumption among children of pre-school age, highlighting the vulnerability of young children to persuasive advertising and supporting recommendations to limit child-directed FF marketing.

Mohawk Tannery Hazardous Waste Site in New Hampshire included on EPA List of Targeted for Immediate Attention

Science.gov (United States)

Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The former Mohawk Tannery facility (a.k.a. Granite State Leathers) is one of the 21 sites on th

Hope for children and families: targeting abusive parenting and the associated impairment of children.

Science.gov (United States)

Bentovim, Arnon; Elliott, Ian

2014-01-01

The purpose of this study is to distill the "effective practice elements" from randomised controlled interventions (RCTs) to prevent the recurrence of abusive and neglectful parenting and the associated health and developmental impairment of children. The resulting elements would be used then to develop a step-by-step modular-systemic approach to intervention that is suitable to the needs of a variety of frontline practitioners in social care, health, and education. A series of 22 randomised RCTs were analysed using the distillation and matching approach to establish the presence of effective practice elements. The focus was physical and sexual abuse, victims and children, and young people as perpetrators; neglect including failure to thrive, emotional abuse (exposure to violence and mental health issues). The studies were analysed for effective practice elements, across different approaches matched to interventions focused on parenting, on children and young people, and on family/professional relationships. The proportion of practice elements utilised in each form of maltreatment was defined. The distillation process resulted in a total of 47 practice elements present across all forms of maltreatment studied. An experienced group of practitioners from statutory and voluntary agencies ordered and integrated the most frequently utilised emerging elements into a series of step-by-step modules, which could fit the complex needs of families when maltreatment had occurred. The resulting manual, Hope for Children and Families, provides a "menu" of evidence-based, step-by-step modular interventions targeting the profile of abusive and neglectful parenting and associated impairments of children. To be effective for frontline practitioners, the manual will need to be delivered in a user-friendly format, training developed, and supervision and support provided.

Using questions sent to an Ask-A-Scientist site to identify children's interests in science

Science.gov (United States)

Baram-Tsabari, Ayelet; Sethi, Ricky J.; Bry, Lynn; Yarden, Anat

2006-11-01

Interest is a powerful motivator; nonetheless, science educators often lack the necessary information to make use of the power of student-specific interests in the reform process of science curricula. This study suggests a novel methodology, which might be helpful in identifying such interests - using children's self-generated questions as an indication of their scientific interests. In this research, children's interests were measured by analyzing 1555 science-related questions submitted to an international Ask-A-Scientist Internet site. The analysis indicated that the popularity of certain topics varies with age and gender. Significant differences were found between children's spontaneous (intrinsically motivated) and school-related (extrinsically motivated) interests. Surprisingly, girls contributed most of the questions to the sample; however, the number of American girls dropped upon entering senior high school. We also found significant differences between girls' and boys' interests, with girls generally preferring biological topics. The two genders kept to their stereotypic fields of interest, in both their school-related and spontaneous questions. Children's science interests, as inferred from questions to Web sites, could ultimately inform classroom science teaching. This methodology extends the context in which children's interests can be investigated.

Contribution of non-target-site resistance in imidazolinone-resistant Imisun sunflower

Directory of Open Access Journals (Sweden)

Gabriela Breccia

2017-08-01

Full Text Available ABSTRACT The first commercial herbicide-resistant trait in sunflower (Helianthus annuus L. is known as ‘Imisun’. Imidazolinone resistance in Imisun cultivars has been reported to be genetically controlled by a major gene (known as Imr1 or Ahasl1-1 and modifier genes. Imr1 is an allelic variant of the Ahasl1 locus that codes for the acetohydroxyacid synthase, which is the target site of these herbicides. The mechanism of resistance endowed by modifier genes has not been characterized and it could be related to non-target-site resistance. The objective of this study was to evaluate the role of cytochrome P450 monooxygenases (P450s in Imisun resistance. The response to imazapyr herbicide in combination with P450s inhibitor malathion was evaluated in 2 Imisun lines, IMI-1 and RHA426. Malathion reduced herbicide efficacy in both lines, but IMI-1 was affected in a greater extent. A significant reduction in plant growth in response to P450s inhibitors 1-aminobenzotriazole and piperonyl butoxide treatment was detected in the Imisun line HA425. The increased susceptibility to imazapyr after P450s-inhibitor treatment indicates that herbicide metabolism by P450s is a mechanism involved in Imisun resistance. These results also suggest the involvement of different P450s isozymes in endowing resistance to imazapyr in Imisun cultivars.

Does Head Start differentially benefit children with risks targeted by the program’s service model?☆

Science.gov (United States)

Miller, Elizabeth B.; Farkas, George; Duncan, Greg J.

2015-01-01

Data from the Head Start Impact Study (N = 3540) were used to test for differential benefits of Head Start after one program year and after kindergarten on pre-academic and behavior outcomes for children at risk in the domains targeted by the program’s comprehensive services. Although random assignment to Head Start produced positive treatment main effects on children’s pre-academic skills and behavior problems, residualized growth models showed that random assignment to Head Start did not differentially benefit the pre-academic skills of children with risk factors targeted by the Head Start service model. The models showed detrimental impacts of Head Start for maternal-reported behavior problems of high-risk children, but slightly more positive impacts for teacher-reported behavior. Policy implications for Head Start are discussed. PMID:26379369

Priority target conditions for algorithms for monitoring children's growth: Interdisciplinary consensus.

Directory of Open Access Journals (Sweden)

Pauline Scherdel

Full Text Available Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define abnormal growth. Optimization of growth monitoring requires standardization of the definition of abnormal growth, and the selection of the priority target conditions is a prerequisite of such standardization.To obtain a consensus about the priority target conditions for algorithms monitoring children's growth.We applied a formal consensus method with a modified version of the RAND/UCLA method, based on three phases (preparatory, literature review, and rating, with the participation of expert advisory groups from the relevant professional medical societies (ranging from primary care providers to hospital subspecialists as well as parent associations. We asked experts in the pilot (n = 11, reading (n = 8 and rating (n = 60 groups to complete the list of diagnostic classification of the European Society for Paediatric Endocrinology and then to select the conditions meeting the four predefined criteria of an ideal type of priority target condition.Strong agreement was obtained for the 8 conditions selected by the experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma, juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic-optochiasmatic astrocytoma (in decreasing order of agreement.This national consensus can be used to evaluate the algorithms currently suggested for growth monitoring. The method used for this national consensus could be re-used to obtain an international consensus.

Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

DEFF Research Database (Denmark)

Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

2014-01-01

Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...

Targeted vaccination in healthy school children - Can primary school vaccination alone control influenza?

Science.gov (United States)

Thorrington, Dominic; Jit, Mark; Eames, Ken

2015-10-05

The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glyphosate-Resistant Parthenium hysterophorus in the Caribbean Islands: Non Target Site Resistance and Target Site Resistance in Relation to Resistance Levels.

Directory of Open Access Journals (Sweden)

Enzo Bracamonte

2016-12-01

of a proline to serine change in Cu-R1, Do-R1 Do-R2. The above-mentioned results indicate that high resistance values are determined by the number of defense mechanisms (target-site and non-target-site resistance possessed by the different P. hysterophorus accessions, concurrently.

Pilot study of a targeted dance class for physical rehabilitation in children with cerebral palsy.

Science.gov (United States)

López-Ortiz, Citlali; Egan, Tara; Gaebler-Spira, Deborah J

2016-01-01

This pilot study evaluates the effects of a targeted dance class utilizing classical ballet principles for rehabilitation of children with cerebral palsy on balance and upper extremity control. Twelve children with cerebral palsy (ages 7-15 years) with Gross Motor Function Classification scores II-IV participated in this study and were assigned to either a control group or targeted dance class group. Targeted dance class group participated in 1-h classes three times per week in a 4-week period. The Pediatric Balance Scale and the Quality of Upper Extremity Skills Test were administered before, after, and 1 month after the targeted dance class. Improvements in the Pediatric Balance Scale were present in the targeted dance class group in before versus after and before versus 1 month follow-up comparisons (p-value = 0.0088 and p-value = 0.019, respectively). The Pediatric Balance Scale changes were not significant in the control group. The Quality of Upper Extremity Skills Test did not reach statistical differences in either group. Classical ballet as an art form involves physical training, musical accompaniment, social interactions, and emotional expression that could serve as adjunct to traditional physical therapy. This pilot study demonstrated improvements in balance control. A larger study with a more homogeneous sample is warranted.

Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay

Directory of Open Access Journals (Sweden)

Ana Giménez

Full Text Available Abstract: Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children’s eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children’s attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products’ sensory and hedonic characteristics. The study’s findings provide additional evidence on the need to regulate packaging of products targeted at children.

An event-related potential study of working memory in children

Institute of Scientific and Technical Information of China (English)

LIU Rong; GUO Chunyan; JIANG Yang

2006-01-01

To examine the neural mechanisms of working memory in children, event-related potentials (ERPs) were recorded from the 12―13 year-old while they performed a delayed match-to-sample task. The ERP results revealed that new and studied objects both evoked a late positive ERP component peaking around 350 ms during the working memory process. New objects evoke a more positive ERP waveform than the studied objects. The scalp distribution showed that the frontal-central electrode sites were associated with object working memory processes. When tracking new or studied targets among visual distracters, ERPs of targets and distracters revealed differential responses as early as 150 ms. The visual targets evoked larger and more positive ERP responses than the distracters. The typical old-new effect was observed between ERPs of studied and new distracters. However, ERPs of new and studied targets differed at about 250 ms, in which new targets evoked more positive-going and slightly earlier ERP responses. In addition, a P3a component was found for new targets only, and was absent in ERPs of studied targets at frontal and central sites. The present study results reveal the spatial and temporal characteristics of neural mechanisms underlying working memory in children, some of which are distinct from those in adults.

Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

Science.gov (United States)

Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

2018-04-18

Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

Use of Different Vegetable Products to Increase Preschool-Aged Children's Preference for and Intake of a Target Vegetable

NARCIS (Netherlands)

Wild, de Victoire W.T.; Graaf, de Kees; Jager, Gerry

2017-01-01

Background: Children's low vegetable consumption requires effective strategies to enhance preference for and intake of vegetables. Objective: The study compared three preparation practices for a target vegetable (spinach) on their effectiveness in increasing preschool-aged children's preference

Nutrition content of food and beverage products on Web sites popular with children.

Science.gov (United States)

Lingas, Elena O; Dorfman, Lori; Bukofzer, Eliana

2009-11-01

We assessed the nutritional quality of branded food and beverage products advertised on 28 Web sites popular with children. Of the 77 advertised products for which nutritional information was available, 49 met Institute of Medicine criteria for foods to avoid, 23 met criteria for foods to neither avoid nor encourage, and 5 met criteria for foods to encourage. There is a need for further research on the nature and extent of food and beverage advertising online to aid policymakers as they assess the impact of this marketing on children.

Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

Science.gov (United States)

Lee, Ciaran M; Davis, Timothy H; Bao, Gang

2018-04-01

What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

CHILDREN AS TARGET MARKET

OpenAIRE

SOMESFALEAN Vasilica

2012-01-01

The purpose of this paper is to highlight the reasons that lead marketers to give greater importance to children, how to explain this increased potential that children have on the existing market and strategies that marketers and companies use in order to reach this market. To this end we analyzed a series of articles, studies and research conducted on the subject, with implications in psychology, sociology, but especially in marketing. The results obtained show very interesting issues regard...

mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation.

Science.gov (United States)

Levy, Oren; Zhao, Weian; Mortensen, Luke J; Leblanc, Sarah; Tsang, Kyle; Fu, Moyu; Phillips, Joseph A; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H; Eimon, Peter; Angel, Matthew; Lin, Charles P; Yanik, Mehmet Fatih; Karp, Jeffrey M

2013-10-03

Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation.

siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

Science.gov (United States)

Vickers, Timothy A; Crooke, Stanley T

2012-07-01

While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

Pilot study of a targeted dance class for physical rehabilitation in children with cerebral palsy

Directory of Open Access Journals (Sweden)

Citlali López-Ortiz

2016-09-01

Full Text Available Introduction: This pilot study evaluates the effects of a targeted dance class utilizing classical ballet principles for rehabilitation of children with cerebral palsy on balance and upper extremity control. Methods: Twelve children with cerebral palsy (ages 7–15 years with Gross Motor Function Classification scores II–IV participated in this study and were assigned to either a control group or targeted dance class group. Targeted dance class group participated in 1-h classes three times per week in a 4-week period. The Pediatric Balance Scale and the Quality of Upper Extremity Skills Test were administered before, after, and 1 month after the targeted dance class. Results: Improvements in the Pediatric Balance Scale were present in the targeted dance class group in before versus after and before versus 1 month follow-up comparisons (p-value = 0.0088 and p-value = 0.019, respectively. The Pediatric Balance Scale changes were not significant in the control group. The Quality of Upper Extremity Skills Test did not reach statistical differences in either group. Conclusion: Classical ballet as an art form involves physical training, musical accompaniment, social interactions, and emotional expression that could serve as adjunct to traditional physical therapy. This pilot study demonstrated improvements in balance control. A larger study with a more homogeneous sample is warranted.

Assessment of mycorrhizal colonisation and soil nutrients in unmanaged fire-impacted soils from two target restoration sites

Energy Technology Data Exchange (ETDEWEB)

Dias, J. M.; Oliveira, R. S.; Franco, A. R.; Ritz, K.; Nunan, N.; Castro, P. M. L.

2010-07-01

The mycorrhizal colonisation of plants grown in unmanaged soils from two restoration sites with a fire history in Northern Portugal was evaluated from the perspective of supporting restoration programmes. To promote restoration of original tree stands, Quercus ilex L. and Pinus pinaster Ait. were used as target species on two sites, denoted Site 1 and 2 respectively. The aim of the study was to assess whether mycorrhizal propagules that survived fire episodes could serve as in situ inoculum sources, and to analyse the spatial distribution of soil nutrients and mycorrhizal parameters. In a laboratory bioassay, P. pinaster and Q. ilex seedlings were grown on soils from the target sites and root colonisation by ectomycorrhizal (ECM) and arbuscular mycorrhizal (AM) fungi was determined. The ECM root colonisation levels found indicated that soil from Site 2 contained sufficient ECM propagules to serve as a primary source of inoculum for P. pinaster. The low levels of ECM and AM colonisation obtained on the roots of plants grown in soil from Site 1 indicated that the existing mycorrhizal propagules might be insufficient for effective root colonisation of Q. ilex. Different ECM morphotypes were found in plants grown in soil from the two sites. At Site 2 mycorrhizal parameters were found to be spatially structured, with significant differences in ECM colonisation and soil P concentrations between regions of either side of an existing watercourse. The spatial distribution of mycorrhizal propagules was related to edaphic parameters (total C and extractable P), and correlations between soil nutrients and mycorrhizal parameters were found. (Author) 31 refs.

Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

Science.gov (United States)

Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

2015-11-18

Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

Empirical estimation of school siting parameter towards improving children's safety

International Nuclear Information System (INIS)

Aziz, I S; Yusoff, Z M; Rasam, A R A; Rahman, A N N A; Omar, D

2014-01-01

Distance from school to home is a key determination in ensuring the safety of hildren. School siting parameters are made to make sure that a particular school is located in a safe environment. School siting parameters are made by Department of Town and Country Planning Malaysia (DTCP) and latest review was on June 2012. These school siting parameters are crucially important as they can affect the safety, school reputation, and not to mention the perception of the pupil and parents of the school. There have been many studies to review school siting parameters since these change in conjunction with this ever-changing world. In this study, the focus is the impact of school siting parameter on people with low income that live in the urban area, specifically in Johor Bahru, Malaysia. In achieving that, this study will use two methods which are on site and off site. The on site method is to give questionnaires to people and off site is to use Geographic Information System (GIS) and Statistical Product and Service Solutions (SPSS), to analyse the results obtained from the questionnaire. The output is a maps of suitable safe distance from school to house. The results of this study will be useful to people with low income as their children tend to walk to school rather than use transportation

Application of the IEUBK model for linking Children's blood lead with environmental exposure in a mining site, south China

International Nuclear Information System (INIS)

Zhang, Xin-Ying; Carpenter, David O.; Song, Yong-Jin; Chen, Ping; Qin, Yaoming; Wei, Ni-Yu; Lin, Shan-Chun

2017-01-01

This study consisted of a site- and age-specific investigation linking children's blood lead level (BLL) to environmental exposures in a historic mining site in south China. A total of 151 children, aged 3–7 years, were included in this study. The geometric mean (GM) BLL was 8.22 μg/dl, indicating an elevated BLL. The Integrated Exposure Uptake Bio-Kinetic (IEUBK) model has proven useful at many sites for study of routes of exposure. Application of the IEUBK model to these children indicated that the GM difference between observed and predicted BLL levels was only 1.07 μg/dl. It was found that the key environmental exposure pathway was soil/dust intake, which contributed 86.3% to the total risk. Younger children had higher BLL than did older children. Therefore, of the various low risk-high benefit solutions, interventions for the children living near the site should be focused on the dust removal and soil remediation. Implementation of the China Eco-village Construction Plan and China New Rural Reconstruction Movement of the government may be a better solution. - Highlights: • BLLs were measured in 151 children aged 3–7 years in a Chinese mining town. • Pb was measured in soil, dust, air, drinking water, home grown vegetables and meat. • IEUBK model predicted BLL was 9.29 μg/dL and observed BLL was 8.22 μg/dL. • Most important exposure pathway was soil/dust which contributed 86.3% of the risk. • Soil and dust remediation is recommended to reduce children's BLLs.

TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

Science.gov (United States)

Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

2016-10-01

As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

Decaleside: a new class of natural insecticide targeting tarsal gustatory sites

Science.gov (United States)

Rajashekar, Yallappa; Rao, Lingamallu J. M.; Shivanandappa, Thimmappa

2012-10-01

Natural sources for novel insecticide molecules hold promise in view of their eco-friendly nature, selectivity, and mammalian safety. Recent progress in understanding the biology of insect olfaction and taste offers new strategies for developing selective pest control agents. We have isolated two natural insecticidal molecules from edible roots of Decalepis hamiltonii named Decalesides I and II, which are novel trisaccharides, highly toxic to household insect pests and stored-product insects. We have experimentally shown that insecticidal activity requires contact with tarsi on the legs but is not toxic orally. The insecticidal activity of molecules is lost by hydrolysis, and various sugars modify toxic response, showing that the insecticidal activity is via gustatory sites on the tarsi. Selective toxicity to insects by virtue of their gustatory site of action and the mammalian safety of the new insecticides is inherent in their chemical structure with 1-4 or 1-1 α linkage that is easily hydrolyzed by digestive enzymes of mammals. Decalesides represent a new chemical class of natural insecticides with a unique mode of action targeting tarsal chemosensory/gustatory system of insects.

Issues in the Development of Children's Centres on Nursery and Primary School Sites

Science.gov (United States)

Lewis, Jane; Finnegan, Cathy; West, Anne

2011-01-01

This paper explores the development of children's centres in England between 2004 and 2008, focusing on the newly created centres that have been located on primary and nursery school sites. Using both an analysis of policy documents and interview data from three urban local authorities, we examine the use of premises and the differing priorities…

Fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.

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Sanggu Kim

Full Text Available Xenotropic murine leukemia virus (MLV-related virus (XMRV is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014.

Science.gov (United States)

Baio, Jon; Wiggins, Lisa; Christensen, Deborah L; Maenner, Matthew J; Daniels, Julie; Warren, Zachary; Kurzius-Spencer, Margaret; Zahorodny, Walter; Robinson Rosenberg, Cordelia; White, Tiffany; Durkin, Maureen S; Imm, Pamela; Nikolaou, Loizos; Yeargin-Allsopp, Marshalyn; Lee, Li-Ching; Harrington, Rebecca; Lopez, Maya; Fitzgerald, Robert T; Hewitt, Amy; Pettygrove, Sydney; Constantino, John N; Vehorn, Alison; Shenouda, Josephine; Hall-Lande, Jennifer; Van Naarden Braun, Kim; Dowling, Nicole F

2018-04-27

, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer

Target Users' Expectations versus the Actual Compilation of a Shona Children's Dictionary

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Esau Mangoya

2011-10-01

Full Text Available Abstract: The article discusses the challenges that confronted the team of compilers working on the monolingual Shona Children's Dictionary (henceforth SCD. It looks at the active involvement of the target users in shaping the project and discusses the considerations for the implementation of their recommenda-tions. Matters of concern include issues of headword selection, especially problems of dialect representation in the dictionary. The article also discusses the inclusion of grammatical information such as tone marking. The SCD is one of the many efforts to promote and raise the functions of the indigenous languages in Zim-babwe. Of special interest in this article is therefore the discussion on the inclusion of international words like those denoting weight, distance and mathematical and scientific concepts. The article also considers the treatment of taboo words in the SCD, which takes into account that society has to open up culturally to be able to unequivocally view some of the aspects of life with which present-day children are confronted. The article lastly discusses how a balance was reached for accommodating the target users' proposal for the inclusion of an elaborate back matter in view of the limited available scope and space of the SCD.

Narrative discourse in children with early focal brain injury.

Science.gov (United States)

Reilly, J S; Bates, E A; Marchman, V A

1998-02-15

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

Target molecular weights for red cell band 3 stilbene and mercurial binding sites

International Nuclear Information System (INIS)

Verkman, A.S.; Skorecki, K.L.; Jung, C.Y.; Ausiello, D.A.

1986-01-01

Radiation inactivation was used to measure the target sizes for binding of disulfonic stilbene anion transport inhibitor 4,4'-dibenzamido-2,2'-disulfonic stilbene (DBDS) and mercurial water transport inhibitor p-chloromercuribenzene sulfonate (pCMBS) to human erythrocytes. The measured target size for erythrocyte ghost acetylcholinesterase was 78 +/- 3 kDa. DBDS binding to ghost membranes was measured by a fluorescence enhancement technique. Radiation (0-26 Mrad) had no effect on total membrane protein and DBDS binding affinity, whereas DBDS binding stoichiometry decreased exponentially with radiation dose, giving a target size of 59 +/- 4 kDa. H2-4,4'-diisothiocyano-2,2'-disulfonic stilbene (H2-DIDS, 5 microM) blocked greater than 95% of DBDS binding at all radiation doses. pCMBS binding was measured from the time course of tryptophan fluorescence quenching in ghosts treated with the sulfhydryl reagent N-ethylmaleimide (NEM). Radiation did not affect the kinetics of tryptophan quenching, whereas the total amplitude of the fluorescence signal inactivated with radiation with a target size of 31 +/- 6 kDa. These results support the notion that DBDS and pCMBS bind to the transmembrane domain of erythrocyte band 3 in NEM-treated ghosts and demonstrate that radiation inactivation may probe a target significantly smaller than a covalently linked protein subunit. The small target size for the band 3 stilbene binding site may correspond to the intramembrane domain of the band 3 monomer (52 kDa), which is physically distinct from the cytoplasmic domain (42 kDa)

Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children.

Science.gov (United States)

Yoshizawa, Kenichi; Ikawa, Kazuro; Ikeda, Kayo; Ohge, Hiroki; Morikawa, Norifumi

2013-11-01

Population pharmacokinetic (PK)-pharmacodynamic target attainment analysis of imipenem was performed to elucidate the PK properties in neonates and children and to rationalize and optimize dosing regimens. Population PK models were separately developed in neonates and children by simultaneously fitting plasma and urine data from 60 neonates and 39 children. The newly developed models were then used to estimate the probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration) against clinical isolates of common bacteria in pediatric patients. The data were best described by a 1-compartment model in neonates and a 2-compartment model in children, respectively. Renal clearance in children (0.187 L/h/kg) was double that of neonates (0.0783 L/h/kg), whereas the volume of distribution at steady-state was approximately 1.8-fold larger in neonates (0.466 L/kg) than in children (0.260 L/kg). Age was not a statistically significant covariate in the PK of both groups. Infusions (0.5 h) of 15 mg/kg every 8 h (45 mg/kg/day) and 25 mg/kg every 12 h (50 mg/kg/day) were shown to be sufficient against common bacterial isolates in both patient populations. However, 1.5-h infusions of 25 mg/kg every 8 h (75 mg/kg/day) in neonates and 25 mg/kg every 6 h (100 mg/kg/day) in children were required to be effective against Pseudomonas aeruginosa (minimum inhibitory concentration for 90% of the isolates=16 μg/mL). These results explain the changes in imipenem PK properties during the human growth process and provide guidance for tailoring dosing regimens in each pediatric age group.

Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children.

Science.gov (United States)

Williams, Olajide; DeSorbo, Alexandra; Sawyer, Vanessa; Apakama, Donald; Shaffer, Michele; Gerin, William; Noble, James

2016-02-01

We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after the intervention (immediate and delayed) in schools. The intervention comprised three 1-hour assembly-style hip-hop-themed multimedia classes. A mean total of 225 children participated in two baseline preintervention sales with and without calorie labels; 149 children participated in immediate postintervention food sales, while 133 children participated in the delayed sales. No significant change in purchased calories was observed in response to labels alone before the intervention. However, a mean decline in purchased calories of 20% (p < .01) and unhealthy foods (p < .01) was seen in immediately following the intervention compared to baseline purchases, and this persisted without significant decay after 7 days and 12 days. A 3-hour culturally targeted calorie label intervention may improve food-purchasing behavior of children. © 2015 Society for Public Health Education.

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

Science.gov (United States)

Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

2017-07-15

Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

A retrospective population-based cohort study identifying target areas for prevention of acute lower respiratory infections in children

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Richmond Peter

2010-12-01

Full Text Available Abstract Background Acute lower respiratory infections (ALRI are a major cause of hospitalisation in young children. Many factors can lead to increased risk of ALRI in children and predispose a child to hospitalisation, but population attributable fractions for different risk factors and how these fractions differ between Indigenous and non-Indigenous children is unknown. This study investigates population attributable fractions of known infant and maternal risk factors for ALRI to inform prevention strategies that target high-risk groups or particular risk factors. Methods A retrospective population-based data linkage study of 245,249 singleton births in Western Australia. Population attributable fractions of known maternal and infant risk factors for hospitalisation with ALRI between 1996 and 2005 were calculated using multiple logistic regression. Results The overall ALRI hospitalisation rate was 16.1/1,000 person-years for non-Aboriginal children and 93.0/1,000 for Aboriginal children. Male gender, being born in autumn, gestational age Conclusions The population attributable fractions estimated in this study should help in guiding public health interventions to prevent ALRI. A key risk factor for all children is maternal smoking during pregnancy, and multiple previous pregnancies and autumnal births are important high-risk groups. Specific key target areas are reducing elective caesareans in non-Aboriginal women and reducing teenage pregnancies and improving access to services and living conditions for the Aboriginal population.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014

Science.gov (United States)

Wiggins, Lisa; Christensen, Deborah L.; Maenner, Matthew J; Daniels, Julie; Warren, Zachary; Kurzius-Spencer, Margaret; Zahorodny, Walter; Robinson Rosenberg, Cordelia; White, Tiffany; Durkin, Maureen S.; Imm, Pamela; Nikolaou, Loizos; Yeargin-Allsopp, Marshalyn; Lee, Li-Ching; Harrington, Rebecca; Lopez, Maya; Fitzgerald, Robert T.; Hewitt, Amy; Pettygrove, Sydney; Constantino, John N.; Vehorn, Alison; Shenouda, Josephine; Hall-Lande, Jennifer; Van Naarden Braun, Kim; Dowling, Nicole F.

2018-01-01

developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). Interpretation Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. Public Health Action Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM

Organelle targeting: third level of drug targeting

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Sakhrani NM

2013-07-01

Full Text Available Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptides

The intensity of non-target site mechanisms influences the level of resistance of sourgrass to glyphosate

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Flávia Regina da Costa

2014-02-01

Full Text Available Non-target site mechanisms are involved in the resistance of sourgrass (Digitaria insularis to glyphosate. Studies on the 14C-glyphosate absorption and translocation as well as the detection of glyphosate and its metabolites in sourgrass plants were carried out under controlled conditions to investigate if the differential response of resistant sourgrass biotypes (R1 and R2 is derived from the intensity of non-target site mechanisms involved in the resistance to glyphosate. Different pattern of absorption was observed between S (susceptible and R2 from 12 up to 48 hours after treatment with glyphosate (HAT, and between S and R1 just at 12 HAT. The initial difference in glyphosate absorption among the biotypes did not maintained at 96 HAT and afterwards. Smaller amount of herbicide left the treated leaf into the rest of shoot and roots in R2 (25% than in S (58% and R1 (52%. In addition, slight difference in glyphosate translocation was observed between S and R1. We found high percentage (81% of glyphosate in the S biotype up to 168 HAT, while just 44% and 2% of glyphosate was recovered from R1 and R2 plant tissues. In addition, high percentage of glyphosate metabolites was found in R2 (98% and R1 (56% biotypes, while a very low percentage (11% was found in the S biotype. As previous studies indicated resistant factors of 3.5 and 5.6 for R1 and R2, respectively, we conclude that the differential response of sourgrass biotypes is derived from the intensity of the non-target site mechanisms involved in the resistance to glyphosate.

First record of target-site-resistance of poverty brome (Bromus sterilis to ACCase inhibitors

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Dicke, Dominik

2014-02-01

Full Text Available In 2011 reduced efficacy of grass weed herbicides to poverty brome (Bromus sterilis was observed in oilseed rape on a site in East Hessen. The field was cultivated by using the ploughless tillage system more than 25 years. The site showed high densities of poverty brome (>1000 plants/m² prior to herbicide treatment. Poverty brome seeds were collected in 2012 in the hessian oilseed rape field and from a site in East Westphalia, where poverty brome appeared at low densities (10 plants/m² and was not suspected to resistance. The seeds were sown in to pots and plants cultivated. The plants were treated with two application rates (normal dose, double dose with herbicides of different HRAC-classes. The time of treatment was adjusted to the best expectable treatment/efficiency conditions of the individual herbicides (see chapter 3. Clear differences in efficacy that were caused by herbicide, the origins of poverty brome and the dosages were recorded via visual rating eight weeks after spraying. The herbicides Agil and Focus Ultra were able to control about 90% of the poverty brome plants of the East Westphalia site origin. However, only 20-30% of the Hessian plants could be knocked out by the same herbicides. The ACCase-gene of single powerty brome leaf samples from the hessian site was analyzed after resistance assessment. A molecular genetic analysis on 7 variable positions identified target site resistance: Isoleucine (Ile was replaced by asparagine (Asn at position 2041.

Targeting the breeding sites of malaria mosquitoes: biological and physical control of malaria mosquito larvae

OpenAIRE

Bukhari, S.T.

2011-01-01

Malaria causes an estimated 225 million cases and 781,000 deaths every year. About 85% of the deaths are in children under five years of age. Malaria is caused by the Plasmodium parasite which is transmitted by the Anopheles mosquito vector. Mainly two methods of intervention are used for vector control, i.e. insecticide-treated bed nets and indoor residual spraying. Both involve the use of insecticides and target Anopheles adults indoors. A rising increase in resistance against these insec...

3% Amuchina is as effective as the 50% concentration in the prevention of exit-site infection in children on chronic peritoneal dialysis.

Science.gov (United States)

Grosman, Mònica D; Mosquera, Vanesa M; Hernandez, Maria G; Agostini, Silvana; Adragna, Marta; Sojo, Ernesto T

2005-01-01

In a previous communication, we demonstrated that, in the prevention of exit-site infection (ESI) in children, the cleansing agent 50% Amuchina (electrolytic chloroxidizer. Amuchina SpA, Genoa, Italy) is more effective than 10% povidone iodine and as effective as 4% chlorhexidine, but with fewer adverse secondary effects. In the present study, we assessed, in an Argentine pediatric population, whether Amuchina 3% is as effective as Amuchina 50% in preventing ESI in children on chronic peritoneal dialysis. In an open-label, single-center prospective study, 27 children (mean age: 7.2 years; range: 1.7-17 years) used 3% Amuchina as a cleansing agent for the daily care of a healthy exit site. Of the 27 children, 14 were switched from 50% Amuchina to 3% Amuchina, and 13 were using the 3% Amuchina for the first time. The control group consisted of 18 patients who had previously used 50% Amuchina as a cleansing agent. We followed the recommendations of the International Society for Peritoneal Dialysis with regard to exit-site care, which include keeping the cleansing agent out of the sinus and rinsing the exit site with sterile water. Amuchina was used from the first post-implantation care of the exit site. No adverse secondary effects were seen with the use of Amuchina at either concentration. Patients using 3% Amuchina presented an ESI rate similar to that of patients using Amuchina 50%. The cost of 3% Amuchina was significantly lower than that of the 50% concentration, and it was even lower than the cost for 10% povidone iodine or 4% chlorhexidine. Although more research trials are needed to assess the efficacy of 3% Amuchina, we conclude that 3% Amuchina is the best and most cost-effective cleansing agent for the daily care of a healthy exit site in children on chronic peritoneal dialysis.

Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

Science.gov (United States)

Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

2014-12-05

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

Exposición infantil al plomo en sitios contaminados Children exposure to lead in contaminated sites

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Rogelio Flores-Ramírez

2012-08-01

Full Text Available OBJETIVO: Determinar el grado de la exposición infantil al plomo en diversos tipos de sitios contaminados. MATERIAL Y MÉTODOS: El estudio se realizó de junio 2008 a diciembre 2009 en cuatro sitios de México: metalúrgica de Ávalos, Chihuahua.; metalúrgica de Morales, San Luis Potosí (SLP; zona alfarera en La Trinidad, Tlaxcala, y sitio minero en Cedral, SLP. Se cuantificó plomo en polvo y se realizó un biomonitoreo humano en niños de la comunidad. RESULTADOS: Los valores obtenidos de plomo en polvo exterior superaron el límite establecido de 400 mg/kg para suelos residenciales en un intervalo de valores para los cuatro sitios de 62 a 5 187 mg/kg. En cuanto al monitoreo biológico, todas las poblaciones presentaron valores extremos, desde los 22 µg/dL en Cedral, 31 µg/dL en Morales, y 32 µg/dL en Ávalos, hasta los 52 µg/dL en La Trinidad. Es importante señalar que encontramos una correlación positiva y significativa entre los valores de plomo en polvo y plomo en sangre en todos los sitios de estudio (pOBJECTIVE: To assess the exposure to lead in children living in various types of contaminated sites. MATERIALS AND METHODS: The study was conducted from June 2008 to December 2009 at four sites in Mexico: Avalos metallurgical, Chihuahua; Morales metallurgical, San Luis Potosí (SLP; Trinidad pottery area, Tlaxcala and Cedral mine site, SLP. These sites contain different sources of lead. The metal levels were quantified in outdoor dust and in peripheral blood of children. RESULTS: Lead dust concentrations exceed the National Guidelines for residential soils (400 mg/kg in a range of values for the four sites from 62 to 5 187 mg/kg. Regarding biological monitoring, the studied children showed maximum lead blood levels of 22 µg/dL in Cedral, 31 µg/dL in Morales, 32 µg/dL in Avalos, and 52 µg/dL in Trinidad. It is important to mention that in all the studied sites, a significative positive correlation was found between blood lead

Impact of Social Networking Sites on Children in Military Families.

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McGuire, Austen B; Steele, Ric G

2016-09-01

Youth in military families experience a relatively unique set of stressors that can put them at risk for numerous psychological and behavior problems. Thus, there is a need to identify potential mechanisms by which children can gain resiliency against these stressors. One potential mechanism that has yet to be empirically studied with military youth is social networking sites (SNSs). SNSs have gained significant popularity among society, especially youth. Given the significance of these communication tools in youths' lives, it is important to analyze how SNS use may affect military youth and their ability to cope with common military life stressors. The current review examines the potential positive and negative consequences associated with SNS use in coping with three common stressors of youth in military families: parent deployment, frequent relocation, and having a family member with a psychological or physical disability. By drawing from SNS and military literature, we predict that SNS use can be a positive tool for helping children in military families to cope with stressors. However, certain SNS behaviors can potentially result in more negative outcomes. Recommendations for future research are also discussed.

Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010.

Science.gov (United States)

2014-03-28

Autism spectrum disorder (ASD). 2010. The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system in the United States that provides estimates of the prevalence of ASD and other characteristics among children aged 8 years whose parents or guardians live in 11 ADDM sites in the United States. ADDM surveillance is conducted in two phases. The first phase consists of screening and abstracting comprehensive evaluations performed by professional providers in the community. Multiple data sources for these evaluations include general pediatric health clinics and specialized programs for children with developmental disabilities. In addition, most ADDM Network sites also review and abstract records of children receiving special education services in public schools. The second phase involves review of all abstracted evaluations by trained clinicians to determine ASD surveillance case status. A child meets the surveillance case definition for ASD if a comprehensive evaluation of that child completed by a qualified professional describes behaviors consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (including atypical autism), or Asperger disorder. This report provides updated prevalence estimates for ASD from the 2010 surveillance year. In addition to prevalence estimates, characteristics of the population of children with ASD are described. For 2010, the overall prevalence of ASD among the ADDM sites was 14.7 per 1,000 (one in 68) children aged 8 years. Overall ASD prevalence estimates varied among sites from 5.7 to 21.9 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and racial/ethnic group. Approximately one in 42 boys and one in 189 girls living in the ADDM Network communities were identified as having ASD

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

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Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

2015-07-01

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

TargetSpy: a supervised machine learning approach for microRNA target prediction.

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Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

TargetSpy: a supervised machine learning approach for microRNA target prediction

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Langenberger David

2010-05-01

Full Text Available Abstract Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I no seed match requirement, II seed match requirement, and III conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on

Targeting Children Online : Young internet users and producers in the commercial media environment

OpenAIRE

Martinez, Carolina

2017-01-01

Children’s daily internet usage takes place to a large extent in a commercial environment, where advertising and the sale of virtual goods are ever-present parts of the online experience. The overall goal of this thesis is to contribute to a critical understanding of children’s commercial online environment as spaces for children’s everyday life activities and participation, and as spaces for commercial interests that seek to target children and monetize their internet usage. Two papers analy...

The comparison of exit-site care with normal saline and povidone-iodine in preventing exit-site infection and peritonitis in children on chronic peritoneal dialysis treatment

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Onder Yavascan

2011-01-01

Full Text Available Peritonitis and catheter exit- site infections (ESI are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis (CPD. The frequency of infection can be reduced by scrupulous exit- site care with or without topical antiseptics. There are no studies showing any benefit in the use of povidone-iodine or normal saline for care of exit- sites in long- term CPD patients. In this study, we aimed to determine the potential effectiveness of the application of povidone-iodine or normal saline at the catheter exit- site in preventing ESI and peritonitis in children on CPD. A total of 98 patients treated with either povidone-iodine or normal saline were included in this study. Group I (34 patients used povidone-iodine and group II (64 patients simply cleansed the exit- site with normal saline (0.9% NaCl. Dressings were changed 2 to 3 times in a week. The total cumulative follow- up time was 3233 patient- months. ESIs occurred in 10 (29.4% of 34 patients using povidone-iodine and in 10 (15.6% of 64 patients using normal saline. The frequency of ESI was significantly high in group I (povidone-iodine patients. The mean rate of ESI was 1 episode/60.8 patient- months for group I versus 1 episode/144 patient- months for group II (P 0.05. In conclusion, exit- site care with normal saline is an effective strategy in reducing the incidence of ESI in children on CPD. It can thus significantly reduce morbidity, catheter loss, and the need to transfer patients on peritoneal dialysis to hemodialysis.

Effects of age, gender, BMI, and anatomical site on skin thickness in children and adults with diabetes.

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José G B Derraik

Full Text Available We aimed to assess the effects of age, sex, body mass index (BMI, and anatomical site on skin thickness in children and adults with diabetes.We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5-19 years, and 140 adults with type 1 and type 2 diabetes aged 20-85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin.There was an age-related thickening of both dermis (p<0.0001 and subcutis (p = 0.013 in children and adolescents. Girls displayed a substantial pubertal increase in subcutis of the thigh (+54%; p = 0.048 and abdomen (+68%; p = 0.009. Adults showed an age-related decrease in dermal (p = 0.021 and subcutis (p = 0.009 thicknesses. Pubertal girls had a thicker subcutis than pubertal boys in both thigh (16.7 vs 7.5 mm; p<0.0001 and abdomen (16.7 vs 8.8 mm; p<0.0001. Men had greater thigh dermal thickness than women (1.89 vs 1.65 mm; p = 0.003, while the subcutis was thicker in women in thigh (21.3 vs 17.9 mm; p = 0.012 and abdomen (17.7 vs 9.8 mm; p<0.0001. In boys, men, and women, both dermis and subcutis were thicker on the abdomen compared to thigh; in girls this was only so for dermal thickness. In both children and adults, the skin (dermis and subcutis became steadily thicker with increasing BMI (p<0.0001.Skin thickness is affected by age, pubertal status, gender, BMI, and anatomical site. Such differences may be important when considering appropriate sites for dermal/subcutaneous injections and other transdermal delivery systems.

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012.

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Christensen, Deborah L; Baio, Jon; Van Naarden Braun, Kim; Bilder, Deborah; Charles, Jane; Constantino, John N; Daniels, Julie; Durkin, Maureen S; Fitzgerald, Robert T; Kurzius-Spencer, Margaret; Lee, Li-Ching; Pettygrove, Sydney; Robinson, Cordelia; Schulz, Eldon; Wells, Chris; Wingate, Martha S; Zahorodny, Walter; Yeargin-Allsopp, Marshalyn

2016-04-01

Autism spectrum disorder (ASD). 2012. The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence and characteristics of ASD among children aged 8 years whose parents or guardians reside in 11 ADDM Network sites in the United States (Arkansas, Arizona, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, South Carolina, Utah, and Wisconsin). Surveillance to determine ASD case status is conducted in two phases. The first phase consists of screening and abstracting comprehensive evaluations performed by professional service providers in the community. Data sources identified for record review are categorized as either 1) education source type, including developmental evaluations to determine eligibility for special education services or 2) health care source type, including diagnostic and developmental evaluations. The second phase involves the review of all abstracted evaluations by trained clinicians to determine ASD surveillance case status. A child meets the surveillance case definition for ASD if one or more comprehensive evaluations of that child completed by a qualified professional describes behaviors that are consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (including atypical autism), or Asperger disorder. This report provides ASD prevalence estimates for children aged 8 years living in catchment areas of the ADDM Network sites in 2012, overall and stratified by sex, race/ethnicity, and the type of source records (education and health records versus health records only). In addition, this report describes the proportion of children with ASD with a score consistent with intellectual disability on a standardized intellectual ability test, the age at which the earliest known

Temperament Is Associated With Outdoor Free Play in Young Children: A TARGet Kids! Study.

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Sharp, Julia R; Maguire, Jonathon L; Carsley, Sarah; Abdullah, Kawsari; Chen, Yang; Perrin, Eliana M; Parkin, Patricia C; Birken, Catherine S

Outdoor free play is important for preschoolers' physical activity, health, and development. Certain temperamental characteristics are associated with obesity, nutrition, and sedentary behaviors in preschoolers, but the relationship between temperament and outdoor play has not been examined. This study examined whether there is an association between temperament and outdoor play in young children. Healthy children aged 1 to 5 years recruited to The Applied Research Group for Kids (TARGet Kids!), a community-based primary care research network, from July 2008 to September 2013 were included. Parent-reported child temperament was assessed using the Childhood Behavior Questionnaire. Outdoor free play and other potential confounding variables were assessed through validated questionnaires. Multivariable linear regression was used to determine the association between temperament and outdoor play, adjusted for potential confounders. There were 3393 children with data on outdoor play. The association between negative affectivity and outdoor play was moderated by sex; in boys, for every 1-point increase in negative affectivity score, mean outdoor play decreased by 4.7 minutes per day. There was no significant association in girls. Surgency was associated with outdoor play; for every 1-point increase in surgency/extraversion, outdoor play increased by 4.6 minutes per day. Young children's temperamental characteristics were associated with their participation in outdoor free play. Consideration of temperament could enhance interventions and strategies to increase outdoor play in young children. Longitudinal studies are needed to elucidate the relationship between children's early temperament and physical activity. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Effect of mild hypothermia combined with VitC and EPO therapy on target organ damage in children with neonatal asphyxia

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Shu-Yun Wang

2017-10-01

Full Text Available Objective: To study the effect of mild hypothermia combined with vitamin C (VitC and erythropoietin (EPO therapy on target organ damage in children with neonatal asphyxia. Methods: Children with neonatal asphyxia who were treated in Taihe County People’s Hospital between April 2014 and February 2017 were selected and randomly divided into two groups, mild hypothermia group received mild hypothermia combined VitC and EPO therapy, and control group received VitC and EPO therapy. Serum levels of of target organ damage markers, oxidative stress indexes and apoptosis indexes were measured before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of both groups of children were significantly lower than those before treatment while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those before treatment, and serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of mild hypothermia group were significantly lower than those of control group while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those of control group. Conclusion: Mild hypothermia combined with VitC and EPO therapy can reduce the target organ damage of children with neonatal asphyxia by inhibiting oxidative stress and apoptosis.

[Isolation of Haemophilus influenzae serotypes from deep sites in sick children].

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Gatti, B M; Ramirez Gronda, G A; Etchevarría, M; Vescina, C M; Varea, A M; González Ayala, S E

2004-01-01

Haemophilus influenzae (Hi) is the causative agent of several human diseases such as sepsis, meningitis, celulitis, and osteoarthritis. We investigated the isolation of Hi serotypes from sterile sites in sick children. One hundred and seventy nine strains from 146 patients were studied, period 1996-2002, at the Microbiology Laboratory, Hospital de Niños Superiora Sor María Ludovica, Argentina. The serotype distribution was:1 a, 112 b,1 c,1 d, 4 e, 3 f y 24 no typable. Since the beginning of universal Hi b vaccination in 1998, we have observed the fast decrease of serotype b and a relative increase of other serotypes.

Children's Reactions to a Children's News Program: Reception, Recognition and Learning.

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Ward, Sara Ann

The major objectives of this study were to determine the reception of "In the News" by children within the target audience's ages, to determine if children within the target audience recognize the news program as a program, to determine if children learn from "In the News," and to compare children's learning from hard news…

Random Tagging Genotyping by Sequencing (rtGBS, an Unbiased Approach to Locate Restriction Enzyme Sites across the Target Genome.

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Elena Hilario

Full Text Available Genotyping by sequencing (GBS is a restriction enzyme based targeted approach developed to reduce the genome complexity and discover genetic markers when a priori sequence information is unavailable. Sufficient coverage at each locus is essential to distinguish heterozygous from homozygous sites accurately. The number of GBS samples able to be pooled in one sequencing lane is limited by the number of restriction sites present in the genome and the read depth required at each site per sample for accurate calling of single-nucleotide polymorphisms. Loci bias was observed using a slight modification of the Elshire et al.some restriction enzyme sites were represented in higher proportions while others were poorly represented or absent. This bias could be due to the quality of genomic DNA, the endonuclease and ligase reaction efficiency, the distance between restriction sites, the preferential amplification of small library restriction fragments, or bias towards cluster formation of small amplicons during the sequencing process. To overcome these issues, we have developed a GBS method based on randomly tagging genomic DNA (rtGBS. By randomly landing on the genome, we can, with less bias, find restriction sites that are far apart, and undetected by the standard GBS (stdGBS method. The study comprises two types of biological replicates: six different kiwifruit plants and two independent DNA extractions per plant; and three types of technical replicates: four samples of each DNA extraction, stdGBS vs. rtGBS methods, and two independent library amplifications, each sequenced in separate lanes. A statistically significant unbiased distribution of restriction fragment size by rtGBS showed that this method targeted 49% (39,145 of BamH I sites shared with the reference genome, compared to only 14% (11,513 by stdGBS.

Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

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Vallecillo-Viejo, Isabel C; Liscovitch-Brauer, Noa; Montiel-Gonzalez, Maria Fernanda; Eisenberg, Eli; Rosenthal, Joshua J C

2018-01-02

Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

Target and identify: triazene linker helps identify azidation sites of labelled proteins via click and cleave strategy.

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Lohse, Jonas; Schindl, Alexandra; Danda, Natasha; Williams, Chris P; Kramer, Karl; Kuster, Bernhard; Witte, Martin D; Médard, Guillaume

2017-10-31

A method for identifying probe modification of proteins via tandem mass spectrometry was developed. Azide bearing molecules are immobilized on functionalised sepharose beads via copper catalysed Huisgen-type click chemistry and selectively released under acidic conditions by chemical cleavage of the triazene linkage. We applied this method to identify the modification site of targeted-diazotransfer on BirA.

Advertising Targeted at Children and Current Approach to It in the Central European Region with Emphasis on Czech and German Examples. A Brief Linguistic-Educational Analysis

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Pavlína Tesařová

2017-11-01

Full Text Available The article deals with the genre of contemporary advertising targeting children. It uses examples from the Czech Republic and Germany and its translations, defines the target audience by age and presents preferences of respective age groups with respect to the type of media used for advertising. The article also pays attention to the sociodemographic factors in the background of marketing strategies. Ethical issues are also mentioned. The study sheds light on the reasons why a certain target group is attractive and with the aid of examples it exposes the principles of advertising targeting children from the visual, perceptional and linguistic-educational point of view.

Analysis of Properties of Reflectance Reference Targets for Permanent Radiometric Test Sites of High Resolution Airborne Imaging Systems

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Eero Ahokas

2010-08-01

Full Text Available Reliable and optimal exploitation of rapidly developing airborne imaging methods requires geometric and radiometric quality assurance of production systems in operational conditions. Permanent test sites are the most promising approach for cost-efficient performance assessment. Optimal construction of permanent radiometric test sites for high resolution airborne imaging systems is an unresolved issue. The objective of this study was to assess the performance of commercially available gravels and painted and unpainted concrete targets for permanent, open-air radiometric test sites under sub-optimal climate conditions in Southern Finland. The reflectance spectrum and reflectance anisotropy and their stability were characterized during the summer of 2009. The management of reflectance anisotropy and stability were shown to be the key issues for better than 5% reflectance accuracy.

Different perceptual sensitivities for Chernoff's face between children and adults.

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Tsurusawa, Reimi; Goto, Yoshinobu; Mitsudome, Akihisa; Nakashima, Taisuke; Tobimatsu, Shozo

2008-02-01

The aim of this study was to investigate the differences between children and adults in recognizing facial expressions of simple line drawings of "Chernoff's face". First, the angles of the eyebrows and mouth of Chernoff's face were changed in a stepwise way with a personal computer, and the emotional response of the subjects was evaluated by a questionnaire. Second, three drawings of non-target stimuli (neutral face, angry face, and wheelchair) and target stimuli were used to elicit event-related potentials (ERPs). Children had higher scores for the facial expressions than adults, and relied much more on the angles of the eyebrows and mouth. The major ERP findings were (1) the latencies of P100 and N170 were significantly longer in children than adults, (2) the amplitudes of P100 were significantly larger in children than adults, but the N170 amplitudes were not significantly different, and (3) a slow negative shift was recorded with a latency of 240-460ms at the posterior-temporal site for angry face compared with neutral face in adults but not in children. These results suggest that the differences in the electrophysiological recognition of facial expressions can be set at 240ms after appearance of the Chernoff's face in adults but not in children.

Liposome as nanocarrier: Site targeted delivery in lung cancer

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Najeeb Ullah

2017-08-01

Full Text Available Lung cancer is fatal and spreading rapidly worldwide. Different clinical strategies are applied to stop this cancer. As the lung is a delicate organ, special clinical applications must be used and nanodrugs delivery systems are the most important applications of all. This review discusses the lung problems such as lung cancer, lung inflammation and bronchi constrictions followed by repetitive intake of some drugs. The objective of this review is to study how nanodrug delivery systems were synthesized and used in lung disorder treatment especially in lung cancer. The authors studied some articles from 1989 to 2015. Liposome encapsulation was done in various ways for the delivery of different drugs such as metaproterenol into liposomes caused bronchodilation, immunoliposomes bearing antibodies for doxorubicin reduced 50% inhibitory effects, radioliposomes with high penetrating ability to peripheral airways, aerosol delivery systems with deep pulmonary deposition, polymeric drug delivery having potential to improve beneficial index of drug, solid lipid liposomes, liposomal gentamicin with altered different clinical susceptibilities of resistance, transferrin conjugated liposomes to deliver cytostatic drugs to site of lungs, anti-inflammatory drugs with mannosylated liposomes, liposomal suspensions with single stranded RNAs and peptide encapsulation of liposomes. This review indicates that many animals perished with intravenous administration of drugs but survived in liposomal targeting groups.

Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

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Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

2014-01-01

The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

NARCIS (Netherlands)

Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

Food marketing targeting children: unveiling the ethical perspectives in the discourse on self-regulation.

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Silva, Dillian Adelaine Cesar da; Cunha, Antonio Carlos Rodrigues da; Cunha, Thiago Rocha da; Rosaneli, Caroline Filla

2017-07-01

When it comes to food marketing, children are one of the major targets. Regulatory actions can play a strategic role in health protection. The objective of this research was to characterize the ethical perspective in the discourse against state regulatory actions on food marketing directed at children, aiming to understand the context of the discourse's production and how it creates meaning. The methodology adopted was qualitative, with documentary analysis and use of concepts and procedures from Discourse Analysis. The work of Hans Jonas, specifically his Responsibility Principle, and Garrafa and Port's Intervention Bioethics oriented the analysis. The self-regulation discourse analysis showed an ethical perspective in which relations of consumption predominate over the children´s vulnerability. The rhetorical excess is constant, as well as the use of resources like naturalization, untruthfulness, ideological dissimulation and euphemism. An erasure of social conflicts takes place, and an ahistorical perspective is present. The discourse does not align with Jonas´ Responsibility Principle, nor those of Intervention Bioethics. Lastly, the ethical perspective of the discourse represents a double paradox, because it is a business discourse that hides its competitive roots and metamorphoses into an ethical one.

Barriers to Liposomal Gene Delivery: from Application Site to the Target.

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Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

2016-01-01

Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

Botulinum Toxin Type A Injections in the Psoas Muscle of Children with Cerebral Palsy: Muscle Atrophy after Motor End Plate-Targeted Injections

Science.gov (United States)

Van Campenhout, Anja; Verhaegen, Ann; Pans, Steven; Molenaers, Guy

2013-01-01

MEP targeting during BoNT-A injections has been demonstrated to improve outcome. Two injection techniques of the psoas muscle--proximal MEP targeting versus a widely used more distal injection technique--are compared using muscle volume assessment by digital MRI segmentation as outcome measure. Method: 7 spastic diplegic children received…

Targeted advertising, platform competition and privacy

NARCIS (Netherlands)

Kox, Henk; Straathof, Bas; Zwart, Gijsbert

2017-01-01

Targeted advertising can benefit consumers through lower prices for access to web sites. Yet, if consumers dislike that web sites collect their personal information, their welfare may go down. We study competition for consumers between web sites that can show targeted advertisements. We find that

Child-targeted fast-food television advertising exposure is linked with fast-food intake among pre-school children

Science.gov (United States)

Dalton, Madeline A; Longacre, Meghan R; Drake, Keith M; Cleveland, Lauren P; Harris, Jennifer L; Hendricks, Kristy; Titus, Linda J

2017-01-01

Objective To determine whether exposure to child-targeted fast-food (FF) television (TV) advertising is associated with children’s FF intake in a non-experimental setting. Design Cross-sectional survey conducted April–December 2013. Parents reported their pre-school child’s TV viewing time, channels watched and past-week FF consumption. Responses were combined with a list of FF commercials (ads) aired on children’s TV channels during the same period to calculate children’s exposure to child-targeted TV ads for the following chain FF restaurants: McDonald’s, Subway and Wendy’s (MSW). Setting Paediatric and Women, Infants, and Children (WIC) clinics in New Hampshire, USA. Subjects Parents (n 548) with a child of pre-school age. Results Children’s mean age was 4·4 years; 43·2 % ate MSW in the past week. Among the 40·8 % exposed to MSW ads, 23·3 % had low, 34·2 % moderate and 42·5 % high exposure. McDonald’s accounted for over 70 % of children’s MSW ad exposure and consumption. Children’s MSW consumption was significantly associated with their ad exposure, but not overall TV viewing time. After adjusting for demographics, socio-economic status and other screen time, moderate MSW ad exposure was associated with a 31 % (95 % CI 1·12, 1·53) increase and high MSW ad exposure with a 26 % (95 % CI 1·13, 1·41) increase in the likelihood of consuming MSW in the past week. Further adjustment for parent FF consumption did not change the findings substantially. Conclusions Exposure to child-targeted FF TV advertising is positively associated with FF consumption among children of pre-school age, highlighting the vulnerability of young children to persuasive advertising and supporting recommendations to limit child-directed FF marketing. PMID:28416041

Targeted hepatic sonography during clinic visits for detection of fatty liver in overweight children: a pilot study.

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Perito, Emily R; Tsai, Patrika M; Hawley, Sarah; Lustig, Robert H; Feldstein, Vickie A

2013-04-01

The purpose of this study was to assess the feasibility and utility of targeted hepatic sonography to evaluate for hepatic steatosis during a subspecialty clinic visit. In this pilot study, we performed targeted hepatic sonography on 25 overweight children aged 7 to 17 years consecutively seen in a pediatric obesity clinic. Long-axis images of the right lobe of the liver and a split-screen image of liver and spleen were taken. Images were interpreted in real time by the radiologist and shown to the family. Demographics, clinical measurements, and laboratory parameters were also collected from the specialty clinic visit on the same day. Sonography required a median of 4 minutes during the visit (interquartile range, 3-5 minutes). All consented patients completed the study. The median alanine aminotransferase (ALT) level was 23 U/L in those with no steatosis (n = 14), 26 U/L with mild steatosis (n = 6), and 41 U/L with moderate/marked steatosis (n = 5). Children with ALT levels of 25 to 50 U/L had very variable sonographic measures of hepatic steatosis. When the participants were categorized by the overall degree of fatty liver, hepatic steatosis was significantly associated with the aspartate aminotransferase level (P = .028), ALT level (P = .003), and diastolic blood pressure (P = .05) but did not correlate with age, sex, Latino race, or insulin resistance. Targeted hepatic sonography added information not apparent from routine ALT screening and provided immediate feedback to clinicians and families about the effect of obesity on end organs. This examination could be a feasible, informative addition to screening for children at high risk for nonalcoholic fatty liver disease who are seen in clinics that specialize in obesity.

Selling Violence: Television Commercials Targeted to Children.

Science.gov (United States)

Palmerton, Patricia R.; Judas, Jeff

Noting that little research has addressed the question of violence in commercials directed to children, a study examined commercials aired during the 21 top-rated children's cartoons during one broadcast week in late spring 1993. Commercials were analyzed for violent content, gender of primary actors and recipients of violent action, primary…

Effects of functionalization on the targeting site of carbon nanotubes inside cells

Energy Technology Data Exchange (ETDEWEB)

Porter, A E; Bendall, J S; Welland, M [UK SuperSTEM, Daresbury Laboratory, Daresbury, Cheshire WA4 4AD (United Kingdom); Gass, M [The Nanoscience Centre, University of Cambridge, 11 J. J. Thompson Avenue, Cambridge CB3 OFF (United Kingdom); Muller, K; Skepper, J [Multiimaging Centre, Department of PDN, Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY (United Kingdom); Midgley, P, E-mail: a.porter@imperial.ac.u [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)

2010-07-01

Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging{sup 1}. However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO{sup -} functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

Effects of functionalization on the targeting site of carbon nanotubes inside cells

International Nuclear Information System (INIS)

Porter, A E; Bendall, J S; Welland, M; Gass, M; Muller, K; Skepper, J; Midgley, P

2010-01-01

Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging 1 . However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO - functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

Health of children living in Panfilov distract of Almaty region after Chernobyl accident and nuclear explosions at Lobnor test site

International Nuclear Information System (INIS)

Mit, A.A.; Chasnikov, I.Ya.; Chastnicova, S.S.; Mukhametzhanov, M.M.; Zhantagulova, T.K.

1999-01-01

It is known that Panfilov district of Almaty region was affected with radiation contamination during nuclear explosions at Lobnor test site and after Chernobyl accident, which impaired the health of its population [1]. In addition, the children's mortality rate was turned out to be the highest one among other districts of the region. This report presents some other information related to an increase of children's sickness rate in Panfilov district

On-site detection of Phytophthora spp.—single-stranded target DNA as the limiting factor to improve on-chip hybridization

International Nuclear Information System (INIS)

Schwenkbier, Lydia; Pollok, Sibyll; Popp, Jürgen; Weber, Karina; König, Stephan; Wagner, Stefan; Werres, Sabine; Weber, Jörg; Hentschel, Martin

2014-01-01

We report on a lab-on-a-chip approach for on-site detection of Phytophthora species that allows visual signal readout. The results demonstrate the significance of single-stranded DNA (ssDNA) generation in terms of improving the intensity of the hybridization signal and to improve the reliability of the method. Conventional PCR with subsequent heat denaturation, sodium hydroxide-based denaturation, lambda exonuclease digestion and two asymmetric PCR methods were investigated for the species P. fragariae, P. kernoviae, and P. ramorum. The positioning of the capture probe within the amplified yeast GTP-binding protein (YPT1) target DNA was also of interest because it significantly influences the intensity of the signal. Statistical tests were used to validate the impact of the ssDNA generation methods and the capture-target probe position. The single-stranded target DNA generated by Linear-After-The-Exponential PCR (LATE-PCR) was found to produce signal intensities comparable to post-PCR exonuclease treatment. The LATE-PCR is the best method for the on-site detection of Phytophthora because the enzymatic digestion after PCR is more laborious and time-consuming. (author)

Making Connections: Navigate the Internet for Early Childhood Sites.

Science.gov (United States)

Larson, Jeanette

1998-01-01

Explains terminology related to the use of the Internet, describes how to find Web sites, and explains some of the sites designed for child-care professionals. The sites included are those related to health and nutrition, early-childhood and parenting organizations, children's television, reading and literature, sites for children, and regional…

Target-site resistance to neonicotinoids.

Science.gov (United States)

Crossthwaite, Andrew J; Rendine, Stefano; Stenta, Marco; Slater, Russell

2014-10-01

Neonicotinoid insecticides selectively target the invertebrate nicotinic acetylcholine receptor and disrupt excitatory cholinergic neurotransmission. First launched over 20 years ago, their broad pest spectrum, variety of application methods and relatively low risk to nontarget organisms have resulted in this class dominating the insecticide market with global annual sales in excess of $3.5 bn. This remarkable commercial success brings with it conditions in the field that favour selection of resistant phenotypes. A number of important pest species have been identified with mutations at the nicotinic acetylcholine receptor associated with insensitivity to neonicotinoids. The detailed characterization of these mutations has facilitated a greater understanding of the invertebrate nicotinic acetylcholine receptor.

Targeted Nanotechnology for Cancer Imaging

Science.gov (United States)

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

Feasibility of subcutaneously implanted magnetic microarrays for site specific drug and gene targeting

Directory of Open Access Journals (Sweden)

M. Babincová

2010-01-01

Full Text Available The magnetic nanoparticles play a crucial role as a drug carriers in the human body. The wedge like magnetic arrays creatinga strongly non-homogeneous magnetic field are considered as a useful way to focus magnetic nanoparticles functionalizedwith various drugs or genes to desired sites. The goal of this study is to develop a numerical model of drug targetingusing subcutaneously implanted magnetic microarrays. The Finite Element Method is applied to solve partial differentialequations describing electromagnetic field (Maxwell equations and motion of these particles in a given magnetic field isobtained solving set of ordinary differential equations expressed by Newton law of motion. The results are encouragingshowing the potential to target drug to the tumour cell locally, without unwanted side effects.

Skipping breakfast is detrimental for primary school children: cross-sectional analysis of determinants for targeted prevention

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Dorothea Kesztyüs

2017-03-01

Full Text Available Abstract Background Skipping breakfast was found to be associated with abdominal obesity in primary school children. The aim of this research was to examine factors associated with skipping breakfast in primary school children in order to develop targeted preventive measures. Methods Baseline data assessment (2010 of a cluster-randomized controlled trial for the evaluation of a school-based health promotion program in primary school children in the state of Baden-Württemberg, Germany. Anthropometric measures of 1,943 primary school children aged 7.1 ± 0.6 years (51.2% boys were conducted according to ISAK-standards (International Standard for Anthropometric Assessment by trained staff. Further information on the health and living conditions of the children and their parents were assessed in parental questionnaires. Generalized linear mixed regression analysis was calculated to define correlates for skipping breakfast in terms of odds ratios (OR and 95% confidence intervals (CI. Results According to the final regression models, significant correlates of skipping breakfast can be divided into modifiable behavioral components (high consumption of soft drinks (OR 2.49, 95% CI 1.81; 3.43, screen media (OR 2.48, 95% CI 1.77; 3.46 and high levels of physical activity (OR 0.64, 95% CI 0.44; 0.93 on the one hand, and more or less static socio-economic factors (migration background (OR 2.81, 95% CI 2.02; 3.91, single parenting (OR 2.13, 95% CI 1.34; 3.40, and high family education level (OR 0.42, 95% CI 0.28; 0.64 on the other hand, and finally individual factors (female gender (OR 1.43, 95% CI 1.03; 1.99 and having a percentage of body fat at or above the 95th percentile (OR 1.47, 95% CI 1.00; 2.17. Conclusion Targeted prevention should aim at health-related behaviors accompanying the habit of skipping breakfast. Focusing on vulnerable groups, characterized by not so easily modifiable socio-economic as well as individual factors, may improve

Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP

Science.gov (United States)

Czulak, J.; Guerreiro, A.; Metran, K.; Canfarotta, F.; Goddard, A.; Cowan, R. H.; Trochimczuk, A. W.; Piletsky, S.

2016-05-01

Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike

Management strategy for site characterization at candidate HLW repository sites

International Nuclear Information System (INIS)

Bartlett, J.W.

1988-01-01

This paper describes a management strategy for HLW repository site characterization which is aimed at producing an optimal characterization trajectory for site suitability and licensing evaluations. The core feature of the strategy is a matrix of alternative performance targets and alternative information-level targets which can be used to allocate and justify program effort. Strategies for work concerning evaluation of expected and disrupted repository performance are distinguished, and the need for issue closure criteria is discussed

Kaiso Directs the Transcriptional Corepressor MTG16 to the Kaiso Binding Site in Target Promoters

Science.gov (United States)

Barrett, Caitlyn W.; Smith, J. Joshua; Lu, Lauren C.; Markham, Nicholas; Stengel, Kristy R.; Short, Sarah P.; Zhang, Baolin; Hunt, Aubrey A.; Fingleton, Barbara M.; Carnahan, Robert H.; Engel, Michael E.; Chen, Xi; Beauchamp, R. Daniel; Wilson, Keith T.; Hiebert, Scott W.; Reynolds, Albert B.; Williams, Christopher S.

2012-01-01

Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the ApcMin mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (4×KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co

The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes

Science.gov (United States)

Leclerc, Julie B.; O’Connor, Kieron P.; J.-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E.

2016-01-01

Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8–12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive–behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12–14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically. PMID:27563292

The effect of a new therapy for children with tics targeting underlying cognitive, behavioral and physiological processes

Directory of Open Access Journals (Sweden)

Julie B. Leclerc

2016-08-01

Full Text Available Tourette disorder (TD is characterized by motor and vocal tics and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder Facotik to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult Cognitive and Psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-minute session contained 20 minutes of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population and seven cases completed therapy and post-treatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem post treatment. The results confirm the conclusion of a previous pilot study which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches which target tics specifically.

The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes.

Science.gov (United States)

Leclerc, Julie B; O'Connor, Kieron P; J-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E

2016-01-01

Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically.

Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala

Directory of Open Access Journals (Sweden)

Rizzo Nidia

2012-10-01

Full Text Available Abstract Background In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. Methods The study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.. The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. Results At baseline (during the dry season a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae. After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed in 970 study

Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala.

Science.gov (United States)

Rizzo, Nidia; Gramajo, Rodrigo; Escobar, Maria Cabrera; Arana, Byron; Kroeger, Axel; Manrique-Saide, Pablo; Petzold, Max

2012-10-30

In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. The study was conducted as a cluster randomized community trial using "reduction of the vector population" as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. At baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and

Building Social Competence in Preschool: The Effects of a Social Skills Intervention Targeting Children Enrolled in Head Start

Science.gov (United States)

Stanton-Chapman, Tina L.; Walker, Virginia; Jamison, Kristen R.

2014-01-01

The current study evaluated the peer-to-peer interactions of at-risk children enrolled in Head Start who participated in a social pragmatic intervention targeting skills such as initiations, responses, name use, proximity, and turn-taking skills. Eight Head Start classroom teams received two workshops and two coaching sessions and were taught to…

Consistent Performance Differences between Children and Adults Despite Manipulation of Cue-Target Variables

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Jessie-Raye Bauer

2017-08-01

Full Text Available Two behavioral experiments assessed the plasticity and short-term improvement of task switching in 215 children and adults. Specifically, we studied manipulations of cued attention to different features of a target stimulus as a way to assess the development of cognitive flexibility. Each experiment had multiple levels of difficulty via manipulation of number of cued features (2–4 and number of response options (2 or 4. Working memory demand was manipulated across the two experiments. Impact of memory demand and task level manipulations on task accuracy and response times were measured. There were three overall goals: First, these task manipulations (number of cued features, response choices, and working memory load were tested to assess the stability of group differences in performance between children ages 6–16 years and adults 18–27 years, with the goal of reducing age group differences. Second, age-related transitions to adult-level performance were examined within subgroups of the child sample. Third, short-term improvement from the beginning to the end of the study session was measured to probe whether children can improve with task experience. Attempts to use task manipulations to reduce age differences in cued task switching performance were unsuccessful: children performed consistently worse and were more susceptible to task manipulations than adults. However, across both studies, adult-like performance was observed around mid-adolescence, by ages 13-16 years. Certain task manipulations, especially increasing number of response options when working memory demand was low, produced differences from adults even in the oldest children. Interestingly, there was similar performance improvement with practice for both child and adult groups. The higher memory demand version of the task (Experiment 2 prompted greater short-term improvement in accuracy and response times than the lower memory demand version (Experiment 1. These results

Discrepancy of target sites between clinician and cytopathological reports in head neck fine needle aspiration: Did I miss the target or did the clinician mistake the organ site?

International Nuclear Information System (INIS)

Khanlari, Mahsa; Daneshbod, Yahya; Shaterzadeh Yazdi, Hanieh; Shirian, Sadegh; Negahban, Shahrzad; Aledavood, Azita; Oryan, Ahmad; Khademi, Bijan; Daneshbod, Khosrow; Field, Andrew

2015-01-01

The diagnostic accuracy of fine needle aspiration cytology (FNAC) of head and neck lesions is relatively high, but cytologic interpretation might be confusing if the sample is lacking typical cytologic features according to labeled site by physician. These errors may have an impact on pathology search engines, healthcare costs or even adverse outcomes. The cytology archive database of multiple institutions in southern Iran and Australia covering the period 2001–2011, were searched using keywords: salivary gland, head, neck, FNAC, and cytology. All the extracted reports were reviewed. The reports which showed discordance between the clinician's impression of the organ involved and subsequent fine needle biopsy request, and the eventual cytological diagnosis were selected. The cytological diagnosis was confirmed by histology or cell block, with assistance from imaging, clinical outcome, physical examination, molecular studies, or microbiological culture. The total number of 10,200 head and neck superficial FNAC were included in the study, from which 48 cases showed discordance between the clinicians request and the actual site of pathology. Apart from the histopathology, the imaging, clinical history, physical examination, immunohistochemical study, microbiologic culture and molecular testing helped to finalize the target organ of pathology in 23, 6, 7, 8, 2, and 1 cases respectively. The commonest discrepancies were for FNAC of “salivary gland” [total: 20 with actual final pathology in: bone (7), soft tissue (5), lymph node (3), odontogenic (3) and skin (2)], “lymph node” [total: 12 with final pathology in: soft tissue (3), skin (3), bone (1) and brain (1)], “soft tissue” [total: 11 with final pathology in: bone (5), skin (2), salivary gland (1), and ocular region (1)] and “skin” [total: 5 with final pathology in: lymph node (2), bone (1), soft tissue (1) and salivary gland (1)]. The primary physician requesting FNAC of head and neck lesions

Targeting children of substance-using parents with the community-based group intervention TRAMPOLINE: A randomised controlled trial - design, evaluation, recruitment issues

Science.gov (United States)

2012-01-01

Background Children of substance-abusing parents are at risk for developing psychosocial development problems. In Germany it is estimated that approx. 2.65 million children are affected by parental substance abuse or dependence. Only ten percent of them receive treatment when parents are treated. To date, no evaluated programme for children from substance-affected families exists in Germany. The study described in this protocol is designed to test the effectiveness of the group programme TRAMPOLINE for children aged 8-12 years with at least one substance-abusing or -dependent caregiver. The intervention is specifically geared to issues and needs of children from substance-affected families. Methods/Design The effectiveness of the manualised nine-session group programme TRAMPOLINE is tested among N = 218 children from substance-affected families in a multicentre randomised controlled trial. Outpatient counselling facilities across the nation from different settings (rural/urban, Northern/Southern/Eastern/Western regions of the country) will deliver the interventions, as they hold the primary access to the target group in Germany. The control condition is a group programme with the same duration that is not addiction-specific. We expect that participants in the intervention condition will show a significant improvement in the use of adaptive coping strategies (in general and within the family) compared to the control condition as a direct result of the intervention. Data is collected shortly before and after as well as six months after the intervention. Discussion In Germany, the study presented here is the first to develop and evaluate a programme for children of substance-abusing parents. Limitations and strengths are discussed with a special focus on recruitment challenges as they appear to be the most potent threat to feasibility in the difficult-to-access target group at hand (Trial registration: ISRCTN81470784). PMID:22439919

Targeting children of substance-using parents with the community-based group intervention TRAMPOLINE: A randomised controlled trial - design, evaluation, recruitment issues

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Bröning Sonja

2012-03-01

Full Text Available Abstract Background Children of substance-abusing parents are at risk for developing psychosocial development problems. In Germany it is estimated that approx. 2.65 million children are affected by parental substance abuse or dependence. Only ten percent of them receive treatment when parents are treated. To date, no evaluated programme for children from substance-affected families exists in Germany. The study described in this protocol is designed to test the effectiveness of the group programme TRAMPOLINE for children aged 8-12 years with at least one substance-abusing or -dependent caregiver. The intervention is specifically geared to issues and needs of children from substance-affected families. Methods/Design The effectiveness of the manualised nine-session group programme TRAMPOLINE is tested among N = 218 children from substance-affected families in a multicentre randomised controlled trial. Outpatient counselling facilities across the nation from different settings (rural/urban, Northern/Southern/Eastern/Western regions of the country will deliver the interventions, as they hold the primary access to the target group in Germany. The control condition is a group programme with the same duration that is not addiction-specific. We expect that participants in the intervention condition will show a significant improvement in the use of adaptive coping strategies (in general and within the family compared to the control condition as a direct result of the intervention. Data is collected shortly before and after as well as six months after the intervention. Discussion In Germany, the study presented here is the first to develop and evaluate a programme for children of substance-abusing parents. Limitations and strengths are discussed with a special focus on recruitment challenges as they appear to be the most potent threat to feasibility in the difficult-to-access target group at hand (Trial registration: ISRCTN81470784.

Targeting children of substance-using parents with the community-based group intervention TRAMPOLINE: a randomised controlled trial--design, evaluation, recruitment issues.

Science.gov (United States)

Bröning, Sonja; Wiedow, Annika; Wartberg, Lutz; Ruths, Sylvia; Haevelmann, Andrea; Kindermann, Sally-Sophie; Moesgen, Diana; Schaunig-Busch, Ines; Klein, Michael; Thomasius, Rainer

2012-03-22

Children of substance-abusing parents are at risk for developing psychosocial development problems. In Germany it is estimated that approx. 2.65 million children are affected by parental substance abuse or dependence. Only ten percent of them receive treatment when parents are treated. To date, no evaluated programme for children from substance-affected families exists in Germany. The study described in this protocol is designed to test the effectiveness of the group programme TRAMPOLINE for children aged 8-12 years with at least one substance-abusing or -dependent caregiver. The intervention is specifically geared to issues and needs of children from substance-affected families. The effectiveness of the manualised nine-session group programme TRAMPOLINE is tested among N = 218 children from substance-affected families in a multicentre randomised controlled trial. Outpatient counselling facilities across the nation from different settings (rural/urban, Northern/Southern/Eastern/Western regions of the country) will deliver the interventions, as they hold the primary access to the target group in Germany. The control condition is a group programme with the same duration that is not addiction-specific. We expect that participants in the intervention condition will show a significant improvement in the use of adaptive coping strategies (in general and within the family) compared to the control condition as a direct result of the intervention. Data is collected shortly before and after as well as six months after the intervention. In Germany, the study presented here is the first to develop and evaluate a programme for children of substance-abusing parents. Limitations and strengths are discussed with a special focus on recruitment challenges as they appear to be the most potent threat to feasibility in the difficult-to-access target group at hand (Trial registration: ISRCTN81470784).

Exit site and tunnel infections in children on chronic peritoneal dialysis: findings from the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative.

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Swartz, Sarah J; Neu, Alicia; Skversky Mason, Amy; Richardson, Troy; Rodean, Jonathan; Lawlor, John; Warady, Bradley; Somers, Michael J G

2018-06-01

The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a quality improvement initiative to reduce dialysis-associated infections. The frequency of peritoneal dialysis (PD) catheter exit site infection (ESI) and variables influencing its development and end result are unclear. We sought to determine ESI rates, to elucidate the epidemiology, risk factors, and outcomes for ESI, and to assess for association between provider compliance with care bundles and ESI risk. We reviewed demographic, dialysis and ESI data, and care bundle adherence and outcomes for SCOPE enrollees from October 2011 to September 2014. ESI involved only the exit site, only the subcutaneous catheter tunnel, or both. A total of 857 catheter insertions occurred in 734 children over 10,110 cumulative months of PD provided to these children. During this period 207 ESIs arose in 124 children or 0.25 ESIs per dialysis year. Median time to ESI was 392 days, with 69% of ESIs involving exit site only, 23% involving the tunnel only, and 8% involving both sites. Peritonitis developed in 6%. ESI incidence was associated with age (p = 0.003), being the lowest in children aged  0 at prior month's visit (p treatment, 24% required hospitalization, and 9% required catheter removal, generally secondary to tunnel infection. Exit site infections occur at an annualized rate of 0.25, typically well into the dialysis course. Younger patient age and documented review of site care are associated with lower ESI rates. Although most ESIs resolve, hospitalization is frequent, and tunnel involvement/catheter loss complicate outcomes.

Target-site resistance to acetolactate synthase (ALS)-inhibiting herbicides in Amaranthus palmeri from Argentina.

Science.gov (United States)

Larran, Alvaro S; Palmieri, Valeria E; Perotti, Valeria E; Lieber, Lucas; Tuesca, Daniel; Permingeat, Hugo R

2017-12-01

Herbicide-resistant weeds are a serious problem worldwide. Recently, two populations of Amaranthus palmeri with suspected cross-resistance to acetolactate synthase (ALS)-inhibiting herbicides (R1 and R2) were found by farmers in two locations in Argentina (Vicuña Mackenna and Totoras, respectively). We conducted studies to confirm and elucidate the mechanism of resistance. We performed in vivo dose-response assays, and confirmed that both populations had strong resistance to chlorimuron-ethyl, diclosulam and imazethapyr when compared with a susceptible population (S). In vitro ALS activity inhibition tests only indicated considerable resistance to imazethapyr and chlorimuron-ethyl, indicating that other non-target mechanisms could be involved in diclosulam resistance. Subsequently, molecular analysis of als nucleotide sequences revealed three single base-pair mutations producing substitutions in amino acids previously associated with resistance to ALS inhibitors, A122, W574, and S653. This is the first report of als resistance alleles in A. palmeri in Argentina. The data support the involvement of a target-site mechanism of resistance to ALS-inhibiting herbicides. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Target-site mutations conferring resistance to glyphosate in feathertop Rhodes grass (Chloris virgata) populations in Australia.

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Ngo, The D; Krishnan, Mahima; Boutsalis, Peter; Gill, Gurjeet; Preston, Christopher

2018-05-01

Chloris virgata is a warm-season, C 4 , annual grass weed affecting field crops in northern Australia that has become an emerging weed in southern Australia. Four populations with suspected resistance to glyphosate were collected in South Australia, Queensland and New South Wales, Australia, and compared with one susceptible (S) population to confirm glyphosate resistance and elucidate possible mechanisms of resistance. Based on the rate of glyphosate required to kill 50% of treated plants (LD 50 ), glyphosate resistance (GR) was confirmed in four populations of C. virgata (V12, V14.2, V14.16 and V15). GR plants were 2-9.7-fold more resistant and accumulated less shikimate after glyphosate treatment than S plants. GR and S plants did not differ in glyphosate absorption and translocation. Target-site EPSPS mutations corresponding to Pro-106-Leu (V14.2) and Pro-106-Ser (V15, V14.16 and V12) substitutions were found in GR populations. The population with Pro-106-Leu substitution was 2.9-4.9-fold more resistant than the three other populations with Pro-106-Ser substitution. This report confirms glyphosate resistance in C. virgata and shows that target-site EPSPS mutations confer resistance to glyphosate in this species. The evolution of glyphosate resistance in C. virgata highlights the need to identify alternative control tactics. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Adenovirus delivered short hairpin RNA targeting a conserved site in the 5' non-translated region inhibits all four serotypes of dengue viruses.

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Anil Babu Korrapati

Full Text Available BACKGROUND: Dengue is a mosquito-borne viral disease caused by four closely related serotypes of Dengue viruses (DENVs. This disease whose symptoms range from mild fever to potentially fatal haemorrhagic fever and hypovolemic shock, threatens nearly half the global population. There is neither a preventive vaccine nor an effective antiviral therapy against dengue disease. The difference between severe and mild disease appears to be dependent on the viral load. Early diagnosis may enable timely therapeutic intervention to blunt disease severity by reducing the viral load. Harnessing the therapeutic potential of RNA interference (RNAi to attenuate DENV replication may offer one approach to dengue therapy. METHODOLOGY/PRINCIPAL FINDINGS: We screened the non-translated regions (NTRs of the RNA genomes of representative members of the four DENV serotypes for putative siRNA targets mapping to known transcription/translation regulatory elements. We identified a target site in the 5' NTR that maps to the 5' upstream AUG region, a highly conserved cis-acting element essential for viral replication. We used a replication-defective human adenovirus type 5 (AdV5 vector to deliver a short-hairpin RNA (shRNA targeting this site into cells. We show that this shRNA matures to the cognate siRNA and is able to inhibit effectively antigen secretion, viral RNA replication and infectious virus production by all four DENV serotypes. CONCLUSION/SIGNIFICANCE: The data demonstrate the feasibility of using AdV5-mediated delivery of shRNAs targeting conserved sites in the viral genome to achieve inhibition of all four DENV serotypes. This paves the way towards exploration of RNAi as a possible therapeutic strategy to curtail DENV infection.

Speech-language pathologists' practices regarding assessment, analysis, target selection, intervention, and service delivery for children with speech sound disorders.

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Mcleod, Sharynne; Baker, Elise

2014-01-01

A survey of 231 Australian speech-language pathologists (SLPs) was undertaken to describe practices regarding assessment, analysis, target selection, intervention, and service delivery for children with speech sound disorders (SSD). The participants typically worked in private practice, education, or community health settings and 67.6% had a waiting list for services. For each child, most of the SLPs spent 10-40 min in pre-assessment activities, 30-60 min undertaking face-to-face assessments, and 30-60 min completing paperwork after assessments. During an assessment SLPs typically conducted a parent interview, single-word speech sampling, collected a connected speech sample, and used informal tests. They also determined children's stimulability and estimated intelligibility. With multilingual children, informal assessment procedures and English-only tests were commonly used and SLPs relied on family members or interpreters to assist. Common analysis techniques included determination of phonological processes, substitutions-omissions-distortions-additions (SODA), and phonetic inventory. Participants placed high priority on selecting target sounds that were stimulable, early developing, and in error across all word positions and 60.3% felt very confident or confident selecting an appropriate intervention approach. Eight intervention approaches were frequently used: auditory discrimination, minimal pairs, cued articulation, phonological awareness, traditional articulation therapy, auditory bombardment, Nuffield Centre Dyspraxia Programme, and core vocabulary. Children typically received individual therapy with an SLP in a clinic setting. Parents often observed and participated in sessions and SLPs typically included siblings and grandparents in intervention sessions. Parent training and home programs were more frequently used than the group therapy. Two-thirds kept up-to-date by reading journal articles monthly or every 6 months. There were many similarities with

Targeting hunter distribution based on host resource selection and kill sites to manage disease risk.

Science.gov (United States)

Dugal, Cherie J; van Beest, Floris M; Vander Wal, Eric; Brook, Ryan K

2013-10-01

Endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. Spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high-risk areas and individuals. We used resource selection functions (RSFs) and selection ratios (SRs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis manitobensis) during the hunting season between 2002 and 2012, in southwestern Manitoba, Canada. Distance to protected area was the most important covariate influencing resource selection and hunter-kill sites of elk (AICw = 1.00). Collared adult males (which are most likely to be infected with bovine tuberculosis (Mycobacterium bovis) and chronic wasting disease) rarely selected for sites outside of parks during the hunting season in contrast to adult females and juvenile males. The RSFs showed selection by adult females and juvenile males to be negatively associated with landscape-level forest cover, high road density, and water cover, whereas hunter-kill sites of these cohorts were positively associated with landscape-level forest cover and increasing distance to streams and negatively associated with high road density. Local-level forest was positively associated with collared animal locations and hunter-kill sites; however, selection was stronger for collared juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts but currently underrepresented in the distribution of kill sites. We present a novel application of widely available data to target hunter distribution based on host resource

Variation in anticonvulsant selection and EEG monitoring following severe traumatic brain injury in children – Understanding resource availability in sites participating in a comparative effectiveness study

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Kurz, Jonathan E.; Poloyac, Samuel M.; Abend, Nicholas S.; Fabio, Anthony; Bell, Michael J.; Wainwright, Mark S.

2016-01-01

Objective Early post-traumatic seizures (PTS) may contribute to worsened outcomes after traumatic brain injury (TBI). Evidence to guide the evaluation and management of early PTS in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring (cEEG), seizure prophylaxis and the management of early PTS to provide essential information for trial design and the development of PTS management pathways. Design Surveys were sent to site principal investigators at all 43 sites participating in the ADAPT (Approaches and Decisions in Acute Pediatric TBI) trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to (i) implement cEEG monitoring, (ii) PTS prophylaxis, (iii) treat acute PTS, (iv) treat status epilepticus (SE) and refractory status epilepticus (RSE) and (v) monitor anti-seizure drug levels. Setting Institutions comprised a mixture of free-standing children’s hospitals and university medical centers across the United States and Europe. Measurements and Main Results cEEG monitoring was available in the pediatric intensive care unit in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic anti-seizure medications is anticipated in children (93%), yet a minority reports that a specified protocol for treatment of PTS is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for RSE (81%). Presence of an treatment protocols for seizure prophylaxis, early PTS, post-traumatic SE and RSE was associated with decreased reported medications (all p pediatric severe TBI. The substantial variation in cEEG implementation, choice of seizure prophylaxis medications, and management of early PTS across institutions was reported, signifying areas of clinical uncertainty that

Confirming therapeutic target of protopine using immobilized β2 -adrenoceptor coupled with site-directed molecular docking and the target-drug interaction by frontal analysis and injection amount-dependent method.

Science.gov (United States)

Liu, Guangxin; Wang, Pei; Li, Chan; Wang, Jing; Sun, Zhenyu; Zhao, Xinfeng; Zheng, Xiaohui

2017-07-01

Drug-protein interaction analysis is pregnant in designing new leads during drug discovery. We prepared the stationary phase containing immobilized β 2 -adrenoceptor (β 2 -AR) by linkage of the receptor on macroporous silica gel surface through N,N'-carbonyldiimidazole method. The stationary phase was applied in identifying antiasthmatic target of protopine guided by the prediction of site-directed molecular docking. Subsequent application of immobilized β 2 -AR in exploring the binding of protopine to the receptor was realized by frontal analysis and injection amount-dependent method. The association constants of protopine to β 2 -AR by the 2 methods were (1.00 ± 0.06) × 10 5 M -1 and (1.52 ± 0.14) × 10 4 M -1 . The numbers of binding sites were (1.23 ± 0.07) × 10 -7 M and (9.09 ± 0.06) × 10 -7 M, respectively. These results indicated that β 2 -AR is the specific target for therapeutic action of protopine in vivo. The target-drug binding occurred on Ser 169 in crystal structure of the receptor. Compared with frontal analysis, injection amount-dependent method is advantageous to drug saving, improvement of sampling efficiency, and performing speed. It has grave potential in high-throughput drug-receptor interaction analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Comic strips help children understand medical research: targeting the informed consent procedure to children's needs.

Science.gov (United States)

Grootens-Wiegers, Petronella; de Vries, Martine C; van Beusekom, Mara M; van Dijck, Laura; van den Broek, Jos M

2015-04-01

Children involved in medical research often fail to comprehend essential research aspects. In order to improve information provision, a participatory approach was used to develop new information material explaining essential concepts of medical research. A draft of a comic strip was developed by a science communicator in collaboration with pediatricians. The draft was presented to children participating in a clinical trial and to two school classes. Children were consulted for further development in surveys and interviews. Subsequently, the material was revised and re-evaluated in four school classes with children of varying ages and educational levels. In the first evaluation, children provided feedback on the storyline, wording and layout. Children thought the comic strip was 'fun' and 'informative'. Understanding of 8 basic research aspects was on average 83% and all above 65%, illustrating that children understood and remembered key messages. A comic strip was developed to support the informed consent process. Children were consulted and provided feedback. The resulting material was well understood and accepted. Involving children in the development of information material can substantially contribute to the quality of the material. Children were excited to participate and to 'be a part of science'. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sunburn risk among children and outdoor workers in South Africa and Reunion Island coastal sites.

Science.gov (United States)

Wright, Caradee Y; Brogniez, Colette; Ncongwane, Katlego P; Sivakumar, Venkataraman; Coetzee, Gerrie; Metzger, Jean-Marc; Auriol, Frédérique; Deroo, Christine; Sauvage, Béatrice

2013-01-01

To estimate potential sunburn risk for schoolchildren and outdoor workers, ground-based ambient solar ultraviolet radiation (UVR) measurements were converted into possible child (5% of ambient solar UVR) and outdoor worker (20% of ambient solar UVR) solar UVR exposures by skin type and season for three coastal sites: Durban, Cape Point (South Africa) and Saint Denis (Reunion Island, France). Cumulative daily ambient solar UVR levels were relatively high at all sites, especially during summer, with maximum values of about 67, 57 and 74 Standard Erythemal Dose (SED) (1 SED = 100 J m(-2)) at Durban, Cape Point and Saint Denis respectively. Sunburn risk was evident for both children and outdoor workers, especially those with skin types I and II (extremely to moderately sensitive) during summer, early autumn and/or late spring at all three sites. Although results need to be verified with real-time, instantaneous and nonintegrated personal solar UVR measurements, this understanding of sunburn risk is useful for initiating the development skin cancer prevention and sun protection awareness campaigns in both countries. © 2013 The American Society of Photobiology.

Relationship of plasma proadrenomedullin and cortisol levels with systemic inflammatory response and target organ damage in children with sepsis after burn

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Xing Wei

2017-08-01

Full Text Available Objective: To study the relationship of plasma proadrenomedullin (pro-ADM and cortisol (Cor levels with systemic inflammatory response and target organ damage in children with sepsis after burn. Methods: A total of 30 children with sepsis after burn who were treated in the hospital between August 2014 and August 2016 were collected as observation group, and 30 normal children who received vaccination in the hospital during the same period were collected as normal control group. The pro-ADM and Cor levels in plasma as well as the levels of inflammatory factors, myocardial injury markers and intestinal barrier function indexes in serum of the two groups were determined. Pearson test was used to assess the correlation of plasma pro-ADM and Cor levels with systemic inflammatory response and target organ damage in patients with sepsis after burn. Results: Plasma pro-ADM and Cor levels in observation group were higher than those in normal control group. Serum inflammatory cytokines IL-1, IL-6, IL-10 and TNF-α levels in observation group were higher than those in normal control group; serum myocardial injury markers CK-MB, cTnⅠ and NT-proBNP levels were higher than those in normal control group; serum intestinal barrier function indexes ET, DAO and D-L levels were higher than those in normal control group. Conclusion: Plasma pro-ADM and Cor levels increase in patients with sepsis after burn, and are highly consistent with systemic inflammatory response and target organ injury.

From heat integration targets toward implementation – A TSA (total site analysis)-based design approach for heat recovery systems in industrial clusters

International Nuclear Information System (INIS)

Hackl, Roman; Harvey, Simon

2015-01-01

The European process industry is facing major challenges to decrease production costs. One strategy to achieve this is by increasing energy efficiency. Single chemical processes are often well-integrated and the tools to target and design such measures are well developed. Site-wide heat integration based on total site analysis tools can be used to identify opportunities to further increase energy efficiency. However, the methodology has to be developed further in order to enable identification of practical heat integration measures in a systematic way. Designing site-wide heat recovery systems across an industrial cluster is complex and involves aspects apart from thermal process and utility flows. This work presents a method for designing a roadmap of heat integration investments based on total site analysis. The method is applied to a chemical cluster in Sweden. The results of the case study show that application of the proposed method can achieve up to 42% of the previously targeted hot utility savings of 129 MW. A roadmap of heat integration systems is suggested, ranging from less complex systems that achieve a minor share of the heat recovery potential to sophisticated, strongly interdependent systems demanding large investments and a high level of collaboration. - Highlights: • Methodology focused on the practical implementation of site-wide heat recovery. • Algorithm to determine a roadmap of heat integration investments. • Case study: 42% hot utility savings potential at a pay-back period of 3.9y.

Novel GABA receptor pesticide targets.

Science.gov (United States)

Casida, John E; Durkin, Kathleen A

2015-06-01

The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use

Targeted liquid chromatography–mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children

Science.gov (United States)

Bhattacharyya, Sudeepa; Yan, Ke; Pence, Lisa; Simpson, Pippa M; Gill, Pritmohinder; Letzig, Lynda G; Beger, Richard D; Sullivan, Janice E; Kearns, Gregory L; Reed, Michael D; Marshall, James D; Van Den Anker, John N; James, Laura P

2014-01-01

Aim Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose (‘overdose’ or toxic ingestion) exposure to APAP. Materials & methods The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography–triple-quadrupole mass spectrometry. Results Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Conclusion Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the β-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity. PMID:24521011

Lineup identification by children: effects of clothing bias.

Science.gov (United States)

Freire, Alejo; Lee, Kang; Williamson, Karen S; Stuart, Sarah J E; Lindsay, R C L

2004-06-01

This study examined effects of clothing cues on children's identification accuracy from lineups. Four- to 14-year-olds (n = 228) saw 12 video clips of individuals, each wearing a distinctly colored shirt. After watching each clip children were presented with a target-present or target-absent photo lineup. Three clothing conditions were included. In 2 conditions all lineup members wore the same colored shirt; in the third, biased condition, the shirt color of only one individual matched that seen in the preceding clip (the target in target-present trials and the replacement in target-absent trials). Correct identifications of the target in target-present trials were most frequent in the biased condition, whereas in target-absent trials the biased condition led to more false identifications of the target replacement. Older children were more accurate than younger children, both in choosing the target from target-present lineups and rejecting target-absent lineups. These findings suggest that a simple clothing cue such as shirt color can have a significant impact on children's lineup identification accuracy.

Glycosylation site-targeted PEGylation of glucose oxidase retains native enzymatic activity.

Science.gov (United States)

Ritter, Dustin W; Roberts, Jason R; McShane, Michael J

2013-04-10

Targeted PEGylation of glucose oxidase at its glycosylation sites was investigated to determine the effect on enzymatic activity, as well as the bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate was characterized using gel electrophoresis, liquid chromatography, mass spectrometry, and dynamic light scattering. Gel electrophoresis data showed that the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the apparent molecular mass of the protein subunit, with complete conversion to the bioconjugate; liquid chromatography data corroborated this large increase in molecular size. Mass spectrometry data proved that the extent of PEGylation was six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light scattering data indicated the absence of higher-order oligomers in the PEGylated GOx sample. To assess stability, enzymatic activity assays were performed in triplicate at multiple time points over the course of 29 days in the absence of glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a confidence level of 95%, the bioconjugate's performance was statistically equivalent to native glucose oxidase in terms of activity retention over the 29 day time period, as well as following the 24h glucose exposure. Finally, the bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel containing an oxygen-sensitive phosphor, and the construct was shown to respond approximately linearly with a 220±73% signal change (n=4, 95% confidence interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to our knowledge, this represents the first demonstration of PEGylated glucose oxidase incorporated into an optical biosensing assay. Copyright © 2013 Elsevier Inc. All rights reserved.

Targets and teamwork

DEFF Research Database (Denmark)

Skinner, Timothy C.; Lange, Karin S.; Hoey, Hilary

2017-01-01

differences in mean HbA1c between centers ranging from 7.3±0.8% (53mmol/mol±8.7) to 8.9±1.1% (74mmol/mol±12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams...

Targeting physical activity and nutrition interventions towards mothers with young children: a review on components that contribute to attendance and effectiveness

NARCIS (Netherlands)

Hartman, Marieke A.; Hosper, Karen; Stronks, Karien

2011-01-01

To gain insight into intervention components targeted specifically to mothers of young children that may contribute to attendance and effectiveness on physical activity and healthy eating. Systematic literature searches were performed using MEDLINE, Embase and cited references. Articles were

Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

Science.gov (United States)

Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

2018-03-30

High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

A trial of an iPad™ intervention targeting social communication skills in children with autism.

Science.gov (United States)

Fletcher-Watson, Sue; Petrou, Alexandra; Scott-Barrett, Juliet; Dicks, Pamela; Graham, Catherine; O'Hare, Anne; Pain, Helen; McConachie, Helen

2016-10-01

This study evaluated a technology-based early intervention for social communication skills in pre-schoolers in a randomised controlled trial. Participants were 54 children aged under 6 years with a diagnosis of autism, assigned to either intervention or control conditions. The app engaged children, who played consistently, regardless of developmental level, and was rated highly by parents. There were no significant group differences in parent-report measures post-intervention, nor in a measure of parent-child play at follow-up. Therefore, this intervention did not have an observable impact on real-world social communication skills and caution is recommended about the potential usefulness of iPad(™) apps for amelioration of difficulties in interaction. However, positive attitudes among participants, lack of harms and the potential of apps to deliver therapeutic content at low economic cost suggest this approach is worth pursuing further, perhaps targeting other skill domains. © The Author(s) 2015.

Sensitivity of the Modified Children's Yale-Brown Obsessive Compulsive Scale to Detect Change: Results from Two Multi-Site Trials

Science.gov (United States)

Scahill, Lawrence; Sukhodolsky, Denis G.; Anderberg, Emily; Dimitropoulos, Anastasia; Dziura, James; Aman, Michael G.; McCracken, James; Tierney, Elaine; Hallett, Victoria; Katz, Karol; Vitiello, Benedetto; McDougle, Christopher

2016-01-01

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism…

Community-based oral health promotion practices targeted at children and adolescents in Finland--developing an assessment tool.

Science.gov (United States)

Blomqvist, Pia; Ojala, Ellinoora; Kettunen, Tarja; Poskiparta, Marita; Kasila, Kirsti

2014-06-01

To develop an assessment tool for evaluating oral health promotion practices and to evaluate community-based oral health promotion practices targeted at children and adolescents with this tool. A theoretical framework about health promotion planning, implementation and evaluation was made on the basis of a literature review. Then, information about Finnish community-based oral health promotion practices (n=12) targeted at children and adolescents was collected using semi-structured interviews. Also, related documents, for example action plans and reports, were collected when available. Next, an assessment tool based on the theoretical framework was developed, and the recorded and transcribed interview data and other documents were evaluated with this tool. The assessment tool proved to be practical: it pointed out the strengths and weaknesses of the practices. The tool revealed strengths in the implementation and deficiencies in the planning and evaluation of oral health promotion practices. One-quarter of the 12 practices assessed could be considered 'good practices'. There is a need to improve the planning and evaluation of oral health promotion practices. The assessment tool developed in this study might be useful for practitioners both in the field of oral health promotion and general health promotion. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radioligand Recognition of Insecticide Targets.

Science.gov (United States)

Casida, John E

2018-04-04

Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH + ubiquinone oxidoreductase. Pyrethroids and other Na + channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

Screen-Time Weight-loss Intervention Targeting Children at Home (SWITCH): a randomized controlled trial.

Science.gov (United States)

Maddison, Ralph; Marsh, Samantha; Foley, Louise; Epstein, Leonard H; Olds, Timothy; Dewes, Ofa; Heke, Ihirangi; Carter, Karen; Jiang, Yannan; Mhurchu, Cliona Ni

2014-09-10

Screen-based activities, such as watching television (TV), playing video games, and using computers, are common sedentary behaviors among young people and have been linked with increased energy intake and overweight. Previous home-based sedentary behaviour interventions have been limited by focusing primarily on the child, small sample sizes, and short follow-up periods. The SWITCH (Screen-Time Weight-loss Intervention Targeting Children at Home) study aimed to determine the effect of a home-based, family-delivered intervention to reduce screen-based sedentary behaviour on body composition, sedentary behaviour, physical activity, and diet over 24 weeks in overweight and obese children. A two-arm, parallel, randomized controlled trial was conducted. Children and their primary caregiver living in Auckland, New Zealand were recruited via schools, community centres, and word of mouth. The intervention, delivered over 20 weeks, consisted of a face-to-face meeting with the parent/caregiver and the child to deliver intervention content, which focused on training and educating them to use a wide range of strategies designed to reduce their child's screen time. Families were given Time Machine TV monitoring devices to assist with allocating screen time, activity packages to promote alternative activities, online support via a website, and monthly newsletters. Control participants were given the intervention material on completion of follow-up. The primary outcome was change in children's BMI z-score from baseline to 24 weeks. Children (n = 251) aged 9-12 years and their primary caregiver were randomized to receive the SWITCH intervention (n = 127) or no intervention (controls; n = 124). There was no significant difference in change of zBMI between the intervention and control groups, although a favorable trend was observed (-0.016; 95% CI: -0.084, 0.051; p = 0.64). There were also no significant differences on secondary outcomes, except for a trend towards

Do television food commercials target children in Germany?

Science.gov (United States)

Effertz, Tobias; Wilcke, Ann-Christin

2012-08-01

To examine whether the German food industry directs commercials for unhealthy products to children and whether self-administered voluntary restrictions on the promotion of less healthy foods (the EU Pledge) are effective to mitigate this exposure. By analysing German data from television (TV) channels, advertised products were categorized and food products classified as core foods (healthy) and non-core foods (less healthy). Marketing techniques were documented. Food commercials were furthermore compared with commercials for toy products, and comparisons were made between advertising patterns before and after the EU Pledge. Data for ten German TV channels were recorded for two weekdays and two weekend days from 06.00 to 22.00 hours in 2007 and 2008. A second sample containing one weekday and one weekend day of three German TV channels was recorded again in 2010 for comparison in the same time period. In total 16 062 advertisements from 2007-2008 and 2657 from 2010 were analysed. In 2007-2008 19·9 % of TV commercials were for food products, of which 73 % were for non-core foods, 21 % for core foods and 6 % not classified. In three specified channels widely viewed by children and youth, 14·5 % of commercials were for food products, of which 88·2 % were for non-core foods. Commercials for unhealthy foods were broadcast significantly more often during children's peak viewing and in children's programmes, with a higher use of promotional characters and premiums than found in commercials for non-food products. In 2010, analysis of the three specified channels found that 18·5 % of commercials were for food products, of which 98·2 % were for non-core foods. While the use of premiums decreased compared with other commercials, the use of promotional characters in non-core food commercials increased, especially during children's programmes. Children in Germany are exposed to large numbers of food commercials. The exposure to commercials for non-core foods and the use of

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men

Science.gov (United States)

Hughes, Lucinda; Ruth, Karen; Rebbeck, Timothy R.; Giri, Veda N.

2013-01-01

Background Men with a family history of prostate cancer and African American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically-diverse, high-risk men undergoing prostate cancer screening. Methods The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. Eligibility includes men ages 35-69 with a family history of prostate cancer or African descent. Participants with ≥ 1 follow-up visit were included in the analyses (n=477). Genetic variants in regions encoding miRNA binding sites in four target genes (ALOX15, IL-16, IL-18, and RAF1) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Results Among 256 African Americans with ≥ one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs. the CC/CT genotypes (p=0.013), with a suggestive association after correction for false-discovery (p=0.065). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among African Americans was 3.0 (95% CI 1.26-7.12). No association to time to diagnosis was detected among Caucasians by IL-16 genotype. No association to time to prostate cancer diagnosis was found for the other miRNA target genotypes. Conclusions Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future. PMID:24061634

Targeted surveillance for postnatal hearing loss: a program evaluation.

Science.gov (United States)

Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

2012-07-01

The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome

Directory of Open Access Journals (Sweden)

Pin Cui

2016-03-01

Full Text Available Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV is currently invading the germline of the koala (Phascolarctos cinereus and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small.

Primary school children\\'s perspectives on common diseases and ...

African Journals Online (AJOL)

Background: Existing school health programmes in Uganda target children above five years for de-worming, oral hygiene and frequent vaccination of girls of reproductive age. Objective:To assess primary school children\\'s perspectives on common diseases they experience and medicines used in order to suggest reforms ...

Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development.

Science.gov (United States)

Armas, Pablo; Margarit, Ezequiel; Mouguelar, Valeria S; Allende, Miguel L; Calcaterra, Nora B

2013-01-01

CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human muscle diseases. CNBP is highly conserved among vertebrates and has been implicated in transcriptional regulation; however, its DNA binding sites and molecular targets remain elusive. The main goal of this work was to identify CNBP DNA binding sites that might reveal target genes involved in vertebrate embryonic development. To accomplish this, we used a recently described yeast one-hybrid assay to identify DNA sequences bound in vivo by CNBP. Bioinformatic analyses revealed that these sequences are G-enriched and show high frequency of putative G-quadruplex DNA secondary structure. Moreover, an in silico approach enabled us to establish the CNBP DNA-binding site and to predict CNBP putative targets based on gene ontology terms and synexpression with CNBP. The direct interaction between CNBP and candidate genes was proved by EMSA and ChIP assays. Besides, the role of CNBP upon the identified genes was validated in loss-of-function experiments in developing zebrafish. We successfully confirmed that CNBP up-regulates tbx2b and smarca5, and down-regulates wnt5b gene expression. The highly stringent strategy used in this work allowed us to identify new CNBP target genes functionally important in different contexts of vertebrate embryonic development. Furthermore, it represents a novel approach toward understanding the biological function and regulatory networks involving CNBP in the biology of vertebrates.

Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development.

Directory of Open Access Journals (Sweden)

Pablo Armas

Full Text Available CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2 and sporadic inclusion body myositis (sIBM human muscle diseases. CNBP is highly conserved among vertebrates and has been implicated in transcriptional regulation; however, its DNA binding sites and molecular targets remain elusive. The main goal of this work was to identify CNBP DNA binding sites that might reveal target genes involved in vertebrate embryonic development. To accomplish this, we used a recently described yeast one-hybrid assay to identify DNA sequences bound in vivo by CNBP. Bioinformatic analyses revealed that these sequences are G-enriched and show high frequency of putative G-quadruplex DNA secondary structure. Moreover, an in silico approach enabled us to establish the CNBP DNA-binding site and to predict CNBP putative targets based on gene ontology terms and synexpression with CNBP. The direct interaction between CNBP and candidate genes was proved by EMSA and ChIP assays. Besides, the role of CNBP upon the identified genes was validated in loss-of-function experiments in developing zebrafish. We successfully confirmed that CNBP up-regulates tbx2b and smarca5, and down-regulates wnt5b gene expression. The highly stringent strategy used in this work allowed us to identify new CNBP target genes functionally important in different contexts of vertebrate embryonic development. Furthermore, it represents a novel approach toward understanding the biological function and regulatory networks involving CNBP in the biology of vertebrates.

MicroRNA target finding by comparative genomics.

Science.gov (United States)

Friedman, Robin C; Burge, Christopher B

2014-01-01

MicroRNAs (miRNAs) have been implicated in virtually every metazoan biological process, exerting a widespread impact on gene expression. MicroRNA repression is conferred by relatively short "seed match" sequences, although the degree of repression varies widely for individual target sites. The factors controlling whether, and to what extent, a target site is repressed are not fully understood. As an alternative to target prediction based on sequence alone, comparative genomics has emerged as an invaluable tool for identifying miRNA targets that are conserved by natural selection, and hence likely effective and important. Here we present a general method for quantifying conservation of miRNA seed match sites, separating it from background conservation, controlling for various biases, and predicting miRNA targets. This method is useful not only for generating predictions but also as a tool for empirically evaluating the importance of various target prediction criteria.

Child-targeted TV advertising and preschoolers' consumption of high-sugar breakfast cereals.

Science.gov (United States)

Longacre, Meghan R; Drake, Keith M; Titus, Linda J; Harris, Jennifer; Cleveland, Lauren P; Langeloh, Gail; Hendricks, Kristy; Dalton, Madeline A

2017-01-01

Breakfast cereals represent the most highly advertised packaged food on child-targeted television, and most ads are for cereals high in sugar. This study examined whether children's TV exposure to child-targeted, high-sugar breakfast cereal (SBC) ads was associated with their consumption of those SBC brands. Parents of 3- to 5-year-old children were recruited from pediatric and Women, Infants, and Children (WIC) clinics in Southern New Hampshire, USA, and completed a cross-sectional survey between April-December 2013. Parents reported their child's consumption of SBC brands; whether their child had watched any of 11 kids' channels in the past week; their child's TV viewing time; and socio-demographics. Children's exposure to child-targeted SBC TV ads was calculated by combining TV channel and viewing time with advertising data for SBC ads aired on kids' TV channels during the same timeframe. Five hundred forty-eight parents completed surveys; 52.7% had an annual household income of $50,000 or less. Children's mean age was 4.4 years, 51.6% were female, and 72.5% were non-Hispanic white. In the past week, 56.9% (N = 312) of children ate SBCs advertised on kids' channels. Overall, 40.6% of children were exposed to child-targeted SBC TV ads in the past week. In fully adjusted analyses, the number of SBC brands children consumed was positively associated with their exposure to child-targeted SBC ads. Children consumed 14% (RR = 1.14, 95% CI: 1.02, 1.27) more SBC brands for every 10 SBC ads seen in the past 7 days. Exposure to child-targeted SBC TV advertising is positively associated with SBC brand consumption among preschool-aged children. These findings support recommendations to limit the marketing of high-sugar foods to young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Five Fabulous Literacy-Oriented Web Sites.

Science.gov (United States)

Kurlychek, Ken

1997-01-01

Profiles six noteworthy web sites on literacy-related information, including sites that deal with issues addressing literacy and deafness, literacy development, family literacy program development, evaluation of family literacy programs, and encouraging young children with deafness to read. Online addresses of the web sites are provided. (CR)

Combination of atomic force microscopy and mass spectrometry for the detection of target protein in the serum samples of children with autism spectrum disorders

Science.gov (United States)

Kaysheva, A. L.; Pleshakova, T. O.; Kopylov, A. T.; Shumov, I. D.; Iourov, I. Y.; Vorsanova, S. G.; Yurov, Y. B.; Ziborov, V. S.; Archakov, A. I.; Ivanov, Y. D.

2017-10-01

Possibility of detection of target proteins associated with development of autistic disorders in children with use of combined atomic force microscopy and mass spectrometry (AFM/MS) method is demonstrated. The proposed method is based on the combination of affine enrichment of proteins from biological samples and visualization of these proteins by AFM and MS analysis with quantitative detection of target proteins.

Drainage Systems Effect on Surgical Site Infection in Children with Perforated Appendicitis

Directory of Open Access Journals (Sweden)

Seref Kilic

2016-09-01

Full Text Available Aim: Effect of replacing open drainage system to closed drainage system on surgical site infection (SSI in children operated for perforated appendicitis was evaluated. Material and Method: Hospital files and computer records of perforated appendicitis cases operated in 2004-2010 were evaluated retrospectively. Open drainage systems were used for 70 in cases (group I and closed systems were used in the others (group II. Results: Eleven of SSI cases had superficial infection and 3 had the organ/space infection. SSI rate was 15.7% for group I and 7.5% for the group II. The antibiotic treatment length was 7.5 ± 3.4 days for group I and 6.4 ± 2.2 days for group II and the difference between groups was not statistically significant. Hospitalization length for group I was 8.2 ± 3.1 days and 6.8 ± 1.9 days for group II and the difference was statistically significant. Discussion: SSI is an important problem increasing morbidity and treatment costs through increasing hospitalization and antibiotic treatment length. Open drainage system used in operation in patients with perforated appendicitis leads an increased frequency of SSI when compared to the closed drainage system. Thus, closed drainage systems should be preferred in when drainage is necessary in operations for perforated appendicitis in children.

Retroviral integration: Site matters

Science.gov (United States)

Demeulemeester, Jonas; De Rijck, Jan

2015-01-01

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

Science.gov (United States)

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

[Social media, children and pediatricians].

Science.gov (United States)

Le Heuzey, M-F

2012-01-01

Using social media web sites is a common activity for children, and any site that allows social interaction (social network, games, virtual worlds...) is a social media site. Pediatricians are in a position to help families understand the benefits and the risks of these sites, and to diagnose problems in children and adolescents as cyberbullying, depression, and post traumatic disorder. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

Science.gov (United States)

2017-10-01

prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

Science.gov (United States)

Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

2014-07-15

Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

International Nuclear Information System (INIS)

Grohmann, Malcolm; Stewart, Claire; Welsh, Gavin; Hunt, Linda; Tavare, Jeremy; Holly, Jeff; Shield, Julian; Sabin, Matt; Crowne, Elizabeth

2005-01-01

Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNFα exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNFα (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNFα also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNFα exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation

Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

Science.gov (United States)

Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

2017-08-15

MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

Trends in characteristics of children served by the Children's Mental Health Initiative: 1994-2007.

Science.gov (United States)

Walrath, Christine; Garraza, Lucas Godoy; Stephens, Robert; Azur, Melissa; Miech, Richard; Leaf, Philip

2009-11-01

Data from 14 years of the national evaluation of the Comprehensive Community Mental Health Services for Children and Their Families Program were used to understand the trends of the emotional and behavioral problems and demographic characteristics of children entering services. The data for this study were derived from information collected at intake into service in 90 sites who received their initial federal funding between 1993 and 2004. The findings from this study suggest children entering services later in a site's funding cycle had lower levels of behavioral problems and children served in sites funded later in the 14 year period had higher levels of behavioral problems. Females have consistently entered services with more severe problems and children referred from non-mental health sources, younger children, and those from non-white racial/ethnic backgrounds have entered system of care services with less severe problems. The policy and programming implications, as well as implications for local system of care program development and implementation are discussed.

Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains.

Science.gov (United States)

Rich, Megan C; Keene, Chesleigh N; Neher, Miriam D; Johnson, Krista; Yu, Zhao-Xue; Ganivet, Antoine; Holers, V Michael; Stahel, Philip F

2016-03-23

Intracerebral complement activation after severe traumatic brain injury (TBI) leads to a cascade of neuroinflammatory pathological sequelae that propagate host-mediated secondary brain injury and adverse outcomes. There are currently no specific pharmacological agents on the market to prevent or mitigate the development of secondary cerebral insults after TBI. A novel chimeric CR2-fH compound (mTT30) provides targeted inhibition of the alternative complement pathway at the site of tissue injury. This experimental study was designed to test the neuroprotective effects of mTT30 in a mouse model of closed head injury. The administration of 500 μg mTT30 i.v. at 1 h, 4 h and 24 h after head injury attenuated complement C3 deposition in injured brains, reduced the extent of neuronal cell death, and decreased post-injury microglial activation, compared to vehicle-injected placebo controls. These data imply that site-targeted alternative pathway complement inhibition may represent a new promising therapeutic avenue for the future management of severe TBI. Copyright © 2016. Published by Elsevier Ireland Ltd.

Direction, site and the muzzle target distance of bullet in the head and neck at close range as an indication of suicide or homicide.

Science.gov (United States)

Suwanjutha, T

1988-05-01

Direction, site and muzzle target distance can indicate suicide or homicide. This conclusion can be drawn from autopsies of 57 cases of suicide and 68 cases of homicide by handgun fired at close range to the head and neck together with going to the crimescene in some cases. This study was carried out in Bangkok during the period from January 1983 to January 1986. In order to determine whether it was suicide or homicide, the path of the bullet, the site, the muzzle target distance must be considered. The angle of the bullet would be either elevated (from below upward), horizontal or an angle of depression (from above downward). For suicide, the direction of the bullet should be at an angle of elevation in the majority of cases. The position of the handgun in relation to the head in suicide was most often in tight contact and near contact. For homicide, the direction of the bullet should be horizontal in most cases. The bullet was at close range in the majority of the cases. There are 8 common sites for suicide and homicide and 10 different sites in the case of homicide which are at neck, left cheek, left aural region, lip, left occipital area orbit, chin, left eyebrow, submental and nose.

Defining a target population at high risk of long-term foster care: barriers to permanency for families of children with serious emotional disturbances.

Science.gov (United States)

Akin, Becci A; Bryson, Stephanie A; McDonald, Tom; Walker, Sheila

2012-01-01

Long-term foster care (LTFC) is an enduring problem that lacks evidence of effective strategies for practice or policy. This article describes initial activities of a statewide project of the national Permanency Innovations Initiative. The authors sought to: (1) verify the relevance of children's mental health as a predictor of LTFC, (2) describe critical barriers encountered by parents of children with serious emotional disturbances, and (3) identify systems barriers that hinder permanency for this target population.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer?s-Associated A? Oligomers

OpenAIRE

Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein int...

Target-site resistance to pyrethroids in European populations of pollen beetle, Meligethes aeneus F

DEFF Research Database (Denmark)

Nauen, Ralf; Zimmer, Christoph T; Andrews, Melanie

2012-01-01

by cytochrome P450 monooxygenases was implicated in the resistance of several pollen beetle populations from different European regions. Here, we have also investigated the possible occurrence of a target-site mechanism caused by modification of the pollen beetle para-type voltage-gated sodium channel gene. We...... resulted in high selection pressure and subsequent development of resistance. Resistance to pyrethroid insecticides in this pest is now widespread and the levels of resistance are often sufficient to result in field control failures at recommended application rates. Recently, metabolic resistance mediated...... detected a single nucleotide change that results in an amino acid substitution (L1014F) within the domain IIS6 region of the channel protein. The L1014F mutation, often termed kdr, has been found in several other insect pests and is known to confer moderate levels of resistance to pyrethroids. We developed...

Development and preliminary evaluation of an integrated treatment targeting parenting and depressive symptoms in mothers of children with attention-deficit/hyperactivity disorder.

Science.gov (United States)

Chronis-Tuscano, Andrea; Clarke, Tana L; O'Brien, Kelly A; Raggi, Veronica L; Diaz, Yamalis; Mintz, Abigail D; Rooney, Mary E; Knight, Laura A; Seymour, Karen E; Thomas, Sharon R; Seeley, John; Kosty, Derek; Lewinsohn, Peter

2013-10-01

More than 50% of mothers of children with attention-deficit/hyperactivity disorder (ADHD) have a lifetime history of major depressive disorder (MDD). Maternal depressive symptoms are associated with impaired parenting and predict adverse developmental and treatment outcomes for children with ADHD. For these reasons, we developed and examined the preliminary efficacy of an integrated treatment targeting parenting and depressive symptoms for mothers of children with ADHD. This integrated intervention incorporated elements of 2 evidence-based treatments: behavioral parent training (BPT) and cognitive behavioral depression treatment. Ninety-eight mothers with at least mild depressive symptoms were randomized to receive either standard BPT (n = 51) or the integrated parenting intervention for ADHD (IPI-A; n = 47). Participants were assessed at baseline, posttreatment, and 3- to 6-month follow-up on measures of (a) self-reported maternal depressive symptoms, (b) observed positive and negative parenting, and (c) observed and mother-reported child disruptive behavior and mother-reported child and family impairment. The IPI-A produced effects of small to moderate magnitude relative to BPT on maternal depressive symptoms, observed negative parenting, observed child deviance, and child impairment at posttreatment and on maternal depressive symptoms, child disruptive behavior, child impairment and family functioning at follow-up. Contrary to expectations, the BPT group demonstrated moderate to large effects relative to IPI-A on observed positive parenting at follow-up. This treatment development study provides encouraging preliminary support for the integrated intervention targeting parenting and depressive symptoms in mothers of children with ADHD. Future studies should examine whether this integrated intervention improves long-term developmental outcomes for children with ADHD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH: A randomized controlled trial study protocol

Directory of Open Access Journals (Sweden)

Tsai Midi

2011-06-01

Full Text Available Abstract Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33% do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention or control (no change. At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI and standardized body mass index (zBMI. Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous, Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight

Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

NARCIS (Netherlands)

T. Niu (Tianhua); N. Liu (Ning); M. Zhao (Ming); G. Xie (Guie); L. Zhang (Lei); J. Li (Jian); Y.-F. Pei (Yu-Fang); H. Shen (Hui); X. Fu (Xiaoying); H. He (Hao); S. Lu (Shan); X. Chen (Xiangding); L. Tan (Lijun); T.-L. Yang (Tie-Lin); Y. Guo (Yan); P.J. Leo (Paul); E.L. Duncan (Emma); J. Shen (Jie); Y.-F. Guo (Yan-fang); G.C. Nicholson (Geoffrey); R.L. Prince (Richard L.); J.A. Eisman (John); G. Jones (Graeme); P.N. Sambrook (Philip); X. Hu (Xiang); P.M. Das (Partha M.); Q. Tian (Qing); X.-Z. Zhu (Xue-Zhen); C.J. Papasian (Christopher J.); M.A. Brown (Matthew); A.G. Uitterlinden (André); Y.-P. Wang (Yu-Ping); S. Xiang (Shuanglin); H.-W. Deng

2015-01-01

textabstractMicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck

Representational constraints on children's suggestibility.

Science.gov (United States)

Ceci, Stephen J; Papierno, Paul B; Kulkofsky, Sarah

2007-06-01

In a multistage experiment, twelve 4- and 9-year-old children participated in a triad rating task. Their ratings were mapped with multidimensional scaling, from which euclidean distances were computed to operationalize semantic distance between items in target pairs. These children and age-mates then participated in an experiment that employed these target pairs in a story, which was followed by a misinformation manipulation. Analyses linked individual and developmental differences in suggestibility to children's representations of the target items. Semantic proximity was a strong predictor of differences in suggestibility: The closer a suggested distractor was to the original item's representation, the greater was the distractor's suggestive influence. The triad participants' semantic proximity subsequently served as the basis for correctly predicting memory performance in the larger group. Semantic proximity enabled a priori counterintuitive predictions of reverse age-related trends to be confirmed whenever the distance between representations of items in a target pair was greater for younger than for older children.

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

Energy Technology Data Exchange (ETDEWEB)

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Karim, Salim S. Abdool; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.; Kwong, Peter D.; Morris, Lynn (NHLS-South Africa); (NIH); (Witwatersrand); (KwaZulu-Natal)

2016-08-31

All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage.

IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

OpenAIRE

de Lange, Elizabeth CM

2013-01-01

Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents.

Directory of Open Access Journals (Sweden)

Anja S Euser

Full Text Available BACKGROUND: Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD] uniquely contributed to P300 amplitude variation above and beyond these other variables. METHODS: Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80 and normal-risk controls (NR;n=100 while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. RESULTS: HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. CONCLUSION: Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.

A tale of two sequences: microRNA-target chimeric reads.

Science.gov (United States)

Broughton, James P; Pasquinelli, Amy E

2016-04-04

In animals, a functional interaction between a microRNA (miRNA) and its target RNA requires only partial base pairing. The limited number of base pair interactions required for miRNA targeting provides miRNAs with broad regulatory potential and also makes target prediction challenging. Computational approaches to target prediction have focused on identifying miRNA target sites based on known sequence features that are important for canonical targeting and may miss non-canonical targets. Current state-of-the-art experimental approaches, such as CLIP-seq (cross-linking immunoprecipitation with sequencing), PAR-CLIP (photoactivatable-ribonucleoside-enhanced CLIP), and iCLIP (individual-nucleotide resolution CLIP), require inference of which miRNA is bound at each site. Recently, the development of methods to ligate miRNAs to their target RNAs during the preparation of sequencing libraries has provided a new tool for the identification of miRNA target sites. The chimeric, or hybrid, miRNA-target reads that are produced by these methods unambiguously identify the miRNA bound at a specific target site. The information provided by these chimeric reads has revealed extensive non-canonical interactions between miRNAs and their target mRNAs, and identified many novel interactions between miRNAs and noncoding RNAs.

Children's (Pediatric) Nuclear Medicine

Science.gov (United States)

... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

Final work plan: Expedited Site Characterization of the IES Industries, Inc., Site at Marshalltown, Iowa. Ames Expedited Site Characterization Project, Version 1.0

Energy Technology Data Exchange (ETDEWEB)

1994-04-04

The overall goal of the Ames Laboratory Expedited Site Characterization (ESC) project is to evaluate and promote both innovative and state-of-the-practice site characterization and/or monitoring technologies. This will be accomplished by fielding both types of technologies together in the context of an expedited site characterization. The first site will be at a former manufactured gas plant (FMGP) in Marshalltown, Iowa. The project will field three areas of technology: geophysical, analytical, and data fusion. Geophysical technologies are designed to understand the subsurface geology to help predict fate and transport of the target contaminants. Analytical technologies/methods are designed to detect and quantify the target contaminants. Data fusion technology consists of software systems designed to rapidly integrate or fuse all site information into a conceptual site model that then becomes the decision making tool for the site team to plan subsequent sampling activity. Not all of the contaminants present can be located at the action level. Polynuclear aromatic hydrocarbons (PAHs) are the signature organics associated with the coal tar activities that took place at the site. As a result, PAHs were selected as the target compounds. Screening analytical instruments and nonintrusive geophysical techniques will be fielded to qualitatively map the spatial contaminant distribution. Soil gas surveys, immunoassay testing (IMA), innovative optical techniques, and passive organic sorbent sensors will be deployed along with the geophysical methods. Gas chromatography/mass spectrometry (GC/MS) instruments and a cone penetrometer system equipped with a laser-induced fluorescence (LIF) probe will quantitatively map the action level edges of the PAH plume(s). Samples will be taken both by the cone penetrometer test system (CPT) and the Geoprobe {reg_sign} sampler system.

Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1.

Science.gov (United States)

Gu, Yongzhong; Bian, Yuehong; Xu, Xiaofei; Wang, Xietong; Zuo, Changting; Meng, Jinlai; Li, Hongyan; Zhao, Shigang; Ning, Yunnan; Cao, Yongzhi; Huang, Tao; Yan, Junhao; Chen, Zi-Jiang

2016-12-01

Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta. Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c. Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/b/c directly target the 3' untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1. Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta. Copyright © 2016 Elsevier Ltd. All rights

Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

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Zhi-Hong Ren

2017-10-01

Full Text Available Objective: To study the changes of serum pancreatic stone protein (PSP and cholinesterase (ChE contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group; serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group; liver function indexes TBIL, ALT and AST contents were higher than those of normal control group; kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.

Demographic survey around proposed nuclear power plant site in Haryana covering 30 km radius area from the site

International Nuclear Information System (INIS)

Garg, V.K.

2013-01-01

This study was planned to have a demographic survey of the households living within 30 km radius of the proposed site. Objectives of the present study were to attain the quantitative baseline demographic data around (within 30 km radius) the proposed site of nuclear power plant, zone-wise and sector-wise distribution of the population around proposed site up to a distance of 30 km from the site, to obtain the data on socio-economic, cultural, and religious perspectives of the target populations, to obtain the data on disease/illness pattern in the target population, health status and mortality rate

Ames expedited site characterization demonstration at the former manufactured gas plant site, Marshalltown, Iowa

International Nuclear Information System (INIS)

Bevolo, A.J.; Kjartanson, B.H.; Wonder, J.D.

1996-03-01

The goal of the Ames Expedited Site Characterization (ESC) project is to evaluate and promote both innovative technologies (IT) and state-of-the-practice technologies (SOPT) for site characterization and monitoring. In April and May 1994, the ESC project conducted site characterization, technology comparison, and stakeholder demonstration activities at a former manufactured gas plant (FMGP) owned by Iowa Electric Services (IES) Utilities, Inc., in Marshalltown, Iowa. Three areas of technology were fielded at the Marshalltown FMGP site: geophysical, analytical and data integration. The geophysical technologies are designed to assess the subsurface geological conditions so that the location, fate and transport of the target contaminants may be assessed and forecasted. The analytical technologies/methods are designed to detect and quantify the target contaminants. The data integration technology area consists of hardware and software systems designed to integrate all the site information compiled and collected into a conceptual site model on a daily basis at the site; this conceptual model then becomes the decision-support tool. Simultaneous fielding of different methods within each of the three areas of technology provided data for direct comparison of the technologies fielded, both SOPT and IT. This document reports the results of the site characterization, technology comparison, and ESC demonstration activities associated with the Marshalltown FMGP site. 124 figs., 27 tabs

Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children

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Han Ting-I

2012-02-01

Full Text Available Abstract Background It is still unclear when latent myofascial trigger points (MTrPs develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs in school children. Methods Five hundreds and five healthy school children (age 4- 11 years were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site, the mid-point of the muscle belly (site B, assumed to be the MTrP site, and the muscle-tendon junction as a control site (site C. Results The results showed that, for all children in this study, the mean PPT values was significantly lower (p p Conclusions It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs.

Children's Input is Vital to Creating an Online Library that meets Children's Information Needs. A review of: Druin, Allison. “What Children Can Teach Us: Developing Digital Libraries for Children with Children.” The Library Quarterly 75.1 (January 2005: 20‐41.

Directory of Open Access Journals (Sweden)

Susan Haigh

2006-03-01

Full Text Available Objective - Through use of an interdisciplinary research team that included children, the study aimed to demonstate that including children in the design of a digital library for children would result in some new approaches that would improve the site's usability for the target user group. Design - Case study. Setting - The research was conducted at University of Maryland over a four-year perioe and involved an interdisciplinary research team of adult researchers from information studies, computer science, education, art, and psychology as well as seven children aged 7-11. Subjects - Seven children participated in the design team over two years; 153 children were obeserved and interviewed in the design phase; and the resulting new approaches were validated post-launch by analysis of International Children's Digital Library (ICDL (http://www.icdlbooks.org users and usage patterns from November 2002- November 2003 (over 90, 000 unique users and 19, 000 optional questionnaire respondents. Method - The study included seven children in the design team for a digital library of international children's books, which resulted in new approaches to collection development, cataloguing and the search interface. In the design phase, research methods involving the seven children included brainstorming techniques, "cooperative inquiry", low tech prototyping; and lab use studies. The team also undertook observation and interviews of 153 children engaged in searching and selecting books from public library catalogues. In validating the new approaches that resulted from the design research, the team employed web log analysis, a voluntary online survey, and working with children in local schools to understand their use of ICDL. Main result - The inclusion of children's viewpoints in the design stage of ICDL had an impact in three areas: collection development, metadata, and interface design. For collection development, the research showed that kids were interested

Children's (Pediatric) Nuclear Medicine

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Children's (Pediatric) Nuclear Medicine

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Children's (Pediatric) Nuclear Medicine

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Full Text Available ... News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging ... the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch ...

Children's (Pediatric) Nuclear Medicine

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Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical ...

Low Herbivory among Targeted Reforestation Sites in the Andean Highlands of Southern Ecuador.

Directory of Open Access Journals (Sweden)

Marc-Oliver Adams

Full Text Available Insect herbivory constitutes an important constraint in the viability and management of targeted reforestation sites. Focusing on young experimental stands at about 2000 m elevation in southern Ecuador, we examined foliar damage over one season as a function of tree species and habitat. Native tree species (Successional hardwood: Cedrela montana and Tabebuia chrysantha; fast-growing pioneer: Heliocarpus americanus have been planted among prevailing local landcover types (abandoned pasture, secondary shrub vegetation, and a Pinus patula plantation in 2003/4. Plantation trees were compared to conspecifics in the spontaneous undergrowth of adjacent undisturbed rainforest matched for height and foliar volume. Specifically, we tested the hypotheses that H. americanus as a pioneer species suffers more herbivory compared to the two successional tree species, and that damage is inversely related to habitat complexity. Overall leaf damage caused by folivorous insects (excluding leafcutter ants was low. Average leaf loss was highest among T. chrysantha (7.50% ± 0.19 SE of leaf area, followed by H. americanus (4.67% ± 0.18 SE and C. montana (3.18% ± 0.15 SE. Contrary to expectations, leaf area loss was highest among trees in closed-canopy natural rainforest, followed by pine plantation, pasture, and secondary shrub sites. Harvesting activity of leafcutter ants (Acromyrmex sp. was strongly biased towards T. chrysantha growing in open habitat (mean pasture: 2.5%; shrub: 10.5% where it could result in considerable damage (> 90.0%. Insect folivory is unlikely to pose a barrier for reforestation in the tropical Andean mountain forest zone at present, but leafcutter ants may become problematic if local temperatures increase in the wake of global warming.

Targeted genome editing in Aedes aegypti using TALENs.

Science.gov (United States)

Aryan, Azadeh; Myles, Kevin M; Adelman, Zach N

2014-08-15

The Culicine mosquito, Aedes aegypti, is both a major vector of arthropod-borne viruses (arboviruses) and a genetic model organism for arbovirus transmission. TALE nucleases (TALENs), a group of artificial enzymes capable of generating site-specific DNA lesions, consist of a non-specific FokI endonuclease cleavage domain fused to an engineered DNA binding domain specific to a target site. While TALENs have become an important tool for targeted gene disruption in a variety of organisms, application to the mosquito genome is a new approach. We recently described the use of TALENs to perform heritable genetic disruptions in A. aegypti. Here, we provide detailed methods that will allow other research laboratories to capitalize on the potential of this technology for understanding mosquito gene function. We describe target site selection, transient embryo-based assays to rapidly assess TALEN activity, embryonic microinjection and downstream screening steps to identify target site mutations. Copyright © 2014 Elsevier Inc. All rights reserved.

Parental awareness and use of online physician rating sites.

Science.gov (United States)

Hanauer, David A; Zheng, Kai; Singer, Dianne C; Gebremariam, Achamyeleh; Davis, Matthew M

2014-10-01

The US public is increasingly using online rating sites to make decisions about a variety of consumer goods and services, including physicians. We sought to understand, within the context of other types of rating sites, parents' awareness, perceptions, and use of physician-rating sites for choosing primary care physicians for their children. This cross-sectional, nationally representative survey of 3563 adults was conducted in September 2012. Participants were asked about rating Web sites in the context of finding a primary care physician for their children and about their previous experiences with such sites. Overall, 2137 (60%) of participants completed the survey. Among these respondents, 1619 were parents who were included in the present analysis. About three-quarters (74%) of parents were aware of physician-rating sites, and about one-quarter (28%) had used them to select a primary care physician for their children. Based on 3 vignettes for which respondents were asked if they would follow a neighbor's recommendation about a primary care physician and using multivariate analyses, respondents exposed to a neighbor's recommendation and positive online physician ratings were significantly more likely to choose the recommended physician (adjusted odds ratio: 3.0 [95% confidence interval: 2.1-4.4]) than respondents exposed to the neighbor's recommendation alone. Conversely, respondents exposed to the neighbor's recommendation and negative online ratings were significantly less likely to choose the neighbor children's physician (adjusted odds ratio: 0.09 [95% confidence interval: 0.03-0.3]). Parents are beginning to use online physician ratings, and these ratings have the potential to influence choices of their children's primary care physician. Copyright © 2014 by the American Academy of Pediatrics.

Anterior and posterior erp rhyming effects in 3- to 5-year-old children

Directory of Open Access Journals (Sweden)

Annika Andersson

2018-04-01

Full Text Available During early literacy skills development, rhyming is an important indicator of the phonological precursors required for reading. To determine if neural signatures of rhyming are apparent in early childhood, we recorded event-related potentials (ERPs from 3- to 5-year-old, preliterate children (N = 62 in an auditory prime-target nonword rhyming paradigm (e.g., bly-gry, blane-vox. Overall, nonrhyming targets elicited a larger negativity (N450 than rhyming targets over posterior regions. In contrast, rhyming targets elicited a larger negativity than nonrhyming targets over fronto-lateral sites. The amplitude of the two rhyming effects was correlated, such that a larger posterior effect occurred with a smaller anterior effect. To determine whether these neural signatures of rhyming related to phonological awareness, we divided the children into two groups based on phonological awareness scores while controlling for age and socioeconomic status. The posterior rhyming effect was stronger and more widely distributed in the group with better phonological awareness, whereas differences between groups for the anterior effect were small and not significant. This pattern of results suggests that the rhyme processes indexed by the anterior effect are developmental precursors to those indexed by the posterior effect. Overall, these findings demonstrate early establishment of distributed neurocognitive networks for rhyme processing. Keywords: Rhyming effect, Event-related potentials, Phonological awareness, Preschoolers, Nonword processing

Inference of miRNA targets using evolutionary conservation and pathway analysis

Directory of Open Access Journals (Sweden)

van Nimwegen Erik

2007-03-01

Full Text Available Abstract Background MicroRNAs have emerged as important regulatory genes in a variety of cellular processes and, in recent years, hundreds of such genes have been discovered in animals. In contrast, functional annotations are available only for a very small fraction of these miRNAs, and even in these cases only partially. Results We developed a general Bayesian method for the inference of miRNA target sites, in which, for each miRNA, we explicitly model the evolution of orthologous target sites in a set of related species. Using this method we predict target sites for all known miRNAs in flies, worms, fish, and mammals. By comparing our predictions in fly with a reference set of experimentally tested miRNA-mRNA interactions we show that our general method performs at least as well as the most accurate methods available to date, including ones specifically tailored for target prediction in fly. An important novel feature of our model is that it explicitly infers the phylogenetic distribution of functional target sites, independently for each miRNA. This allows us to infer species-specific and clade-specific miRNA targeting. We also show that, in long human 3' UTRs, miRNA target sites occur preferentially near the start and near the end of the 3' UTR. To characterize miRNA function beyond the predicted lists of targets we further present a method to infer significant associations between the sets of targets predicted for individual miRNAs and specific biochemical pathways, in particular those of the KEGG pathway database. We show that this approach retrieves several known functional miRNA-mRNA associations, and predicts novel functions for known miRNAs in cell growth and in development. Conclusion We have presented a Bayesian target prediction algorithm without any tunable parameters, that can be applied to sequences from any clade of species. The algorithm automatically infers the phylogenetic distribution of functional sites for each miRNA, and

EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

Science.gov (United States)

Dines, M; Lamprecht, R

2014-09-30

Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

Site-specific quantification of lysine acetylation in the N-terminal tail of histone H4 using a double-labelling, targeted UHPLC MS/MS approach

NARCIS (Netherlands)

D'Urzo, Annalisa; Boichenko, Alexander P.; van den Bosch, Thea; Hermans, Jos; Dekker, Frank; Andrisano, Vincenza; Bischoff, Rainer

We developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the site-specific quantification of lysine acetylation in the N-terminal region of histone H4 by combining chemical derivatization at the protein and peptide levels with digestion using chymotrypsin and

[Parents support for the ban on television food advertising to children is particularly high in France, especially compared to the USA. This result should influence political decision-making to restrict food marketing targeting young people].

Science.gov (United States)

Escalon, Hélène; Cogordan, Chloé; Arwidson, Pierre

2016-01-01

Massive exposure of children to low-nutrient food advertising combined with the increasing prevalence of obesity have led to growing support for statutory regulations concerning food marketing targeting children. Food and advertising industries lobbies have nevertheless managed to stop such measures in many countries. In this context, civil society support for statutory regulation, especially by parents, is essential. The objective of this study was to describe and analyse factors associated with parents' opinion on the impact and possible banning of food TV advertisements targeting children. An online survey of 2,387 parents of children aged 3 to 17 was conducted in 2013. Associations between parents'opinion on food advertising and their socio-demographic characteristics were analysed by multivariate logistic regressions. The influence of food advertising on children' preferences was perceived by 64.7% of parents, 68.8% of parents were at least occasionally asked by their children to purchase food or beverages seen on television, 43.5% reported that their children influenced their food purchases and 73.7% supported a statutory regulation that would ban advertisements for excessively fatty, salty and sugary beverages and foods during television programmes for children or teenagers. This view was positively associated with high socio-economic status and a high perceived impact of advertising on children's food preferences. Parents support for the ban on television food advertising to children is particularly high in France, especially compared to the USA. This result should influence political decision-making to restrict food marketing targeting young people.

Description of the Northwest hazardous waste site data base and preliminary analysis of site characteristics

International Nuclear Information System (INIS)

Woodruff, D.L.; Hartz, K.E.; Triplett, M.B.

1988-08-01

The Northwest Hazardous Waste RD and D Center (the Center) conducts research, development, and demonstration (RD and D) activities for hazardous and radioactive mixed-waste technologies applicable to remediating sites in the states of Idaho, Montana, Oregon, and Washington. To properly set priorities for these RD and D activities and to target development efforts it is necessary to understand the nature of the sites requiring remediation. A data base of hazardous waste site characteristics has been constructed to facilitate this analysis. The data base used data from EPA's Region X Comprehensive Environmental Response, Compensation, and Liability Information System (CERCLIS) and from Preliminary Assessment/Site Investigation (PA/SI) forms for sites in Montana. The Center's data base focuses on two sets of sites--those on the National Priorities List (NPL) and other sites that are denoted as ''active'' CERCLIS sites. Active CERCLIS sites are those sites that are undergoing active investigation and analysis. The data base contains information for each site covering site identification and location, type of industry associated with the site, waste categories present (e.g., heavy metals, pesticides, etc.), methods of disposal (e.g., tanks, drums, land, etc.), waste forms (e.g., liquid, solid, etc.), and hazard targets (e.g., surface water, groundwater, etc.). As part of this analysis, the Northwest region was divided into three geographic subregions to identify differences in disposal site characteristics within the Northwest. 2 refs., 18 figs., 5 tabs

Adherence to the Obesity-related Lifestyle Intervention Targets in the IDEFICS Study

DEFF Research Database (Denmark)

Kovács, Eva; Siani, Alfonso; Konstabel, Kenn

2014-01-01

Background/objectives: To address behaviours associated with childhood obesity, certain target values are recommended that should be met to improve children’s health. In the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study...... such lifestyle recommendations were conveyed as six key messages. Here, we investigate the adherence of European children to these messages. Methods: The IDEFICS intervention was based on the intervention mapping approach with the following six targets: increase water consumption (to replace sugar......-containing beverages), increase fruit/vegetable consumption, reduce daily screen time, increase daily physical activity, improve the quality of family life and ensure adequate sleep duration. Internationally recommended target values were applied to determine the prevalence of children meeting these targets. Results...

Comparative studies of the endonucleases from two related Xenopus laevis retrotransposons, Tx1L and Tx2L: target site specificity and evolutionary implications.

Science.gov (United States)

Christensen, S; Pont-Kingdon, G; Carroll, D

2000-01-01

In the genome of the South African frog, Xenopus laevis, there are two complex families of transposable elements, Tx1 and Tx2, that have identical overall structures, but distinct sequences. In each family there are approximately 1500 copies of an apparent DNA-based element (Tx1D and Tx2D). Roughly 10% of these elements in each family are interrupted by a non-LTR retrotransposon (Tx1L and Tx2L). Each retrotransposon is flanked by a 23-bp target duplication of a specific D element sequence. In earlier work, we showed that the endonuclease domain (Tx1L EN) located in the second open reading frame (ORF2) of Tx1L encodes a protein that makes a single-strand cut precisely at the expected site within its target sequence, supporting the idea that Tx1L is a site-specific retrotransposon. In this study, we express the endonuclease domain of Tx2L (Tx2L EN) and compare the target preferences of the two enzymes. Each endonuclease shows some preference for its cognate target, on the order of 5-fold over the non-cognate target. The observed discrimination is not sufficient, however, to explain the observation that no cross-occupancy is observed - that is, L elements of one family have never been found within D elements of the other family. Possible sources of additional specificity are discussed. We also compare two hypotheses regarding the genome duplication event that led to the contemporary pseudotetraploid character of Xenopus laevis in light of the Tx1L and Tx2L data.

A standardized perioperative surgical site infection care process among children with stoma closure: a before-after study.

Science.gov (United States)

Porras-Hernandez, Juan; Bracho-Blanchet, Eduardo; Tovilla-Mercado, Jose; Vilar-Compte, Diana; Nieto-Zermeño, Jaime; Davila-Perez, Roberto; Teyssier-Morales, Gustavo; Lule-Dominguez, Martha

2008-10-01

We report on the effectiveness of a standardized perioperative care process for lowering surgical site infection (SSI) rates among children with stoma closure at a tertiary-care public pediatric teaching hospital in Mexico City. All consecutive children with stoma closure operated on between November 2003 and October 2005 were prospectively followed for 30 days postoperatively. We conducted a before-after study to evaluate standardized perioperative bowel- and abdominal-wall care process results on SSI rates. Seventy-one patients were operated on, and all completed follow-up. SSI rates declined from 42.8% (12/28) before to 13.9% (6/43) after the standardization procedure (relative risk (RR) = 3.1; 95% confidence interval (CI) = 1.3-7.2; p = 0.006). SSI independently associated risk factors comprised peristomal skin inflammation >3 mm (odds ratio (OR) = 9.6; 95% CI = 1.8-49.6; p = 0.007) and intraoperative complications (OR = 13.3; 95% CI = 1.4-127.2; p = 0.02). Being operated on during the after-study period was shown to be a protective factor against SSI (OR = 0.2; 95% CI = 0.4-0.97; p = 0.04). Standardization was able to reduce SSI rates threefold in children with stoma closure in a short period of time.

PATTERN BASED DETECTION OF POTENTIALLY DRUGGABLE BINDING SITES BY LIGAND SCREENING

Directory of Open Access Journals (Sweden)

Uttam Pal

2018-03-01

Full Text Available This article describes an innovative way of finding the potentially druggable sites on a target protein, which can be used for orthosteric and allosteric lead detection in a single virtual screening setup. Druggability estimation for an alternate binding site other than the canonical ligand-binding pocket of an enzyme is rewarding for several inherent benefits. Allostery is a direct and efficient way of regulating biomacromolecule function. The allosteric modulators can fine-tune protein mechanics. Besides, allosteric sites are evolutionarily less conserved/more diverse even in very similarly related proteins, thus, provides high degree of specificity in targeting a particular protein. Therefore, targeting of allosteric sites is gaining attention as an emerging strategy in rational drug design. However, the experimental approaches provide a limited degree of characterization of new allosteric sites. Computational approaches are useful to analyze and select potential allosteric sites for drug discovery. Here, the use of molecular docking, which has become an integral part of the drug discovery process, has been discussed to predict the druggability of novel allosteric sites as well as the active site on target proteins by ligand screening. Genetic algorithm was used for docking and the whole protein was placed in the search space. For each ligand in the library of small molecules, the genetic algorithm was run for multiple times to populate all the druggable sites in the target protein, which was then translated into two dimensional density maps or “patterns”. High density clusters were observed for lead like molecules in these pattern diagrams. Each cluster in such a pattern diagram indicated a plausible binding site and the density gave its druggability score in terms of weighted probabilities. The patterns were filtered to find the leads for each of the druggable sites on the target protein. Such a novel pattern based analysis of the

Covalent binding of benzo(a)pyrene-diol-epoxide to histone H2A in rat liver nuclei: target site specificity

International Nuclear Information System (INIS)

Kurokawa, M.; MacLeod, M.C.

1986-01-01

The authors have recently found that 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE-I), a strong carcinogen, binds selectively to histone H2A-2 variant in rat liver nuclei, using a high performance liquid chromatography (HPLC) system which can separate H4, H2B, 3 different fractions of H2A variants and 3 different H3 variants in an hour. Here the authors examined the binding site of BPDE-I to the H2A-2 variant. The H2A-2 variants were purified from the acid extracted core histones of rat liver nuclei treated with ( 3 H)-BPDE-I by the HPLC system with a semi-preparative Aquapore RP-300 column. HPLC analysis of cyanogen bromide treated-H2A-2, which has one methionine residue, showed that the binding site is located in C-terminal half of H2A-2. In addition, digestions with V8-protease, trypsin and different types of carboxypeptides suggested that there are some target amino acid residues for BPDE-I in the V8-proteolytic C-terminal octapeptide which contains 2 histadine and 3 lysine residues. Currently identification of the target amino acid is proceeding, using amino acid-BPDE adducts prepared in vitro

ParticipACTION: A mass media campaign targeting parents of inactive children; knowledge, saliency, and trialing behaviours

Directory of Open Access Journals (Sweden)

Gauvin Lise

2009-12-01

Full Text Available Abstract Background In late 2007, Canada's ParticipACTION national physical activity mass media campaign was re-launched, with an initial campaign targeting parents of elementary school-aged children. The campaign informed them about the risks of physical inactivity for children and youth. The purpose of this study was to assess campaign awareness and understanding following the campaign, and to identify whether exposure to this campaign was likely associated with behaviour change. Methods A convenience sample of 1,500 adults was recruited though an existing panel (n = 60,000 of Canadian adults to participate in online surveys. Initial campaign exposure included "prompted" and "unprompted" recall of specific physical activity messages from the 2007 ParticipACTION campaign, knowledge of the benefits of PA, saliency, and initial trial behaviours to help their children become more active. Results One quarter of respondents showed unprompted recall of specific message content from the ParticipACTION campaign, and prompted recall was 57%. Message recall and understanding was associated with knowledge about physical activity, and that in turn was related to high saliency. Saliency was associated with each of the physical activity-related trial behaviours asked. Conclusion Campaign awareness and understanding was high following this ParticipACTION campaign, and was associated with intermediate campaign outcomes, including saliency and trial behaviours. This is relevant to campaign evaluations, as it suggests that an initial focus on influencing awareness and understanding is likely to lead to more substantial change in campaign endpoints.

Targeted modulation of reactive oxygen species in the vascular endothelium.

Science.gov (United States)

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins

Directory of Open Access Journals (Sweden)

Selbig Joachim

2009-04-01

Full Text Available Abstract Background Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites. Results We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D structural information available in the protein data bank (PDB and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information. Conclusion While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as

Polymeric micelles as a drug carrier for tumor targeting

Directory of Open Access Journals (Sweden)

Neha M Dand

2013-01-01

Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

Children's (Pediatric) CT (Computed Tomography)

Medline Plus

Full Text Available ... News Physician Resources Professions Site Index A-Z Children's (Pediatric) CT (Computed Tomography) Pediatric computed tomography (CT) ... are the limitations of Children's CT? What is Children's CT? Computed tomography, more commonly known as a ...

Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

Science.gov (United States)

Checkley, William; Deza, Maria P; Klawitter, Jost; Romero, Karina M; Klawitter, Jelena; Pollard, Suzanne L; Wise, Robert A; Christians, Uwe; Hansel, Nadia N

2016-12-01

The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p  13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of non-target-site-resistance on herbicidal activity of imazamox on blackgrass (Alopecurus myosuroides Huds. in comparison to other ALS-graminicides

Directory of Open Access Journals (Sweden)

Sievernich, Bernd

2014-02-01

Full Text Available A black-grass (Alopecurus myosuroides Huds. resistance-monitoring conducted by BASF in 2010 - 2012 revealed a high number of accessions with resistance against imazamox. However, application of imazamoxbased products in a winter crop was limited to winter beans in France and United Kingdom only until the introduction of the Clearfield®-production system in autumn 2012 in winter oilseed rape. It is therefore assumed that the resistance mechanisms were probably selected by the frequent use of ACCase- and ALSinhibitors in winter crop rotations during the last 2 decades. Resistance level for each product-biotype combination was calculated according the “R”-classification system (S, R?, RR, RRR by directly comparing the product performance on a biotype versus untreated control. Majority of resistant biotypes did not show a target-site mutation at the known codon Pro197 or Trp574. In order to better evaluate the impact of Non-Target-Site-Resistance (NTSR on the activity of BEYOND (imazamox, ATLANTIS WG (mesosulfuron+iodosulfuron and ABAK (pyroxsulam, biotypes who have shown an ALS-target-site mutation were removed from further analysis. At the dose rate of 35 g ai/ha BEYOND provided good activity on susceptible biotypes of black-grass almost matching up with ATLANTIS WG and ABAK. However, activity of BEYOND declined stronger on biotypes classified as R? or RR for that product, while ATLANTIS WG and ABAK hardly showed any decline in control on this group of biotypes when applied at the recommended dose rate. It is assumed that the underlying NTSR-mechanism is not effective enough yet to confer resistance to ATLANTIS WG and ABAK, but on BEYOND. In contrast, biotypes classified as R? for ATLANTIS WG did show a stronger impact on the activity of BEYOND and ABAK then of ATLANTIS WG. These differences in control level probably do translate into differences in selection pressure as well.

Target Site Recognition by a Diversity-Generating Retroelement

OpenAIRE

Guo, Huatao; Tse, Longping V.; Nieh, Angela W.; Czornyj, Elizabeth; Williams, Steven; Oukil, Sabrina; Liu, Vincent B.; Miller, Jeff F.

2011-01-01

Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype...

Children's (Pediatric) CT (Computed Tomography)

Medline Plus

Full Text Available ... Site Index A-Z Children's (Pediatric) CT (Computed Tomography) Pediatric computed tomography (CT) is a fast, painless exam that uses ... of Children's CT? What is Children's CT? Computed tomography, more commonly known as a CT or CAT ...

Site description of Forsmark at completion of the site investigation phase. SDM-Site Forsmark

Energy Technology Data Exchange (ETDEWEB)

2008-12-15

north-western part of the candidate area lacks hydraulically conductive, gently dipping fracture zones at potential repository depth and was selected as the target area for the complete site investigation work, following the initial investigations at the site. Prior to the presentation of the SDM-Site report, three versions of a site descriptive model have been completed for the Forsmark area and presented for peer review. The last version, referred to as version 1.2, was a preliminary site description that concluded the initial site investigation work and was presented in 2005. This preliminary site description formed the basis for a preliminary safety evaluation (PSE) of the Forsmark area, a preliminary repository layout (step D1), and the first evaluation of the long-term safety of this layout for KBS-3 repositories in the context of the SR-Can project. The final site descriptive model, SDM-Site, builds on a coordinated geological model in 3D, into which other discipline-specific models have been integrated without any major conflicting interpretations. In particular, the thermal properties of the bedrock at the site have been coupled to identified rock domains in the geological model and an integrated model that links the current stress regime, the hydrogeology and the chemistry of the groundwater to fracture domains and fracture zones in the geological model has evolved. These mutually consistent results demonstrate that a fundamental understanding of the current state of conditions and the on-going processes in the Forsmark area, from the surface down to potential repository depth, has been achieved. In addition, the properties of the area can be explained in the context of an understanding of the past evolution, throughout a long period of geological history. This integrated understanding of the area is presented in chapter 11 of this report and this chapter serves as an executive summary. A systematic assessment of the confidence in the model, including

Site description of Forsmark at completion of the site investigation phase. SDM-Site Forsmark

International Nuclear Information System (INIS)

2008-12-01

north-western part of the candidate area lacks hydraulically conductive, gently dipping fracture zones at potential repository depth and was selected as the target area for the complete site investigation work, following the initial investigations at the site. Prior to the presentation of the SDM-Site report, three versions of a site descriptive model have been completed for the Forsmark area and presented for peer review. The last version, referred to as version 1.2, was a preliminary site description that concluded the initial site investigation work and was presented in 2005. This preliminary site description formed the basis for a preliminary safety evaluation (PSE) of the Forsmark area, a preliminary repository layout (step D1), and the first evaluation of the long-term safety of this layout for KBS-3 repositories in the context of the SR-Can project. The final site descriptive model, SDM-Site, builds on a coordinated geological model in 3D, into which other discipline-specific models have been integrated without any major conflicting interpretations. In particular, the thermal properties of the bedrock at the site have been coupled to identified rock domains in the geological model and an integrated model that links the current stress regime, the hydrogeology and the chemistry of the groundwater to fracture domains and fracture zones in the geological model has evolved. These mutually consistent results demonstrate that a fundamental understanding of the current state of conditions and the on-going processes in the Forsmark area, from the surface down to potential repository depth, has been achieved. In addition, the properties of the area can be explained in the context of an understanding of the past evolution, throughout a long period of geological history. This integrated understanding of the area is presented in chapter 11 of this report and this chapter serves as an executive summary. A systematic assessment of the confidence in the model, including

DeepMirTar: a deep-learning approach for predicting human miRNA targets.

Science.gov (United States)

Wen, Ming; Cong, Peisheng; Zhang, Zhimin; Lu, Hongmei; Li, Tonghua

2018-06-01

MicroRNAs (miRNAs) are small noncoding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression by targeting messenger RNAs (mRNAs). Because the underlying mechanisms associated with miRNA binding to mRNA are not fully understood, a major challenge of miRNA studies involves the identification of miRNA-target sites on mRNA. In silico prediction of miRNA-target sites can expedite costly and time-consuming experimental work by providing the most promising miRNA-target-site candidates. In this study, we reported the design and implementation of DeepMirTar, a deep-learning-based approach for accurately predicting human miRNA targets at the site level. The predicted miRNA-target sites are those having canonical or non-canonical seed, and features, including high-level expert-designed, low-level expert-designed, and raw-data-level, were used to represent the miRNA-target site. Comparison with other state-of-the-art machine-learning methods and existing miRNA-target-prediction tools indicated that DeepMirTar improved overall predictive performance. DeepMirTar is freely available at https://github.com/Bjoux2/DeepMirTar_SdA. lith@tongji.edu.cn, hongmeilu@csu.edu.cn. Supplementary data are available at Bioinformatics online.

SCIENTIFIC RATIONALE FOR TARGETED VITAMIN A SUPPLEMENTATION TO CHILDREN IN INDIA

Directory of Open Access Journals (Sweden)

Umesh Kapil

2011-06-01

Full Text Available In India, presently Vitamin A deficiency (VAD is common amongst young children belonging to the underprivileged populations. The risk of deficiency is greatest   in children under three years   because their requirements are relatively higher and dietary intake is low.  Also, these have higher risk   of illnesses such as diarrhea, acute respiratory tract infection and measles, which deplete vitamin A reserves.   In India, Severe deficiency of VA with corneal involvement was an important cause of nutritional blindness in   sixties and early seventies children amongst children belonging to poor communities however presently, this is an extremely rare disease.

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.

Science.gov (United States)

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank

2016-07-22

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets.

Geographic spread, genetics and functional characteristics of ryanodine receptor based target-site resistance to diamide insecticides in diamondback moth, Plutella xylostella.

Science.gov (United States)

Steinbach, Denise; Gutbrod, Oliver; Lümmen, Peter; Matthiesen, Svend; Schorn, Corinna; Nauen, Ralf

2015-08-01

Anthranilic diamides and flubendiamide belong to a new chemical class of insecticides acting as conformation sensitive activators of the insect ryanodine receptor (RyR). These compounds control a diverse range of different herbivorous insects including diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae), a notorious global pest on cruciferous crops, which recently developed resistance due to target-site mutations located in the trans-membrane domain of the Plutella RyR. In the present study we further investigated the genetics and functional implications of a RyR G4946E target-site mutation we recently identified in a Philippine diamondback moth strain (Sudlon). Strain Sudlon is homozygous for the G4946E mutation and has been maintained under laboratory conditions without selection pressure for almost four years, and still exhibit stable resistance ratios of >2000-fold to all commercial diamides. Its F1 progeny resulting from reciprocal crosses with a susceptible strain (BCS-S) revealed no maternal effects and a diamide susceptible phenotype, suggesting an autosomally almost recessive mode of inheritance. Subsequent back-crosses indicate a near monogenic nature of the diamide resistance in strain Sudlon. Radioligand binding studies with Plutella thoracic microsomal membrane preparations provided direct evidence for the dramatic functional implications of the RyR G4946E mutation on both diamide specific binding and its concentration dependent modulation of [(3)H]ryanodine binding. Computational modelling based on a cryo-EM structure of rabbit RyR1 suggests that Plutella G4946E is located in trans-membrane helix S4 close to S4-S5 linker domain supposed to be involved in the modulation of the voltage sensor, and another recently described mutation, I4790M in helix S2 approx. 13 Å opposite of G4946E. Genotyping by pyrosequencing revealed the presence of the RyR G4946E mutation in larvae collected in 2013/14 in regions of ten different countries where

Development of behavioral parameters and ERPs in a novel-target visual detection paradigm in children, adolescents and young adults.

Science.gov (United States)

Rojas-Benjumea, María Ángeles; Sauqué-Poggio, Ana María; Barriga-Paulino, Catarina I; Rodríguez-Martínez, Elena I; Gómez, Carlos M

2015-07-04

The present study analyzes the development of ERPs related to the process of selecting targets based on their novelty. One hundred and sixty-seven subjects from 6 to 26 years old were recorded with 30 electrodes during a visual target novelty paradigm. Behavioral results showed good performance in children that improved with age: a decrease in RTs and errors and an increase in the d' sensitivity parameter with age were obtained. In addition, the C response bias parameter evolved from a conservative to a neutral bias with age. Fronto-polar Selection Positivity (FSP) was statistically significant in all the age groups when standards and targets were compared. There was a statistically significant difference in the posterior Selection Negativity (SN) between the target and standard conditions in all age groups. The P3a component obtained was statistically significant in the emergent adult (18-21 years) and young adult (22-26 years) groups. The modulation of the P3b component by novel targets was statistically significant in all the age groups, but it decreased in amplitude with age. Peak latencies of the FSP and P3b components decreased with age. The results reveal differences in the ERP indexes for the cognitive evaluation of the stimuli presented, depending on the age of the subjects. The ability of the target condition to induce the modulation of the studied components would depend on the posterior-anterior gradient of cortex maturation and on the gradient of maturation of the low to higher order association areas.

CERCLA site assessment workbook

International Nuclear Information System (INIS)

1994-08-01

This contains comments for each chapter of exercises (in Vol. 1) which illustrate how to conduct site assessments for CERCLA regulation. A through analysis of the exercises is provided so that work and solutions from Vol 1 can be critiqued and comments are also included on the strategy of site assessment whereas the exercises illustrate the principles involved. Covered exercises include the following: A preliminary assessment of a ground water site; waste characteristics and characterization of sources; documentation of observed releases and actual contamination of targets; the strategy of an SI at a surface water site; the soil exposure pathway; the air pathway

Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

Science.gov (United States)

Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

2016-03-01

Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

Attachment Narratives in Refugee Children

DEFF Research Database (Denmark)

De Haene, L.; Dalgård, Nina Thorup; Montgomery, E.

2013-01-01

J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study.......J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study....

EFFECTIVNESS OF TARGET ANTIMICROBIAL THERAPY OF SEVERE CHRONIC PERIODONTITIS PART I: REDUCTION OF GINGIVAL INFLAMATION AND ACTIVE PERIODONTAL DISEASE SITES

Directory of Open Access Journals (Sweden)

Kamen Kotsilkov

2010-10-01

Full Text Available The correlation between recurrent bleeding on probing and the progression of periodontal destruction is suggested in many studies. One of the main goals of the periodontal treatment is the achievement of good control of the gingival inflammation and the reduction of the active periodontal sites.Aim: Evaluation of the effectiveness of treatment of severe chronic periodontitis with additional target antibiotic administration in comparison with the therapy with adjunctive antimicrobial combination amoxicillin + metronidazole and conventional mechanical periodontal treatment regarding the achieved control of the gingival inflammation and BoP.Results: Significant reduction of the gingival bleeding and the BoP is achieved in all groups. In the group with target antibiotic administration the final mean values of the GB (gingival bleeding and BoP (bleeding on probing are the lowest and could suggest a low risk for progression of the periodontal disease.

Effect of a trunk-targeted intervention using vibration on posture and gait in children with spastic type cerebral palsy: a randomized control trial.

Science.gov (United States)

Unger, Marianne; Jelsma, Jennifer; Stark, Christina

2013-01-01

This study aimed to determine whether strengthening trunk muscles using vibration can improve posture and gait in children with spastic-type cerebral palsy (STCP). A total of 27 children (6-13 years) participated in a single-blinded pre-post crossover experimental trial. The 1-Minute Walk Test, 2D-posturography, ultrasound imaging and sit-ups in one minute were used to assess effect on gait, posture, resting abdominal muscle thickness and functional strength. Significant increase in distance walked (p posture, an increase in sit-ups executed (p posture were maintained at 4-weeks post-intervention. A trunk-targeted intervention using vibration can improve posture and gait in children with STCP without any known side effects. It is recommended that vibration and specific trunk strengthening is included in training or rehabilitation programmes. Effects of vibration on force generation and spasticity need further investigation.

Connectome hubs at resting state in children and adolescents: Reproducibility and psychopathological correlation

Directory of Open Access Journals (Sweden)

João Ricardo Sato

2016-08-01

Full Text Available Functional brain hubs are key integrative regions in brain networks. Recently, brain hubs identified through resting-state fMRI have emerged as interesting targets to increase understanding of the relationships between large-scale functional networks and psychopathology. However, few studies have directly addressed the replicability and consistency of the hub regions identified and their association with symptoms. Here, we used the eigenvector centrality (EVC measure obtained from graph analysis of two large, independent population-based samples of children and adolescents (7–15 years old; total N = 652; 341 subjects for site 1 and 311 for site 2 to evaluate the replicability of hub identification. Subsequently, we tested the association between replicable hub regions and psychiatric symptoms. We identified a set of hubs consisting of the anterior medial prefrontal cortex and inferior parietal lobule/intraparietal sulcus (IPL/IPS. Moreover, lower EVC values in the right IPS were associated with psychiatric symptoms in both samples. Thus, low centrality of the IPS was a replicable sign of potential vulnerability to mental disorders in children. The identification of critical and replicable hubs in functional cortical networks in children and adolescents can foster understanding of the mechanisms underlying mental disorders.

Site observational work plan for the UMTRA Project site at Falls City, Texas

International Nuclear Information System (INIS)

1995-06-01

Produced by the US Department of Energy (DOE), this site observational work plan (SOWP) will be used to determine site-specific activities to comply with the US Environmental Protection Agency (EPA) ground water standards at this Uranium Mill Tailings Remedial Action (UMTRA) Project site. The purpose of the SOWP is to recommend a site-specific ground water compliance strategy at the Falls City UMTRA Project site. The Falls City SOWP presents a comprehensive summary of site hydrogeological data, delineates a conceptual model of the aquifer system, and discusses the origins of milling-related ground water contamination. It also defines the magnitude of ground water contamination, potential environmental and health risks associated with ground water contamination and data gaps, and targets a proposed compliance strategy

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

Directory of Open Access Journals (Sweden)

Kyle C Wilcox

Full Text Available Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs. AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs. This method gives a soluble membrane protein library (SMPL--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

Science.gov (United States)

Wilcox, Kyle C; Marunde, Matthew R; Das, Aditi; Velasco, Pauline T; Kuhns, Benjamin D; Marty, Michael T; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G; Klein, William L

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug discovery

Bullying involvement and empathy: Child and target characteristics

NARCIS (Netherlands)

Noorden, T.H.J. van; Cillessen, A.H.N.; Haselager, G.J.T.; Lansu, T.A.M.; Bukowski, W.M.

2017-01-01

This study investigated how the bullying involvement of a child and a target peer are related to empathy. The role of gender was also considered. We hypothesized that empathy primarily varies depending on the bullying role of the target peer. Participants were 264 7-12-year-old children

Allegheny County Summer Food Sites

Data.gov (United States)

Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This data set shows the Summer Food Sites located within Allegheny County for children (18 years and younger) for breakfast and lunch during summer recess. OPEN...

FLP recombinase-mediated site-specific recombination in silkworm, Bombyx mori.

Directory of Open Access Journals (Sweden)

Ding-Pei Long

Full Text Available A comprehensive understanding of gene function and the production of site-specific genetically modified mutants are two major goals of genetic engineering in the post-genomic era. Although site-specific recombination systems have been powerful tools for genome manipulation of many organisms, they have not yet been established for use in the manipulation of the silkworm Bombyx mori genome. In this study, we achieved site-specific excision of a target gene at predefined chromosomal sites in the silkworm using a FLP/FRT site-specific recombination system. We first constructed two stable transgenic target silkworm strains that both contain a single copy of the transgene construct comprising a target gene expression cassette flanked by FRT sites. Using pre-blastoderm microinjection of a FLP recombinase helper expression vector, 32 G3 site-specific recombinant transgenic individuals were isolated from five of 143 broods. The average frequency of FLP recombinase-mediated site-specific excision in the two target strains genome was approximately 3.5%. This study shows that it is feasible to achieve site-specific recombination in silkworms using the FLP/FRT system. We conclude that the FLP/FRT system is a useful tool for genome manipulation in the silkworm. Furthermore, this is the first reported use of the FLP/FRT system for the genetic manipulation of a lepidopteran genome and thus provides a useful reference for the establishment of genome manipulation technologies in other lepidopteran species.

Discovering the 'Magic' of Target Marketing.

Science.gov (United States)

Grier, Linda J.; Ackenbom, Charles R.

1988-01-01

Describes target marketing of children's summer camps, emphasizing the benefits of collaborative advertising campaigns. Discusses the scope and economics of four model campaigns. Outlines the design, implementation, and evaluation of collaborative marketing projects. (SV)

Establishing Contextual Control over Symmetry and Asymmetry Performances in Typically Developing Children and Children with Autism

Science.gov (United States)

O'Connor, Jennifer; Barnes-Holmes, Yvonne; Barnes-Holmes, Dermot

2011-01-01

Experiments 1, 2, and 3 investigated generalized contextually controlled symmetry and asymmetry in typically developing children and children with autism. In Experiment 1, eight typically developing children demonstrated the target performances without intervention. In Experiment 2, multiple-exemplar training and the use of familiar stimuli…

Wild rodents (Dipodomys merriami) used as biomonitors in contaminated mining sites.

Science.gov (United States)

Espinosa-Reyes, Guillermo; Torres-Dosal, Arturo; Ilizaliturri, Cesar; Gonzalez-Mille, Donaji; Diaz-Barriga, Fernando; Mejia-Saavedra, Jesus

2010-01-01

Mining is one of the most important industrial activities globally; however, mining processes have critical environmental impacts, as mining is a major source of metals and metalloids that contribute significantly to the pollution of soil, sediment, water and air. Heavy metals can impact the health of exposed human populations and nonhuman receptors. This study focused on arsenic because its genotoxicity is well-known. Previously, we proposed a methodology to evaluate and integrate risk from a single source affecting different biologic receptors. Here, we propose an alternative approach estimating arsenic exposure in children and kangaroo rats using probabilistic simulation with Monte Carlo modeling. The estimates are then associated to measured DNA damage and compared to both populations of children and rodents living in contaminated and in reference areas. Finally, based on the integrated analysis of the generated information, we evaluate the potential use of wild rodents (Dipodomys merriami) as a biomonitor at mining sites. Results indicate that the variation of genotoxicity in children of the reference site is approximately 2 units when compared to the children of the contaminated site. In the rodents we observed a variation of approximately 4 units between those of the reference site when compared to those living on the contaminated site. We propose that D. merriami can be used as a biomonitor organism in sites with mining activity, and that a non-lethal test can be used to evaluate risk from metal exposure.

Throat swabs in children with respiratory tract infection: associations with clinical presentation and potential targets for point-of-care testing.

Science.gov (United States)

Thornton, Hannah V; Hay, Alastair D; Redmond, Niamh M; Turnbull, Sophie L; Christensen, Hannah; Peters, Tim J; Leeming, John P; Lovering, Andrew; Vipond, Barry; Muir, Peter; Blair, Peter S

2017-08-01

Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Cross-sectional study of children ≥3 months to presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52-0.56)] or ≥1 virus [0.64 (95% CI 0.61-0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation [AUROC 0.80 (0.77-0.84)]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial. © The Author 2017. Published by Oxford University Press.

Participative Teaching with Mobile Devices and Social Networks for K-12 Children

Directory of Open Access Journals (Sweden)

Livia Stefan

2016-08-01

Full Text Available This article details a set of participatory pedagogical experiments conducted within a research grant PN II IDEI (”Time Maps. Real communities, virtual worlds, experimented pasts” performed with the purpose of helping rural communities in identifying their cultural heritage andtransmitting it to the younger generations by means of modern IT technologies, including web 2.0. In a Danubian rural community, several points of archaeological interest (POIs were identified, which were then included in a geographic Augmented Reality application for smartphones and tablets. Subsequently, the geographic data were collected from the archaeological site by the K-12 children, under the coordination of an academic staff member of the National University of Arts in Bucharest, and stored on their devices using Google Maps. The augmented information provided onthe site was annotated and shared with other K-12 children, through different social networks sites (SNS and content postings. This first stage experiment was extended to the development of a social learning environment complementary to the educational site (www.timemaps.net to support thetransmission of several traditional technologies (textile, ceramic, glass in a collaborative manner. We consider that our experiments can significantly increase the visibility of the information pertaining to the identity of target places and communities among the younger generation. A mobile-learning paradigm, in combination with web 2.0 technologies, was the support for a distributed and low-cost platform for communication and collaboration. Social networks linked thearchaeological heritage and the academic research with the larger community of rural K-12 children. The article analyzes this platform as a solution for creating, collecting and sharingeducational content, and presents conclusions on using social media for effective blended learning and transmittal of the cultural heritage.

Impaired Visual Attention in Children with Dyslexia.

Science.gov (United States)

Heiervang, Einar; Hugdahl, Kenneth

2003-01-01

A cue-target visual attention task was administered to 25 children (ages 10-12) with dyslexia. Results showed a general pattern of slower responses in the children with dyslexia compared to controls. Subjects also had longer reaction times in the short and long cue-target interval conditions (covert and overt shift of attention). (Contains…

Increasing the Structural Coverage of Tuberculosis Drug Targets

Science.gov (United States)

Baugh, Loren; Phan, Isabelle; Begley, Darren W.; Clifton, Matthew C.; Armour, Brianna; Dranow, David M.; Taylor, Brandy M.; Muruthi, Marvin M.; Abendroth, Jan; Fairman, James W.; Fox, David; Dieterich, Shellie H.; Staker, Bart L.; Gardberg, Anna S.; Choi, Ryan; Hewitt, Stephen N.; Napuli, Alberto J.; Myers, Janette; Barrett, Lynn K.; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W.; Stacy, Robin; Stewart, Lance J.; Edwards, Thomas E.; Van Voorhis, Wesley C.; Myler, Peter J.

2015-01-01

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD 85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. PMID:25613812

Children's media culture in the new millennium: mapping the digital landscape.

Science.gov (United States)

Montgomery, K C

2000-01-01

A new "children's digital media culture" is swiftly moving into place on the Internet. In this article, the author describes the technological, demographic, and market forces shaping this new digital media culture and the rich array of Web sites being created for children and teens. Many nonprofit organizations, museums, educational institutions, and government agencies are playing a significant role in developing online content for children, offering them opportunities to explore the world, form communities with other children, and create their own works of art and literature. For the most part, however, the heavily promoted commercial sites, sponsored mainly by media conglomerates and toy companies, are overshadowing the educational sites. Because of the unique interactive features of the Internet, companies are able to integrate advertising and Web site content to promote "brand awareness" and "brand loyalty" among children, encouraging them to become consumers beginning at a very early age. The possibility that a child's exploration on the Internet might lead to inappropriate content, aggressive advertising, or even dangerous contact with strangers has given rise to a number of efforts to create "safe zones" for children--that is, places in cyberspace where children can be protected from both marketers and predators. Federal legislation now requires parental permission before commercial Web sites can collect personal information from children under age 13. Several companies offer filtering, blocking, and monitoring software to safeguard children from harmful content or predators. Generally lacking in debates concerning children's use of the Internet, however, is a more proactive definition of quality--one that would help ensure the creation and maintenance of Web sites that enhance children's learning and development and not merely keep them from harm. In the concluding section of this article, the author recommends actions to promote development of a quality

Combinatorial microRNA target predictions

DEFF Research Database (Denmark)

Krek, Azra; Grün, Dominic; Poy, Matthew N.

2005-01-01

MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed...... in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published micro......RNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results...

[Application of single nucleotide polymorphism-microarray and target gene sequencing in the study of genetic etiology of children with unexplained intellectual disability or developmental delay].

Science.gov (United States)

Gao, Z J; Jiang, Q; Cheng, D Z; Yan, X X; Chen, Q; Xu, K M

2016-10-02

Objective: To evaluate the application of single nucleotide polymorphism (SNP)-microarray and target gene sequencing technology in the clinical molecular genetic diagnosis of unexplained intellectual disability(ID) or developmental delay (DD). Method: Patients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and February 2016. The intellectual assessment of the patients was performed using 0-6-year-old pediatric examination table of neuropsychological development or Wechsler intelligence scale (>6 years). Patients with a DQ less than 49 or IQ less than 51 were included in this study. The patients were scanned by SNP-array for detection of genomic copy number variations (CNV), and the revealed genomic imbalance was confirmed by quantitative real time-PCR. Candidate gene mutation screening was carried out by target gene sequencing technology.Causal mutations or likely pathogenic variants were verified by polymerase chain reaction and direct sequencing. Result: There were 15 children with ID or DD enrolled, 9 males and 6 females. The age of these patients was 7 months-16 years and 9 months. SNP-array revealed that two of the 15 patients had genomic CNV. Both CNV were de novo micro deletions, one involved 11q24.1q25 and the other micro deletion located on 21q22.2q22.3. Both micro deletions were proved to have a clinical significance due to their association with ID, brain DD, unusual faces etc. by querying Decipher database. Thirteen patients with negative findings in SNP-array were consequently examined with target gene sequencing technology, genotype-phenotype correlation analysis and genetic analysis. Five patients were diagnosed with monogenic disorder, two were diagnosed with suspected genetic disorder and six were still negative. Conclusion: Sequential use of SNP-array and target gene sequencing technology can significantly increase the molecular genetic etiologic

Hierarchical effects on target detection and conflict monitoring

Science.gov (United States)

Cao, Bihua; Gao, Feng; Ren, Maofang; Li, Fuhong

2016-01-01

Previous neuroimaging studies have demonstrated a hierarchical functional structure of the frontal cortices of the human brain, but the temporal course and the electrophysiological signature of the hierarchical representation remains unaddressed. In the present study, twenty-one volunteers were asked to perform a nested cue-target task, while their scalp potentials were recorded. The results showed that: (1) in comparison with the lower-level hierarchical targets, the higher-level targets elicited a larger N2 component (220–350 ms) at the frontal sites, and a smaller P3 component (350–500 ms) across the frontal and parietal sites; (2) conflict-related negativity (non-target minus target) was greater for the lower-level hierarchy than the higher-level, reflecting a more intensive process of conflict monitoring at the final step of target detection. These results imply that decision making, context updating, and conflict monitoring differ among different hierarchical levels of abstraction. PMID:27561989

Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs

Science.gov (United States)

Schnall-Levin, Michael; Rissland, Olivia S.; Johnston, Wendy K.; Perrimon, Norbert; Bartel, David P.; Berger, Bonnie

2011-01-01

MicroRNAs (miRNAs) regulate numerous biological processes by base-pairing with target messenger RNAs (mRNAs), primarily through sites in 3′ untranslated regions (UTRs), to direct the repression of these targets. Although miRNAs have sometimes been observed to target genes through sites in open reading frames (ORFs), large-scale studies have shown such targeting to be generally less effective than 3′ UTR targeting. Here, we show that several miRNAs each target significant groups of genes through multiple sites within their coding regions. This ORF targeting, which mediates both predictable and effective repression, arises from highly repeated sequences containing miRNA target sites. We show that such sequence repeats largely arise through evolutionary duplications and occur particularly frequently within families of paralogous C2H2 zinc-finger genes, suggesting the potential for their coordinated regulation. Examples of ORFs targeted by miR-181 include both the well-known tumor suppressor RB1 and RBAK, encoding a C2H2 zinc-finger protein and transcriptional binding partner of RB1. Our results indicate a function for repeat-rich coding sequences in mediating post-transcriptional regulation and reveal circumstances in which miRNA-mediated repression through ORF sites can be reliably predicted. PMID:21685129

Non-target-site resistance to ALS-inhibiting herbicides in a Sagittaria trifolia L. population.

Science.gov (United States)

Zhao, Bochui; Fu, Danni; Yu, Yang; Huang, Chengtian; Yan, Kecheng; Li, Pingsheng; Shafi, Jamil; Zhu, He; Wei, Songhong; Ji, Mingshan

2017-08-01

Sagittaria trifolia L. is one of the most competitive weeds in rice fields in northeastern China. The continuous use of acetolactate synthase (ALS)-inhibitors has led to the evolution of herbicide resistant S. trifolia. A subpopulation BC1, which was derived from the L1 population, was analyzed using DNA sequencing and ALS enzyme activity assays and levels of resistance to five ALS-inhibiting herbicides was determined. DNA sequencing and ALS enzyme assays revealed no amino acid substitutions and no significant differences in enzyme sensitivity between susceptible and resistant populations. Whole-plant dose-response experiments showed that the BC1 population exhibited different levels of resistance (resistance ratios ranging from 2.14 to 51.53) to five ALS herbicides, and the addition of malathion (P450 inhibitor) to bensulfuron-methyl, penoxsulam and bispyribac-sodium strongly reduced the dry weight accumulation of the BC1 population compared with the effects of the three herbicides alone. The results of the present study demonstrated that the BC1 population has evolved non-target-site resistance to ALS-inhibiting herbicides. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of preschool education in mixed and targeted classrooms

NARCIS (Netherlands)

de Haan, A.K.E.

2015-01-01

One of the remaining questions in the field of early childhood education is whether efforts aiming to promote the school readiness skills of young learners should be targeted specifically at children at risk for delays in these basic skills or whether efforts should be aimed at all young children

Melanocytic Nevi and Sun Exposure in a Cohort of Colorado Children: Anatomic Distribution and Site-Specific Sunburn

Science.gov (United States)

Dodd, Athena T.; Morelli, Joseph; Mokrohisky, Stefan T.; Asdigian, Nancy; Byers, Tim E.; Crane, Lori A.

2010-01-01

Sun exposure and high prevalence of melanocytic nevi are major risk factors for melanoma, but the relationship between them is not well understood. This study examines the relationship between sun exposure (detailed by anatomic location and history of site-specific sunburns) and the presence of melanocytic nevi on 743 White children in Denver, Colorado. Parental reports of site-specific sunburns were collected annually for 2 years starting at ages 5 to 6 years. In the third year, nevi were counted and mapped by anatomic location. Nevus density was higher for boys (36.0 nevi/m2) than for girls (31.0 nevi/m2; P = 0.04). Nevus density was highest on the face, neck, and lateral forearms and was significantly higher in chronically versus intermittently sun-exposed areas (P sunburn. The face, shoulders, and back were the most frequently sunburned areas of the body. When adjusted for host factors, total number of sunburns was significantly associated with higher total nevus prevalence (P = 0.01 for one burn). Site-specific sunburns were significantly associated with nevus prevalence on the back (P = 0.03 for three or more sunburns), but not on the face, arms, or legs. In this high-risk population, there is evidence for two pathways to nevus accumulation: by chronic sun exposure and by intermittent exposure related to sunburns. PMID:17932362

Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.

Science.gov (United States)

Lee, Jangwook; Min, Hyun-Su; You, Dong Gil; Kim, Kwangmeyung; Kwon, Ick Chan; Rhim, Taiyoun; Lee, Kuen Yong

2016-02-10

The development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. Although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. We demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (US) imaging and treating neuroblastoma. We encapsulated calcium carbonate using poly(d,l-lactide-co-glycolide) and created gas-generating polymer nanoparticles (GNPs). These nanoparticles release carbon dioxide bubbles under acidic conditions and enhance US signals. When GNPs are modified using rabies virus glycoprotein (RVG) peptide, a targeting moiety to neuroblastoma, RVG-GNPs effectively accumulate at the tumor site and substantially enhance US signals in a tumor-bearing mouse model. Intravenous administration of RVG-GNPs also reduces tumor growth in the mouse model without the use of conventional therapeutic agents. This approach to developing theranostic agents with disease-targeting ability may provide useful strategy for the detection and treatment of cancers, allowing safe and efficient clinical applications with fewer side effects than may occur with conventional agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted marketing and public health.

Science.gov (United States)

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging

Directory of Open Access Journals (Sweden)

Shukui Zhao

2004-07-01

Full Text Available Ultrasonic molecular imaging employs contrast agents, such as microbubbles, nanoparticles, or liposomes, coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. In this article, we show that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. We provide a theoretical evaluation of the magnitude of acoustic radiation force and show that it is possible to displace micron-sized agents physiologically relevant distances. Following this, we show in a series of experiments that acoustic radiation force can enhance the binding of targeted agents: The number of biotinylated microbubbles adherent to a synthetic vessel coated with avidin increases as much as 20-fold when acoustic radiation force is applied; the adhesion of contrast agents targeted to αvβ3 expressed on human umbilical vein endothelial cells increases 27-fold within a mimetic vessel when radiation force is applied; and finally, the image signal-to-noise ratio in a phantom vessel increases up to 25 dB using a combination of radiation force and a targeted contrast agent, over use of a targeted contrast agent alone.

Quantum mechanical design of enzyme active sites.

Science.gov (United States)

Zhang, Xiyun; DeChancie, Jason; Gunaydin, Hakan; Chowdry, Arnab B; Clemente, Fernando R; Smith, Adam J T; Handel, T M; Houk, K N

2008-02-01

The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels-Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.

Targeting for energy efficiency and improved energy collaboration between different companies using total site analysis (TSA)

International Nuclear Information System (INIS)

Hackl, Roman; Andersson, Eva; Harvey, Simon

2011-01-01

Rising fuel prices, increasing costs associated with emissions of green house gases and the threat of global warming make efficient use of energy more and more important. Industrial clusters have the potential to significantly increase energy efficiency by energy collaboration. In this paper Sweden's largest chemical cluster is analysed using the total site analysis (TSA) method. TSA delivers targets for the amount of utility consumed and generated through excess energy recovery by the different processes. The method enables investigation of opportunities to deliver waste heat from one process to another using a common utility system. The cluster consists of 5 chemical companies producing a variety of products, including polyethylene (PE), polyvinyl chloride (PVC), amines, ethylene, oxygen/nitrogen and plasticisers. The companies already work together by exchanging material streams. In this study the potential for energy collaboration is analysed in order to reach an industrial symbiosis. The overall heating and cooling demands of the site are around 442 MW and 953 MW, respectively. 122 MW of heat is produced in boilers and delivered to the processes. TSA is used to stepwise design a site-wide utility system which improves energy efficiency. It is shown that heat recovery in the cluster can be increased by 129 MW, i.e. the current utility demand could be completely eliminated and further 7 MW excess steam can be made available. The proposed retrofitted utility system involves the introduction of a site-wide hot water circuit, increased recovery of low pressure steam and shifting of heating steam pressure to lower levels in a number heat exchangers when possible. Qualitative evaluation of the suggested measures shows that 60 MW of the savings potential could to be achieved with moderate changes to the process utility system corresponding to 50% of the heat produced from purchased fuel in the boilers of the cluster. Further analysis showed that after implementation

Canonical A-to-I and C-to-U RNA editing is enriched at 3'UTRs and microRNA target sites in multiple mouse tissues.

Directory of Open Access Journals (Sweden)

Tongjun Gu

Full Text Available RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3' UTRs, specifically at microRNA target sites, suggesting both regulatory and functional consequences for RNA editing.

Factors affecting computer mouse use for young children: implications for AAC.

Science.gov (United States)

Costigan, F Aileen; Light, Janice C; Newell, Karl M

2012-06-01

More than 12% of preschoolers receiving special education services have complex communication needs, including increasing numbers of children who do not have significant motor impairments (e.g., children with autism spectrum disorders, Down syndrome, etc.). In order to meet their diverse communication needs (e.g., face-to-face, written, Internet, telecommunication), these children may use mainstream technologies accessed via the mouse, yet little is known about factors that affect the mouse performance of young children. This study used a mixed factorial design to investigate the effects of age, target size, and angle of approach on accuracy and time required for accurate target selection with a mouse for 20 3-year-old and 20 4-year-old children. The 4-year-olds were generally more accurate and faster than the 3-year-olds. Target size and angle mediated differences in performance within age groups. The 3-year-olds were more accurate and faster in selecting the medium and large targets relative to the small target, were faster in selecting the large relative to the medium target, and were faster in selecting targets along the vertical relative to the diagonal angle. The 4-year-olds were faster in selecting the medium and large targets relative to the small target. Implications for improving access to AAC include the preliminary suggestion of age-related threshold target sizes that support sufficient accuracy, the possibility of efficiency benefits when target size is increased up to an age-related threshold, and identification of the potential utility of the vertical angle as a context for training navigational input device use.

Parenting practices were associated with children's TV viewing among overweight and obese children

Science.gov (United States)

An expert panel recommended that TV reduction should be a component in obesity treatment programs. Parents are an important social influence on children and could be a target for interventions. Valid measures of TV-parenting practices (PP) are needed to understand parental influences on children's T...

Lineup member similarity effects on children's eyewitness identification

OpenAIRE

Fitzgerald, Ryan J.; Whiting, Brittany F.; Therrien, Natalie M.; Price, Heather L.

2014-01-01

To date, research investigating the similarity among lineup members has focused on adult eyewitnesses. In the present research, children made identifications from lineups containing members of lower or higher similarity to a target person. In Experiment 1, following a live interaction, children's (6–14 years) correct identification rate was reduced in higher-similarity relative to lower-similarity lineups. In Experiment 2, children (6–12 years) and adults watched a video containing a target p...

Increasing the structural coverage of tuberculosis drug targets.

Science.gov (United States)

Baugh, Loren; Phan, Isabelle; Begley, Darren W; Clifton, Matthew C; Armour, Brianna; Dranow, David M; Taylor, Brandy M; Muruthi, Marvin M; Abendroth, Jan; Fairman, James W; Fox, David; Dieterich, Shellie H; Staker, Bart L; Gardberg, Anna S; Choi, Ryan; Hewitt, Stephen N; Napuli, Alberto J; Myers, Janette; Barrett, Lynn K; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W; Stacy, Robin; Stewart, Lance J; Edwards, Thomas E; Van Voorhis, Wesley C; Myler, Peter J

2015-03-01

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD 85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tracking the quality of care for sick children using lot quality assurance sampling: targeting improvements of health services in Jigawa, Nigeria.

Directory of Open Access Journals (Sweden)

Edward Adekola Oladele

Full Text Available BACKGROUND: In Nigeria, 30% of child deaths are due to malaria. The National Malaria Control Program of Nigeria (NMCP during 2009 initiated a program to improve the quality of paediatric malaria services delivered in health facilities (HF. This study reports a rapid approach used to assess the existing quality of services in Jigawa state at decentralised levels of the health system. METHODS: NMCP selected Lot Quality Assurance Sampling (LQAS to identify the variation in HF service quality among Senatorial Districts (SD. LQAS was selected because it was affordable and could be used by local health workers (HW in a population-based survey. NMCP applied a 2-stage LQAS using a structured Rapid Health Facility Assessment (R-HFA tool to identify high and low performing SD for specified indicators. FINDINGS: LQAS identified variations in HF performance (n = 21 and enabled resources to be targeted to address priorities. All SD exhibited deficient essential services, supplies and equipment. Only 9.7% of HF had Artemisinin-based Combination Therapies and other first-line treatments for childhood illnesses. No SD and few HF exhibited adequate HW performance for the assessment, treatment or counselling of sick children. Using the IMCI algorithm, 17.5% of HW assessed the child's vaccination status, 46.8% assessed nutritional status, and 65.1% assessed children for dehydration. Only 5.1% of HW treatments were appropriate for the assessment. Exit interviews revealed that 5.1% of caregivers knew their children's illness, and only 19.9% could accurately describe how to administer the prescribed drug. CONCLUSION: This R-HFA, using LQAS principles, is a rapid, simple tool for assessing malaria services and can be used at scale. It identified technical deficiencies that could be corrected by improved continuing medical education, targeted supervision, and recurrent R-HFA assessments of the quality of services.

Tracking the quality of care for sick children using lot quality assurance sampling: targeting improvements of health services in Jigawa, Nigeria.

Science.gov (United States)

Oladele, Edward Adekola; Ormond, Louise; Adeyemi, Olusegun; Patrick, David; Okoh, Festus; Oresanya, Olusola Bukola; Valadez, Joseph J

2012-01-01

In Nigeria, 30% of child deaths are due to malaria. The National Malaria Control Program of Nigeria (NMCP) during 2009 initiated a program to improve the quality of paediatric malaria services delivered in health facilities (HF). This study reports a rapid approach used to assess the existing quality of services in Jigawa state at decentralised levels of the health system. NMCP selected Lot Quality Assurance Sampling (LQAS) to identify the variation in HF service quality among Senatorial Districts (SD). LQAS was selected because it was affordable and could be used by local health workers (HW) in a population-based survey. NMCP applied a 2-stage LQAS using a structured Rapid Health Facility Assessment (R-HFA) tool to identify high and low performing SD for specified indicators. LQAS identified variations in HF performance (n = 21) and enabled resources to be targeted to address priorities. All SD exhibited deficient essential services, supplies and equipment. Only 9.7% of HF had Artemisinin-based Combination Therapies and other first-line treatments for childhood illnesses. No SD and few HF exhibited adequate HW performance for the assessment, treatment or counselling of sick children. Using the IMCI algorithm, 17.5% of HW assessed the child's vaccination status, 46.8% assessed nutritional status, and 65.1% assessed children for dehydration. Only 5.1% of HW treatments were appropriate for the assessment. Exit interviews revealed that 5.1% of caregivers knew their children's illness, and only 19.9% could accurately describe how to administer the prescribed drug. This R-HFA, using LQAS principles, is a rapid, simple tool for assessing malaria services and can be used at scale. It identified technical deficiencies that could be corrected by improved continuing medical education, targeted supervision, and recurrent R-HFA assessments of the quality of services.

Contamination and UV ageing of diffuser targets used in satellite inflight and ground reference test site calibrations

Science.gov (United States)

Vaskuri, Anna; Greenwell, Claire; Hessey, Isabel; Tompkins, Jordan; Woolliams, Emma

2018-02-01

Diffuser reflectance targets are key components in in-orbit calibrations and for verifying ground reference test sites. In this work, Spectralon, Diffusil, and Heraeus diffusers were exposed to exhaust gases and ultraviolet (UV) radiation in the ambient air conditions and their degradations were monitored by measuring changes in spectral reflectances. Spectralon is a state-of-the-art diffuser made of polytetrafluoroethylene, and Diffusil and Heraeus diffusers are made of fused silica with gas bubbles inside. Based on the contamination tests, Spectralon degrades faster than fused silica diffusers. For the samples exposed to contamination for 20 minutes, the 250 nm - 400 nm total diffuse spectral reflectance of Spectralon degraded 3-5 times more when exposed to petrol-like emission and 16-23 times more when exposed to diesel-like emission, compared with Diffusil. When the reflectance changes of Spectralon were compared with those of Heraeus, Spectralon degraded 3-4 times more when exposed to petrol-like emission for 20 minutes and 5-7 times more when exposed to diesel-like emission for 7.5 minutes. When the samples contaminated were exposed to UV radiation in the ambient air, their reflectance gradually restored back to the original level. In conclusion, fused silica diffusers are more resistant to hydrocarbon contaminants present in ground reference test sites, and thus more stable under UV radiation in the air.

Sweet promises: Candy advertising to children and implications for industry self-regulation.

Science.gov (United States)

Harris, Jennifer L; LoDolce, Megan; Dembek, Cathryn; Schwartz, Marlene B

2015-12-01

Candy advertising illustrates limitations of the Children's Food and Beverage Advertising Initiative (CFBAI) self-regulatory program to improve food marketing to children. Participating companies pledge to not advertise candy in child-directed media. Yet independent analyses show that children viewed 65% more candy ads on U.S. television in 2011 than in 2007, before CFBAI implementation. The present research corroborates these findings, characterizes the increase, and examines how CFBAI-participating and non-participating companies use child-targeted techniques and media placement to advertise candy on U.S. television. Content analysis identified child-targeted messages and techniques in 2011 television candy ads, and Nielsen data (2008-2011) quantified candy advertising viewed on children's and other types of television programming. Differences between brands according to CFBAI status and use of child-targeted techniques in ads are evaluated. Data were obtained and analyzed in 2013. CFBAI-company non-approved brands represented 65% of candy ads viewed by children in 2011, up from 45% in 2008, and 77% of these ads contained child-targeted techniques. Although CFBAI companies only placed ads for approved brands on children's networks, 31% of ads viewed by children for CFBAI non-approved brands appeared on networks with higher-than-average youth audiences. CFBAI non-participating companies placed child-targeted candy ads primarily on children's networks. Despite CFBAI pledges, companies continue to advertise candy during programming with large youth audiences utilizing techniques that appeal to children. Both increased CFBAI participation and a more effective definition of "child-directed advertising" are required to reduce children's exposure to targeted advertising for foods that can harm their health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeted enzyme prodrug therapies.

Science.gov (United States)

Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

2010-09-01

The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers

Science.gov (United States)

Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer’s dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)—a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer’s model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug

Fostering Children's Interests in Gardening

Science.gov (United States)

Lekies, Kristi S.; Sheavly, Marcia Eames

2007-01-01

Despite the rapidly growing interest in children's gardens and attention to the positive benefits of gardening for children, little is known about the ways in which young people actually form interests in gardening. Using a sample of 9- and 10-year-old children at a school garden site in New York State, this study examined the ways in which…

Targeted gene insertion for molecular medicine.

Science.gov (United States)

Voigt, Katrin; Izsvák, Zsuzsanna; Ivics, Zoltán

2008-11-01

Genomic insertion of a functional gene together with suitable transcriptional regulatory elements is often required for long-term therapeutical benefit in gene therapy for several genetic diseases. A variety of integrating vectors for gene delivery exist. Some of them exhibit random genomic integration, whereas others have integration preferences based on attributes of the targeted site, such as primary DNA sequence and physical structure of the DNA, or through tethering to certain DNA sequences by host-encoded cellular factors. Uncontrolled genomic insertion bears the risk of the transgene being silenced due to chromosomal position effects, and can lead to genotoxic effects due to mutagenesis of cellular genes. None of the vector systems currently used in either preclinical experiments or clinical trials displays sufficient preferences for target DNA sequences that would ensure appropriate and reliable expression of the transgene and simultaneously prevent hazardous side effects. We review in this paper the advantages and disadvantages of both viral and non-viral gene delivery technologies, discuss mechanisms of target site selection of integrating genetic elements (viruses and transposons), and suggest distinct molecular strategies for targeted gene delivery.

India: From SITE to INSAT.

Science.gov (United States)

Chaudhri, M. M.

1986-01-01

Identifies core of India's illiteracy problem and describes use of educational technology to educate rural children. Highlights include descriptions of the Satellite Instructional Television Experiment (SITE) project; motivation behind low-cost educational aids development in rural areas; an educational radio pilot project; and development and…

Discrimination of single features and conjunctions by children.

Science.gov (United States)

Taylor, M J; Chevalier, H; Lobaugh, N J

2003-12-01

Stimuli that are discriminated by a conjunction of features can show more rapid early processing in adults. To determine how this facilitation effect develops, the processing of visual features and their conjunction was examined in 7-12-year-old children. The children completed a series of tasks in which they made a target-non-target judgement as a function of shape only, colour only or shape and colour features, while event-related potentials were recorded. To assess early stages of feature processing the posteriorly distributed P1 and N1 were analysed. Attentional effects were seen for both components. P1 had a shorter latency and P1 and N1 had larger amplitudes to targets than non-targets. Task effects were driven by the conjunction task. P1 amplitude was largest, while N1 amplitude was smallest for the conjunction targets. In contrast to larger left-sided N1 in adults, N1 had a symmetrical distribution in the children. N1 latency was shortest for the conjunction targets in the 9-10-year olds and 11-12-year olds, demonstrating facilitation in children, but which continued to develop over the pre-teen years. These data underline the sensitivity of early stages of processing to both top-down modulations and the parallel binding of non-spatial features in young children. Furthermore, facilitation effects, increased speed of processing when features need to be conjoined, mature in mid-childhood, arguing against a hierarchical model of visual processing, and supporting a rapid, integrated facilitative model.

Targeting self-regulation to promote health behaviors in children.

Science.gov (United States)

Miller, Alison L; Gearhardt, Ashley N; Fredericks, Emily M; Katz, Benjamin; Shapiro, Lilly Fink; Holden, Kelsie; Kaciroti, Niko; Gonzalez, Richard; Hunter, Christine; Lumeng, Julie C

2018-02-01

Poor self-regulation (i.e., inability to harness cognitive, emotional, motivational resources to achieve goals) is hypothesized to contribute to unhealthy behaviors across the lifespan. Enhancing early self-regulation may increase positive health outcomes. Obesity is a major public health concern with early-emerging precursors related to self-regulation; it is therefore a good model for understanding self-regulation and health behavior. Preadolescence is a transition when children increase autonomy in health behaviors (e.g., eating, exercise habits), many of which involve self-regulation. This paper presents the scientific rationale for examining self-regulation mechanisms that are hypothesized to relate to health behaviors, specifically obesogenic eating, that have not been examined in children. We describe novel intervention protocols designed to enhance self-regulation skills, specifically executive functioning, emotion regulation, future-oriented thinking, and approach bias. Interventions are delivered via home visits. Assays of self-regulation and obesogenic eating behaviors using behavioral tasks and self-reports are implemented and evaluated to determine feasibility and psychometrics and to test intervention effects. Participants are low-income 9-12 year-old children who have been phenotyped for self-regulation, stress, eating behavior and adiposity through early childhood. Study goals are to examine intervention effects on self-regulation and whether change in self-regulation improves obesogenic eating. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

Science.gov (United States)

De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

2014-01-01

ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

Willingness to pay for lipid-based nutrient supplements for young children in four urban sites of Ethiopia.

Science.gov (United States)

Segrè, Joel; Winnard, Kim; Abrha, Teweldebrhan Hailu; Abebe, Yewelsew; Shilane, David; Lapping, Karin

2015-12-01

Malnutrition in children under 5 years of age is pervasive in Ethiopia across all wealth quintiles. The objective of this study was to determine the willingness to pay (WTP) for a week's supply of Nutributter® (a lipid-based nutrient supplement, or LNS) through typical urban Ethiopian retail channels. In February, 2012, 128 respondents from 108 households with 6-24-month-old children had the opportunity to sample Nutributter® for 2 days in their homes as a complementary food. Respondents were asked directly and indirectly what they were willing to pay for the product, and then participated in market simulation where they could demonstrate their WTP through an exchange of real money for real product. Nearly all (96%) of the respondents had a positive WTP, and 25% were willing to pay the equivalent of at least $1.05, which we calculated as the likely minimum, unsubsidised Ethiopian retail price of Nutributter® for 1 week for one child. Respondents willing to pay at least $1.05 included urban men and women with children 6-24 months old from low-, middle- and high-wealth groups from four study sites across three cities. Additionally, we estimated the initial annual market size for Nutributter® in the cities where the study took place to be around $500 000. The study has important implications for retail distribution of LNS in Ethiopia, showing who the most likely customers could be, and also suggesting why the initial market may be too small to be of interest to food manufacturers seeking profit maximisation. © 2012 Blackwell Publishing Ltd.

A qualitative study of programs for parents with serious mental illness and their children: building practice-based evidence.

Science.gov (United States)

Nicholson, Joanne; Hinden, Beth R; Biebel, Kathleen; Henry, Alexis D; Katz-Leavy, Judith

2007-10-01

The rationale for the development of effective programs for parents with serious mental illness and their children is compelling. Using qualitative methods and a grounded theory approach with data obtained in site visits, seven existing programs for parents with mental illness and their children in the United States are described and compared across core components: target population, theory and assumptions, funding, community and agency contexts, essential services and intervention strategies, moderators, and outcomes. The diversity across programs is strongly complemented by shared characteristics, the identification of which provides the foundation for future testing and the development of an evidence base. Challenges in program implementation and sustainability are identified. Qualitative methods are useful, particularly when studying existing programs, in taking steps toward building the evidence base for effective programs for parents with serious mental illness and their children.

Hydrogen peroxide (H2O2) irreversibly inactivates creatine kinase from Pelodiscus sinensis by targeting the active site cysteine.

Science.gov (United States)

Wang, Wei; Lee, Jinhyuk; Hao, Hao; Park, Yong-Doo; Qian, Guo-Ying

2017-12-01

Creatine kinase (EC 2.7.3.2, CK) plays an important role in cellular energy metabolism and homeostasis by catalysing the transfer of phosphate between ATP and creatine phosphate. In this study, we investigated the effects of H 2 O 2 on PSCKM (muscle type creatine kinase from Pelodiscus sinensis) by the integrating method between enzyme kinetics and docking simulations. We found that H 2 O 2 strongly inactivated PSCKM (IC 50 =0.25mM) in a first-order kinetic process, and targeted the active site cysteine directly. A conformational study showed that H 2 O 2 did not induce the tertiary structural changes in PSCKM with no extensive exposure of hydrophobic surfaces. Sequential docking simulations between PSCKM and H 2 O 2 indicated that H 2 O 2 interacts with the ADP binding region of the active site, consistent with experimental results that demonstrated H 2 O 2 -induced inactivation. Our study demonstrates the effect of H 2 O 2 on PSCKM enzymatic function and unfolding, and provides important insight into the changes undergone by this central metabolic enzyme in ectothermic animals in response to the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Children as Consumers: Advertising and Marketing

Science.gov (United States)

Calvert, Sandra L.

2008-01-01

Marketing and advertising support the U.S. economy by promoting the sale of goods and services to consumers, both adults and children. Sandra Calvert addresses product marketing to children and shows that although marketers have targeted children for decades, two recent trends have increased their interest in child consumers. First, both the…

New "persona" concept helps site designers cater to target user segments' needs.

Science.gov (United States)

2004-09-01

Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.

Target sites for chemical regulation of strigolactone signaling

Directory of Open Access Journals (Sweden)

Hidemitsu eNakamura

2014-11-01

Full Text Available Demands for plant growth regulators (chemicals that control plant growth are increasing globally, especially in developing countries. Both positive and negative plant growth regulators are widely used to enhance crop production and to suppress unwanted shoot growth, respectively. Strigolactones (SLs are multifunctional molecules that function as phytohormones, inhibiting shoot branching and also functioning in the rhizospheric communication with symbiotic fungi and parasitic weeds. Therefore, it is anticipated that chemicals that regulate the functions of SLs will be widely used in agricultural applications. Although the SL biosynthetic pathway is not fully understood, it has been demonstrated that beta-carotene isomerases, carotenoid cleavage dioxygenases (CCDs, and a cytochrome P450 monooxygenase are involved in strigolactone biosynthesis. A CCD inhibitor, abamine, which is also an inhibitor of abscisic acid biosynthesis, reduces the levels of SL in several plant species and reduces the germination rate of Orobanche minor seeds grown with tobacco. On the basis of the structure of abamine, several chemicals have been designed to specifically inhibit CCDs during SL synthesis. Cytochrome P450 monooxygenase is another target enzyme in the development of SL biosynthesis inhibitors, and the triazole-derived TIS series of chemicals is known to include SL biosynthesis inhibitors, although their target enzyme has not been identified. Recently, DWARF14 (D14 has been shown to be a receptor for SLs, and the D-ring moiety of SL is essential for its recognition by D14. A variety of SL agonists are currently under development and most agonists commonly contain the D-ring or a D-ring-like moiety. Several research groups have also resolved the crystal structure of D14 in the last two years. It is expected that this information on the D14 structure will be invaluable not only for developing SL agonists with novel structures but also in the design of inhibitors

Attentional selection and suppression in children and adults.

Science.gov (United States)

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies

National Research Council Canada - National Science Library

Huang, Shuang

2004-01-01

.... Our proposal is designed to develop an endothelial cell-targeted adenoviral vector and to use the targeted vector to express high levels of anticancer therapeutic genes in the sites of angiogenenic...

Prevalence of urinary tract infection (UTI) in sequential acutely unwell children presenting in primary care: exploratory study.

Science.gov (United States)

O'Brien, Kathryn; Stanton, Naomi; Edwards, Adrian; Hood, Kerenza; Butler, Christopher C

2011-03-01

Due to the non-specific nature of symptoms of UTI in children and low levels of urine sampling, the prevalence of UTI amongst acutely ill children in primary care is unknown. To undertake an exploratory study of acutely ill children consulting in primary care, determine the feasibility of obtaining urine samples, and describe presenting symptoms and signs, and the proportion with UTI. Exploratory, observational study. Four general practices in South Wales. A total of 99 sequential attendees with acute illness aged less than five years. UTI defined by >10(5) organisms/ml on laboratory culture of urine. Urine samples were obtained in 75 (76%) children. Three (4%) met microbiological criteria for UTI. GPs indicated they would not normally have obtained urine samples in any of these three children. However, all had received antibiotics for suspected alternative infections. Urine sample collection is feasible from the majority of acutely ill children in primary care, including infants. Some cases of UTI may be missed if children thought to have an alternative site of infection are excluded from urine sampling. A larger study is needed to more accurately determine the prevalence of UTI in children consulting with acute illness in primary care, and to explore which symptoms and signs might help clinicians effectively target urine sampling.

Umbilical site for temporary colostomy in anorectal malformations: is ...

African Journals Online (AJOL)

Umbilical site for temporary colostomy in anorectal malformations: is it cosmetically preferable? Taha Alkhatrawi, Radi Elsherbini and Djamal Ouslimane. Purpose In an attempt to minimize the scars and improve the cosmetic outcome in children, the umbilical site has been chosen for colostomy formation in patients with.

Children's Food and Beverage Promotion on Television to Parents.

Science.gov (United States)

Emond, Jennifer A; Smith, Marietta E; Mathur, Suman J; Sargent, James D; Gilbert-Diamond, Diane

2015-12-01

Nutritionally poor foods are heavily advertised to children on television. Whether those same products are also advertised to parents on television has not been systematically examined. This study is a content analysis of advertisements for children's packaged foods and beverages aired over US network, cable, and syndicated television for 1 year (2012 to 2013). The target audience of each advertisement was defined as children or parents based on advertisement content, where parent-directed advertisements included emotional appeals related to family bonding and love. Advertisement characteristics and patterns of airtime were compared across target audience, and the proportion of total airtime devoted to advertisements targeting parents was computed. Fifty-one children's food or beverage products were advertised over the study year, 25 (49%) of which were advertised directly to parents. Parent-directed advertisements more often featured nutrition and health messaging and an active lifestyle than child-directed advertisements, whereas child-directed advertisements more frequently highlighted fun and product taste. Over all products, 42.4% of total airtime was devoted to advertisements that targeted parents. The products with the most amount of airtime over the study year were ready-to-eat cereals, sugar-sweetened beverages, and children's yogurt, and the proportion of total advertisement airtime for those products devoted to parents was 24.4%, 72.8%, and 25.8%, respectively. Television advertisements for children's packaged foods and beverages frequently targeted parents with emotional appeals and messaging related to nutrition and health. Findings are of concern if exposure to such advertisements among parents may shape their beliefs about the appropriateness of nutritionally questionable children's foods and beverages. Copyright © 2015 by the American Academy of Pediatrics.

Tradition and Modernization: Siting Philosophy for Children within the African Outlook

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Ndofirepi, Amasa Philip; Cross, Michael

2016-01-01

In this philosophical paper, we investigate the project of doing philosophy with children in Africa. While the philosophy for children program has its roots in the Anglo-Saxon world, we contend that it can sit well in Africa if given an African outlook. We challenge Eurocentric specialists, who are attempting a wholesale introduction of the…

Estimating the Causal Impact of Proximity to Gold and Copper Mines on Respiratory Diseases in Chilean Children: An Application of Targeted Maximum Likelihood Estimation.

Science.gov (United States)

Herrera, Ronald; Berger, Ursula; von Ehrenstein, Ondine S; Díaz, Iván; Huber, Stella; Moraga Muñoz, Daniel; Radon, Katja

2017-12-27

In a town located in a desert area of Northern Chile, gold and copper open-pit mining is carried out involving explosive processes. These processes are associated with increased dust exposure, which might affect children's respiratory health. Therefore, we aimed to quantify the causal attributable risk of living close to the mines on asthma or allergic rhinoconjunctivitis risk burden in children. Data on the prevalence of respiratory diseases and potential confounders were available from a cross-sectional survey carried out in 2009 among 288 (response: 69 % ) children living in the community. The proximity of the children's home addresses to the local gold and copper mine was calculated using geographical positioning systems. We applied targeted maximum likelihood estimation to obtain the causal attributable risk (CAR) for asthma, rhinoconjunctivitis and both outcomes combined. Children living more than the first quartile away from the mines were used as the unexposed group. Based on the estimated CAR, a hypothetical intervention in which all children lived at least one quartile away from the copper mine would decrease the risk of rhinoconjunctivitis by 4.7 percentage points (CAR: - 4.7 ; 95 % confidence interval ( 95 % CI): - 8.4 ; - 0.11 ); and 4.2 percentage points (CAR: - 4.2 ; 95 % CI: - 7.9 ; - 0.05 ) for both outcomes combined. Overall, our results suggest that a hypothetical intervention intended to increase the distance between the place of residence of the highest exposed children would reduce the prevalence of respiratory disease in the community by around four percentage points. This approach could help local policymakers in the development of efficient public health strategies.

Engaging teachers & students in geosciences by exploring local geoheritage sites

Science.gov (United States)

Gochis, E. E.; Gierke, J. S.

2014-12-01

Understanding geoscience concepts and the interactions of Earth system processes in one's own community has the potential to foster sound decision making for environmental, economic and social wellbeing. School-age children are an appropriate target audience for improving Earth Science literacy and attitudes towards scientific practices. However, many teachers charged with geoscience instruction lack awareness of local geological significant examples or the pedagogical ability to integrate place-based examples into their classroom practice. This situation is further complicated because many teachers of Earth science lack a firm background in geoscience course work. Strategies for effective K-12 teacher professional development programs that promote Earth Science literacy by integrating inquiry-based investigations of local and regional geoheritage sites into standards based curriculum were developed and tested with teachers at a rural school on the Hannahville Indian Reservation located in Michigan's Upper Peninsula. The workshops initiated long-term partnerships between classroom teachers and geoscience experts. We hypothesize that this model of professional development, where teachers of school-age children are prepared to teach local examples of earth system science, will lead to increased engagement in Earth Science content and increased awareness of local geoscience examples by K-12 students and the public.

Children's analogical reasoning about natural phenomena.

Science.gov (United States)

Pauen, S; Wilkening, F

1997-10-01

This report investigates children's analogical reasoning in a physics task, using an analogy generated by the children rather than by the experimenter. A total of 127 elementary school children took part in three related studies. Children learned to predict the behavior of a balance scale. Later, they were asked to solve a force interaction problem. Two versions of the balance scale training were devised: version A suggested an incorrect solution to the target problem (negative analogy), and version B suggested a correct solution to the target problem (positive analogy). In Study 1, 9- to 10-year-olds showed spontaneous transfer in both training conditions. In Study 2, 7-year-olds did not show any transfer in the positive analogy condition. Study 3 revealed that the lack of transfer in younger children was not due to a failure either to notice the analogy or to perform the mapping. Instead, 7-year-olds transferred only selected aspects of the correct solution. Copyright 1997 Academic Press.

Drug-targeting methodologies with applications: A review

Science.gov (United States)

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

Pripper: prediction of caspase cleavage sites from whole proteomes

Directory of Open Access Journals (Sweden)

Salmi Jussi

2010-06-01

Full Text Available Abstract Background Caspases are a family of proteases that have central functions in programmed cell death (apoptosis and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments. Results Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from http://users.utu.fi/mijopi/Pripper. Conclusions We have developed Pripper, a tool for

Subject Gateway Sites and Search Engine Ranking.

Science.gov (United States)

Thelwall, Mike

2002-01-01

Discusses subject gateway sites and commercial search engines for the Web and presents an explanation of Google's PageRank algorithm. The principle question addressed is the conditions under which a gateway site will increase the likelihood that a target page is found in search engines. (LRW)

Crystal structure of ryanodine receptor N-terminal domain from Plutella xylostella reveals two potential species-specific insecticide-targeting sites.

Science.gov (United States)

Lin, Lianyun; Liu, Chen; Qin, Juan; Wang, Jie; Dong, Shengjie; Chen, Wei; He, Weiyi; Gao, Qingzhi; You, Minsheng; Yuchi, Zhiguang

2018-01-01

Ryanodine receptors (RyRs) are large calcium-release channels located in sarcoplasmic reticulum membrane. They play a central role in excitation-contraction coupling of muscle cells. Three commercialized insecticides targeting pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the structure of insect RyRs remains elusive, hindering our understanding of the mode of action of RyR-targeting insecticides and the development of insecticide resistance in pests. Here we present the crystal structure of RyR N-terminal domain (NTD) (residue 1-205) at 2.84 Å resolution from the diamondback moth (DBM), Plutella xylostella, a destructive pest devouring cruciferous crops all over the world. Similar to its mammalian homolog, DBM RyR NTD consists of a beta-trefoil folding motif and a flanking alpha helix. Interestingly, two regions in NTD interacting with neighboring domains showed distinguished conformations in DBM relative to mammalian RyRs. Using homology modeling and molecular dynamics simulation, we created a structural model of the N-terminal three domains, showing two unique binding pockets that could be targeted by potential species-specific insecticides. Thermal melt experiment showed that the stability of DBM RyR NTD was higher than mammalian RyRs, probably due to a stable intra-domain disulfide bond observed in the crystal structure. Previously DBM NTD was shown to be one of the two critical regions to interact with insecticide flubendiamide, but isothermal titration calorimetry experiments negated DBM NTD alone as a major binding site for flubendiamide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

Science.gov (United States)

Joseph, Thomas T; Osman, Roman

2012-01-01

In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of

CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool.

Directory of Open Access Journals (Sweden)

Manuel Stemmer

Full Text Available Engineering of the CRISPR/Cas9 system has opened a plethora of new opportunities for site-directed mutagenesis and targeted genome modification. Fundamental to this is a stretch of twenty nucleotides at the 5' end of a guide RNA that provides specificity to the bound Cas9 endonuclease. Since a sequence of twenty nucleotides can occur multiple times in a given genome and some mismatches seem to be accepted by the CRISPR/Cas9 complex, an efficient and reliable in silico selection and evaluation of the targeting site is key prerequisite for the experimental success. Here we present the CRISPR/Cas9 target online predictor (CCTop, http://crispr.cos.uni-heidelberg.de to overcome limitations of already available tools. CCTop provides an intuitive user interface with reasonable default parameters that can easily be tuned by the user. From a given query sequence, CCTop identifies and ranks all candidate sgRNA target sites according to their off-target quality and displays full documentation. CCTop was experimentally validated for gene inactivation, non-homologous end-joining as well as homology directed repair. Thus, CCTop provides the bench biologist with a tool for the rapid and efficient identification of high quality target sites.

Cohort Profile: The Applied Research Group for Kids (TARGet Kids!).

Science.gov (United States)

Carsley, Sarah; Borkhoff, Cornelia M; Maguire, Jonathon L; Birken, Catherine S; Khovratovich, Marina; McCrindle, Brian; Macarthur, Colin; Parkin, Patricia C

2015-06-01

The Applied Research Group for Kids (TARGet Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the TARGet Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. TARGet Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

TALE-PvuII fusion proteins--novel tools for gene targeting.

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens.

Science.gov (United States)

Ahmadi, Hamed; Ahmadi, Ali; Azimzadeh-Jamalkandi, Sadegh; Shoorehdeli, Mahdi Aliyari; Salehzadeh-Yazdi, Ali; Bidkhori, Gholamreza; Masoudi-Nejad, Ali

2013-02-01

MiRNAs play an essential role in the networks of gene regulation by inhibiting the translation of target mRNAs. Several computational approaches have been proposed for the prediction of miRNA target-genes. Reports reveal a large fraction of under-predicted or falsely predicted target genes. Thus, there is an imperative need to develop a computational method by which the target mRNAs of existing miRNAs can be correctly identified. In this study, combined pattern recognition neural network (PRNN) and principle component analysis (PCA) architecture has been proposed in order to model the complicated relationship between miRNAs and their target mRNAs in humans. The results of several types of intelligent classifiers and our proposed model were compared, showing that our algorithm outperformed them with higher sensitivity and specificity. Using the recent release of the mirBase database to find potential targets of miRNAs, this model incorporated twelve structural, thermodynamic and positional features of miRNA:mRNA binding sites to select target candidates. Copyright © 2012 Elsevier Inc. All rights reserved.

Human antibody recognition of antigenic site IV on Pneumovirus fusion proteins.

Science.gov (United States)

Mousa, Jarrod J; Binshtein, Elad; Human, Stacey; Fong, Rachel H; Alvarado, Gabriela; Doranz, Benjamin J; Moore, Martin L; Ohi, Melanie D; Crowe, James E

2018-02-01

Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years of age. The RSV fusion (F) protein is a primary target of human antibodies, and it has several antigenic regions capable of inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre-fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV have been described that bind and neutralize both RSV and human metapneumovirus (hMPV). To explore the diversity of binding modes at antigenic site IV, we generated a panel of four new human monoclonal antibodies (mAbs) and competition-binding suggested the mAbs bind at antigenic site IV. Mutagenesis experiments revealed that binding and neutralization of two mAbs (3M3 and 6F18) depended on arginine (R) residue R429. We discovered two R429-independent mAbs (17E10 and 2N6) at this site that neutralized an RSV R429A mutant strain, and one of these mAbs (17E10) neutralized both RSV and hMPV. To determine the mechanism of cross-reactivity, we performed competition-binding, recombinant protein mutagenesis, peptide binding, and electron microscopy experiments. It was determined that the human cross-reactive mAb 17E10 binds to RSV F with a binding pose similar to 101F, which may be indicative of cross-reactivity with hMPV F. The data presented provide new concepts in RSV immune recognition and vaccine design, as we describe the novel idea that binding pose may influence mAb cross-reactivity between RSV and hMPV. Characterization of the site IV epitope bound by human antibodies may inform the design of a pan-Pneumovirus vaccine.

Attribution of human characteristics and bullying involvement in childhood: Distinguishing between targets

NARCIS (Netherlands)

Noorden, T.H.J. van; Haselager, G.J.T.; Lansu, T.A.M.; Cillessen, A.H.N.; Bukowski, W.M.

2016-01-01

This investigation researched the association between the attribution of human characteristics and bullying involvement in children by distinguishing between targets. Study 1 focused on the attribution of human characteristics by bullies, victims, bully/victims, and non-involved children toward

Therapeutic targeting strategies using endogenous cells and proteins.

Science.gov (United States)

Parayath, Neha N; Amiji, Mansoor M

2017-07-28

Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells.

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Silva, Luisa H A; Cruz, Fernanda F; Morales, Marcelo M; Weiss, Daniel J; Rocco, Patricia R M

2017-03-09

Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

Science.gov (United States)

Kabakyenga, Jerome; Barigye, Celestine; Brenner, Jennifer; Maling, Samuel; Buchner, Denise; Nettle-Aquirre, Alberto; Singhal, Nalini; Kyomuhangi, Teddy; Tumusiime, David; Finch, Janet; MacLeod, Stuart

2016-03-01

Benefits of mobile phone deployment for children mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

Federal health web sites: current & future roles.

Science.gov (United States)

Cronin, Carol

2002-09-01

An examination of the current and possible future roles of federal health Web sites, this paper provides an overview of site categories, functions, target audiences, marketing approaches, knowledge management, and evaluation strategies. It concludes with a look at future opportunities and challenges for the federal government in providing health information online.

Protein and Peptide in Drug Targeting and its Therapeutic Approach

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Raj K. Keservani

2015-09-01

Full Text Available Aim: The main aim of this review article is to provide information like advantages of protein and peptides via different routes of drug administration, targeted to a particular site and its implication in drug delivery system. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the development of protein and peptide drug targeting as well as its therapeutic activity. Results: In recent years many researchers use protein and peptide as a target site of drug by a different delivery system. Proteins and peptides are used as specific and effective therapeutic agents, due to instability and side effects their use is complicated. Protein kinases are important regulators of most, if not all, biological processes. Abnormal activity of proteins and peptides has been implicated in many human diseases, such as diabetes, cancer and neurodegenerative disorders. Conclusions: It is concluded that the protein and peptide were used in drug targeting to specific site and also used in different diseased states like cancer, diabetes, immunomodulating, neurodegenerative effects and antimicrobial activity.

Signatures of RNA binding proteins globally coupled to effective microRNA target sites

DEFF Research Database (Denmark)

Jacobsen, Anders; Wen, Jiayu; Marks, Debora S

2010-01-01

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs), bound to Argonaute proteins (RISC), destabilize mRNAs through base-pairing with the mRNA. However, the gene expression changes after perturbations of these small RNAs are only partially explained by predicted miRNA/siRNA targeting. Targeting...

A family-based intervention targeting parents of preschool children with overweight and obesity: conceptual framework and study design of LOOPS- Lund overweight and obesity preschool study

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Önnerfält Jenny

2012-10-01

Full Text Available Abstract Background As the rate of overweight among children is rising there is a need for evidence-based research that will clarify what the best interventional strategies to normalize weight development are. The overall aim of the Lund Overweight and Obesity Preschool Study (LOOPS is to evaluate if a family-based intervention, targeting parents of preschool children with overweight and obesity, has a long-term positive effect on weight development of the children. The hypothesis is that preschool children with overweight and obesity, whose parents participate in a one-year intervention, both at completion of the one-year intervention and at long term follow up (2-, 3- and 5-years will have reduced their BMI-for-age z-score. Methods/Design The study is a randomized controlled trial, including overweight (n=160 and obese (n=80 children 4-6-years-old. The intervention is targeting the parents, who get general information about nutrition and exercise recommendations through a website and are invited to participate in a group intervention with the purpose of supporting them to accomplish preferred lifestyle changes, both in the short and long term. To evaluate the effect of various supports, the parents are randomized to different interventions with the main focus of: 1 supporting the parents in limit setting by emphasizing the importance of positive interactions between parents and children and 2 influencing the patterns of daily activities to induce alterations of everyday life that will lead to healthier lifestyle. The primary outcome variable, child BMI-for-age z-score will be measured at referral, inclusion, after 6 months, at the end of intervention and at 2-, 3- and 5-years post intervention. Secondary outcome variables, measured at inclusion and at the end of intervention, are child activity pattern, eating habits and biochemical markers as well as parent BMI, exercise habits, perception of health, experience of parenthood and level of

A family-based intervention targeting parents of preschool children with overweight and obesity: conceptual framework and study design of LOOPS- Lund overweight and obesity preschool study.

Science.gov (United States)

Önnerfält, Jenny; Erlandsson, Lena-Karin; Orban, Kristina; Broberg, Malin; Helgason, Christina; Thorngren-Jerneck, Kristina

2012-10-17

As the rate of overweight among children is rising there is a need for evidence-based research that will clarify what the best interventional strategies to normalize weight development are. The overall aim of the Lund Overweight and Obesity Preschool Study (LOOPS) is to evaluate if a family-based intervention, targeting parents of preschool children with overweight and obesity, has a long-term positive effect on weight development of the children. The hypothesis is that preschool children with overweight and obesity, whose parents participate in a one-year intervention, both at completion of the one-year intervention and at long term follow up (2-, 3- and 5-years) will have reduced their BMI-for-age z-score. The study is a randomized controlled trial, including overweight (n=160) and obese (n=80) children 4-6-years-old. The intervention is targeting the parents, who get general information about nutrition and exercise recommendations through a website and are invited to participate in a group intervention with the purpose of supporting them to accomplish preferred lifestyle changes, both in the short and long term. To evaluate the effect of various supports, the parents are randomized to different interventions with the main focus of: 1) supporting the parents in limit setting by emphasizing the importance of positive interactions between parents and children and 2) influencing the patterns of daily activities to induce alterations of everyday life that will lead to healthier lifestyle. The primary outcome variable, child BMI-for-age z-score will be measured at referral, inclusion, after 6 months, at the end of intervention and at 2-, 3- and 5-years post intervention. Secondary outcome variables, measured at inclusion and at the end of intervention, are child activity pattern, eating habits and biochemical markers as well as parent BMI, exercise habits, perception of health, experience of parenthood and level of parental stress. The LOOPS project will provide

Helical Tomotherapy in Children and Adolescents: Dosimetric Comparisons, Opportunities and Issues

Energy Technology Data Exchange (ETDEWEB)

Mascarin, Maurizio, E-mail: mascarin@cro.it [Pediatric Radiotherapy Unit, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Department of Radiation Therapy, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Giugliano, Francesca Maria [Pediatric Radiotherapy Unit, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Seconda Università di Napoli, Napoli 80138 (Italy); Coassin, Elisa [Pediatric Radiotherapy Unit, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Drigo, Annalisa; Chiovati, Paola; Dassie, Andrea [Department of Radiation Therapy, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Department of Medical Physics, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy); Franchin, Giovanni; Minatel, Emilio; Trovò, Mauro Gaetano [Department of Radiation Therapy, Centro di Riferimento Oncologico- National Cancer Institute/Via Franco Gallini, 2 33081 Aviano (PN) (Italy)

2011-10-25

Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1–24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac-based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory.

Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

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Francesco Gentile

2018-04-01

Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

Targeting the Brain with Nanomedicine.

Science.gov (United States)

Rueda, Felix; Cruz, Luis J

2017-01-01

Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Food advertising targeted at school-age children: a content analysis.

Science.gov (United States)

Folta, Sara C; Goldberg, Jeanne P; Economos, Christina; Bell, Rick; Meltzer, Rachel

2006-01-01

To determine whether the contents of food and beverage advertisements are associated with physical activity and athletic ability more often than those for toys and games, and to describe persuasive techniques used in advertising food and beverages to children. A content analysis of advertisements during 31 hours of school-age children's television programming. Chi-square tests were used to examine differences in depictions of physical activity. Types of persuasive techniques were tabulated and, within each advertisement, categorized as implicit or explicit. Food and beverage ads depicted children engaged in physical activity and associated the advertised product with athletic ability significantly more than toy and game ads. Food was most often associated with fun and good times (75%), pleasant taste (54.1%), being hip or cool (43.2%), and feelings of happiness (43.2%). These findings raise concern that greater levels of physical activity and athletic ability in food advertising, in which the product is frequently associated with fun, may promote overconsumption, especially of calorie-dense, nutrient-poor foods. Further research would elucidate whether this concern is warranted. On the other hand, since food advertisements are presumably effective, health educators can use these techniques to formulate messages for nutritious foods. This concept should be tested with well-designed interventions.

Artificial Intelligence Support for Landing Site Selection on Mars

Science.gov (United States)

Rongier, G.; Pankratius, V.

2017-12-01

Mars is a key target for planetary exploration; a better understanding of its evolution and habitability requires roving in situ. Landing site selection is becoming more challenging for scientists as new instruments generate higher data volumes. The involved engineering and scientific constraints make site selection and the anticipation of possible onsite actions into a complex optimization problem: there may be multiple acceptable solutions depending on various goals and assumptions. Solutions must also account for missing data, errors, and potential biases. To address these problems, we propose an AI-informed decision support system that allows scientists, mission designers, engineers, and committees to explore alternative site selection choices based on data. In particular, we demonstrate first results of an exploratory case study using fuzzy logic and a simulation of a rover's mobility map based on the fast marching algorithm. Our system computes favorability maps of the entire planet to facilitate landing site selection and allows a definition of different configurations for rovers, science target priorities, landing ellipses, and other constraints. For a rover similar to NASA's Mars 2020 rover, we present results in form of a site favorability map as well as four derived exploration scenarios that depend on different prioritized scientific targets, all visualizing inherent tradeoffs. Our method uses the NASA PDS Geosciences Node and the NASA/ICA Integrated Database of Planetary Features. Under common assumptions, the data products reveal Eastern Margaritifer Terra and Meridiani Planum to be the most favorable sites due to a high concentration of scientific targets and a flat, easily navigable surface. Our method also allows mission designers to investigate which constraints have the highest impact on the mission exploration potential and to change parameter ranges. Increasing the elevation limit for landing, for example, provides access to many additional

The Research Progress of Targeted Drug Delivery Systems

Science.gov (United States)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Search for over 2000 current and legacy micropollutants on a wastewater infiltration site with a UPLC-high resolution MS target screening method.

Science.gov (United States)

Wode, Florian; van Baar, Patricia; Dünnbier, Uwe; Hecht, Fabian; Taute, Thomas; Jekel, Martin; Reemtsma, Thorsten

2015-02-01

A target screening method using ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was developed. The method was applied to 14 groundwater and 11 surface water samples of a former wastewater infiltration site, where raw wastewater was applied until 1985 and treated wastewater is applied since 2005. The measured data are compared with mass spectrometric data of over 2000 organic micropollutants (OMPs), including pharmaceuticals, personal care products, pesticides, industrial chemicals and metabolites of these classes. A total number of 151 and 159 OMPs were detected in groundwater and surface water, respectively, of which 12 have not been reported before in these matrices. Among these 12 compounds were 11 pharmaceuticals and one personal care product. The identity of 55 of the detected OMPs (35%) was verified by analysis of standard compounds. Based on the distribution in the study area, two groups of OMPs were clearly distinguished: current OMPs introduced with treated municipal wastewater since 2005 and legacy OMPs originating from infiltration of untreated wastewater until 1985. A third group included OMPs contained in historic as well as in current wastewater. During infiltration, OMPs with molecular mass >500 g/mol and log DOW > 3.9 were preferentially removed. Speciation had a strong impact with cationic OMPs showing high, neutral OMPs medium and anionic OMPs lowest elimination during infiltration. This target screening method proved useful to study a wide range of compounds, even in retrospect and at sites with poorly documented history and with a complex and variable hydrological situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Untrivial Pursuit: Measuring Motor Procedures Learning in Children with Autism.

Science.gov (United States)

Sparaci, Laura; Formica, Domenico; Lasorsa, Francesca Romana; Mazzone, Luigi; Valeri, Giovanni; Vicari, Stefano

2015-08-01

Numerous studies have underscored prevalence of motor impairments in children with autism spectrum disorders (ASD), but only few of them have analyzed motor strategies exploited by ASD children when learning a new motor procedure. To evaluate motor procedure learning and performance strategies in both ASD and typically developing (TD) children, we built a virtual pursuit rotor (VPR) task, requiring tracking a moving target on a computer screen using a digitalized pen and tablet. Procedural learning was measured as increased time on target (TT) across blocks of trials on the same day and consolidation was assessed after a 24-hour rest. The program and the experimental setting (evaluated in a first experiment considering two groups of TD children) allowed also measures of continuous time on target (CTT), distance from target (DT) and distance from path (DP), as well as 2D reconstructions of children's trajectories. Results showed that the VPR was harder for children with ASD than for TD controls matched for chronological age and intelligence quotient, but both groups displayed comparable motor procedure learning (i.e., similarly incremented their TT). However, closer analysis of CTT, DT, and DP as well as 2D trajectories, showed different motor performance strategies in ASD, highlighting difficulties in overall actions planning. Data underscore the need for deeper investigations of motor strategies exploited by children with ASD when learning a new motor procedure. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Errata: Reasons For Tooth Extraction Among Nigerian Children ...

African Journals Online (AJOL)

Dental caries was the predominant reason for exodontia in Nigeria children attending a general dental practice in Uselu, Edo State. Extensive prevention programmes targeted at children with high caries risk in schools and the communities is a necessity. Key words: exodontia, reasons, children, general dental practice ...

Targeted metabolomic profiling indicates structure-based perturbations in serum phospholipids in children with acetaminophen overdose

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Sudeepa Bhattacharyya

Full Text Available Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC and lysophosphatidylcholine (lysoPC metabolism in acetaminophen (APAP-treated animals or cell cultures. However, little is known about phospholipid perturbations in humans with APAP toxicity. In the current study, targeted metabolomic analysis of 180 different metabolites including 14 lysoPCs and 73 PCs was performed in serum samples from children and adolescents hospitalized for APAP overdose. Metabolite profiles in the overdose group were compared to those of healthy controls and hospitalized children receiving low dose APAP for treatment of pain or fever (therapeutic group. PCs and lysoPCs with very long chain fatty acids (VLCFAs were significantly decreased in the overdose group, while those with comparatively shorter chain lengths were increased in the overdose group compared to the therapeutic and control groups. All ether linked PCs were decreased in the overdose group compared to the controls. LysoPC-C26:1 was highly reduced in the overdose group and could discriminate between the overdose and control groups with 100% sensitivity and specificity. The PCs and lysoPCs with VLCFAs showed significant associations with changes in clinical indicators of drug metabolism (APAP protein adducts and liver injury (alanine aminotransferase, or ALT. Thus, a structure-dependent reduction in PCs and lysoPCs was observed in the APAP-overdose group, which may suggest a structure-activity relationship in inhibition of enzymes involved in phospholipid metabolism in APAP toxicity. Keywords: Metabolomics, Phospholipids, Acetaminophen, Hepatotoxicity, Drug

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

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Thomas T Joseph

Full Text Available In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the

Dual-band infrared capabilities for imaging buried object sites

Energy Technology Data Exchange (ETDEWEB)

Del Grande, N.K.; Durbin, P.F.; Gorvad, M.R.; Perkins, D.E.; Clark, G.A.; Hernandez, J.E.; Sherwood, R.J.

1993-04-02

We discuss dual-band infrared (DBIR) capabilities for imaging buried object sizes. We identify physical features affecting thermal contrast needed to distinguish buried object sites from undisturbed sites or surface clutter. Apart from atmospheric transmission and system performance, these features include: object size, shape, and burial depth; ambient soil, disturbed soil and object site thermal diffusivity differences; surface temperature, emissivity, plant-cover, slope, albedo and roughness variations; weather conditions and measurement times. We use good instrumentation to measure the time-varying temperature differences between buried object sites and undisturbed soil sites. We compare near surface soil temperature differences with radiometric infrared (IR) surface temperature differences recorded at 4.7 {plus_minus} 0.4 {mu}m and at 10.6 {plus_minus} 1.0 {mu}m. By producing selective DBIR image ratio maps, we distinguish temperature-difference patterns from surface emissivity effects. We discuss temperature differences between buried object sites, filled hole site (without buried objects), cleared (undisturbed) soil sites, and grass-covered sites (with and without different types of surface clutter). We compare temperature, emissivity-ratio, visible and near-IR reflectance signatures of surface objects, leafy plants and sod. We discuss the physical aspects of environmental, surface and buried target features affecting interpretation of buried targets, surface objects and natural backgrounds.

ERP markers of target selection discriminate children with high vs. low working memory capacity.

Science.gov (United States)

Shimi, Andria; Nobre, Anna Christina; Scerif, Gaia

2015-01-01

Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM) system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults' selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children's selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults' selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc). However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the "adult time-window" related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children's neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM performance in children.

Children's Perceptions of Gender Discrimination

Science.gov (United States)

Brown, Christia Spears; Bigler, Rebecca S.

2004-01-01

Children (N = 76; ages 5-10 years) participated in a study designed to examine perceptions of gender discrimination. Children were read scenarios in which a teacher determined outcomes for 2 students (1 boy and 1 girl). Contextual information (i.e., teacher's past behavior), the gender of the target of discrimination (i.e., student), and the…

Watch Out for Children: A Mothers' Statement to Advertisers.

Science.gov (United States)

Institute for American Values, New York, NY.

This report explains that all adults must watch out for all children, cautioning that marketing is harmful to children. Advertisers are aggressively targeting age groups that, until recently, have been considered off-limits and occupying more of children's psychic and physical space. The report presents a commitment by mothers to all children to…

Epitope-Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent in Cell Inhibitor of Botulinum Neurotoxin**

OpenAIRE

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M.; Das, Samir; Nag, Arundhati; Agnew, Heather D.; Heath, James R.

2015-01-01

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ ...

Effective intervention for expressive grammar in children with specific language impairment.

Science.gov (United States)

Smith-Lock, Karen M; Leitao, Suze; Lambert, Lara; Nickels, Lyndsey

2013-01-01

Children with specific language impairment are known to struggle with expressive grammar. While some studies have shown successful intervention under laboratory conditions, there is a paucity of evidence for the effectiveness of grammar treatment in young children in community settings. To evaluate the effectiveness of a school-based intervention programme for expressive grammar in 5-year-olds with specific language impairment. Thirty-four 5-year-old children attending a specialized school for children with language impairment participated in the study. Nineteen children received treatment for expressive grammar (experimental group) and 15 children received a control treatment. Treatment consisted of weekly 1-h sessions of small group activities in a classroom setting for 8 weeks. Techniques included direct instruction, focused stimulation, recasting and imitation. Results were analysed at the group level and as a case series with each child as their own control in a single-subject design. There was a significant difference in grammatical performance pre- and post-treatment for children who received grammar treatment (Cohen's d = 1.24), but not for a group of children who received a control treatment. Further, no difference in performance was found in the equivalent time period prior to treatment, nor for an untreated target. Treatment success was more pronounced in children without articulation difficulties which interfered with their ability to produce the grammatical targets (Cohen's d = 1.66). Individual analyses indicated the treatment effect was significant for the majority of children. Individually targeted intervention delivered in small groups in a classroom setting was effective in improving production of expressive grammatical targets in 5-year-old children with specific language impairment. © 2013 Royal College of Speech and Language Therapists.

A cocktail-party listening experiment with children

Science.gov (United States)

Wightman, Frederic; Callahan, Michael; Kistler, Doris

2003-04-01

In an experiment modeled after one reported recently by Brungart and Simpson [J. Acoust. Soc. Am. 112, 2985-2995 (2002)], 38 children (ages 4-16) and 10 adults responded to a monaural target speech signal in the presence of one or two distracter speech signals. The target speaker was a male and the distracter speakers were females. When two distracters were present they were in different ears. Performance at several different target ear S/N was measured and psychometric functions were fitted to estimate threshold, or the 50% performance level. The youngest children required approximately 20 dB higher S/N than adults to achieve threshold with a single distracter. This difference disappeared by age 16. The impact of adding the contralateral distracter, which is thought to contribute only informational masking, was roughly constant across age, however. Adult thresholds increased about 11 dB and the thresholds for the youngest children increased about 10 dB. This was surprising given previous experiments that showed much larger informational masking effects in young children. Also inconsistent with previous results is the lack of individual differences. Nearly all listeners showed almost the same contralateral distracter effect. [Work supported by NICHD.

The Effect of Target Age on the Activation of Gender Stereotypes.

Science.gov (United States)

Powlishta, Kimberly K.

2000-01-01

Investigated the impact of target age on gender stereotyping. College and elementary students viewed photographs of men, women, boys, and girls, rating each for masculine, feminine, and neutral personality traits. Adults also rated likelihood of masculine and feminine traits in adults versus children. Target age had important implications for…

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Target Capture during Mos1 Transposition*

Science.gov (United States)

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-01

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

Characteristics of Incarcerated Fathers and Mothers: Implications for Preventive Interventions Targeting Children and Families.

Science.gov (United States)

Kjellstrand, Jean; Cearley, Jennifer; Eddy, J Mark; Foney, Dana; Martinez, Charles R

2012-12-01

The number of children of incarcerated parents in the U.S. has grown dramatically in recent years. These children appear to be at risk for various problems, and a number of family-focused preventive efforts have been attempted. The current study examines differences between incarcerated mothers, incarcerated fathers, and their families on factors that might be important to consider when creating the content and process of preventive intervention programs. Participants were 359 inmates (54% women; 41% minority) who were parents of children between the ages of 3 and 11 years and who parented their children prior to imprisonment. Mothers and fathers were similar on a number of dimensions including age, education-level, number and age of children, and family criminal history, but differences were observed on key variables relevant to outcomes for children and families, including employment history and income, substance use, mental health, trauma experiences and criminal history. Implications for prevention programs are discussed.

Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children.

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Wu, Guojun; Zhang, Chenhong; Wang, Jing; Zhang, Feng; Wang, Ruirui; Shen, Jian; Wang, Linghua; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping; Zhang, Menghui

2016-04-05

The gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 10(6) microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome.

Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

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Kammermeier, Jochen; Drury, Suzanne; James, Chela T; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip; Lench, Nicholas; Uhlig, Holm H; Bacchelli, Chiara; Shah, Neil

2014-11-01

Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important. We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20). TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes. Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Children's metacognitive judgments in an eyewitness identification task.

Science.gov (United States)

Keast, Amber; Brewer, Neil; Wells, Gary L

2007-08-01

Two experiments examined children's metacognitive monitoring of recognition judgments within an eyewitness identification paradigm. A confidence-accuracy (CA) calibration approach was used to examine patterns of calibration, over-/underconfidence, and resolution. In Experiment 1, children (n=619, mean age=11 years 10 months) and adults (n=600) viewed a simulated crime and attempted two separate identifications from 8-person target-present or target-absent lineups given lineup instructions that manipulated witnesses choosing patterns by varying the degree of social pressure. For choosers, but not nonchoosers, meaningful CA relations were observed for adults but not for children. Experiment 2 tested a guided hypothesis disconfirmation manipulation designed to improve the realism of children's metacognitive judgments. Children (N=796, mean age=11 years 11 months) in experimental and control conditions viewed a crime and attempted two separate identifications. The manipulation had minimal impact on the CA relation for choosers and nonchoosers. In contrast to adults, children's identification confidence provides no useful guide for investigators about the likely guilt or innocence of a suspect. These experiments revealed limitations in children's metacognitive monitoring processes that have not been apparent in previous research on recall and recognition with younger children.

Consumer behaviours: Teaching children to save energy

Science.gov (United States)

Grønhøj, Alice

2016-08-01

Energy-saving programmes are increasingly targeted at children to encourage household energy conservation. A study involving the assignment of energy-saving interventions to Girl Scouts shows that a child-focused intervention can improve energy-saving behaviours among children and their parents.

Characteristics of Clinico-pathologic Presentations of Chronic Gastroduodenitis in Children with Lambliasis Invasion

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Matveeva O.V.

2012-03-01

Full Text Available The analysis of anamnestic and clinical indices, and also morphological investigation of biopsy materials of mucous coat of stomach and duodenum in children with chronic gastroduodenitis of different etiology including lambliasis invasion is carried out with the purpose of detecting features of clinicopathologic presentations of chronic gastroduodenitis in children with and without lambliasis invasion. Material and methods. 100 patients (50 children with confirmed lambliasis invasion and 50 patients without lambliasis invasion aged from 2 up to 16 were under observation. The material for histologic study was received as a result of fibrogastroduodenoscopy carried out with target biopsy of fundic, antrum and duodenum mucosa. Results. As a result of the findings moderate pains sited in epigastric and periumbilical regions are characteristic for children with lambliasis invasion; irradiation and cramping characteristics of pains are typical. Conclusion. Manifestation of pains is not connected with the time of day and food intake, manifestation of seasonal prevalence is not typical as well, and progression of inflammatory process in the mucous coat of the stomach and duodenum is declared itself as a diffuse gastritis of the fundic part, a diffuse gastritis of the antral part, subatrophic duodenitis with cyst formation of Brunner's glands, and also the presence of eosinophilic leucocytes in the cellular infiltrate

Tumor-targeting peptides from combinatorial libraries*

Science.gov (United States)

Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

2018-01-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

A theoretical alternative intraosseous infusion site in severely hypovolemic children

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Nkhensani Mogale

2015-07-01

Full Text Available Background: Studies have shown that the venous system tends to collapse during hypovolemic shock. The use of the bone marrow space for infusions is an effective alternative, with the tibial insertion site being the norm. Objectives: This study was conducted to determine a quick intraosseous infusion method that could be an alternative to the tibial route in neonates during emergency situations. Method: A sample of 30 neonatal cadavers was dissected to explore a possible alternative to the tibial insertion site. The needle was inserted in the superolateral aspect of the humerus. The needle infusion site was then dissected to determine possible muscular and neurovascular damage that might occur during the administration of this procedure, with the greatest concern being the posterior circumflex humeral artery and axillary nerve exiting the quadrangular space. The distance of the needle insertion site was measured in relation to the soft tissue aswell as to bony landmarks. Results: The calculated 95% confidence interval shows that the needle can be safely inserted into the intraosseous tissue at the greater tubercle of the humerus 9.5 mm – 11.1 mm from the acromion. This is about a little finger’s width from the acromioclavicular joint. Conclusion: Anatomically, the described site is suggested to offer a safe alternative access point for emergency infusion in severely hypovolemic newborns and infants, without the risk of damage to any anatomical structures.

Binding-site assessment by virtual fragment screening.

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Niu Huang

2010-04-01

Full Text Available The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock approximately 11,000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature

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Alexander Patronis

2018-04-01

Full Text Available Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.. We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow.

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature.

Science.gov (United States)

Patronis, Alexander; Richardson, Robin A; Schmieschek, Sebastian; Wylie, Brian J N; Nash, Rupert W; Coveney, Peter V

2018-01-01

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow.

Kinetic analysis of the effects of target structure on siRNA efficiency

Science.gov (United States)

Chen, Jiawen; Zhang, Wenbing

2012-12-01

RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.

Malignant melanoma in children: imaging spectrum

International Nuclear Information System (INIS)

Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

1996-01-01

Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

Science.gov (United States)

Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

2018-01-01

The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Marketing Strategies Used to Promote Children's Medicine Sold on Internet Sites of Pharmaceutical Stores.

Science.gov (United States)

Basch, Corey H; Roberts, Katherine J; Zagnit, Emily A; Martinez, Amairany

2016-12-01

Retail sales of over the counter (OTC) medications have risen steadily over the years; however, these products are not without potential risk. The aim of this study was to describe the marketing strategies used to promote OTC medicines to children and their parents. Data were collected from 187 product packaging of fever reducer, allergy, and cough medicines posted on the Internet sites of three of the largest pharmacies in the United States. Specific marketing information was collected related to flavorings and pictures appearing on the packaging. There was no significant difference between the type of medicine and whether they were flavored or not, as almost every product (95.7 %) indicated that it resembles a food flavoring. On almost all the packaging (92.5 %) the flavor was also indicated by words in different font sizes. Most of the products (83.4 %) showed a picture of a food product on their packaging. There was a significant difference between the medicine types by picture, with fever medicines having more pictures of food than either cough or allergy medicine. Stronger regulations of marketing strategies of these products are needed.

Target Marketing and Ethics Brand Advertising and Marketing Campaigns

OpenAIRE

Gyongyi K. Fogel; Lorinda F. Lewis

2010-01-01

Marketing to a targeted minority can provide a competitive advantage for an organization. However, there are ethical and legal concerns that must be carefully evaluated. Youth, children, and protected minorities, including women and the elderly, are a high target of advertising because of the increasing importance of these segments in making purchasing decisions. Recent population and demographic factors continue to impact marketing to address minority marketing issues with careful attention ...

The impact of social media on children, adolescents, and families.

Science.gov (United States)

O'Keeffe, Gwenn Schurgin; Clarke-Pearson, Kathleen

2011-04-01

Using social media Web sites is among the most common activity of today's children and adolescents. Any Web site that allows social interaction is considered a social media site, including social networking sites such as Facebook, MySpace, and Twitter; gaming sites and virtual worlds such as Club Penguin, Second Life, and the Sims; video sites such as YouTube; and blogs. Such sites offer today's youth a portal for entertainment and communication and have grown exponentially in recent years. For this reason, it is important that parents become aware of the nature of social media sites, given that not all of them are healthy environments for children and adolescents. Pediatricians are in a unique position to help families understand these sites and to encourage healthy use and urge parents to monitor for potential problems with cyberbullying, "Facebook depression," sexting, and exposure to inappropriate content.

Violence in Children's Television Programming: Assessing the Risks.

Science.gov (United States)

Wilson, Barbara J.; Smith, Stacy L.; Potter, W. James; Kunkel, Dale; Linz, Daniel; Colvin, Carolyn M.; Donnerstein, Edward

2002-01-01

Investigates the nature and extent of violence contained in television programming that targets children aged 12 and younger. Notes that the violence itself is just as likely to be glamorized in children's as in nonchildren's shows, but it is even more sanitized and more likely to be trivialized. Documents five subgenres of children's programming…

How important is the choice of the nutrient profile model used to regulate broadcast advertising of foods to children? A comparison using a targeted data set.

Science.gov (United States)

Scarborough, P; Payne, C; Agu, C G; Kaur, A; Mizdrak, A; Rayner, M; Halford, J C G; Boyland, E

2013-08-01

The World Health Assembly recommends that children's exposure to marketing of unhealthy foods should be reduced. Nutrient profile models have been developed that define 'unhealthy' to support regulation of broadcast advertising of foods to children. The level of agreement between these models is not clear. The objective of this study was to measure the agreement between eight nutrient profile models that have been proposed for the regulation of marketing to children over (a) how many and (b) what kind of foods should be permitted to be advertised during television viewed by children. A representative data set of commercials for foods broadcast during television viewed by children in the UK was collected in 2008. The data set consisted of 11,763 commercials for 336 different products or brands. This data set was supplemented with nutrition data from company web sites, food packaging and a food composition table, and the nutrient profile models were applied. The percentage of commercials that would be permitted by the different nutrient profile models ranged from 2.1% (0.4%, 3.7%) to 47.4% (42.1%, 52.6%). Half of the pairwise comparisons between models yielded kappa statistics less than 0.2, indicating that there was little agreement between models. Policy makers considering the regulation of broadcast advertising to children should carefully consider the choice of nutrient profile model to support the regulation, as this choice will have considerable influence on the outcome of the regulation.

The State of the World's Children 2014 in Numbers: Every Child Counts. Revealing Disparities, Advancing Children's Rights

Science.gov (United States)

Aslam, Abid; Grojec, Anna; Little, Céline; Maloney, Ticiana; Tamagni, Jordan

2014-01-01

"The State of the World's Children 2014 In Numbers: Every Child Counts" highlights the critical role data and monitoring play in realizing children's rights. Credible data, disseminated effectively and used correctly, make it possible to target interventions that help right the wrong of exclusion. Data do not, of themselves, change the…

Outcomes of a pilot obesity prevention plus intervention targeting children and parenting practices

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Prevention-Plus interventions for primary care offer a venue to intervene with both children and parents for child obesity treatment. Such interventions can promote effective parenting practices that encourage healthy eating, physical activity (PA), and lower TV use among children. Test for feasibil...

Antecedents of children's satisfaction with company websites and their links with brand awareness

DEFF Research Database (Denmark)

Sermanet, L.; Goethals, F.; Carugati, Andrea

2011-01-01

the classic Information Systems success model of DeLone and McLean to IS success with children. They carried out a survey of a sample of 76 children aged 11 to 14, located in various cities in France. The results show that children get higher brand awareness if they are more satisfied with the kids website...... of the brand. The chapter finds the satisfaction with the site depends upon the personalization that is possible and the presence of dynamic elements on the site. Characters and animations that help navigatin the site are also appreciated. A good presentation of the site’s rules could not be shown...... to be a significant antecedent of satisfaction. Qualitative data that was gathered suggests that children are not really aware of the link between symbols they see on the site and products that are sold....

Identification accuracy of children versus adults: a meta-analysis.

Science.gov (United States)

Pozzulo, J D; Lindsay, R C

1998-10-01

Identification accuracy of children and adults was examined in a meta-analysis. Preschoolers (M = 4 years) were less likely than adults to make correct identifications. Children over the age of 5 did not differ significantly from adults with regard to correct identification rate. Children of all ages examined were less likely than adults to correctly reject a target-absent lineup. Even adolescents (M = 12-13 years) did not reach an adult rate of correct rejection. Compared to simultaneous lineup presentation, sequential lineups increased the child-adult gap for correct rejections. Providing child witnesses with identification practice or training did not increase their correct rejection rates. Suggestions for children's inability to correctly reject target-absent lineups are discussed. Future directions for identification research are presented.

Detection of helicopter landing sites in unprepared terrain

Science.gov (United States)

Peinecke, Niklas

2014-06-01

The primary usefulness of helicopters shows in missions where regular aircraft cannot be used, especially HEMS (Helicopter Emergency Medical Services). This might be due to requirements for landing in unprepared areas without dedicated runway structures, and an extended exibility to y to more than one previously unprepared target. One example of such missions are search and rescue operations. An important task of such a mission is to locate a proper landing spot near the mission target. Usually, the pilot would have to evaluate possible landing sites by himself, which can be time-intensive, fuel-costly, and generally impossible when operating in degraded visual environments. We present a method for pre-selecting a list of possible landing sites. After specifying the intended size, orientation and geometry of the site, a choice of possibilities is presented to the pilot that can be ordered by means of wind direction, terrain constraints like maximal slope and roughness, and proximity to a mission target. The possible choices are calculated automatically either from a pre-existing terrain data base, or from sensor data collected during earlier missions, e.g., by collecting data with radar or laser sensors. Additional data like water-body maps and topological information can be taken into account to avoid landing in dangerous areas under adverse view conditions. In case of an emergency turnaround the list can be re-ordered to present alternative sites to the pilot. We outline the principle algorithm for selecting possible landing sites, and we present examples of calculated lists.

Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins

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Gayani N. P. Dedduwa-Mudalige

2015-09-01

Full Text Available Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human.

Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

Science.gov (United States)

Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

2017-12-17

In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

Outdoor Education for Bereaved Children?

Science.gov (United States)

Renner, Hans-Georg

2011-01-01

For many outdoor education providers, bereaved children and young people at first appear to be a new target audience. A new target audience naturally raises questions of programme planning and can give the provider a pressurised need to succeed: "Do I as the organiser have to develop a whole new programme?", "May I be required to provide some form…

Children with social phobia have lower quality friendships than children with other anxiety disorders.

Science.gov (United States)

Baker, J R; Hudson, J L

2015-01-01

Whilst shy, socially anxious or socially withdrawn children in nonclinical community samples report lower friendship quality (FQ) than nonanxious children, no study has examined the FQ of clinically anxious children. The aim of the study was to examine the FQ of children with anxiety disorders; and whether it differs for clinical children with or without a diagnosis of social phobia (SP). The study design was cross-sectional self-report. Clinical children - 39 anxiety-disordered children with SP and 28 anxiety-disordered children without SP (No-SP) - presented for psychological treatment, and 29 nonclinical children were recruited from the community. Same-sex close friends were invited to participate using an unrestricted nomination procedure. All children were aged between 7 and 13 years. Both target child and friend completed the Friendship Quality Questionnaire and the Spence Children's Anxiety Scale. Using multilevel modeling within the framework of the Actor-Partner Interdependence Model, SP dyads were found to report lower overall FQ than No-SP dyads. SP dyads did not report lower overall FQ than nonclinical dyads. Children with SP in their diagnostic profile may be unique in their friendship experiences relative to children with other anxiety disorders.

Sex difference in choice of concealed or exposed refuge sites by preschool children viewing a model leopard in a playground simulation of antipredator behavior

Directory of Open Access Journals (Sweden)

Richard G. Coss

2016-07-01

Full Text Available The current study of preschool children characterizes a semi-natural extension of experimental questions on how human ancestors evaded predation when encountering dangerous felids. In a pretend game on a playground, we presented full-size leopard and deer models to children (N = 39 in a repeatedmeasures experimental design. Prior to viewing the model presented 15-m away, each child was instructed by the experimenter to go where she or he would feel safe. The rationale for this study was based on the anthropological construct of “sexual dinichism,” positing that, during the Pliocene, smaller-bodied hominin females engaged in more arboreal behavior than larger-bodied males. Consistent with this construct, our previous simulation research using images of an African rock outcrop showed that, after viewing a lion, girls preferred a tree as refuge rather than a crevice or large boulder whereas boys did not differentiate these refuge sites. In this follow-up study, we predicted that, after viewing the model leopard, the preschool girls would differ from the boys by not choosing enclosed refuge sites analogous to the crevice. Analyses of a contingency table for the leopard model supported this hypothesis by yielding a significant interaction of sex and refuge location (p = .031, d = .76, the source of which was a reliably larger percentage of girls not choosing concealed refuge (p = .005, d = 2.3. The interaction of sex and refuge location for the model deer was not significant (p > .5. Our findings suggest that, in contrast to the deer, the girls selected exposed playground refuge sites rather than concealing ones to maintain visual contact with the leopard as a contingency for future action

Hand fractures: A study of their site and type in childhood

International Nuclear Information System (INIS)

Rajesh, Arumugam; Basu, Avi K.; Vaidhyanath, Ramachandran; Finlay, David

2001-01-01

AIM: The purpose of the study was to document the site and type of fractures of the hand in children up to 16 years of age. MATERIALS AND METHODS: The radiographs of 280 children who were found to have a fracture in Accident and Emergency over a one-year period were reviewed. A total of 293 fractures of the hand and 3 distal interphalangeal joint dislocations without fracture were identified. There were 293 fractures as some children had more than one fracture. RESULTS: Distal tuft fractures were commonest in the 0 to 4-year age-group; fractures of distal phalanx (both transverse and tuft) in the 5 to 8-year age-group; transverse fractures of the proximal phalanx of little finger in the 9 to 12-year age-group and transverse fractures of neck of the fifth metacarpal in the 13 to 16-year age-groups. CONCLUSION: Hand fractures are more common in older children, with a male preponderance in most groups except in the 0-4 age-group. The site of injury is different in the various corresponding age-groups, reflecting the differing mechanisms of injury. The management of hand fractures rely on a correct diagnosis and a knowledge of their common site in each age-group should aid diagnosis. Rajesh, A. et al. (2001)

Total Site Heat Integration Considering Pressure Drops

Directory of Open Access Journals (Sweden)

Kew Hong Chew

2015-02-01

Full Text Available Pressure drop is an important consideration in Total Site Heat Integration (TSHI. This is due to the typically large distances between the different plants and the flow across plant elevations and equipment, including heat exchangers. Failure to consider pressure drop during utility targeting and heat exchanger network (HEN synthesis may, at best, lead to optimistic energy targets, and at worst, an inoperable system if the pumps or compressors cannot overcome the actual pressure drop. Most studies have addressed the pressure drop factor in terms of pumping cost, forbidden matches or allowable pressure drop constraints in the optimisation of HEN. This study looks at the implication of pressure drop in the context of a Total Site. The graphical Pinch-based TSHI methodology is extended to consider the pressure drop factor during the minimum energy requirement (MER targeting stage. The improved methodology provides a more realistic estimation of the MER targets and valuable insights for the implementation of the TSHI design. In the case study, when pressure drop in the steam distribution networks is considered, the heating and cooling duties increase by 14.5% and 4.5%.