Effects of variability of practice in music: a pilot study on fast goal-directed movements in pianists

PubMed Central

Bangert, Marc; Wiedemann, Anna; Jabusch, Hans-Christian

2014-01-01

Variability of Practice (VOP) refers to the acquisition of a particular target movement by practicing a range of varying targets rather than by focusing on fixed repetitions of the target only. VOP has been demonstrated to have beneficial effects on transfer to a novel task and on skill consolidation. This study extends the line of research to musical practice. In a task resembling a barrier-knockdown paradigm, 36 music students trained to perform a wide left-hand interval leap on the piano. Performance at the target distance was tested before and after a 30-min standardized training session. The high-variability group (VAR) practiced four different intervals including the target. Another group (FIX) practiced the target interval only. A third group (SPA) performed spaced practice on the target only, interweaving with periods of not playing. Transfer was tested by introducing an interval novel to either group. After a 24-h period with no further exposure to the instrument, performance was retested. All groups performed at comparable error levels before training, after training, and after the retention (RET) interval. At transfer, however, the FIX group, unlike the other groups, committed significantly more errors than in the target task. After the RET period, the effect was washed out for the FIX group but then was present for VAR. Thus, the results provide only partial support for the VOP hypothesis for the given setting. Additional exploratory observations suggest tentative benefits of VOP regarding execution speed, loudness, and performance confidence. We derive specific hypotheses and specific recommendations regarding sample selection and intervention duration for future investigations. Furthermore, the proposed leap task measurement is shown to be (a) robust enough to serve as a standard framework for studies in the music domain, yet (b) versatile enough to allow for a wide range of designs not previously investigated for music on a standardized basis. PMID:25157223

Adults with Dyslexia Demonstrate Space-Based and Object-Based Covert Attention Deficits: Shifting Attention to the Periphery and Shifting Attention between Objects in the Left Visual Field

ERIC Educational Resources Information Center

Buchholz, J.; Davies, A.A.

2005-01-01

Performance on a covert visual attention task is compared between a group of adults with developmental dyslexia (specifically phonological difficulties) and a group of age and IQ matched controls. The group with dyslexia were generally slower to detect validly-cued targets. Costs of shifting attention toward the periphery when the target was…

Phylum- and Class-Specific PCR Primers for General Microbial Community Analysis

PubMed Central

Blackwood, Christopher B.; Oaks, Adam; Buyer, Jeffrey S.

2005-01-01

Amplification of a particular DNA fragment from a mixture of organisms by PCR is a common first step in methods of examining microbial community structure. The use of group-specific primers in community DNA profiling applications can provide enhanced sensitivity and phylogenetic detail compared to domain-specific primers. Other uses for group-specific primers include quantitative PCR and library screening. The purpose of the present study was to develop several primer sets targeting commonly occurring and important groups. Primers specific for the 16S ribosomal sequences of Alphaproteobacteria, Betaproteobacteria, Bacilli, Actinobacteria, and Planctomycetes and for parts of both the 18S ribosomal sequence and the internal transcribed spacer region of Basidiomycota were examined. Primers were tested by comparison to sequences in the ARB 2003 database, and chosen primers were further tested by cloning and sequencing from soil community DNA. Eighty-five to 100% of the sequences obtained from clone libraries were found to be placed with the groups intended as targets, demonstrating the specificity of the primers under field conditions. It will be important to reevaluate primers over time because of the continual growth of sequence databases and revision of microbial taxonomy. PMID:16204538

Telecommunications technology and rural education in the United States

NASA Technical Reports Server (NTRS)

Perrine, J. R.

1975-01-01

The rural sector of the US is examined from the point of view of whether telecommunications technology can augment the development of rural education. Migratory farm workers and American Indians were the target groups which were examined as examples of groups with special needs in rural areas. The general rural population and the target groups were examined to identify problems and to ascertain specific educational needs. Educational projects utilizing telecommunications technology in target group settings were discussed. Large scale regional ATS-6 satellite-based experimental educational telecommunications projects were described. Costs and organizational factors were also examined for large scale rural telecommunications projects.

Ubiquitin chain specificities of E6AP E3 ligase and its HECT domain.

PubMed

Kobayashi, Fuminori; Nishiuchi, Takumi; Takaki, Kento; Konno, Hiroki

2018-02-05

Ubiquitination of target proteins is accomplished by isopeptide bond formation between the carboxy group of the C-terminal glycine (Gly) residue of ubiquitin (Ub) and the ɛ-amino group of lysine (Lys) on the target proteins. The formation of an isopeptide bond between Ubs that gives rise to a poly-Ub chain on the target proteins and the types of poly-Ub chains formed depend on which of the seven Lys residues or N-terminal methionine (Met) residue on Ub is used for chain elongation. To understand the linkage specificity mechanism of Ub chains on E3, the previous study established an assay to monitor the formation of a free diubiquitin chain (Ub 2 chain synthesis assay) by HECT type E3 ligase. In this study, we investigated Ub 2 chain specificity using E6AP HECT domain. We here demonstrate the importance of the N-terminal domain of full length E6AP for Ub 2 chain specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Antisense oligonucleotides effectively inhibit the co-transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics.

PubMed

Zhang, Libin; Leibowitz, Michael J; Zhang, Yi

2009-02-18

Self-splicing of group I intron from the 26S rRNA of Candida albicans is essential for maturation of the host RNA. Here, we demonstrated that the co-transcriptional splicing of the intron in vitro was blocked by antisense oligonucleotides (AONs) targeting the P3-P7 core of the intron. The core-targeted AON effectively and specifically inhibited the intron splicing from its host RNA in living C. albicans. Furthermore, flow cytometry experiments showed that the growth inhibition was caused by a fungicidal effect. For the first time, we showed that an AON targeting the ribozyme core folding specifically inhibits the endogenous ribozyme splicing in living cells and specifically kills the intron-containing fungal strains, which sheds light on the development of antifungal drugs in the future.

Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices.

PubMed

Liang, Zhibing; Liu, Fuxian; Gao, Jiale

2018-01-01

For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms.

Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices

PubMed Central

Liu, Fuxian; Gao, Jiale

2018-01-01

For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms. PMID:29444144

Preclinical Evaluation to Specifically Target Ovarian Cancer with Folic Acid conjugated Nanoceria

DTIC Science & Technology

2013-06-01

function (creatinine; urea ; albumin, uric acid ) in plasma collected, showed no significant difference in the untreated and treated mice. All values were...Transaminase), AST (Aspartate Transaminase), Albumin, Creatinine, urea and uric acid . groups (Fig 9). These data show that FA-NCe treatment...Specifically Target Ovarian Cancer with Folic Acid conjugated Nanoceria. PRINCIPAL INVESTIGATOR: Ramandeep Rattan, PhD CONTRACTING ORGANIZATION

Targeted polymeric micelles for delivery of poorly soluble drugs.

PubMed

Torchilin, V P

2004-10-01

Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.

A glossary of policy frameworks: the many forms of 'universalism' and policy 'targeting'.

PubMed

Carey, Gemma; Crammond, Brad

2017-03-01

The recognition that certain characteristics (such as poverty, disadvantage or membership of marginalised social or cultural groups) can make individuals more susceptible to illness has reignited interest in how to combine universal programmes and policies with ones targeted at specific groups. However, 'universalism' and 'targeting' are used in different ways for different purposes. In this glossary, we define different types and approaches to universalism and targeting. We anticipate that greater clarity in relation to what is meant by 'universalism' and 'targeting' will lead to a more nuanced debate and practice in this area. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Beyond capacity limitations II: Effects of lexical processes on word recall in verbal working memory tasks in children with and without specific language impairment

PubMed Central

Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

2010-01-01

Purpose This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method Participants were 42 children (ages 8;2–12;3), 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a sentence span task where target words to be recalled varied in word frequency and neighborhood density. Two measures of lexical processes were examined, the number of non-target competitor words activated during a gating task (lexical cohort competition) and word definitions. Results Neighborhood density had no effect on word recall for either group. However, both groups recalled significantly more high than low frequency words. Lexical cohort competition and specificity of semantic representations accounted for unique variance in the number of target word recalled in the SLI and CA groups combined. Conclusions Performance on verbal working memory span tasks for both SLI and CA children is influenced by word frequency, lexical cohorts, and semantic representations. Future studies need to examine the extent to which verbal working memory capacity is a cognitive construct independent of extant language knowledge representations. PMID:20705747

Targeting core groups for gonorrhoea control: feasibility and impact.

PubMed

Giguère, Katia; Alary, Michel

2015-06-01

We aimed to outline why core groups should be targeted in Neisseria gonorrhoeae control and suggest several important and timely interventions to target core groups while highly resistant strains are spreading. Core group definition, feasibility and impact of gonorrhoea core group interventions as well as gonorrhoea resistance development have been reviewed in the paper. Core group interventions have proven effective in gonorrhoea control in the past but are compromised by the spread of highly resistant strains. Worldwide functional Gonorrhoea Antimicrobial Surveillance Program, better screening and better treatment programmes are needed. Prevention through condom promotion aimed at core groups remains essential. More specific treatment guidance for low-income and middle-income countries without resistance data is required in the meantime to achieve a better use of antibiotics. 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.

The whole-genome landscape of medulloblastoma subtypes

PubMed Central

Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Groebner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

2018-01-01

Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients. PMID:28726821

Dose and Time Dependencies in Stress Pathway Responses during Chemical Exposure: Novel Insights from Gene Regulatory Networks.

PubMed

Souza, Terezinha M; Kleinjans, Jos C S; Jennen, Danyel G J

2017-01-01

Perturbation of biological networks is often observed during exposure to xenobiotics, and the identification of disturbed processes, their dynamic traits, and dose-response relationships are some of the current challenges for elucidating the mechanisms determining adverse outcomes. In this scenario, reverse engineering of gene regulatory networks (GRNs) from expression data may provide a system-level snapshot embedded within accurate molecular events. Here, we investigate the composition of GRNs inferred from groups of chemicals with two distinct outcomes, namely carcinogenicity [azathioprine (AZA) and cyclophosphamide (CYC)] and drug-induced liver injury (DILI; diclofenac, nitrofurantoin, and propylthiouracil), and a non-carcinogenic/non-DILI group (aspirin, diazepam, and omeprazole). For this, we analyzed publicly available exposed in vitro human data, taking into account dose and time dependencies. Dose-Time Network Identification (DTNI) was applied to gene sets from exposed primary human hepatocytes using four stress pathways, namely endoplasmic reticulum (ER), NF-κB, NRF2, and TP53. Inferred GRNs suggested case specificity, varying in interactions, starting nodes, and target genes across groups. DILI and carcinogenic compounds were shown to directly affect all pathway-based GRNs, while non-DILI/non-carcinogenic chemicals only affected NF-κB. NF-κB-based GRNs clearly illustrated group-specific disturbances, with the cancer-related casein kinase CSNK2A1 being a target gene only in the carcinogenic group, and opposite regulation of NF-κB subunits being observed in DILI and non-DILI/non-carcinogenic groups. Target genes in NRF2-based GRNs shared by DILI and carcinogenic compounds suggested markers of hepatotoxicity. Finally, we indicate several of these group-specific interactions as potentially novel. In summary, our reversed-engineered GRNs are capable of revealing dose dependent, chemical-specific mechanisms of action in stress-related biological networks.

Motivation of restraint system usage among specific target groups of drivers and passengers

DOT National Transportation Integrated Search

1983-07-14

Thirty focus groups were conducted in seven different cities. These focus groups were used to determine potentially effective motivational approaches, develop appropriate themes and general content of messages and, finally, to identify corresponding ...

IT-25DEVELOPMENTALLY REGULATED ANTIGENS FOR IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES

PubMed Central

Pham, Christina; Flores, Catherine; Pei, Yanxin; Wechsler-Reya, Robert; Mitchell, Duane

2014-01-01

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy presents a promising alternative by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Emerging evidence from integrated genomic studies has suggested MB variants arise from deregulation of pathways affecting proliferation of progenitor cell populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and can be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.

Synthesis of galactosyl compounds for targeted gene delivery.

PubMed

Ren, T; Zhang, G; Liu, D

2001-11-01

Cell-specific DNA delivery offers a great potential for targeted gene therapy. Toward this end, we have synthesized a series of compounds carrying galactose residues as a targeting ligand for asialoglycoprotein receptors of hepatocytes and primary amine groups as a functional domain for DNA binding. Biological activity of these galactosyl compounds in DNA delivery was evaluated in HepG2 and BL-6 cells and compared with respect to the number of galactose residues as well as primary amine groups in each molecule. Transfection experiments using a firefly luciferase gene as a reporter revealed that compounds with multivalent binding properties were more active in DNA delivery. An optimal transfection activity in HepG2 cells requires seven primary amine groups and a minimum of two galactose residues in each molecule. The transfection activity of compounds carrying multi-galactose residues can be inhibited by asialofetuin, a natural substrate for asialoglycoprotein receptors of hepatocytes, suggesting that gene transfer by these galactosyl compounds is asialoglycoprotein receptor-mediated. These results provide direct evidence in support of our new strategy for the use of small and synthetic compounds for cell specific and targeted gene delivery.

Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

NASA Astrophysics Data System (ADS)

Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

2014-04-01

Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe3O4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe3O4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue.

Genus-specific PCR Primers Targeting Intracellular Parasite Euduboscquella (Dinoflagellata: Syndinea)

NASA Astrophysics Data System (ADS)

Jung, Jae-Ho; Choi, Jung Min; Kim, Young-Ok

2018-03-01

We designed a genus-specific primer pair targeting the intracellular parasite Euduboscquella. To increase target specificity and inhibit untargeted PCR, two nucleotides were added at the 3' end of the reverse primer, one being a complementary nucleotide to the Euduboscquella-specific SNP (single-nucleotide polymorphism) and the other a deliberately mismatched nucleotide. Target specificity of the primer set was verified experimentally using PCR of two Euduboscquella species (positive controls) and 15 related species (negative controls composed of ciliates, diatoms and dinoflagellates), and analytical comparison with SILVA SSU rRNA gene database (release 119) in silico. In addition, we applied the Euduboscquella-specific primer set to four environmental samples previously determined by cytological staining to be either positive or negative for Euduboscquella. As expected, only positive controls and environmental samples known to contain Euduboscquella were successfully amplified by the primer set. An inferred SSU rRNA gene phylogeny placed environmental samples containing aloricate ciliates infected by Euduboscquella in a cluster discrete from Euduboscquella groups a-d previously reported from loricate, tintinnid ciliates.

Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.

PubMed

Enyeart, Peter J; Mohr, Georg; Ellington, Andrew D; Lambowitz, Alan M

2014-01-13

Mobile group II introns are bacterial retrotransposons that combine the activities of an autocatalytic intron RNA (a ribozyme) and an intron-encoded reverse transcriptase to insert site-specifically into DNA. They recognize DNA target sites largely by base pairing of sequences within the intron RNA and achieve high DNA target specificity by using the ribozyme active site to couple correct base pairing to RNA-catalyzed intron integration. Algorithms have been developed to program the DNA target site specificity of several mobile group II introns, allowing them to be made into 'targetrons.' Targetrons function for gene targeting in a wide variety of bacteria and typically integrate at efficiencies high enough to be screened easily by colony PCR, without the need for selectable markers. Targetrons have found wide application in microbiological research, enabling gene targeting and genetic engineering of bacteria that had been intractable to other methods. Recently, a thermostable targetron has been developed for use in bacterial thermophiles, and new methods have been developed for using targetrons to position recombinase recognition sites, enabling large-scale genome-editing operations, such as deletions, inversions, insertions, and 'cut-and-pastes' (that is, translocation of large DNA segments), in a wide range of bacteria at high efficiency. Using targetrons in eukaryotes presents challenges due to the difficulties of nuclear localization and sub-optimal magnesium concentrations, although supplementation with magnesium can increase integration efficiency, and directed evolution is being employed to overcome these barriers. Finally, spurred by new methods for expressing group II intron reverse transcriptases that yield large amounts of highly active protein, thermostable group II intron reverse transcriptases from bacterial thermophiles are being used as research tools for a variety of applications, including qRT-PCR and next-generation RNA sequencing (RNA-seq). The high processivity and fidelity of group II intron reverse transcriptases along with their novel template-switching activity, which can directly link RNA-seq adaptor sequences to cDNAs during reverse transcription, open new approaches for RNA-seq and the identification and profiling of non-coding RNAs, with potentially wide applications in research and biotechnology.

Modeling health gains and cost savings for ten dietary salt reduction targets.

PubMed

Wilson, Nick; Nghiem, Nhung; Eyles, Helen; Mhurchu, Cliona Ni; Shields, Emma; Cobiac, Linda J; Cleghorn, Christine L; Blakely, Tony

2016-04-26

Dietary salt reduction is included in the top five priority actions for non-communicable disease control internationally. We therefore aimed to identify health gain and cost impacts of achieving a national target for sodium reduction, along with component targets in different food groups. We used an established dietary sodium intervention model to study 10 interventions to achieve sodium reduction targets. The 2011 New Zealand (NZ) adult population (2.3 million aged 35+ years) was simulated over the remainder of their lifetime in a Markov model with a 3 % discount rate. Achieving an overall 35 % reduction in dietary salt intake via implementation of mandatory maximum levels of sodium in packaged foods along with reduced sodium from fast foods/restaurant food and discretionary intake (the "full target"), was estimated to gain 235,000 QALYs over the lifetime of the cohort (95 % uncertainty interval [UI]: 176,000 to 298,000). For specific target components the range was from 122,000 QALYs gained (for the packaged foods target) down to the snack foods target (6100 QALYs; and representing a 34-48 % sodium reduction in such products). All ten target interventions studied were cost-saving, with the greatest costs saved for the mandatory "full target" at NZ$1260 million (US$820 million). There were relatively greater health gains per adult for men and for Māori (indigenous population). This work provides modeling-level evidence that achieving dietary sodium reduction targets (including specific food category targets) could generate large health gains and cost savings for a national health sector. Demographic groups with the highest cardiovascular disease rates stand to gain most, assisting in reducing health inequalities between sex and ethnic groups.

One session treatment for specific phobias in children: Comorbid anxiety disorders and treatment outcome.

PubMed

Ryan, Sarah M; Strege, Marlene V; Oar, Ella L; Ollendick, Thomas H

2017-03-01

One-Session Treatment (OST) for specific phobias has been shown to be effective in reducing phobia severity; however, the effect of different types of co-occurring anxiety disorders on OST outcomes is unknown. The present study examined (1) the effects of co-occurring generalized anxiety disorder (GAD), social anxiety disorder (SAD), or another non-targeted specific phobia (OSP) on the efficacy of OST for specific phobias, and (2) the effects of OST on these co-occurring disorders following treatment. Three groups of 18 youth (7-15 years) with a specific phobia and comorbid GAD, SAD, or OSP were matched on age, gender, and phobia type. Outcome measures included diagnostic status and severity, and clinician rated improvement. All groups demonstrated an improvement in their specific phobia following treatment. Treatment was equally effective regardless of co-occurring anxiety disorder. In addition, comorbid anxiety disorders improved following OST; however, this effect was not equal across groups. The SAD group showed poorer improvement in their comorbid disorder than the GAD group post-treatment. However, the SAD group continued to improve and this differential effect was not evident six-months following treatment. The current study sample was small, with insufficient power to detect small and medium effect sizes. Further, the sample only included a portion of individuals with primary GAD or SAD, which may have attenuated the findings. The current study demonstrated that co-occurring anxiety disorders did not interfere with phobia treatment. OST, despite targeting a single specific phobia type, significantly reduced comorbid symptomatology across multiple anxiety disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electrical resistance behavior of oxyfluorinated graphene under oxidizing and reducing gas exposure.

PubMed

Im, Ji Sun; Bae, Tae-Sung; Shin, Eunjeong; Lee, Young-Seak

2014-03-01

The electrical resistance behavior of graphene was studied under oxidizing and reducing gas exposure. The graphene surface was modified via oxyfluorination to obtain a specific surface area and oxygen functional groups. Fluorine radicals provided improved pore structure and introduction of an oxygen functional group. A high-performance gas sensor was obtained based on enlarged target gas adsorption sites and an enhanced electron charge transfer between the target gas and carbon surface via improved pore structure and the introduction of oxygen functional groups, respectively.

Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

PubMed Central

Mohr, Georg; Ghanem, Eman; Lambowitz, Alan M.

2010-01-01

Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelments hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting ∼1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases. PMID:20543989

Development of Quantitative PCR Assays Targeting the 16S rRNA Genes of Enterococcus spp. and Their Application to the Identification of Enterococcus Species in Environmental Samples

PubMed Central

Ryu, Hodon; Henson, Michael; Elk, Michael; Toledo-Hernandez, Carlos; Griffith, John; Blackwood, Denene; Noble, Rachel; Gourmelon, Michèle; Glassmeyer, Susan

2013-01-01

The detection of environmental enterococci has been determined primarily by using culture-based techniques that might exclude some enterococcal species as well as those that are nonculturable. To address this, the relative abundances of enterococci were examined by challenging fecal and water samples against a currently available genus-specific assay (Entero1). To determine the diversity of enterococcal species, 16S rRNA gene-based group-specific quantitative PCR (qPCR) assays were developed and evaluated against eight of the most common environmental enterococcal species. Partial 16S rRNA gene sequences of 439 presumptive environmental enterococcal strains were analyzed to study further the diversity of enterococci and to confirm the specificities of group-specific assays. The group-specific qPCR assays showed relatively high amplification rates with targeted species (>98%), although some assays cross-amplified with nontargeted species (1.3 to 6.5%). The results with the group-specific assays also showed that different enterococcal species co-occurred in most fecal samples. The most abundant enterococci in water and fecal samples were Enterococcus faecalis and Enterococcus faecium, although we identified more water isolates as Enterococcus casseliflavus than as any of the other species. The prevalence of the Entero1 marker was in agreement with the combined number of positive signals determined by the group-specific assays in most fecal samples, except in gull feces. On the other hand, the number of group-specific assay signals was lower in all water samples tested, suggesting that other enterococcal species are present in these samples. While the results highlight the value of genus- and group-specific assays for detecting the major enterococcal groups in environmental water samples, additional studies are needed to determine further the diversity, distributions, and relative abundances of all enterococcal species found in water. PMID:23087032

Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers.

PubMed

Pashkunova-Martic, Irena; Kremser, Christian; Galanski, Markus; Schluga, Petra; Arion, Vladimir; Debbage, Paul; Jaschke, Werner; Keppler, Bernhard

2011-06-01

Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by (1)H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.

Adults with dyslexia demonstrate space-based and object-based covert attention deficits: shifting attention to the periphery and shifting attention between objects in the left visual field.

PubMed

Buchholz, Judy; Aimola Davies, Anne

2005-02-01

Performance on a covert visual attention task is compared between a group of adults with developmental dyslexia (specifically phonological difficulties) and a group of age and IQ matched controls. The group with dyslexia were generally slower to detect validly-cued targets. Costs of shifting attention toward the periphery when the target was invalidly cued were significantly higher for the group with dyslexia, while costs associated with shifts toward the fovea tended to be lower. Higher costs were also shown by the group with dyslexia for up-down shifts of attention in the periphery. A visual field processing difference was found, in that the group with dyslexia showed higher costs associated with shifting attention between objects in they LVF. These findings indicate that these adults with dyslexia have difficulty in both the space-based and the object-based components of covert visual attention, and more specifically to stimuli located in the periphery.

A comparison of hemisphere-specific training pattern in Inter-limb Learning Transfer (ILT) for stroke patients with hemiparesis.

PubMed

Yoo, In-gyu; Jung, Min-ye; Yoo, Eun-young; Park, Ji-hyuk; Kang, Dae-hyuk; Lee, Jin

2014-01-01

Stroke patients have major problems with impaired upper-extremity function. Unfortunately, many patients do not experience a full recovery from movement deficits in the upper extremities. The purpose of this study was to compare the effectiveness of inter-limb learning transfer (ILT) to the contralateral upper limb after both hemisphere-specific and -unspecific ipsilateral upper limb training for stroke patients with hemiparesis. Twenty-four stroke patients with hemiparesis participated. The hemisphere-specific training group performed reaching movements in a customized training setting in which non-dominant limb training participants began from a single starting location and proceeded to one of three target locations (1S3T condition); the dominant limb training participants started from one of three starting locations and proceeded to a single target location (3S1T condition). The hemisphere-unspecific training group performed these movements starting under reverse-start and target conditions. The non-dominant to dominant limb transfer, the hemisphere-specific training group performance time decreased significantly as compared with the pre-training session (p < 0.05). Also, the isolation contraction ratio was decreased significantly from that of the pre-training session in the biceps brachii muscles and increased significantly in the upper trapezius muscles (p < 0.05). And, dominant to non-dominant limb transfer in the hemisphere-specific training group significantly increased RMS amplitudes from the pre-training session in the biceps brachii and triceps muscles (p < 0.05). Also, the isolation contraction ratio was increased significantly from that of the pre-training session in the biceps brachii muscles and decreased significantly in the upper trapezius muscles (p < 0.05). However, the hemisphere-unspecific training group showed no significant differences in inter-limb learning transfer (ILT). The transfer of hemisphere-specific training from one arm to the other had a more positive influence on functional recovery than did hemisphere-unspecific training for patients with stroke and hemiparesis.

Specific muscle stabilizing as home exercises for persistent pelvic girdle pain after pregnancy: a randomized, controlled clinical trial.

PubMed

Gutke, Annelie; Sjödahl, Jenny; Oberg, Birgitta

2010-11-01

To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain. A prospective, randomized, single-blinded, clinically controlled study. Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery. The treatment consisted of specific stabilizing exercises targeting the local trunk muscles. The reference group had a single telephone contact with a physiotherapist. Primary outcome was disability measured with Oswestry Disability Index. Secondary outcomes were pain, health-related quality of life (EQ-5D), symptom satisfaction, and muscle function. No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability. Within-group comparisons showed some improvement in both groups in terms of disability, pain, symptom satisfaction and muscle function compared with baseline, although the majority still experienced pelvic girdle pain. Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinically natural course. Regardless of whether treatment with specific stabilizing exercises was carried out, the majority of women still experienced some back pain almost one year after pregnancy.

Monitoring Processes in Visual Search Enhanced by Professional Experience: The Case of Orange Quality-Control Workers

PubMed Central

Visalli, Antonino; Vallesi, Antonino

2018-01-01

Visual search tasks have often been used to investigate how cognitive processes change with expertise. Several studies have shown visual experts' advantages in detecting objects related to their expertise. Here, we tried to extend these findings by investigating whether professional search experience could boost top-down monitoring processes involved in visual search, independently of advantages specific to objects of expertise. To this aim, we recruited a group of quality-control workers employed in citrus farms. Given the specific features of this type of job, we expected that the extensive employment of monitoring mechanisms during orange selection could enhance these mechanisms even in search situations in which orange-related expertise is not suitable. To test this hypothesis, we compared performance of our experimental group and of a well-matched control group on a computerized visual search task. In one block the target was an orange (expertise target) while in the other block the target was a Smurfette doll (neutral target). The a priori hypothesis was to find an advantage for quality-controllers in those situations in which monitoring was especially involved, that is, when deciding the presence/absence of the target required a more extensive inspection of the search array. Results were consistent with our hypothesis. Quality-controllers were faster in those conditions that extensively required monitoring processes, specifically, the Smurfette-present and both target-absent conditions. No differences emerged in the orange-present condition, which resulted to mainly rely on bottom-up processes. These results suggest that top-down processes in visual search can be enhanced through immersive real-life experience beyond visual expertise advantages. PMID:29497392

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2008-04-08

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2010-10-05

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Characterizing Health Information for Different Target Audiences.

PubMed

Sun, Yueping; Hou, Zhen; Hou, Li; Li, Jiao

2015-01-01

Different groups of audiences in health care: health professionals and health consumers, each have different information needs. Health monographs targeting different audiences are created by leveraging readers' background knowledge. The NCI's Physician Data Query (PDQ®) Cancer Information Summaries provide parallel cancer information and education resources with different target audiences. In this paper, we used targeted audience-specific cancer information PDQs to measure characteristic differences on the element level between audiences. In addition, we compared vocabulary coverage. Results show a significant difference between the professional and patient version of cancer monographs in both content organization and vocabulary. This study provides a new view to assess targeted audience-specific health information, and helps editors to improve the quality and readability of health information.

Functionality of In vitro Reconstituted Group II Intron RmInt1-Derived Ribonucleoprotein Particles.

PubMed

Molina-Sánchez, Maria D; García-Rodríguez, Fernando M; Toro, Nicolás

2016-01-01

The functional unit of mobile group II introns is a ribonucleoprotein particle (RNP) consisting of the intron-encoded protein (IEP) and the excised intron RNA. The IEP has reverse transcriptase activity but also promotes RNA splicing, and the RNA-protein complex triggers site-specific DNA insertion by reverse splicing, in a process called retrohoming. In vitro reconstituted ribonucleoprotein complexes from the Lactococcus lactis group II intron Ll.LtrB, which produce a double strand break, have recently been studied as a means of developing group II intron-based gene targeting methods for higher organisms. The Sinorhizobium meliloti group II intron RmInt1 is an efficient mobile retroelement, the dispersal of which appears to be linked to transient single-stranded DNA during replication. The RmInt1IEP lacks the endonuclease domain (En) and cannot cut the bottom strand to generate the 3' end to initiate reverse transcription. We used an Escherichia coli expression system to produce soluble and active RmInt1 IEP and reconstituted RNPs with purified components in vitro . The RNPs generated were functional and reverse-spliced into a single-stranded DNA target. This work constitutes the starting point for the use of group II introns lacking DNA endonuclease domain-derived RNPs for highly specific gene targeting methods.

Functionality of In vitro Reconstituted Group II Intron RmInt1-Derived Ribonucleoprotein Particles

PubMed Central

Molina-Sánchez, Maria D.; García-Rodríguez, Fernando M.; Toro, Nicolás

2016-01-01

The functional unit of mobile group II introns is a ribonucleoprotein particle (RNP) consisting of the intron-encoded protein (IEP) and the excised intron RNA. The IEP has reverse transcriptase activity but also promotes RNA splicing, and the RNA-protein complex triggers site-specific DNA insertion by reverse splicing, in a process called retrohoming. In vitro reconstituted ribonucleoprotein complexes from the Lactococcus lactis group II intron Ll.LtrB, which produce a double strand break, have recently been studied as a means of developing group II intron-based gene targeting methods for higher organisms. The Sinorhizobium meliloti group II intron RmInt1 is an efficient mobile retroelement, the dispersal of which appears to be linked to transient single-stranded DNA during replication. The RmInt1IEP lacks the endonuclease domain (En) and cannot cut the bottom strand to generate the 3′ end to initiate reverse transcription. We used an Escherichia coli expression system to produce soluble and active RmInt1 IEP and reconstituted RNPs with purified components in vitro. The RNPs generated were functional and reverse-spliced into a single-stranded DNA target. This work constitutes the starting point for the use of group II introns lacking DNA endonuclease domain-derived RNPs for highly specific gene targeting methods. PMID:27730127

A simple rapid approach using coupled multivariate statistical methods, GIS and trajectory models to delineate areas of common oil spill risk

NASA Astrophysics Data System (ADS)

Guillen, George; Rainey, Gail; Morin, Michelle

2004-04-01

Currently, the Minerals Management Service uses the Oil Spill Risk Analysis model (OSRAM) to predict the movement of potential oil spills greater than 1000 bbl originating from offshore oil and gas facilities. OSRAM generates oil spill trajectories using meteorological and hydrological data input from either actual physical measurements or estimates generated from other hydrological models. OSRAM and many other models produce output matrices of average, maximum and minimum contact probabilities to specific landfall or target segments (columns) from oil spills at specific points (rows). Analysts and managers are often interested in identifying geographic areas or groups of facilities that pose similar risks to specific targets or groups of targets if a spill occurred. Unfortunately, due to the potentially large matrix generated by many spill models, this question is difficult to answer without the use of data reduction and visualization methods. In our study we utilized a multivariate statistical method called cluster analysis to group areas of similar risk based on potential distribution of landfall target trajectory probabilities. We also utilized ArcView™ GIS to display spill launch point groupings. The combination of GIS and multivariate statistical techniques in the post-processing of trajectory model output is a powerful tool for identifying and delineating areas of similar risk from multiple spill sources. We strongly encourage modelers, statistical and GIS software programmers to closely collaborate to produce a more seamless integration of these technologies and approaches to analyzing data. They are complimentary methods that strengthen the overall assessment of spill risks.

A new methodology based on functional principal component analysis to study postural stability post-stroke.

PubMed

Sánchez-Sánchez, M Luz; Belda-Lois, Juan-Manuel; Mena-Del Horno, Silvia; Viosca-Herrero, Enrique; Igual-Camacho, Celedonia; Gisbert-Morant, Beatriz

2018-05-05

A major goal in stroke rehabilitation is the establishment of more effective physical therapy techniques to recover postural stability. Functional Principal Component Analysis provides greater insight into recovery trends. However, when missing values exist, obtaining functional data presents some difficulties. The purpose of this study was to reveal an alternative technique for obtaining the Functional Principal Components without requiring the conversion to functional data beforehand and to investigate this methodology to determine the effect of specific physical therapy techniques in balance recovery trends in elderly subjects with hemiplegia post-stroke. A randomized controlled pilot trial was developed. Thirty inpatients post-stroke were included. Control and target groups were treated with the same conventional physical therapy protocol based on functional criteria, but specific techniques were added to the target group depending on the subjects' functional level. Postural stability during standing was quantified by posturography. The assessments were performed once a month from the moment the participants were able to stand up to six months post-stroke. The target group showed a significant improvement in postural control recovery trend six months after stroke that was not present in the control group. Some of the assessed parameters revealed significant differences between treatment groups (P < 0.05). The proposed methodology allows Functional Principal Component Analysis to be performed when data is scarce. Moreover, it allowed the dynamics of recovery of two different treatment groups to be determined, showing that the techniques added in the target group increased postural stability compared to the base protocol. Copyright © 2018 Elsevier Ltd. All rights reserved.

The whole-genome landscape of medulloblastoma subtypes.

PubMed

Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

2017-07-19

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Literature Review on Anti-Terrorism and Selected Bibliography on Terrorism.

DTIC Science & Technology

1988-04-01

quickly outdated because of the frequency with which new events must be listed, catalogued, and analyzed. For example, in the first months of this b...likely, the 4P terrorist group) attempts to make the target government appear unable to respond credibly to threats to the public security. Because pure...usually outdated by publication time. While a historical perspective can be gained from the chronologies of specific target groups and areas, such as

Global Comparison of Warring Groups in 2002–2007: Fatalities from Targeting Civilians vs. Fighting Battles

PubMed Central

Hicks, Madelyn Hsiao-Rei; Lee, Uih Ran; Sundberg, Ralph; Spagat, Michael

2011-01-01

Background Warring groups that compete to dominate a civilian population confront contending behavioral options: target civilians or battle the enemy. We aimed to describe degrees to which combatant groups concentrated lethal behavior into intentionally targeting civilians as opposed to engaging in battle with opponents in contemporary armed conflict. Methodology/Principal Findings We identified all 226 formally organized state and non-state groups (i.e. actors) that engaged in lethal armed conflict during 2002–2007: 43 state and 183 non-state. We summed civilians killed by an actor's intentional targeting with civilians and combatants killed in battles in which the actor was involved for total fatalities associated with each actor, indicating overall scale of armed conflict. We used a Civilian Targeting Index (CTI), defined as the proportion of total fatalities caused by intentional targeting of civilians, to measure the concentration of lethal behavior into civilian targeting. We report actor-specific findings and four significant trends: 1.) 61% of all 226 actors (95% CI 55% to 67%) refrained from targeting civilians. 2.) Logistic regression showed actors were more likely to have targeted civilians if conflict duration was three or more years rather than one year. 3.) In the 88 actors that targeted civilians, multiple regressions showed an inverse correlation between CTI values and the total number of fatalities. Conflict duration of three or more years was associated with lower CTI values than conflict duration of one year. 4.) When conflict scale and duration were accounted for, state and non-state actors did not differ. We describe civilian targeting by actors in prolonged conflict. We discuss comparable patterns found in nature and interdisciplinary research. Conclusions/Significance Most warring groups in 2002–2007 did not target civilians. Warring groups that targeted civilians in small-scale, brief conflict concentrated more lethal behavior into targeting civilians, and less into battles, than groups in larger-scale, longer conflict. PMID:21915272

In silico design, synthesis, and assays of specific substrates for proteinase 3: influence of fluorogenic and charged groups.

PubMed

Narawane, Shailesh; Budnjo, Adnan; Grauffel, Cédric; Haug, Bengt Erik; Reuter, Nathalie

2014-02-13

Neutrophil serine proteases are specific regulators of the immune response, and proteinase 3 is a major target antigen in antineutrophil cytoplasmic antibody-associated vasculitis. FRET peptides containing 2-aminobenzoic acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as fluorophore and quencher groups, respectively, have been widely used to probe proteases specificity. Using in silico design followed by enzymatic assays, we show that Abz and EDDnp significantly contribute to substrate hydrolysis by PR3. We also propose a new substrate specific for PR3.

Training and transfer effects of N-back training for brain-injured and healthy subjects.

PubMed

Lindeløv, Jonas Kristoffer; Dall, Jonas Olsen; Kristensen, Casper Daniel; Aagesen, Marie Holt; Olsen, Stine Almgren; Snuggerud, Therese Ruud; Sikorska, Anna

2016-10-01

Working memory impairments are prevalent among patients with acquired brain injury (ABI). Computerised training targeting working memory has been researched extensively using samples from healthy populations but this field remains isolated from similar research in ABI patients. We report the results of an actively controlled randomised controlled trial in which 17 patients and 18 healthy subjects completed training on an N-back task. The healthy group had superior improvements on both training tasks (SMD = 6.1 and 3.3) whereas the ABI group improved much less (SMD = 0.5 and 1.1). Neither group demonstrated transfer to untrained tasks. We conclude that computerised training facilitates improvement of specific skills rather than high-level cognition in healthy and ABI subjects alike. The acquisition of these specific skills seems to be impaired by brain injury. The most effective use of computer-based cognitive training may be to make the task resemble the targeted behaviour(s) closely in order to exploit the stimulus-specificity of learning.

Three forms of immune myasthenia.

PubMed

Agius, Mark A; Richman, David P; Fairclough, Robert H; Aarli, Johan; Gilhus, Nils Erik; Romi, Fredrik

2003-09-01

We propose a new classification for immune myasthenia based on antibody pattern. The types of immune myasthenia presently characterized by known antibody targets segregate into three groups: type 1, in which the muscle target is the acetylcholine receptor only; type 2, in which titin antibodies are present in addition to acetylcholine receptor antibodies; and type 3, in which muscle-specific kinase antibodies are present in the absence of acetylcholine receptor antibodies. The immune target is unknown in the patients with immune myasthenia not associated with these antibodies. This classification has advantages over the present classifications as regards homogeneity of groups, etiology, mechanism of disease, and prognosis.

An oyster species-specific miRNA scaffold42648_5080 modulates haemocyte migration by targeting integrin pathway.

PubMed

Chen, Hao; Wang, Hao; Jiang, Shuai; Xu, Jiachao; Wang, Lingling; Qiu, Limei; Song, Linsheng

2016-10-01

miRNAs are important gene regulators at post-transcriptional level and can modulate diverse biological processes, including immune response. Dozens of species-specific miRNAs have been identified in oyster Crassostrea gigas while their functions remain largely unknown. In the present study, an oyster species-specific miRNA scaffold42648_5080 was found responsive to LPS stimulation and might target a total of 31 oyster genes possibly involved in cell communication, cellular localization and cellular response to stimulus. Besides, in gain-of-function assay of scaffold42648_5080 in vivo, the phagocytosis (30.90% in miRNA group verse 23.20% in miRNA control group), apoptosis (3.10% in miRNA group verse 5.30% in miRNA control group) and migration rate (13.88% in miRNA group verse 21.03% in miRNA control group) of oyster haemocytes were found significantly altered after the injection of scaffold42648_5080 mimics. Among the target genes, integrin-linked kinase (CgILK) was considered crucial in cell migration and its interaction with scaffold42648_5080 was then verified both in vitro and in vivo. Consequently, a significant decrease of relative luciferase ratio was observed in CgILK 3'-UTR luciferase reporter assay after transfection of scaffold42648_5080 mimics (0.70-fold of that in blank group, p < 0.01). Meanwhile, when scaffold42648_5080 was overexpressed in vivo (5.41-fold of miRNA control group, p < 0.01), the expression of CgILK declined significantly to 0.25-fold of miRNA control group (p < 0.01). Comparatively, a significant decrease of the haemocyte migration rate (19.76% verse 34.82% in siEGFP control group, p < 0.01) was observed after knock-down of CgILK in vivo. The present study, as far as we know, for the first time revealed the immunomodulation role of an oyster species-specific miRNA, which might provide new insights into miRNA-mediated adaptation mechanism of oysters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential for off-peak freight deliveries to commercial areas : implementation plan

DOT National Transportation Integrated Search

2007-12-21

This document discusses three groups of policies to foster off-peak deliveries. The first group, Industry wide policies, considers policies that target specific industry segments, e.g., tax incentives to restaurants in exchange for their commitment t...

Functionalized Media and Methods of Making and Using Therefor

NASA Technical Reports Server (NTRS)

Huang, Yongsong (Inventor); Dillon, James (Inventor)

2017-01-01

Methods, compositions, devices and kits are provided herein for separating, scavenging, capturing or identifying a metal from a target using a medium or scaffold with a selenium-containing functional group. The medium or the scaffold including the selenium-containing functional group has affinity and specificity to metal ions or compounds having one or more metals, and efficiently separates, recovers, and scavenges of the metals from a target such as a sample, solution, suspension, or mixture.

Fault-tolerant control of electric vehicles with in-wheel motors using actuator-grouping sliding mode controllers

NASA Astrophysics Data System (ADS)

Li, Boyuan; Du, Haiping; Li, Weihua

2016-05-01

Although electric vehicles with in-wheel motors have been regarded as one of the promising vehicle architectures in recent years, the probability of in-wheel motor fault is still a crucial issue due to the system complexity and large number of control actuators. In this study, a modified sliding mode control (SMC) is applied to achieve fault-tolerant control of electric vehicles with four-wheel-independent-steering (4WIS) and four-wheel-independent-driving (4WID). Unlike in traditional SMC, in this approach the steering geometry is re-arranged according to the location of faulty wheels in the modified SMC. Three SMC control laws for longitudinal velocity control, lateral velocity control and yaw rate control are designed based on specific vehicle motion scenarios. In addition the actuator-grouping SMC method is proposed so that driving actuators are grouped and each group of actuators can be used to achieve the specific control target, which avoids the strong coupling effect between each control target. Simulation results prove that the proposed modified SMC can achieve good vehicle dynamics control performance in normal driving and large steering angle turning scenarios. In addition, the proposed actuator-grouping SMC can solve the coupling effect of different control targets and the control performance is improved.

UAHuntsville-NASA MSFC Heliophysics REU: A Model for Recruiting Targeted Groups

NASA Astrophysics Data System (ADS)

Farid, S.; Heerikhuisen, J.; Winebarger, A. R.

2014-12-01

In 2011, researchers from the University of Alabama-Huntsville Center for Space Plasma and Aeronomic Research Center (CSPAR) and NASA Marshall Space Fight Center (MSFC) received a 3-year NSF award to create a REU site specifically designed to increase the participation of underrepresented groups in the Geo-sciences, specifically Heliophysics, and to reduce the attrition rate of sophomores by engaging them in research. This program has been highly successful. In three years of operation, we have increased in the diversity of applicant pool and selected participants, increased the number of inexperienced participants and made measurable impacts on the students' perceptions of graduate school and Heliophysics careers, and produced research with significant scientific merit. We attribute the success of the program to our proactive recruitment of first and second year students, underrepresented groups, and students from small universities. Key factors in our efforts include: 1) In person school visits of targeted schools 2.) Establishing relationships with faculty at targeted schools. 3.) An inclusive selection process that considers the availability of research at the students home institution 4.) A reduced focus on GPA and more focus on recommendation letters as indicators of success 5.) A successful cohort of experienced and inexperienced students 6.) The unique learning environment fostered by UAH-CSPAR and NASA-MSFC scientists. In this presentation, we review our strategies and suggest techniques to recruit targeted groups to similar REU programs.

Targeted Jobs Tax Credit. Hearing before the Subcommittee on Economic Growth, Employment, and Revenue Sharing of the Committee on Finance, United States Senate, Ninety-Eighth Congress, Second Session. S.2185.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Committee on Finance.

Testimony is presented from a hearing held to consider a bill (S. 2185) to extend the Targeted Jobs Tax Credit for an additional year. (Originally passed in 1978, the Targeted Jobs Tax Credit focuses tax incentives for employment on specific target groups found to experience high unemployment rates.) Included in the hearings is testimony provided…

Quantitative analysis of aberrant protein glycosylation in liver cancer plasma by AAL-enrichment and MRM mass spectrometry.

PubMed

Ahn, Yeong Hee; Shin, Park Min; Kim, Yong-Sam; Oh, Na Ree; Ji, Eun Sun; Kim, Kwang Hoe; Lee, Yeon Jung; Kim, Sung Ho; Yoo, Jong Shin

2013-11-07

A lectin-coupled mass spectrometry (MS) approach was employed to quantitatively monitor aberrant protein glycosylation in liver cancer plasma. To do this, we compared the difference in the total protein abundance of a target glycoprotein between hepatocellular carcinoma (HCC) plasmas and hepatitis B virus (HBV) plasmas, as well as the difference in lectin-specific protein glycoform abundance of the target glycoprotein. Capturing the lectin-specific protein glycoforms from a plasma sample was accomplished by using a fucose-specific aleuria aurantia lectin (AAL) immobilized onto magnetic beads via a biotin-streptavidin conjugate. Following tryptic digestion of both the total plasma and its AAL-captured fraction of each HCC and HBV sample, targeted proteomic mass spectrometry was conducted quantitatively by a multiple reaction monitoring (MRM) technique. From the MRM-based analysis of the total plasmas and AAL-captured fractions, differences between HCC and HBV plasma groups in fucosylated glycoform levels of target glycoproteins were confirmed to arise from both the change in the total protein abundance of the target proteins and the change incurred by aberrant fucosylation on target glycoproteins in HCC plasma, even when no significant change occurs in the total protein abundance level. Combining the MRM-based analysis method with the lectin-capturing technique proved to be a successful means of quantitatively investigating aberrant protein glycosylation in cancer plasma samples. Additionally, it was elucidated that the differences between HCC and control groups in fucosylated biomarker candidates A1AT and FETUA mainly originated from an increase in fucosylation levels on these target glycoproteins, rather than an increase in the total protein abundance of the target glycoproteins.

Spatial Light Rebroadcaster Architecture Study

DTIC Science & Technology

1992-12-01

specifications on the lenslet arrays described in [ Borelli ] and summarized 3 here: Lenslet diameter: 70,m < D < 1000/Am Lenslet spacing: 151m < Delta Focal...which leads to k2 < 1/3. We will use as our baseline, a lenslet array with D, = 300 um and3 A1 = 45 14m which is within the specifications of [ Borelli ...Target Recognizer Working Group), "Automatic Target Recognizer Component Definitions," ATRWG Report No. 87-002, April 1987. Borelli , N., et al

EVENT-RELATED POTENTIAL STUDY OF ATTENTION REGULATION DURING ILLUSORY FIGURE CATEGORIZATION TASK IN ADHD, AUTISM SPECTRUM DISORDER, AND TYPICAL CHILDREN.

PubMed

Sokhadze, Estate M; Baruth, Joshua M; Sears, Lonnie; Sokhadze, Guela E; El-Baz, Ayman S; Williams, Emily; Klapheke, Robert; Casanova, Manuel F

2012-01-01

Autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD) are very common developmental disorders which share some similar symptoms of social, emotional, and attentional deficits. This study is aimed to help understand the differences and similarities of these deficits using analysis of dense-array event-related potentials (ERP) during an illusory figure recognition task. Although ADHD and ASD seem very distinct, they have been shown to share some similarities in their symptoms. Our hypothesis was that children with ASD will show less pronounced differences in ERP responses to target and non-target stimuli as compared to typical children, and to a lesser extent, ADHD. Participants were children with ASD (N=16), ADHD (N=16), and controls (N=16). EEG was collected using a 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. There were no between group differences in reaction time (RT) to target stimuli, but both ASD and ADHD committed more errors, specifically the ASD group had statistically higher commission error rate than controls. Post-error RT in ASD group was exhibited in a post-error speeding rather than corrective RT slowing typical for the controls. The ASD group also demonstrated an attenuated error-related negativity (ERN) as compared to ADHD and controls. The fronto-central P200, N200, and P300 were enhanced and less differentiated in response to target and non-target figures in the ASD group. The same ERP components were marked by more prolonged latencies in the ADHD group as compared to both ASD and typical controls. The findings are interpreted according to the "minicolumnar" hypothesis proposing existence of neuropathological differences in ASD and ADHD, specifically minicolumnar number/width morphometry spectrum differences. In autism, a model of local hyperconnectivity and long-range hypoconnectivity explains many of the behavioral and cognitive deficits present in the condition, while the inverse arrangement of local hypoconnectivity and long-range hyperconnectivity in ADHD explains some deficits typical for this disorder. The current ERP study supports the proposed suggestion that some between group differences could be manifested in the frontal ERP indices of executive functions during performance on an illusory figure categorization task.

Inhibition of duck hepatitis B virus replication by mimic peptides in vitro

PubMed Central

JIA, HONGYU; LIU, CHANGHONG; YANG, YING; ZHU, HAIHONG; CHEN, FENG; LIU, JIHONG; ZHOU, LINFU

2015-01-01

The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (P<0.05). The cytoplasmic DHBV-DNA content of the cells treated with mimic peptide 7 was lower than that in the other groups (P<0.05). In addition, the DHBV-DNA content of the nuclear fractions following the intracellular expression of mimic peptide 7 was significantly lower than that in the other groups (P<0.05). Mimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro. PMID:26640539

Inhibition of duck hepatitis B virus replication by mimic peptides in vitro.

PubMed

Jia, Hongyu; Liu, Changhong; Yang, Ying; Zhu, Haihong; Chen, Feng; Liu, Jihong; Zhou, Linfu

2015-11-01

The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (P<0.05). The cytoplasmic DHBV-DNA content of the cells treated with mimic peptide 7 was lower than that in the other groups (P<0.05). In addition, the DHBV-DNA content of the nuclear fractions following the intracellular expression of mimic peptide 7 was significantly lower than that in the other groups (P<0.05). Mimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro .

Extrinsic grouping factors in motion-induced blindness

PubMed Central

2018-01-01

We investigated how various grouping factors altered subjective disappearances of the individual targets in the motion-induced blindness display. The latter relies on a moving mask to render highly salient static targets temporarily subjectively invisible. Specifically, we employed two extrinsic grouping factors, the connectedness and the common region, and examined whether their presence would make targets more resilient against the suppression. In addition, we investigated whether the presence of an illusory Kanizsa triangle would affect the suppression of the inducing Pac-Man elements. We quantified the perceptual dynamics using the proportion of the disappearance time (this indicates whether targets became more resilient against the suppression), and the proportion of simultaneous disappearance and reappearance events (characterizes the tendency for the targets to disappear or reappear as a group). We report that a single mask that encompassed all targets (a common region grouping) significantly increased the proportion of simultaneous disappearance and reappearance events, but had no effect on the proportion of the disappearance time. In contrast, a line that connected two targets significantly decreased the total invisibility time, but had no impact on the simultaneity of the disappearance and reappearance events. We found no statistically significant effect of the presence of the illusory Kanizsa triangle on either measure. Finally, we found no interaction either between the common region and the connectedness or between the common region and the presence of the illusory Kanizsa triangle. Our results indicate that extrinsic grouping factors might influence the perception differently than the intrinsic ones and highlight the importance of using several measures to characterize the perceptual dynamics, as various grouping factors might affect it differentially. PMID:29381747

Vocabulary Intervention for Children with Down Syndrome: Parent Training Using Focused Stimulation.

ERIC Educational Resources Information Center

Girolametto, Luigi; Weitzman, Elaine; Clements-Baartman, Jill

1998-01-01

This study explored effects of training six mothers to use focused stimulation to teach specific target words to their toddlers with Down syndrome. Following treatment, trained mothers used the focused stimulation technique more often than mothers in the control group. Concomitantly, their children used target words more often, as reported by…

76 FR 70954 - Idaho Panhandle National Forests, Idaho; Idaho Panhandle National Forest Noxious Weed Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... registered herbicides is one of the various treatment methods that are proposed. The overall project goal is... insects; and herbicides that target specific invasive plant species. The application of herbicides would... spraying would be the primary method of applying herbicide in order to target individual and groups of...

Improved Targeting Through Collaborative Decision-Making and Brain Computer Interfaces

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Barrero, David F.; McDonald-Maier, Klaus

2013-01-01

This paper reports a first step toward a brain-computer interface (BCI) for collaborative targeting. Specifically, we explore, from a broad perspective, how the collaboration of a group of people can increase the performance on a simple target identification task. To this end, we requested a group of people to identify the location and color of a sequence of targets appearing on the screen and measured the time and accuracy of the response. The individual results are compared to a collective identification result determined by simple majority voting, with random choice in case of drawn. The results are promising, as the identification becomes significantly more reliable even with this simple voting and a small number of people (either odd or even number) involved in the decision. In addition, the paper briefly analyzes the role of brain-computer interfaces in collaborative targeting, extending the targeting task by using a BCI instead of a mechanical response.

Target-specific NMR detection of protein-ligand interactions with antibody-relayed 15N-group selective STD.

PubMed

Hetényi, Anasztázia; Hegedűs, Zsófia; Fajka-Boja, Roberta; Monostori, Éva; Kövér, Katalin E; Martinek, Tamás A

2016-12-01

Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein-ligand interactions is a key element. 1 H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed 15 N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A 15 N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

Changes in Renal Function of Patients with Metastatic Renal Cell Carcinoma During Treatment with Molecular-Targeted Agents.

PubMed

Miyake, Hideaki; Muramaki, Mototsugu; Imai, Satoshi; Harada, Ken-Ichi; Fujisawa, Masato

2016-06-01

Impairment of renal function is a serious issue that should be considered in patients undergoing treatment with molecular-targeted agents for metastatic renal cell carcinoma (mRCC). The objective of this study was to assess the impact of molecular-targeted therapy on changes in renal function among patients with mRCC. The study included 408 mRCC patients treated with sunitinib, sorafenib, axitinib, everolimus and/or temsirolimus. Among these, 185, 128 and 95 received molecular-targeted agents as first-line (group 1), second-line (group 2) and third-line (group 3) therapy, respectively. No significant differences between the estimated glomerular filtration rate (eGFR) at baseline and that at the end of molecular-targeted therapy were noted among the three groups of patients. In addition, there were no significant differences between eGFR prior to the introduction of molecular-targeted therapy and that at the end of therapy across agents and lines of targeted therapy, with the exception of patients treated with axitinib and everolimus in second-line and third-line therapy, respectively. In group 1, a reduction in eGFR of >10 % from baseline was independently associated with performance status, hypertension and treatment duration, while in groups 2 and 3, only treatment duration was independently related to a reduction in eGFR of >10 %. It appears that renal function in patients with mRCC is not markedly impaired by molecular-targeted therapies, irrespective of the specific agents introduced; however, it may be necessary to pay special attention to deterioration in renal function when molecular-targeted therapy is continued for longer periods.

Robust multi-atlas label propagation by deep sparse representation

PubMed Central

Zu, Chen; Wang, Zhengxia; Zhang, Daoqiang; Liang, Peipeng; Shi, Yonghong; Shen, Dinggang; Wu, Guorong

2016-01-01

Recently, multi-atlas patch-based label fusion has achieved many successes in medical imaging area. The basic assumption in the current state-of-the-art approaches is that the image patch at the target image point can be represented by a patch dictionary consisting of atlas patches from registered atlas images. Therefore, the label at the target image point can be determined by fusing labels of atlas image patches with similar anatomical structures. However, such assumption on image patch representation does not always hold in label fusion since (1) the image content within the patch may be corrupted due to noise and artifact; and (2) the distribution of morphometric patterns among atlas patches might be unbalanced such that the majority patterns can dominate label fusion result over other minority patterns. The violation of the above basic assumptions could significantly undermine the label fusion accuracy. To overcome these issues, we first consider forming label-specific group for the atlas patches with the same label. Then, we alter the conventional flat and shallow dictionary to a deep multi-layer structure, where the top layer (label-specific dictionaries) consists of groups of representative atlas patches and the subsequent layers (residual dictionaries) hierarchically encode the patchwise residual information in different scales. Thus, the label fusion follows the representation consensus across representative dictionaries. However, the representation of target patch in each group is iteratively optimized by using the representative atlas patches in each label-specific dictionary exclusively to match the principal patterns and also using all residual patterns across groups collaboratively to overcome the issue that some groups might be absent of certain variation patterns presented in the target image patch. Promising segmentation results have been achieved in labeling hippocampus on ADNI dataset, as well as basal ganglia and brainstem structures, compared to other counterpart label fusion methods. PMID:27942077

Robust multi-atlas label propagation by deep sparse representation.

PubMed

Zu, Chen; Wang, Zhengxia; Zhang, Daoqiang; Liang, Peipeng; Shi, Yonghong; Shen, Dinggang; Wu, Guorong

2017-03-01

Recently, multi-atlas patch-based label fusion has achieved many successes in medical imaging area. The basic assumption in the current state-of-the-art approaches is that the image patch at the target image point can be represented by a patch dictionary consisting of atlas patches from registered atlas images. Therefore, the label at the target image point can be determined by fusing labels of atlas image patches with similar anatomical structures. However, such assumption on image patch representation does not always hold in label fusion since (1) the image content within the patch may be corrupted due to noise and artifact; and (2) the distribution of morphometric patterns among atlas patches might be unbalanced such that the majority patterns can dominate label fusion result over other minority patterns. The violation of the above basic assumptions could significantly undermine the label fusion accuracy. To overcome these issues, we first consider forming label-specific group for the atlas patches with the same label. Then, we alter the conventional flat and shallow dictionary to a deep multi-layer structure, where the top layer ( label-specific dictionaries ) consists of groups of representative atlas patches and the subsequent layers ( residual dictionaries ) hierarchically encode the patchwise residual information in different scales. Thus, the label fusion follows the representation consensus across representative dictionaries. However, the representation of target patch in each group is iteratively optimized by using the representative atlas patches in each label-specific dictionary exclusively to match the principal patterns and also using all residual patterns across groups collaboratively to overcome the issue that some groups might be absent of certain variation patterns presented in the target image patch. Promising segmentation results have been achieved in labeling hippocampus on ADNI dataset, as well as basal ganglia and brainstem structures, compared to other counterpart label fusion methods.

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.

PubMed

Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

2016-01-01

To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.

Fanning the flames of prejudice: the influence of specific incidental emotions on implicit prejudice.

PubMed

Dasgupta, Nilanjana; Desteno, David; Williams, Lisa A; Hunsinger, Matthew

2009-08-01

Three experiments examined the impact of incidental emotions on implicit intergroup evaluations. Experiment 1 demonstrated that for unknown social groups, two negative emotions that are broadly applicable to intergroup conflict (anger and disgust) both created implicit bias where none had existed before. However, for known groups about which perceivers had prior knowledge, emotions increased implicit prejudice only if the induced emotion was applicable to the outgroup stereotype. Disgust increased bias against disgust-relevant groups (e.g., homosexuals) but anger did not (Experiment 2); anger increased bias against anger-relevant groups (e.g., Arabs) but disgust did not (Experiment 3). Consistent with functional theories of emotion, these findings suggest that negative intergroup emotions signal specific types of threat. If the emotion-specific threat is applicable to prior expectations of a group, the emotion ratchets up implicit prejudice toward that group. However, if the emotion-specific threat is not applicable to the target group, evaluations remain unchanged. 2009 APA, all rights reserved.

A Pilot Study of Social Competence Group Training for Adolescents with Borderline Intellectual Functioning and Emotional and Behavioural Problems (SCT-ABI)

ERIC Educational Resources Information Center

Nestler, J.; Goldbeck, L.

2011-01-01

Background: Emotional and behavioural problems as well as a lack of social competence are common in adolescents with borderline intellectual functioning and impair their social and vocational integration. Group interventions specifically developed for this target group are scarce and controlled evaluation studies are absent. Methods: A…

Targeting Academic Programs to Student Diversity Utilizing Learning Styles and Learning-Study Strategies.

ERIC Educational Resources Information Center

Grimes, Sue K.

1995-01-01

A diagnostic, prescriptive model was utilized (n=394) in identification of learning styles and learning-study strategies of diverse student groups and in the analysis of prescriptive methods to address their specific needs. High-risk groups demonstrated auditory, tactile concrete, and group learning style preferences and were weaker on cognitive,…

A historical analysis of public health, the law, and stigmatized social groups: the need for both obesity and weight bias legislation.

PubMed

Pomeranz, Jennifer L

2008-11-01

History teaches that discrimination against socially undesirable groups leads to societal and governmental neglect of the stigmatized group's health problem. By placing weight discrimination in a historical context, this article demonstrates that legislation specifically aimed at rectifying obesity is less likely while weight bias is socially acceptable. Beyond obesity legislation, public health professionals may consider advocating for legislation directly targeting discrimination based on weight. This article reviews the history of discrimination against distinct groups and provides statutory solutions for discrimination based on weight. In addition to revising current statutes and regulatory rules, a unique statute targeting weight bias in the employment context is considered.

ENVRI PLUS: European initiative towards technical and research cultural solutions for across-disciplines accessible Research Infrastructure products

NASA Astrophysics Data System (ADS)

Asmi, A.; Kutsch, W. L.

2015-12-01

Environmental Research Infrastructures are often built as bottom-up initiatives to provide products for specific target group, which often is very discipline specific. However, the societal or environmental challenges are typically not concentrated on specific disciplines, and require usage of data sets from many RIs. ENVRI PLUS is an initiative where the European environmental RIs work together to provide common technical background (in physical observation technologies and in data products and descriptions) to make the RI products more usable to user groups outside of the original RI target groups. ENVRI PLUS also includes many policy and dissemination concentrated actions to make the RI operations coherent and understandable to both scientists and other potential users. The actions include building common technological capital of the RIs (physical and data-oriented), creating common access procedures (especially for cross-diciplinary access), developing ethical guidelines and related policies, distributing know-how between RIs and building common communication and collaboration system for European environmental RIs. All ENVRI PLUS products are free to use, e.g. for use of new or existing environmental RIs worldwide.

Sequencing of the variable region of rpsB to discriminate between Streptococcus pneumoniae and other streptococcal species.

PubMed

Wyllie, Anne L; Pannekoek, Yvonne; Bovenkerk, Sandra; van Engelsdorp Gastelaars, Jody; Ferwerda, Bart; van de Beek, Diederik; Sanders, Elisabeth A M; Trzciński, Krzysztof; van der Ende, Arie

2017-09-01

The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, the most pathogenic is Mitis group member, Streptococcus pneumoniae Phenotypic and genetic similarities between streptococci can cause difficulties in species identification. Using ribosomal S2-gene sequences extracted from whole-genome sequences published from 501 streptococci, we developed a method to identify streptococcal species. We validated this method on non-pneumococcal isolates cultured from cases of severe streptococcal disease ( n = 101) and from carriage ( n = 103), and on non-typeable pneumococci from asymptomatic individuals ( n = 17) and on whole-genome sequences of 1157 pneumococcal isolates from meningitis in the Netherlands. Following this, we tested 221 streptococcal isolates in molecular assays originally assumed specific for S. pneumoniae , targeting cpsA , lytA , piaB , ply , Spn9802, zmpC and capsule-type-specific genes. Cluster analysis of S2-sequences showed grouping according to species in line with published phylogenies of streptococcal core genomes. S2-typing convincingly distinguished pneumococci from non-pneumococcal species (99.2% sensitivity, 100% specificity). Molecular assays targeting regions of lytA and piaB were 100% specific for S. pneumoniae , whereas assays targeting cpsA , ply , Spn9802, zmpC and selected serotype-specific assays (but not capsular sequence typing) showed a lack of specificity. False positive results were over-represented in species associated with carriage, although no particular confounding signal was unique for carriage isolates. © 2017 The Authors.

Sequencing of the variable region of rpsB to discriminate between Streptococcus pneumoniae and other streptococcal species

PubMed Central

Pannekoek, Yvonne; Bovenkerk, Sandra; van Engelsdorp Gastelaars, Jody; Ferwerda, Bart; van de Beek, Diederik; Sanders, Elisabeth A. M.; Trzciński, Krzysztof; van der Ende, Arie

2017-01-01

The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, the most pathogenic is Mitis group member, Streptococcus pneumoniae. Phenotypic and genetic similarities between streptococci can cause difficulties in species identification. Using ribosomal S2-gene sequences extracted from whole-genome sequences published from 501 streptococci, we developed a method to identify streptococcal species. We validated this method on non-pneumococcal isolates cultured from cases of severe streptococcal disease (n = 101) and from carriage (n = 103), and on non-typeable pneumococci from asymptomatic individuals (n = 17) and on whole-genome sequences of 1157 pneumococcal isolates from meningitis in the Netherlands. Following this, we tested 221 streptococcal isolates in molecular assays originally assumed specific for S. pneumoniae, targeting cpsA, lytA, piaB, ply, Spn9802, zmpC and capsule-type-specific genes. Cluster analysis of S2-sequences showed grouping according to species in line with published phylogenies of streptococcal core genomes. S2-typing convincingly distinguished pneumococci from non-pneumococcal species (99.2% sensitivity, 100% specificity). Molecular assays targeting regions of lytA and piaB were 100% specific for S. pneumoniae, whereas assays targeting cpsA, ply, Spn9802, zmpC and selected serotype-specific assays (but not capsular sequence typing) showed a lack of specificity. False positive results were over-represented in species associated with carriage, although no particular confounding signal was unique for carriage isolates. PMID:28931649

Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

PubMed Central

Kesharwani, Prashant; Iyer, Arun K.

2015-01-01

Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

Recognition of Typhus Group Rickettsia-Infected Targets by Human Lymphokine-Activated Killer Cells

DTIC Science & Technology

1988-09-01

rick- Similar problems in detection of antigens of Theileria parva ettsia-specific cell surface antigens by performing polyacryl- (7) or influenza virus...infected with the protozoan parasite Theileria parva: workers in our laboratory are now in the process of cloning parasite strain specificity and class I

Importance of public relations in recycling strategies: principles and case studies.

PubMed

Salhofer, Stefan; Isaac, Nicole A

2002-07-01

The separate collection of waste, and especially of recyclables with specific collection systems, would not be possible without the involvement of the users. Apart from the physical installations such as collection containers, collection points, etc., the motivation of the users is an essential component. Motivation can be reinforced through public relations work. In addition to the underlying technical considerations, this paper describes the difference between communication in general and public relations and specifically examines public involvement in recycling. Through the use of examples, we look at the targeted users and typical media employed. Furthermore, we analyzes the development of public involvement. The examples show that public relations for recycling strategies relies to a great extent on attitudes, habits, and access to the target group. Thus, standardized procedures cannot be developed. For these reasons, public relation activities must be planned carefully and professionally and include an analysis of the target group, choice of media, and verification of success.

Translating the link between social identity and health behavior into effective health communication strategies: An experimental application using antismoking advertisements.

PubMed

Moran, Meghan Bridgid; Sussman, Steve

2014-01-01

Social identity is a construct that has been linked to health behavior. Yet, limited research has attempted to translate this relationship into health communication strategies. The current study addresses this gap by examining the efficacy of social identity targeting (constructing ads so that they target a specific group with which an individual identifies) to increase anti-cigarette smoking beliefs among adolescents. Two hundred and fifty one adolescents aged 12-15, randomly selected from a nationally representative sample, completed an online survey. Participants indicated which of 11 peer groups (determined in pre-testing) they most identified with. Each participant was then randomly assigned to view an ad that either did or did not target that group. One week later participants reported level of agreement with two key antismoking beliefs presented in the ad. Multiple regression analyses indicated that if an individual identified with the group targeted by the ad, antismoking beliefs were more strongly endorsed. Based on these findings, we conclude that social identity targeting has the potential to increase the effectiveness of antismoking messages and should be considered when designing antismoking campaigns.

Targeting anxiety to improve quality of life in patients with schizophrenia.

PubMed

Buonocore, M; Bosia, M; Bechi, M; Spangaro, M; Cavedoni, S; Cocchi, F; Bianchi, L; Guglielmino, C; Mastromatteo, A R; Cavallaro, R

2017-09-01

Several studies suggested that anxiety can significantly affect the outcome of schizophrenia. Despite this evidence, non-pharmacological interventions targeting anxiety are still heterogenous. This study aims to test the efficacy of a novel training specifically designed to target anxiety in patients with schizophrenia. Innovatively, this training, beyond psychoeducation and problem solving, also targets Theory of Mind, as it provides coping strategies. Twenty-seven outpatients with schizophrenia received a novel rehabilitative training targeting anxiety (Anxiety Management Group [AMG]) combined with a Computer-Assisted Cognitive Remediation (CACR), and twenty received CACR plus a control intervention (Control Newspaper discussion Group [CNG]). All patients were assessed at baseline and after treatment for quality of life, neurocognition and anxiety. After training, patients treated with AMG+CACR showed significantly greater improvements on anxiety. A significant increase in quality of life was observed only for AMG+CACR group. Moreover, the participants' appraisal showed a significant difference between treatment groups with higher ratings among patients who received the AMG+CACR. This study thus suggests feasibility and efficacy of the proposed intervention, that could be implemented in rehabilitative programs for patients with schizophrenia with potential benefits also on disease course and outcome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Working Memory: Its Role in Dyslexia and Other Specific Learning Difficulties

ERIC Educational Resources Information Center

Jeffries, Sharman; Everatt, John

2004-01-01

This paper reports a study contrasting dyslexic children against a control group of children without special educational needs (SEN) and a group with varied SENs. Children's abilities were compared on tasks assessing phonological processing, visuo-spatial/motor coordination and executive/inhibitory functioning; being targeted for assessment based…

Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.

PubMed

Kang, H W; Weissleder, R; Bogdanov, A

2002-01-01

Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.

Sentence comprehension in specific language impairment: a task designed to distinguish between cognitive capacity and syntactic complexity.

PubMed

Leonard, Laurence B; Deevy, Patricia; Fey, Marc E; Bredin-Oja, Shelley L

2013-04-01

This study examined sentence comprehension in children with specific language impairment (SLI) in a manner designed to separate the contribution of cognitive capacity from the effects of syntactic structure. Nineteen children with SLI, 19 typically developing children matched for age (TD-A), and 19 younger typically developing children (TD-Y) matched according to sentence comprehension test scores responded to sentence comprehension items that varied in either length or their demands on cognitive capacity, based on the nature of the foils competing with the target picture. The TD-A children were accurate across all item types. The SLI and TD-Y groups were less accurate than the TD-A group on items with greater length and, especially, on items with the greatest demands on cognitive capacity. The types of errors were consistent with failure to retain details of the sentence apart from syntactic structure. The difficulty in the more demanding conditions seemed attributable to interference. Specifically, the children with SLI and the TD-Y children appeared to have difficulty retaining details of the target sentence when the information reflected in the foils closely resembled the information in the target sentence.

23 CFR 1345.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., the District of Columbia, Puerto Rico, the Virgin Islands, Guam, American Samoa or the Commonwealth of... fiscal year beginning after September 30, 2003. Targeted population means a specific group of people...

Using a pattern-centered approach to assess sexual risk-taking in study abroad students.

PubMed

Marcantonio, Tiffany; Angelone, D J; Sledjeski, Eve

2016-01-01

The purpose of this study was to examine the impact of several potential factors related to sexually risky behaviors in study abroad students. The authors utilized a pattern-centered analysis to identify specific groups that can be targeted for intervention. The sample consisted of 173 students who studied abroad in a variety of international locations for an average of 4 months. Participants completed questionnaires informed by the Triandis Theory of Interpersonal Behavior that have been predictive of risky sex in traditional traveling environments. The analyses revealed 3 different pathways for risky sexual behavior: Environmental involvement, historical condom use, and intentions to engage in risky sex. These findings can be used for identification of specific high-risk groups of students who can be targeted for predeparture prevention programs.

Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.

PubMed

Shakir, Nabeel A; George, Arvin K; Siddiqui, M Minhaj; Rothwax, Jason T; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L; Merino, Maria J; Wood, Bradford J; Pinto, Peter A

2014-12-01

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Aptamers: Active Targeting Ligands for Cancer Diagnosis and Therapy

PubMed Central

Wu, Xu; Chen, Jiao; Wu, Min; Zhao, Julia Xiaojun

2015-01-01

Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells. Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required. They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment). In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics. The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer. Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy. Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment. PMID:25699094

Predicting Ideological Prejudice

PubMed Central

Brandt, Mark J.

2017-01-01

A major shortcoming of current models of ideological prejudice is that although they can anticipate the direction of the association between participants’ ideology and their prejudice against a range of target groups, they cannot predict the size of this association. I developed and tested models that can make specific size predictions for this association. A quantitative model that used the perceived ideology of the target group as the primary predictor of the ideology-prejudice relationship was developed with a representative sample of Americans (N = 4,940) and tested against models using the perceived status of and choice to belong to the target group as predictors. In four studies (total N = 2,093), ideology-prejudice associations were estimated, and these observed estimates were compared with the models’ predictions. The model that was based only on perceived ideology was the most parsimonious with the smallest errors. PMID:28394693

Approaches for grouping of pesticides into cumulative assessment groups for risk assessment of pesticide residues in food.

PubMed

Colnot, Thomas; Dekant, Wolfgang

2017-02-01

The European Food Safety Authority (EFSA) is developing approaches to cumulative risk assessment of pesticides by assigning individual pesticides to cumulative assessment groups (CAGs). For assignment to CAGs, EFSA recommended to rely on adverse effects on the specific target system. Contractors to EFSA have proposed to allocate individual pesticides into CAGs relying on NOAELs for effects on target organs. This manuscript evaluates the assignments by applying EFSAs criteria to the CAGs "Toxicity to the nervous system" and "Toxicity to the thyroid hormone system (gland or hormones)". Assignment to the CAG "Toxicity to the nervous system" based, for example, on neurochemical effects like choline esterase inhibition is well supported, whereas assignment to the CAG "Toxicity to the thyroid hormone system (gland or hormones)" has been based in the examined case studies on non-reproducible effects seen in single studies or on observations that are not adverse. Therefore, a more detailed effects evaluation is required to assign a pesticide to a CAG for a target organ where many confounders regarding effects are present. Relative potency factors in cumulative risk assessment should be based on benchmark doses from studies in one species with identical study design and human relevance of effects on specific target organs should be analyzed to define minimal margins of exposure. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis].

PubMed

Su, Fei; Zheng, Ke; Fu, Yiyun; Wu, Qian; Tang, Yuan; Wang, Weiya; Jiang, Lili

2018-05-20

Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

PubMed

Stimac, Monika; Dolinsek, Tanja; Lampreht, Ursa; Cemazar, Maja; Sersa, Gregor

2015-01-01

Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

PubMed Central

Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

2016-01-01

Objective To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). Methods The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. Results The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. Conclusion The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level. PMID:27120181

MicroRNA signature of the human developing pancreas.

PubMed

Rosero, Samuel; Bravo-Egana, Valia; Jiang, Zhijie; Khuri, Sawsan; Tsinoremas, Nicholas; Klein, Dagmar; Sabates, Eduardo; Correa-Medina, Mayrin; Ricordi, Camillo; Domínguez-Bendala, Juan; Diez, Juan; Pastori, Ricardo L

2010-09-22

MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase algorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in parallel by other microRNAs as well. This study may further the understanding of gene expression regulation in the human developing pancreas.

MicroRNA signature of the human developing pancreas

PubMed Central

2010-01-01

Background MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. Results The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase altgorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. Conclusions We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in parallel by other microRNAs as well. This study may further the understanding of gene expression regulation in the human developing pancreas. PMID:20860821

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

PubMed

Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

[Trans-Cultural Prevention of Alcohol-Related Disorders in Elderly Immigrants].

PubMed

Bermejo, I; Frank, F

2015-09-01

In migrants alcohol-related problems increase with increasing age. This group, in particular, is hardly reached by alcohol-specific care offers. Thus our project aimed at the identification of target group-specific barriers to health-care use by means of a cross-sectional study (n=435). Based on these results a trans-cultural concept for alcohol prevention among elderly migrants was developed and evaluated in a cluster-randomised controlled trial (n=176). © Georg Thieme Verlag KG Stuttgart · New York.

Development and Validation of Videotaped Scenarios: A Method for Targeting Specific Participant Groups

ERIC Educational Resources Information Center

Noel, Nora E.; Maisto, Stephen A.; Johnson, James D.; Jackson, Lee A., Jr.; Goings, Christopher D.; Hagman, Brett T.

2008-01-01

Researchers using scenarios often neglect to validate perceived content and salience of embedded stimuli specifically with intended participants, even when such meaning is integral to the study. For example, sex and aggression stimuli are heavily influenced by culture, so participants may not perceive what researchers intended in sexual aggression…

75 FR 29776 - Tobacco Product Advertising and Promotion to Youth and Racial and Ethnic Minority Populations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... designed to appeal to specific racial and ethnic minority populations in the United States. For the same... Tobacco products are responsible for more than 440,000 deaths each year. The rates of tobacco use and..., ``[t]argeting of various population groups--including * * * specific racial and ethnic populations...

Measuring Field-Normalized Impact of Papers on Specific Societal Groups: An Altmetrics Study Based on Mendeley Data

ERIC Educational Resources Information Center

Bornmann, Lutz; Haunschild, Robin

2017-01-01

Bibliometrics is successful in measuring impact because the target is clearly defined: the publishing scientist who is still active and working. Thus, citations are a target-oriented metric which measures impact on science. In contrast, societal impact measurements based on altmetrics are as a rule intended to measure impact in a broad sense on…

Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism.

PubMed

Teotia, Pooja; Chopra, Divyan A; Dravid, Shashank Manohar; Van Hook, Matthew J; Qiu, Fang; Morrison, John; Rizzino, Angie; Ahmad, Iqbal

2017-03-01

Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585. © 2016 AlphaMed Press.

Fostering the Exploitation of Open Educational Resources

ERIC Educational Resources Information Center

Richter, Thomas; Veith, Patrick

2014-01-01

The central concept behind Open Educational Resources (OER) is opening up the access to educational resources for stakeholders who are not the usual target user group. This concept must be perceived as innovative because it describes a general economic and social paradigm shift: Education, which formerly was limited to a specific group of…

Improving the quality of communication in organised cervical cancer screening programmes.

PubMed

Giordano, Livia; Webster, Premila; Anthony, Charles; Szarewski, Anne; Davies, Philip; Arbyn, Marc; Segnan, Nereo; Austoker, Joan

2008-07-01

To provide health professionals involved in cervical cancer screening with an insight into the complex issues relating to communication about screening and to provide a framework for a more effective communication strategy. This paper has been compiled by a multidisciplinary pan-European group of health professionals and cancer advocates from several European screening programmes. European surveys on screening communication, literature reviews and group discussion were used for this purpose. Information on cervical screening must be accessible, relevant, comprehensible, comprehensive, client-centred, phase-specific and multilevel. An effective communication strategy should consider health professionals' screening knowledge and their communication skills, consumers' health literacy skills and the communication needs of specific sub-groups in the target population. Co-operation between screening professionals, advocacy groups and journalists should be promoted. To communicate effectively and appropriately is a complex task which can be influenced by a number of factors. Screening workers need better information themselves and must take into account the needs and characteristics of the target population. This document should provide a useful tool to help screening professionals in designing and developing good quality and effective communication strategies.

Phage Wrapping with Cationic Polymers Eliminates Non-specific Binding between M13 Phage and High pI Target Proteins

PubMed Central

Lamboy, Jorge A.; Arter, Jessica A.; Knopp, Kristeene A.; Der, Denise; Overstreet, Cathie M.; Palermo, Edmund; Urakami, Hiromitsu; Yu, Ting-Bin; Tezgel, Ozgul; Tew, Gregory; Guan, Zhibin; Kuroda, Kenichi; Weiss, Gregory A.

2011-01-01

M13 phage have provided scaffolds for nanostructure synthesis based upon self-assembled inorganic and hard materials interacting with phage-displayed peptides. Additionally, phage display has been used to identify binders to plastic, TiO2, and other surfaces. However, synthesis of phage-based materials through the hybridization of soft materials with the phage surface remains unexplored. Here, we present an efficient “phage wrapping” strategy for the facile synthesis of phage coated with soluble, cationic polymers. Polymers bearing high positive charge densities demonstrated the most effective phage wrapping, as shown by assays for blocking non-specific binding of the anionic phage coat to a high pI target protein. The results establish the functional group requirements for hybridizing phage with soft materials, and solve a major problem in phage display – non-specific binding by the phage to high pI target proteins. PMID:19856910

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

PubMed Central

Niks, Irene; Gevers, Josette

2018-01-01

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care. PMID:29438350

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.

PubMed

Niks, Irene; de Jonge, Jan; Gevers, Josette; Houtman, Irene

2018-02-13

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.

Skin cancer interventions across the cancer control continuum: A review of experimental evidence (1/1/2000-6/30/2015) and future research directions.

PubMed

Geller, Alan C; Dickerman, Barbra A; Taber, Jennifer M; Dwyer, Laura A; Hartman, Anne M; Perna, Frank M

2018-06-01

While the general efficacy of skin cancer interventions have been reviewed, employing the cancer control continuum would be useful to identify research gaps at specific cancer control points. We characterized the intervention evidence base for specific behavioral targets (e.g., tanning, sun protection, screening) and clinically related targets (e.g., sunburn, skin exams, cancers) at each point in the cancer control continuum. The review included articles published from 1/1/2000-6/30/15 that had an experimental design and targeted behavioral intervention in skin cancer (e.g., specific behaviors or clinically related targets). The search yielded 86 articles, including seven dissemination studies. Of the 79 non-dissemination studies, 57 exclusively targeted primary prevention behaviors, five exclusively targeted screening, 10 targeted both detection and prevention, and eight addressed cancer survivorship. Among prevention studies (n=67), 29 (43%) targeted children and 38 (57%) targeted adults. Of the 15 screening studies, nine targeted high-risk groups (e.g., men aged ≥50 years) and six targeted the general population. Although research has focused on skin cancer prevention, empirically validated interventions are still needed for youth engaged in indoor tanning and for behavioral interventions to pursue change in clinically relevant targets. Research must also address detection among those at highest risk for skin cancer, amelioration of emotional distress attendant to diagnosis and treatment, and survivorship concerns. We discuss essential qualities and opportunities for intervention development and translational research to inform the field. Copyright © 2018 Elsevier Inc. All rights reserved.

Dominant intraprostatic cancer confirmed by direct MRI-guided biopsy: Concordance with histopathological findings.

PubMed

Meermeier, Nicholas P; Turner, Kevin R; Foster, Bryan R; Várallyay, Csanád; Liu, Jen-Jane; Coakley, Fergus V

2018-06-09

To investigate the concordance between dominant intraprostatic cancer seen on endorectal multiparametric MRI and confirmed by MRI-targeted biopsy with histopathological findings at radical prostatectomy, since existing literature has emphasized the miss rather than the concordance rate of MRI. We retrospectively identified 20 patients who underwent radical prostatectomy after a dominant intraprostatic cancer focus was identified at endorectal multiparametric MRI and confirmed by MRI-targeted biopsy. Concordance was determined by comparing the location and Gleason grade group of dominant tumor at MRI with the location and Gleason grade group determined at histopathological review. Mean patient age was 65 years (range, 48 to 76) and median serum prostatic specific antigen level was 9.4 ng/mL (range, 4.6 to 58.0). In all 20 patients, the location of dominant tumor based on MRI and targeted biopsy corresponded with the dominant tumor location at histopathology. In 9 patients, Gleason grade group was the same at targeted biopsy and final histopathology. In 9 patients, final Gleason grade group was higher and in two patients it was lower. Our preliminary results suggest dominant tumor as determined by endorectal multiparametric MRI and confirmed by a positive MRI-targeted biopsy has high concordance with histopathological findings at radical prostatectomy for location, and reasonable concordance for Gleason grade group. Copyright © 2018 Elsevier Inc. All rights reserved.

Using formative research to lay the foundation for community level HIV prevention efforts: an example from the AIDS Community Demonstration Projects.

PubMed Central

Higgins, D L; O'Reilly, K; Tashima, N; Crain, C; Beeker, C; Goldbaum, G; Elifson, C S; Galavotti, C; Guenther-Grey, C

1996-01-01

The AIDS Community Demonstration Projects provided community-level HIV prevention interventions to historically hard-to-reach groups at high risk for HIV infection. The projects operated under a common research protocol which encompassed formative research, intervention delivery, process evaluation, and outcome evaluation. A formative research process specifically focusing on intervention development was devised to assist project staff in identifying, prioritizing, accessing, and understanding the intervention target groups. This process was central to the creation of interventions that were acceptable and unique to the target populations. Intended to be rapid, the process took 6 months to complete. Drawn from the disciplines of anthropology, community psychology, sociology, and public health, the formative research process followed distinct steps which included (a) defining the populations at high-risk for HIV; (b) gathering information about these populations through interviews with persons who were outside of, but who had contact with, the target groups (such as staff from the health department and alcohol and drug treatment facilities, as well as persons who interacted in an informal manner with the target groups, such as clerks in neighborhood grocery stores and bartenders); (c) interviewing people with access to the target populations (gatekeepers), and conducting observations in areas where these high-risk groups were reported to gather (from previous interviews); (d) interviewing members of these groups at high risk for HIV infection or transmission; and (e) systematically integrating information throughout the process. Semistructured interview schedules were used for all data collection in this process. This standardized systematic method yielded valuable information about the focal groups in each demonstration project site. The method, if adopted by others, would assist community intervention specialists in developing interventions that are culturally appropriate and meaningful to their respective target populations. PMID:8862154

Lipid Management in a Japanese Community:Attainment Rate of Target Set by the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Nohara, Atsushi; Inazu, Akihiro; Kobayashi, Junji; Yasuda, Kenji; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

2017-03-01

The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic diseases 2012 (JAS2012) proposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups. A total of 85,716 subjects (male=29,282, 34.2%) aged 40-74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets. The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends ＜0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value ＜0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value ＜0.001). Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.

Nurse opinions and pulse oximeter saturation target limits for preterm infants.

PubMed

Nghiem, Tuyet-Hang; Hagadorn, James I; Terrin, Norma; Syke, Sally; MacKinnon, Brenda; Cole, Cynthia H

2008-05-01

The objectives of this study were to compare pulse oximeter saturation limits targeted by nurses for extremely preterm infants during routine care with nurse opinions regarding appropriate pulse oximeter saturation limits and with policy-specified pulse oximeter saturation limits and to identify factors that influence pulse oximeter saturation limits targeted by nurses. We surveyed nurses in US NICUs with neonatal-perinatal fellowships in 2004. Data collected included pulse oximeter saturation limits targeted by nurses and by NICU policy when present, nurses' opinions about appropriate pulse oximeter saturation limits, and NICU and nurse characteristics. Factors associated with pulse oximeter saturation limits targeted by nurses were identified with hierarchical linear modeling. Among those eligible, 2805 (45%) nurses in 59 (60%) NICUs responded. Forty (68%) of 59 NICUs had a policy that specified a pulse oximeter saturation target range for extremely preterm infants. Among 1957 nurses at NICUs with policies, 540 (28%) accurately identified the upper and lower limits of their NICU's policy and also targeted these values in practice. NICU-specific SDs for individual nurse target limits were less at NICUs with versus without a policy for both upper and lower limits. Hierarchical linear modeling identified presence of pulse oximeter saturation policy, NICU-specific nurse group opinion, and individual nurse opinion as factors significantly associated with individual pulse oximeter saturation target limits. For each percentage point increase in individual opinion upper limit, the individual target upper limit increased by 0.41 percentage point at NICUs with a policy compared with 0.6 percentage point at NICUs with no policy. Presence of policy-specified pulse oximeter saturation limits, nurse group opinion, and individual nurse opinion were independently associated with individual nurse pulse oximeter saturation target limits during routine care of extremely preterm infants. The presence of a policy reduced the influence of individual nurse opinion on targeted pulse oximeter saturation limits and reduced variation among nurse target limits within NICUs.

Sensitizing Black Adult and Youth Consumers to Targeted Food Marketing Tactics in Their Environments

PubMed Central

Isselmann DiSantis, Katherine; Kumanyika, Shiriki; Rohm Young, Deborah; Grier, Sonya A.; Lassiter, Vikki

2017-01-01

Food marketing environments of Black American consumers are heavily affected by ethnically-targeted marketing of sugar sweetened beverages, fast foods, and other products that may contribute to caloric overconsumption. This qualitative study assessed Black consumers’ responses to targeted marketing. Black adults (2 mixed gender groups; total n = 30) and youth (2 gender specific groups; total n = 35) from two U.S. communities participated before and after a sensitization procedure—a critical practice used to understand social justice concerns. Pre-sensitization focus groups elicited responses to scenarios about various targeted marketing tactics. Participants were then given an informational booklet about targeted marketing to Black Americans, and all returned for the second (post-sensitization) focus group one week later. Conventional qualitative content analysis of transcripts identified several salient themes: seeing the marketer’s perspective (“it’s about demand”; “consumers choose”), respect for community (“marketers are setting us up for failure”; “making wrong assumptions”), and food environments as a social justice issue (“no one is watching the door”; “I didn’t realize”). Effects of sensitization were reflected in participants’ stated reactions to the information in the booklet, and also in the relative occurrence of marketer-oriented themes and social justice-oriented themes, respectively, less and more after sensitization. PMID:29109377

Sensitizing Black Adult and Youth Consumers to Targeted Food Marketing Tactics in Their Environments.

PubMed

Isselmann DiSantis, Katherine; Kumanyika, Shiriki; Carter-Edwards, Lori; Rohm Young, Deborah; Grier, Sonya A; Lassiter, Vikki

2017-10-29

Food marketing environments of Black American consumers are heavily affected by ethnically-targeted marketing of sugar sweetened beverages, fast foods, and other products that may contribute to caloric overconsumption. This qualitative study assessed Black consumers' responses to targeted marketing. Black adults (2 mixed gender groups; total n = 30) and youth (2 gender specific groups; total n = 35) from two U.S. communities participated before and after a sensitization procedure-a critical practice used to understand social justice concerns. Pre-sensitization focus groups elicited responses to scenarios about various targeted marketing tactics. Participants were then given an informational booklet about targeted marketing to Black Americans, and all returned for the second (post-sensitization) focus group one week later. Conventional qualitative content analysis of transcripts identified several salient themes: seeing the marketer's perspective ("it's about demand"; "consumers choose"), respect for community ("marketers are setting us up for failure"; "making wrong assumptions"), and food environments as a social justice issue ("no one is watching the door"; "I didn't realize"). Effects of sensitization were reflected in participants' stated reactions to the information in the booklet, and also in the relative occurrence of marketer-oriented themes and social justice-oriented themes, respectively, less and more after sensitization.

Explaining efficient search for conjunctions of motion and form: evidence from negative color effects.

PubMed

Dent, Kevin

2014-05-01

Dent, Humphreys, and Braithwaite (2011) showed substantial costs to search when a moving target shared its color with a group of ignored static distractors. The present study further explored the conditions under which such costs to performance occur. Experiment 1 tested whether the negative color-sharing effect was specific to cases in which search showed a highly serial pattern. The results showed that the negative color-sharing effect persisted in the case of a target defined as a conjunction of movement and form, even when search was highly efficient. In Experiment 2, the ease with which participants could find an odd-colored target amongst a moving group was examined. Participants searched for a moving target amongst moving and stationary distractors. In Experiment 2A, participants performed a highly serial search through a group of similarly shaped moving letters. Performance was much slower when the target shared its color with a set of ignored static distractors. The exact same displays were used in Experiment 2B; however, participants now responded "present" for targets that shared the color of the static distractors. The same targets that had previously been difficult to find were now found efficiently. The results are interpreted in a flexible framework for attentional control. Targets that are linked with irrelevant distractors by color tend to be ignored. However, this cost can be overridden by top-down control settings.

Non-Invasive Nanodiagnostics of Cancer (NINOC)

DTIC Science & Technology

2010-04-01

tested. CONCLUSIONS Well-defined diblock copolymers of poly(ethylene glycol) and polymethacrylic acid (PEG-b-PMA) with aldehyde functionality were...treatment of cancer, tumor-specific targeting has been proposed using a variety of targeting moieties such as folic acid , transferrin, RGD-peptides...tert-butyl and PEG groups (Table 1). In order to obtain the final block copolymer 6, the hydrolysis of copolymer 5 was carried out in the acidic

Targeting gender: A content analysis of alcohol advertising in magazines.

PubMed

Jung, A-Reum; Hovland, Roxanne

2016-01-01

Creating target specific advertising is fundamental to maximizing advertising effectiveness. When crafting an advertisement, message and creative strategies are considered important because they affect target audiences' attitudes toward advertised products. This study endeavored to find advertising strategies that are likely to have special appeal for men or women by examining alcohol advertising in magazines. The results show that the substance of the messages is the same for men and women, but they only differ in terms of presentation. However, regardless of gender group, the most commonly used strategies in alcohol advertising are appeals to the target audience's emotions.

Verbal Short-Term Memory Deficits in Chinese Children with Dyslexia may not be a Problem with the Activation of Phonological Representations.

PubMed

Zhao, Jing; Yang, Yang; Song, Yao-Wu; Bi, Hong-Yan

2015-11-01

This study explored the underlying mechanism of the verbal short-term memory deficit in Chinese children with developmental dyslexia. Twenty-four children with dyslexia and 28 age-matched normal readers participated in the study. They were required to memorize a visually presented series of six Chinese characters and identify them from a list also including code-specific distracters and non-code-specific distracters. Error rates were recorded and were higher for code-specific distracters in all three conditions, revealing phonological, visual, and semantic similarity effects respectively. Group comparisons showed a stronger phonological similarity effect in dyslexic group, suggesting intact activation of phonological representations of target characters. Children with dyslexia also exhibited a greater semantic similarity effect, revealing stronger activation of semantic representations, while visual similarity effects were equivalent to controls. These results suggest that the verbal short-term memory deficit in Chinese dyslexics might not stem from insufficient activation of phonological information. Based the semantic activation of target characters in dyslexics is greater than in controls, it is possible that the memory deficit of dyslexia is related with deficient inhibition of target semantic representations in short-term memory. Copyright © 2015 John Wiley & Sons, Ltd.

Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1)

PubMed Central

Lingner, Thomas; Kataya, Amr R. A.; Reumann, Sigrun

2012-01-01

We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences.1 As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity.” Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals. PMID:22415050

Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1).

PubMed

Lingner, Thomas; Kataya, Amr R A; Reumann, Sigrun

2012-02-01

We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences. As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity." Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals.

Creating and virtually screening databases of fluorescently-labelled compounds for the discovery of target-specific molecular probes

NASA Astrophysics Data System (ADS)

Kamstra, Rhiannon L.; Dadgar, Saedeh; Wigg, John; Chowdhury, Morshed A.; Phenix, Christopher P.; Floriano, Wely B.

2014-11-01

Our group has recently demonstrated that virtual screening is a useful technique for the identification of target-specific molecular probes. In this paper, we discuss some of our proof-of-concept results involving two biologically relevant target proteins, and report the development of a computational script to generate large databases of fluorescence-labelled compounds for computer-assisted molecular design. The virtual screening of a small library of 1,153 fluorescently-labelled compounds against two targets, and the experimental testing of selected hits reveal that this approach is efficient at identifying molecular probes, and that the screening of a labelled library is preferred over the screening of base compounds followed by conjugation of confirmed hits. The automated script for library generation explores the known reactivity of commercially available dyes, such as NHS-esters, to create large virtual databases of fluorescence-tagged small molecules that can be easily synthesized in a laboratory. A database of 14,862 compounds, each tagged with the ATTO680 fluorophore was generated with the automated script reported here. This library is available for downloading and it is suitable for virtual ligand screening aiming at the identification of target-specific fluorescent molecular probes.

Development and use of fluorescent 16S rRNA-targeted probes for the specific detection of Methylophaga species by in situ hybridization in marine sediments.

PubMed

Janvier, Monique; Regnault, Béatrice; Grimont, Patrick

2003-09-01

Methylotrophic bacteria are widespread in nature. They may play an important role in the cycling of carbon and in the metabolism of dimethylsulfide in a marine environment. Bacteria belonging to the genus Methylophaga are a unique group of aerobic, halophilic, non-methane-utilizing methylotrophs. Two 16S rRNA-targeted oligonucleotide probes were developed for the specific detection of Methylophaga species, marine methylobacteria, by fluorescence in situ hybridization. Probe MPH-730 was highly specific for all members of the genus Methylophaga while probe MPHm-994 targeted exclusively M. marina. The application of these probes were demonstrated by the detection of Methylophaga species in enrichment cultures from various marine sediments. All isolates recovered were visualized by using the genus specific probe MPH-730. The results were confirmed by 16S rDNA sequencing which demonstrated that all selected isolates belong to Methylophaga. Five isolates could be detected by the M. marina-specific probe MPHm-994 and were confirmed by rRNA gene restriction pattern (ribotyping). With the development of these specific probes, fluorescence in situ hybridization shows that the genus Methylophaga is widespread in marine samples.

Outside over There: "My Book House" Divides the World, 1919-1954

ERIC Educational Resources Information Center

Levstik, Linda S.

2016-01-01

The rise of mass-marketed literature specifically targeting child readers is a significant if often overlooked piece of a larger historical pattern in which contending cultural groups attempt to control the words and worlds available to different groups within and between societies. The work of Olive Beaupré Miller, author/editor from 1919-1954 of…

Sex Education Targeting African Communities in the United Kingdom: Is It Fit for Purpose?

ERIC Educational Resources Information Center

Schmidt, E.; Olomo, F.; Corcoran, N.

2012-01-01

This study addresses the issue of the sexual needs of ethnic minority groups in the UK. Using focus group discussions with health service users and third-sector providers, it explores the perception of sex education by Black African communities living in a culturally diverse area in East London, focusing specifically on participants' understanding…

Statewide Needs Assessment: Target Populations--Displaced Homemakers, Single Heads of Households, and Other Special Groups.

ERIC Educational Resources Information Center

Bromley, Ann

A statewide needs assessment in vocational education focused on the needs of displaced homemakers and other special groups in Florida. Specifically, the survey provided (1) a demographic profile of adults in Florida, particularly those described as displaced homemakers, single heads of households, part-time workers, and people desiring work in…

77 FR 46092 - Agency Information Collection Activities; Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... at www.admongo.gov . The proposed evaluation will test a large group of students in these skills and..., one hour of online game playing, one hour of homework assignments, and 20 minutes for the test). With... specific skills: How to identify ads, how to identify the ways advertisers target certain groups of...

Galactosylated pullulan-curcumin conjugate micelles for site specific anticancer activity to hepatocarcinoma cells.

PubMed

Sarika, P R; James, Nirmala Rachel; Nishna, N; Anil Kumar, P R; Raj, Deepa K

2015-09-01

Galactosylated pullulan-curcumin conjugate (LANH2-Pu Ald-Cur SA) is developed for target specific delivery of curcumin to hepatocarcinoma cells by five step synthetic strategy, which includes oxidation of pullulan (Pu Ald), introduction of amino group to the targeting ligand (LANH2), grafting of the LANH2 to Pu Ald, modification of curcumin (Cur SA) and conjugation of Cur SA to pullulan. Nongalactosylated pullulan-curcumin conjugate (Pu-Cur SA) is also prepared to compare the enhancement in cytotoxicity offered by the targeting group. Both LANH2-Pu Ald-Cur SA and Pu-Cur SA conjugates could self assemble to micelle in water with hydrodynamic diameters of 355±9nm and 363±10nm, respectively. Both conjugates show spherical morphology and enhance stability of curcumin in physiological pH. Compared to Pu-Cur SA, LANH2-Pu Ald-Cur SA exhibits higher toxicity and internalization towards HepG2 cells. This indicates the enhanced uptake of LANH2-Pu Ald-Cur SA conjugate via ASGPR (asialoglycoprotein receptor) mediated endocytosis into HepG2 cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier.

PubMed

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma.

Evaluating Level of Specificity of Normative Referents in Relation to Personal Drinking Behavior*

PubMed Central

Larimer, Mary E.; Kaysen, Debra L.; Lee, Christine M.; Kilmer, Jason R.; Lewis, Melissa A.; Dillworth, Tiara; Montoya, Heidi D.; Neighbors, Clayton

2009-01-01

Objective: Research has found perceived descriptive norms to be one of the strongest predictors of college student drinking, and several intervention approaches have incorporated normative feedback to correct misperceptions of peer drinking behavior. Little research has focused on the role of the reference group in normative perceptions. The current study sought to examine whether normative perceptions vary based on specificity of the reference group and whether perceived norms for more specific reference-group norms are related to individual drinking behavior. Method: Participants were first-year undergraduates (n = 1,276, 58% female) randomly selected from a university list of incoming students. Participants reported personal drinking behavior and perceived descriptive norms for eight reference groups, including typical student; same gender, ethnicity, or residence; and combinations of those reference groups (e.g., same gender and residence). Results: Findings indicated that participants distinguished among different reference groups in estimating descriptive drinking norms. Moreover, results indicated misperceptions in drinking norms were evident at all levels of specificity of the reference group. Additionally, findings showed perceived norms for more specific groups were uniquely related to participants' own drinking. Conclusions: These results suggest that providing normative feedback targeting at least one level of specificity to the participant (i.e., beyond what the “typical” student does) may be an important tool in normative feedback interventions. PMID:19538919

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

PubMed

Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

2015-01-01

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

PubMed Central

Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

2015-01-01

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS. PMID:26604753

[Growing up as an occupation child of World War II in Germany: Rationale and methods of a study on German occupation children].

PubMed

Kaiser, Marie; Kuwert, Philipp; Glaesmer, Heide

2015-01-01

To date the experiences of German occupation children (GOC) have been described solely in historical studies; empirical research on the psychosocial consequences growing up as German occupation children was missing. This paper provides an introduction to the background, methodological approaches and descriptive information on a sample for the first German-based empirical study on this topic. It also touches on methodical challenges and solution processes. Children born of war resemble a target group that is difficult to reach (hidden population). Therefore, an investigation needs consultation of both people from the target group and scientific experts (participatory approach) as well as specific methodological approaches. The questionnaire utilized contains adaptations of established and psychometrically validated instruments as well as adapted self-developed items. N = 146 occupation children were surveyed (mean age 63.4, 63.0% women) via press release and contact to platforms of children born of war. Despite methodological challenges an instrument to assess the target group was developed through participatory methods. The instrument shows high relevance for the target group and is highly accepted. High rates of American and French participants show the influence of networking in platforms on successful recruitment.

‘Peer pressure’ in larval Drosophila?

PubMed Central

Niewalda, Thomas; Jeske, Ines; Michels, Birgit; Gerber, Bertram

2014-01-01

ABSTRACT Understanding social behaviour requires a study case that is simple enough to be tractable, yet complex enough to remain interesting. Do larval Drosophila meet these requirements? In a broad sense, this question can refer to effects of the mere presence of other larvae on the behaviour of a target individual. Here we focused in a more strict sense on ‘peer pressure’, that is on the question of whether the behaviour of a target individual larva is affected by what a surrounding group of larvae is doing. We found that innate olfactory preference of a target individual was neither affected (i) by the level of innate olfactory preference in the surrounding group nor (ii) by the expression of learned olfactory preference in the group. Likewise, learned olfactory preference of a target individual was neither affected (iii) by the level of innate olfactory preference of the surrounding group nor (iv) by the learned olfactory preference the group was expressing. We conclude that larval Drosophila thus do not take note of specifically what surrounding larvae are doing. This implies that in a strict sense, and to the extent tested, there is no social interaction between larvae. These results validate widely used en mass approaches to the behaviour of larval Drosophila. PMID:24907371

'Peer pressure' in larval Drosophila?

PubMed

Niewalda, Thomas; Jeske, Ines; Michels, Birgit; Gerber, Bertram

2014-06-06

Understanding social behaviour requires a study case that is simple enough to be tractable, yet complex enough to remain interesting. Do larval Drosophila meet these requirements? In a broad sense, this question can refer to effects of the mere presence of other larvae on the behaviour of a target individual. Here we focused in a more strict sense on 'peer pressure', that is on the question of whether the behaviour of a target individual larva is affected by what a surrounding group of larvae is doing. We found that innate olfactory preference of a target individual was neither affected (i) by the level of innate olfactory preference in the surrounding group nor (ii) by the expression of learned olfactory preference in the group. Likewise, learned olfactory preference of a target individual was neither affected (iii) by the level of innate olfactory preference of the surrounding group nor (iv) by the learned olfactory preference the group was expressing. We conclude that larval Drosophila thus do not take note of specifically what surrounding larvae are doing. This implies that in a strict sense, and to the extent tested, there is no social interaction between larvae. These results validate widely used en mass approaches to the behaviour of larval Drosophila. © 2014. Published by The Company of Biologists Ltd.

Social exclusion impairs distractor suppression but not target enhancement in selective attention.

PubMed

Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

2017-11-01

Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

16S rRNA beacons for bacterial monitoring during human space missions.

PubMed

Larios-Sanz, Maia; Kourentzi, Katerina D; Warmflash, David; Jones, Jeffrey; Pierson, Duane L; Willson, Richard C; Fox, George E

2007-04-01

Microorganisms are unavoidable in space environments and their presence has, at times, been a source of problems. Concerns about disease during human space missions are particularly important considering the significant changes the immune system incurs during spaceflight and the history of microbial contamination aboard the Mir space station. Additionally, these contaminants may have adverse effects on instrumentation and life-support systems. A sensitive, highly specific system to detect, characterize, and monitor these microbial populations is essential. Herein we describe a monitoring approach that uses 16S rRNA targeted molecular beacons to successfully detect several specific bacterial groupings. This methodology will greatly simplify in-flight monitoring by minimizing sample handling and processing. We also address and provide solutions to target accessibility problems encountered in hybridizations that target 16S rRNA.

Increased subjective experience of non-target emotions in patients with frontotemporal dementia and Alzheimer’s disease

PubMed Central

Chen, Kuan-Hua; Lwi, Sandy J.; Hua, Alice Y.; Haase, Claudia M.; Miller, Bruce L.; Levenson, Robert W.

2017-01-01

Although laboratory procedures are designed to produce specific emotions, participants often experience mixed emotions (i.e., target and non-target emotions). We examined non-target emotions in patients with frontotemporal dementia (FTD), Alzheimer’s disease (AD), other neurodegenerative diseases, and healthy controls. Participants watched film clips designed to produce three target emotions. Subjective experience of non-target emotions was assessed and emotional facial expressions were coded. Compared to patients with other neurodegenerative diseases and healthy controls, FTD patients reported more positive and negative non-target emotions, whereas AD patients reported more positive non-target emotions. There were no group differences in facial expressions of non-target emotions. We interpret these findings as reflecting deficits in processing interoceptive and contextual information resulting from neurodegeneration in brain regions critical for creating subjective emotional experience. PMID:29457053

An eHealth Intervention to Promote Physical Activity and Social Network of Single, Chronically Impaired Older Adults: Adaptation of an Existing Intervention Using Intervention Mapping

PubMed Central

Peels, Denise A; Berendsen, Brenda AJ; Bolman, Catherine AW; Lechner, Lilian

2017-01-01

Background Especially for single older adults with chronic diseases, physical inactivity and a poor social network are regarded as serious threats to their health and independence. The Active Plus intervention is an automated computer-tailored eHealth intervention that has been proven effective to promote physical activity (PA) in the general population of adults older than 50 years. Objective The aim of this study was to report on the methods and results of the systematic adaptation of Active Plus to the wishes and needs of the subgroup of single people older than 65 years who have one or more chronic diseases, as this specific target population may encounter specific challenges regarding PA and social network. Methods The Intervention Mapping (IM) protocol was used to systematically adapt the existing intervention to optimally suit this specific target population. A literature study was performed, and quantitative as well as qualitative data were derived from health care professionals (by questionnaires, n=10) and the target population (by focus group interviews, n=14), which were then systematically integrated into the adapted intervention. Results As the health problems and the targeted behavior are largely the same in the original and adapted intervention, the outcome of the needs assessment was that the performance objectives remained the same. As found in the literature study and in data derived from health professionals and focus groups, the relative importance and operationalization of the relevant psychosocial determinants related to these objectives are different from the original intervention, resulting in a refinement of the change objectives to optimally fit the specific target population. This refinement also resulted in changes in the practical applications, program components, intervention materials, and the evaluation and implementation strategy for the subgroup of single, chronically impaired older adults. Conclusions This study demonstrates that the adaptation of an existing intervention is an intensive process in which adopting the IM protocol is an invaluable tool. The study provides a broad insight in adapting interventions aimed at single older adults with a chronic disease. It is concluded that even when the new target population is a sizable segment of the original target population, the adapted intervention still needs considerable changes to optimally fit the needs and situational differences of the narrower target population. PMID:29170146

IMMUNOCHEMICAL APPLICATIONS IN ENVIRONMENTAL SCIENCE

EPA Science Inventory

Immunochemical methods are based on selective antibodies combining with a particular target analyte or analyte group. The specific binding between antibody and analyte can be used to detect environmental contaminants in a variety of sample matrixes. Immunoassay methods provide ...

Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

PubMed Central

Butts, Arielle; DeJarnette, Christian; Peters, Tracy L.; Parker, Josie E.; Kerns, Morgan E.; Eberle, Karen E.; Kelly, Steve L.

2017-01-01

ABSTRACT Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. PMID:28989971

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

PubMed

Kasivisvanathan, Veeru; Rannikko, Antti S; Borghi, Marcelo; Panebianco, Valeria; Mynderse, Lance A; Vaarala, Markku H; Briganti, Alberto; Budäus, Lars; Hellawell, Giles; Hindley, Richard G; Roobol, Monique J; Eggener, Scott; Ghei, Maneesh; Villers, Arnauld; Bladou, Franck; Villeirs, Geert M; Virdi, Jaspal; Boxler, Silvan; Robert, Grégoire; Singh, Paras B; Venderink, Wulphert; Hadaschik, Boris A; Ruffion, Alain; Hu, Jim C; Margolis, Daniel; Crouzet, Sébastien; Klotz, Laurence; Taneja, Samir S; Pinto, Peter; Gill, Inderbir; Allen, Clare; Giganti, Francesco; Freeman, Alex; Morris, Stephen; Punwani, Shonit; Williams, Norman R; Brew-Graves, Chris; Deeks, Jonathan; Takwoingi, Yemisi; Emberton, Mark; Moore, Caroline M

2018-05-10

Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Emergence of the benefits and costs of grouping for visual search.

PubMed

Wu, Rachel; McGee, Brianna; Rubenstein, Madelyn; Pruitt, Zoe; Cheung, Olivia S; Aslin, Richard N

2018-04-16

The present study investigated how grouping related items leads to the emergence of benefits (facilitation when related items are search targets) and costs (interference when related items are distractors) in visual search. Participants integrated different views (related items) of a novel Lego object via (a) assembling the object, (b) disassembling the object, or (c) sitting quietly without explicit instructions. An omnibus ANOVA revealed that neural responses (N2pc ERP) for attentional selection increased between pretest to posttest regardless of the training condition when a specific target view appeared (benefit) and when a nontarget view from the same object as the target view appeared (cost). Bonferroni-corrected planned comparisons revealed that assembling the object (but not disassembling the object or no training) had a significant impact from pretest to posttest, although the ANOVA did not reveal any interaction effects, suggesting that the effects might not differ across training conditions. This study is one of the first to demonstrate the emergence of the costs and benefits of grouping novel targets on visual search efficiency. © 2018 Society for Psychophysiological Research.

Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance

PubMed Central

McHugh, R. Kathryn; Otto, Michael W.

2011-01-01

Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763

Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease.

PubMed

Matsuda, H; Mizumura, S; Nemoto, K; Yamashita, F; Imabayashi, E; Sato, N; Asada, T

2012-06-01

The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.

Africa takes a more male-friendly approach to family planning.

PubMed

Omuodo, D O

1996-12-01

It has been demonstrated that men are more likely to support family planning (FP) and to use a method themselves if services and educational programs are targeted to them. Because men fear that contraception reduces their control over their wives' sexuality, male-friendly approaches can enhance gender equality in reproductive health decisions. In Togo, the media is being used to encourage positive attitudes towards FP in specific male groups. In Ghana, FP services targeted to men have resulted in increased male involvement. In Swaziland, male audiences are targeted with FP education. In Sierra Leone, men have met in groups to learn about how to prevent sexually transmitted diseases and about the benefits of FP, and in Kenya, three male-only clinics exist to provide FP services to men.

Viral Capsid DNA Aptamer Conjugates as Multivalent Cell Targeting Vehicles

PubMed Central

Tong, Gary J.; Hsiao, Sonny C.; Carrico, Zachary M.; Francis, Matthew B.

2009-01-01

Nucleic acid aptamers offer significant potential as convenient and evolvable targeting groups for drug delivery. To attach them to the surface of a genome-free viral capsid carrier, an efficient oxidative coupling strategy has been developed. The method involves the periodate-mediated reaction of phenylene diamine substituted oligonucleotides with aniline groups installed on the outer surface of the capsid shells. Up to 60 DNA strands can be attached to each viral capsid with no apparent loss of base-pairing capabilities or protein stability. The ability of the capsids to bind specific cellular targets was demonstrated through the attachment of a 41-nucleotide sequence that targets a tyrosine kinase receptor on Jurkat T cells. After the installation of a fluorescent dye on the capsid interior, capsids bearing the cell-targeting sequence showed significant levels of binding to the cells relative to control samples. Colocalization experiments using confocal microscopy indicated that the capsids were endocytosed and trafficked to lysosomes for degradation. These observations suggest that aptamer-labeled capsids could be used for the targeted drug delivery of acid-labile prodrugs that would be preferentially released upon lysosomal acidification. PMID:19603808

The NASA Goddard Group's Source Monitoring Database and Program

NASA Astrophysics Data System (ADS)

Gipson, John; Le Bail, Karine; Ma, Chopo

2014-12-01

Beginning in 2003, the Goddard VLBI group developed a program to purposefully monitor when sources were observed and to increase the observations of ``under-observed'' sources. The heart of the program consists of a MySQL database that keeps track of, on a session-by-session basis: the number of observations that are scheduled for a source, the number of observations that are successfully correlated, and the number of observations that are used in a session. In addition, there is a table that contains the target number of successful sessions over the last twelve months. Initially this table just contained two categories. Sources in the geodetic catalog had a target of 12 sessions/year; the remaining ICRF-1 defining sources had a target of two sessions/year. All other sources did not have a specific target. As the program evolved, different kinds of sources with different observing targets were added. During the scheduling process, the scheduler has the option of automatically selecting N sources which have not met their target. We discuss the history and present some results of this successful program.

Improved group-specific primers based on the full SILVA 16S rRNA gene reference database.

PubMed

Pfeiffer, Stefan; Pastar, Milica; Mitter, Birgit; Lippert, Kathrin; Hackl, Evelyn; Lojan, Paul; Oswald, Andreas; Sessitsch, Angela

2014-08-01

Quantitative PCR (qPCR) and community fingerprinting methods, such as the Terminal Restriction Fragment Length Polymorphism (T-RFLP) analysis,are well-suited techniques for the examination of microbial community structures. The use of phylum and class-specific primers can provide enhanced sensitivity and phylogenetic resolution as compared with domain-specific primers. To date, several phylum- and class-specific primers targeting the 16S ribosomal RNA gene have been published. However, many of these primers exhibit low discriminatory power against non-target bacteria in PCR. In this study, we evaluated the precision of certain published primers in silico and via specific PCR. We designed new qPCR and T-RFLP primer pairs (for the classes Alphaproteobacteria and Betaproteobacteria, and the phyla Bacteroidetes, Firmicutes and Actinobacteria) by combining the sequence information from a public dataset (SILVA SSU Ref 102 NR) with manual primer design. We evaluated the primer pairs via PCR using isolates of the above-mentioned groups and via screening of clone libraries from environmental soil samples and human faecal samples. As observed through theoretical and practical evaluation, the primers developed in this study showed a higher level of precision than previously published primers, thus allowing a deeper insight into microbial community dynamics.

Training in Basic Internet Skills for Special Target Groups in Non-Formal Educational Settings--Conclusions from Three Pilot Projects

ERIC Educational Resources Information Center

Berger, Andrea; Croll, Jutta

2012-01-01

With the progress of Digital Inclusion, it becomes important to address marginalised groups that face specific barriers in being part of the information society. From 2009 to 2011 within the framework of the nation-wide Initiative "Internet erfahren", funded by the German Federal Ministry of Economics, Stiftung Digitale Chancen has…

Using focus groups in the consumer research phase of a social marketing program to promote moderate-intensity physical activity and walking trail use in Sumter County, South Carolina.

PubMed

Burroughs, Ericka; Peck, Lara E; Sharpe, Patricia A; Granner, Michelle L; Bryant, Carol A; Fields, Regina

2006-01-01

The use of social marketing approaches in public health practice is increasing. Using marketing concepts such as the "four Ps" (product, price, place, and promotion), social marketing borrows from the principles of commercial marketing but promotes beneficial health behaviors. Consumer research is used to segment the population and develop a strategy based on those marketing concepts. In a community-based participatory research study, 17 focus groups were used in consumer research to develop a social marketing program to promote walking and other moderate-intensity physical activities. Two phases of focus groups were conducted. Phase 1 groups, which included both men and women, were asked to respond to questions that would guide the development of a social marketing program based on social marketing concepts. Phase 1 also determined the intervention's target audience, which was irregularly active women aged 35 to 54. Phase 2 groups, composed of members of the target audience, were asked to further define the product and discuss specific promotion strategies. Phase 1 participants determined that the program product, or target behavior, should be walking. In addition, they identified price, place, and promotion strategies. Phase 2 participants determined that moderate-intensity physical activity is best promoted using the term exercise and offered suggestions for marketing walking, or exercise, to the target audience. There have been few published studies of social marketing campaigns to promote physical activity. In this study, focus groups were key to understanding the target audience in a way that would not have been accomplished with quantitative data alone. The group discussions generated important insights into values and motivations that affect consumers' decisions to adopt a product or behavior. The focus group results guided the development of a social marketing program to promote physical activity in the target audience in Sumter County, South Carolina.

Beyond the "general public": implications of audience characteristics for promoting species conservation in the Western Ghats hotspot, India.

PubMed

Kanagavel, Arun; Raghavan, Rajeev; Veríssimo, Diogo

2014-03-01

Understanding how different audience groups perceive wildlife is crucial for the promotion of biodiversity conservation, especially given the key role of flagship species in conservation campaigns. Although the heterogeneity in preferences reinforces the need for campaigns tailored to specific target audiences, many conservation education and awareness campaigns still claim to target the "general public". Audiences can be segmented according to social, economic, and cultural criteria across which species perceptions are known to vary. Different studies have investigated the preferences of different groups towards certain wildlife species, but these are largely confined to a single conservation stakeholder group, such as tourists, local communities, or potential donors in western countries. In this study, we seek to determine from a multi-stakeholder perspective, audience characteristics that influence perceptions towards wildlife at Valparai, a fragmented plateau in the Western Ghats region of the Western Ghats-Sri Lanka Hotspot. We found that stakeholder group membership was the most important characteristic followed by gender. While some characteristics had a wide-scale effect others were restricted to a few species. Our results emphasize the need to design conservation campaigns with specific audiences in mind, instead of the very often referred to "general public".

Today's Recruitment Trends.

ERIC Educational Resources Information Center

Sugarman, Joe

1996-01-01

Five trends in the creation of college student recruitment publications are identified: (1) using market research and marketing principles; (2) targeting specific groups; (3) honesty about campus personality and reputation; (4) cost-effectiveness; and (5) creativity in using effective copy and design. (MSE)

The long flow to freedom

DOE PAGES

Aharony, Ofer; Razamat, Shlomo S.; Seiberg, Nathan; ...

2017-02-10

Two-dimensional field theories do not have a moduli space of vacua. Instead, it is common that their low-energy behavior is a sigma model with a target space. When this target space is compact its renormalization group flow is standard. When it is non-compact the continuous spectrum of operators can change the qualitative behavior. Here we discuss two-dimensional gauge theories with N = (2,2) supersymmetry. We focus on two specific theories, for which we argue that they flow to free chiral multiplets at low energies: the U(1) gauge theory with one flavor (two chiral superfields with charges plus and minus one)more » and a non-zero Fayet-Iliopoulos term, and pure SU( N) gauge theories. We argue that the renormalization group flow of these theories has an interesting order of limits issue. Holding the position on the target space fixed, the space flattens out under the renormalization group. On the other hand, if we first go to infinity on the target space and then perform the renormalization group, we always have a non-trivial space, e.g. a cone with a deficit angle. We explain how to interpret low-energy dualities between theories with non-compact target spaces. As a result, we expect a similar qualitative behavior also for other non-compact sigma models, even when they do not flow to free theories.« less

The effect of surface functionality on cellular trafficking of dendrimers.

PubMed

Perumal, Omathanu P; Inapagolla, Rajyalakshmi; Kannan, Sujatha; Kannan, Rangaramanujam M

2008-01-01

Dendrimers are an emerging group of nanostructured, polymeric biomaterials that have potential as non-viral vehicles for delivering drugs and genetic material to intracellular targets. They have a high charge density with tunable surface functional groups, which can alter the local environment and influence cellular interactions. This can have a significant impact on the intracellular trafficking of dendrimer-based nanodevices. With the help of flow cytometry, fluorescence microscopy, and by using specific inhibitors, the influence of surface functionality on their uptake in A549 lung epithelial cells, and subsequent intracellular distribution was investigated. In this paper, we have shown that even though all the dendrimers are taken up by fluid-phase endocytosis, significant differences in uptake mechanisms exist. Anionic dendrimers appear to be mainly taken up by caveolae mediated endocytosis in A549 lung epithelial cells, while cationic and neutral dendrimers appear to be taken in by a non-clathrin, non-caveolae mediated mechanism that may be by electrostatic interactions or other non-specific fluid-phase endocytosis. These findings open up new possibilities of targeting therapeutic agents to specific cell organelles based on surface charge.

Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries

PubMed Central

Horst, J.A.; Pieper, U.; Sali, A.; Zhan, L.; Chopra, G.; Samudrala, R.; Featherstone, J.D.B.

2012-01-01

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries. PMID:22899687

Beyond the usual suspects: target group- and behavior-specific factors add to a theory-based sun protection intervention for teenagers.

PubMed

Schüz, Natalie; Eid, Michael

2013-10-01

Sun protection standards among teenagers are low while sun exposure peaks in this age group. Study 1 explores predictors of adolescent protection intentions and exposure behavior. Study 2 tests the effectiveness of an intervention based on these predictors. Study 1(cross-sectional, N = 207, ages 15-18) and Study 2 (RCT, N = 253, ages 13-19) were conducted in schools. Path models were used to analyze data. Self-efficacy (β = .26, p < .001) and time perspective (β = .17, p = .014) were the strongest predictors of intentions; appearance motivation (β = .54, p < .001) and intention (β = -.18, p = .015) predicted behavior. The intervention effected changes in all predictors except self-efficacy. Changes in outcome expectancies (β = .19, p < .001) and time perspective (β = .09, p = .039) predicted changes in intention, while changes in intention (β = -.17, p = .002) and appearance motivation (β = .29, p < .001) predicted behavior changes. Target group- and behavior-specific intervention components are as important for changes in intentions and behavior as components derived from common health behavior theories.

Plant Secondary Metabolites as Rodent Repellents: a Systematic Review.

PubMed

Hansen, Sabine C; Stolter, Caroline; Imholt, Christian; Jacob, Jens

2016-09-01

The vast number of plant secondary metabolites (PSMs) produced by higher plants has generated many efforts to exploit their potential for pest control. We performed a systematic literature search to retrieve relevant publications, and we evaluated these according to PSM groups to derive information about the potential for developing plant-derived rodent repellents. We screened a total of 54 publications where different compounds or plants were tested regarding rodent behavior/metabolism. In the search for widely applicable products, we recommend multi-species systematic screening of PSMs, especially from the essential oil and terpenoid group, as laboratory experiments have uniformly shown the strongest effects across species. Other groups of compounds might be more suitable for the management of species-specific or sex-specific issues, as the effects of some compounds on particular rodent target species or sex might not be present in non-target species or in both sexes. Although plant metabolites have potential as a tool for ecologically-based rodent management, this review demonstrates inconsistent success across laboratory, enclosure, and field studies, which ultimately has lead to a small number of currently registered PSM-based rodent repellents.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

Direct measurement of IgM-Antigen interaction energy on individual red blood cells.

PubMed

Yeow, Natasha; Tabor, Rico F; Garnier, Gil

2017-07-01

Most blood grouping tests rely on the principle of red blood cells (RBCs) agglutination. Agglutination is triggered by the binding of specific blood grouping antibodies to the corresponding RBC surface antigen on multiple cells. The interaction energies between blood grouping antibodies and antigens have been poorly defined in immunohaematology. Here for the first time, we functionalized atomic force microscope (AFM) cantilevers with the IgM form of blood grouping antibodies to probe populations of individual RBCs of different groups under physiological conditions. The force-mapping mode of AFM allowed us to measure specific antibody - antigen interactions, and simultaneously localize and quantify antigen sites on the scanned cell surface. This study provides a new insight of the interactions between IgM antibodies and its corresponding antigen. The technique and information can be translated to develop better blood typing diagnostics and optimize target-specific drug delivery for medical applications. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Meeting report from the Prostate Cancer Foundation PSMA-directed radionuclide scientific working group.

PubMed

Miyahira, Andrea K; Pienta, Kenneth J; Morris, Michael J; Bander, Neil H; Baum, Richard P; Fendler, Wolfgang P; Goeckeler, William; Gorin, Michael A; Hennekes, Hartwig; Pomper, Martin G; Sartor, Oliver; Tagawa, Scott T; Williams, Scott; Soule, Howard R

2018-05-01

The Prostate Cancer Foundation (PCF) convened a PSMA-Directed Radionuclide Scientific Working Group on November 14, 2017, at Weill Cornell Medicine, New York, NY. The meeting was attended by 35 global investigators with expertise in prostate cancer biology, radionuclide therapy, molecular imaging, prostate-specific membrane antigen (PSMA)-targeted agents, drug development, and prostate cancer clinical trials. The goal of this meeting was to discuss the potential for using PSMA-targeted radionuclide agents for the treatment of advanced prostate cancer and to define the studies and clinical trials necessary for validating and optimizing the use of these agents. Several major topic areas were discussed including the overview of PSMA biology, lessons and applications of PSMA-targeted PET imaging, the nuances of designing PSMA-targeted radionuclide agents, clinical experiences with PSMA-targeted radionuclides, PCF-funded projects to accelerate PSMA-targeted radionuclide therapy, and barriers to the use of radionuclide treatments in widespread clinical practice. This article reviews the major topics discussed at the meeting with the goal of promoting research that will validate and optimize the use of PSMA-targeted radionuclide therapies for the treatment of advanced prostate cancer. © 2018 Wiley Periodicals, Inc.

Assessing the relationship between toxicity and economic cost of oncological target agents: A systematic review of clinical trials

PubMed Central

Tartari, Francesca; Conti, Alessandro

2017-01-01

Target agents are peculiar oncological drugs which differ from the traditional therapies in their ability of recognizing specific molecules expressed by tumor cells and microenvironment. Thus, their toxicity is generally lower than that associated to chemotherapy, and they represent nowadays a new standard of care in a number of tumors. This paper deals with the relationship between economic costs and toxicity of target agents. At this aim, a cluster analysis-based exploration of the main features of a large collection of them is carried out, with a specific focus on the variables leading to the identification of their toxicity and related costs. The analysis of the toxicity is based on the Severe Adverse Events (SAE) and Discontinuation (D) rates of each target agent considering data published on PubMed from 1965 to 2016 in the phase II and III studies that have led to the approval of these drugs for cancer patients by US Food and Drug Administration. The construction of the dataset represents a key step of the research, and is grounded on the critical analysis of a wide set of clinical studies. In order to capture different evaluation strategies of the toxicity, clustering is performed according to three different criteria (including Voronoi tessellation). Our procedure allows us to identify 5 different groups of target agents pooled by similar SAE and D rates and, at the same time, 3 groups based on target agents’ costs for 1 month and for the median whole duration of therapy. Results highlight several specific regularities for toxicity and costs. This study present several limitations, being realized starting from clinical trials and not from individual patients’ data. However, a macroscopic perspective suggests that costs are rather heterogeneous, and they do not clearly follow the clustering based on SAE and D rates. PMID:28829823

Using Intervention Mapping to develop a programme to prevent sexually transmittable infections, including HIV, among heterosexual migrant men

PubMed Central

Wolfers, Mireille EG; van den Hoek, Caty; Brug, Johannes; de Zwart, Onno

2007-01-01

Background There is little experience with carefully developed interventions in the HIV/STI prevention field aimed at adult heterosexual target groups in the Netherlands. The ability to apply intervention development protocols, like Intervention Mapping, in daily practice outside of academia, is a matter of concern. An urgent need also exists for interventions aimed at the prevention of STI in migrant populations in the Netherlands. This article describes the theory and evidence based development of HIV/STI prevention interventions by the Municipal Public Health Service Rotterdam Area (MPHS), the Netherlands, for heterosexual migrant men with Surinamese, Dutch-Caribbean, Cape Verdean, Turkish and Moroccan backgrounds. Methods First a needs assessment was carried out. Then, a literature review was done, key figures were interviewed and seven group discussions were held. Subsequently, the results were translated into specific objectives ("change objectives") and used in intervention development for two subgroups: men with an Afro-Caribbean background and unmarried men with a Turkish and Moroccan background. A matrix of change objectives was made for each subgroup and suitable theoretical methods and practical strategies were selected. Culturally-tailored interventions were designed and were pre-tested among the target groups. Results This development process resulted in two interventions for specific subgroups that were appreciated by both the target groups and the migrant prevention workers. The project took place in collaboration with a university center, which provided an opportunity to get expert advice at every step of the Intervention Mapping process. At relevant points of the development process, migrant health educators and target group members provided advice and feedback on the draft intervention materials. Conclusion This intervention development project indicates that careful well-informed intervention development using Intervention Mapping is feasible in the daily practice of the MPHS, provided that sufficient time and expertise on this approach is available. Further research should test the effectiveness of these interventions. PMID:17615052

"Don't wait for them to come to you, you go to them". A qualitative study of recruitment approaches in community based walking programmes in the UK.

PubMed

Matthews, Anne; Brennan, Graham; Kelly, Paul; McAdam, Chloe; Mutrie, Nanette; Foster, Charles

2012-08-10

This study aimed to examine the experiences of walking promotion professionals on the range and effectiveness of recruitment strategies used within community based walking programmes within the United Kingdom. Two researchers recruited and conducted semi-structured interviews with managers and project co-ordinators of community based walking programmes, across the UK, using a purposive sampling frame. Twenty eight interviews were conducted, with community projects targeting participants by age, physical activity status, socio-demographic characteristics (i.e. ethnic group) or by health status. Three case studies were also conducted with programmes aiming to recruit priority groups and also demonstrating innovative recruitment methods. Data analysis adopted an approach using analytic induction. Two types of programmes were identified: those with explicit health aims and those without. Programme aims which required targeting of specific groups adopted more specific recruitment methods. The selection of recruitment method was dependent on the respondent's awareness of 'what works' and the resource capacity at their disposal. Word of mouth was perceived to be the most effective means of recruitment but using this approach took time and effort to build relationships with target groups, usually through a third party. Perceived effectiveness of recruitment was assessed by number of participants rather than numbers of the right participants. Some programmes, particularly those targeting younger adult participants, recruited using new social communication media. Where adopted, social marketing recruitment strategies tended to promote the 'social' rather than the 'health' benefits of walking. Effective walking programme recruitment seems to require trained, strategic, labour intensive, word-of-mouth communication, often in partnerships, in order to understand needs and develop trust and motivation within disengaged sedentary communities. Walking promotion professionals require better training and resources to deliver appropriate recruitment strategies to reach priority groups.

Targeting latent function: Encouraging effective encoding for successful memory training and transfer

PubMed Central

Lustig, Cindy; Flegal, Kristin E.

2009-01-01

Cognitive training programs for older adults often result in improvements at the group level. However, there are typically large age and individual differences in the size of training benefits. These differences may be related to the degree to which participants implement the processes targeted by the training program. To test this possibility, we tested older adults in a memory-training procedure either under specific strategy instructions designed to encourage semantic, integrative encoding, or in a condition that encouraged time and attention to encoding but allowed participants to choose their own strategy. Both conditions improved the performance of old-old adults relative to an earlier study (Bissig & Lustig, 2007) and reduced self-reports of everyday memory errors. Performance in the strategy-instruction group was related to pre-existing ability, performance in the strategy-choice group was not. The strategy-choice group performed better on a laboratory transfer test of recognition memory, and training performance was correlated with reduced everyday memory errors. Training programs that target latent but inefficiently-used abilities while allowing flexibility in bringing those abilities to bear may best promote effective training and transfer. PMID:19140647

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Engaging Parents of Children with and without Asthma in Smoking-Specific Parenting: Results from a 3-Year Randomized Controlled Trial Evaluation

ERIC Educational Resources Information Center

Ringlever, Linda; Hiemstra, Marieke; Engels, Rutger C. M. E.; van Schayck, Onno C. P.; Otten, Roy

2016-01-01

The present study evaluated long-term effects of a home-based smoking prevention program targeting smoking-specific parenting in families with children with and without asthma. A total of 1398 non-smoking children ("mean age" 10.1) participated, of which 197 (14.1%) were diagnosed with asthma. Families were blinded to group assignment.…

Hetero-bivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2012-09-01

functions of PSMA for PCa, we have designed and prepared PSMA-based imaging probes to evaluate its biological activity in vivo in a variety of...nucleophilic functional group to be coupled with radionuclides, i.e., 125I or 18F, or optical dyes. C. Accomplishments in Year 2 1...position of the lysine or N-terminus isoleucine with the imaging prosthetic groups such as optical dyes and radionuclides. The alloc group was

Gene-Specific Demethylation as Targeted Therapy in MDS

DTIC Science & Technology

2017-07-01

SUPPLEMENTARY NOTES 14. ABSTRACT Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic disorders characterized by bone marrow failure and...clonal hematopoietic disorders characterized by bone marrow failure and risk of progression to Acute Myeloid Leukemia (AML) in approximately 30 percent

Communicating polar science to the general public: sharing the social media experience of @OceanSeaIceNPI

NASA Astrophysics Data System (ADS)

Rösel, Anja; Pavlov, Alexey K.; Granskog, Mats A.; Gerland, Sebastian; Meyer, Amelie; Hudson, Stephen R.; King, Jennifer; Itkin, Polona; Cohen, Lana; Dodd, Paul; de Steur, Laura

2016-04-01

The findings of climate science need to be communicated to the general public. Researchers are encouraged to do so by journalists, policy-makers and funding agencies and many of us want to become better science communicators. But how can we do this at the lab or small research group level without specifically allocated resources in terms of funds and communication officers? And how do we sustain communication on a regular basis and not just during the limited lifetime of a specific project? One of the solutions is to use the emerging platform of social media, which has become a powerful and inexpensive tool for communicating science to different target audiences. Many research institutions and individual researchers are already advanced users of social media, but small research groups and labs remain underrepresented. The group of oceanographers, sea ice and atmospheric scientists at the Norwegian Polar Institute (@OceanSeaIceNPI( will share our experiences developing and maintaining researcher-driven outreach for over a year through Instagram, Twitter and Facebook. We will present our solutions to some of the practical considerations such as identifying key target groups, defining the framework for sharing responsibilities and interactions within the research group, and choosing an up-to-date and appropriate social medium. By sharing this information, we aim to inspire and assist other research groups and labs in conducting their own effective science communication.

Atypical category processing and hemispheric asymmetries in high-functioning children with autism: revealed through high-density EEG mapping.

PubMed

Fiebelkorn, Ian C; Foxe, John J; McCourt, Mark E; Dumas, Kristina N; Molholm, Sophie

2013-05-01

Behavioral evidence for an impaired ability to group objects based on similar physical or semantic properties in autism spectrum disorders (ASD) has been mixed. Here, we recorded brain activity from high-functioning children with ASD as they completed a visual-target detection task. We then assessed the extent to which object-based selective attention automatically generalized from targets to non-target exemplars from the same well-known object class (e.g., dogs). Our results provide clear electrophysiological evidence that children with ASD (N=17, aged 8-13 years) process the similarity between targets (e.g., a specific dog) and same-category non-targets (SCNT) (e.g., another dog) to a lesser extent than do their typically developing (TD) peers (N=21). A closer examination of the data revealed striking hemispheric asymmetries that were specific to the ASD group. These findings align with mounting evidence in the autism literature of anatomic underconnectivity between the cerebral hemispheres. Years of research in individuals with TD have demonstrated that the left hemisphere (LH) is specialized toward processing local (or featural) stimulus properties and the right hemisphere (RH) toward processing global (or configural) stimulus properties. We therefore propose a model where a lack of communication between the hemispheres in ASD, combined with typical hemispheric specialization, is a root cause for impaired categorization and the oft-observed bias to process local over global stimulus properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

CRISPR Is an Optimal Target for the Design of Specific PCR Assays for Salmonella enterica Serotypes Typhi and Paratyphi A

PubMed Central

Fabre, Laetitia; Le Hello, Simon; Roux, Chrystelle; Issenhuth-Jeanjean, Sylvie; Weill, François-Xavier

2014-01-01

Background Serotype-specific PCR assays targeting Salmonella enterica serotypes Typhi and Paratyphi A, the causal agents of typhoid and paratyphoid fevers, are required to accelerate formal diagnosis and to overcome the lack of typing sera and, in some situations, the need for culture. However, the sensitivity and specificity of such assays must be demonstrated on large collections of strains representative of the targeted serotypes and all other bacterial populations producing similar clinical symptoms. Methodology Using a new family of repeated DNA sequences, CRISPR (clustered regularly interspaced short palindromic repeats), as a serotype-specific target, we developed a conventional multiplex PCR assay for the detection and differentiation of serotypes Typhi and Paratyphi A from cultured isolates. We also developed EvaGreen-based real-time singleplex PCR assays with the same two sets of primers. Principal findings We achieved 100% sensitivity and specificity for each protocol after validation of the assays on 188 serotype Typhi and 74 serotype Paratyphi A strains from diverse genetic groups, geographic origins and time periods and on 70 strains of bacteria frequently encountered in bloodstream infections, including 29 other Salmonella serotypes and 42 strains from 38 other bacterial species. Conclusions The performance and convenience of our serotype-specific PCR assays should facilitate the rapid and accurate identification of these two major serotypes in a large range of clinical and public health laboratories with access to PCR technology. These assays were developed for use with DNA from cultured isolates, but with modifications to the assay, the CRISPR targets could be used in the development of assays for use with clinical and other samples. PMID:24498453

Guidelines for integrating population education into primary education and literacy programmes.

PubMed

1989-01-01

In recent seminars and workshops in the Asia and Pacific region the integration of population education into primary schools and literacy programs were the main topics. In most of the countries in this area separate courses in population education appear to be unfeasible for primary and secondary schools. In the nonformal area experience has indicated that population education acquires more meaning and relevance if it is integrated into an ongoing development program. The integration approach requires knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of population education. Guidelines suggested include the following steps in developing an integrated curriculum and instructional materials. First determine the needs, characteristics and other background information needed on the target group. Next prioritize the problems and needs of the target group, and formulate educational objectives from the identified needs and problems. Next determine and sequence the curriculum contents and then determine specific population education objectives and contents for integration, and what specific materials have to be developed. Then identify the specific type of format of materials to be developed, and write the first draft of the material. Also prepare illustrations and other art and graphic materials. Then the draft material should be reviewed and translated into the language of the target audience if needed. The materials should then be pretested, or field tested, using a sample of the intended users. To make sure the materials are reaching the target groups and being used effectively, a user's guide should be prepared and teachers and facilitators, as well as supervisors, should be prepared on the use of the material. In addition, a distribution and utilization plan should be prepared. Nonformal education materials can be distributed through libraries, reading center, residences of village leaders, neighborhood stores, and direct mail. The material distribution and utilization should be monitored and evaluated.

Reduced posterior parietal cortex activation after training on a visual search task.

PubMed

Bueichekú, Elisenda; Miró-Padilla, Anna; Palomar-García, María-Ángeles; Ventura-Campos, Noelia; Parcet, María-Antonia; Barrós-Loscertales, Alfonso; Ávila, César

2016-07-15

Gaining experience on a cognitive task improves behavioral performance and is thought to enhance brain efficiency. Despite the body of literature already published on the effects of training on brain activation, less research has been carried out on visual search attention processes under well controlled conditions. Thirty-six healthy adults divided into trained and control groups completed a pre-post letter-based visual search task fMRI study in one day. Twelve letters were used as targets and ten as distractors. The trained group completed a training session (840 trials) with half the targets between scans. The effects of training were studied at the behavioral and brain levels by controlling for repetition effects using both between-subjects (trained vs. control groups) and within-subject (trained vs. untrained targets) controls. The trained participants reduced their response speed by 31% as a result of training, maintaining their accuracy scores, whereas the control group hardly changed. Neural results revealed that brain changes associated with visual search training were circumscribed to reduced activation in the posterior parietal cortex (PPC) when controlling for group, and they included inferior occipital areas when controlling for targets. The observed behavioral and brain changes are discussed in relation to automatic behavior development. The observed training-related decreases could be associated with increased neural efficiency in specific key regions for task performance. Copyright © 2016 Elsevier Inc. All rights reserved.

[Prevention among migrants: Participation, migrant sensitive strategies and programme characteristics].

PubMed

Brand, T; Kleer, D; Samkange-Zeeb, F; Zeeb, Hajo

2015-06-01

Health promotion and prevention can contribute to a long, healthy life in populations both with and without migrant background. This paper provides an overview on migrant participation in prevention programmes in Germany. Furthermore, we describe migrant sensitive prevention strategies and characteristics of prevention programmes for migrants in Germany. With regard to participation in prevention programmes, lower vaccination rates are found among children and adolescents who migrated to Germany after birth. Among adults with a migrant background, we found lower participation in general health check-ups, oral health check-ups, cancer screening programs and influenza vaccination. Migrant sensitive prevention strategies address the visual style of the material, a target group specific risk communication, language requirements, a systematic involvement of the target group, and the recognition of deeply rooted sociocultural practices and beliefs. On analyzing a large database on prevention programs in Germany, we found only a few programmes that were exclusively targeted to migrant groups (0.6%). In 16.6% of the programs migrants were addressed as the target group among others. Compared to general population programs, programs for migrants were more often exclusively directed towards girls or women. Moreover, programs for migrants used community-based approaches more often and addressed different age groups. Although information on migrant participation in prevention programs and utilization of migrant sensitive strategies is still incomplete, we can assume that there is a need for diversity-oriented, migrant sensitive prevention.

Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

PubMed

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.

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study

PubMed Central

2012-01-01

Background Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Methods Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. Results 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis. PMID:22873682

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study.

PubMed

Waters, Lauren; George, Alexis S; Chey, Tien; Bauman, Adrian

2012-08-08

Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis.

Are all interventions created equal? A multi-threat approach to tailoring stereotype threat interventions.

PubMed

Shapiro, Jenessa R; Williams, Amy M; Hambarchyan, Mariam

2013-02-01

To date, stereotype threat interventions have been considered interchangeable. Across 4 experiments, the present research demonstrates that stereotype threat interventions need to be tailored to the specific form of experienced stereotype threat to be effective. The Multi-Threat Framework (Shapiro & Neuberg, 2007) distinguishes between group-as-target stereotype threats-concerns that a stereotype-relevant performance will reflect poorly on the abilities of one's group-and self-as-target stereotype threats-concerns that a stereotype-relevant performance will reflect poorly on one's own abilities. The present experiments explored Black college students' performance on diagnostic intelligence tests (Experiments 1 and 3) and women's interest (Experiment 2) and performance (Experiment 4) in science, technology, engineering, and math (STEM). Across the 4 experiments, participants were randomly assigned to experience either a group-as-target or self-as-target stereotype threat. Experiments 1 and 2 revealed that role model interventions were successful at protecting only against group-as-target stereotype threats, and Experiments 3 and 4 revealed that self-affirmation interventions were successful at protecting only against self-as-target stereotype threats. The present research provides an experimental test of the Multi-Threat Framework across different negatively stereotyped groups (Black students, female students), different negatively stereotyped domains (general intelligence, STEM), and different outcomes (test performance, career interest). This research suggests that interventions should address the range of possible stereotype threats to effectively protect individuals against these threats. Through an appreciation of the distinct forms of stereotype threats and the ways in which interventions work to reduce them, this research aims to facilitate a more complete understanding of stereotype threat. (c) 2013 APA, all rights reserved.

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application

PubMed Central

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-01-01

Background microRNAs (miRNAs) are single-stranded RNA molecules of about 20–23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. Results GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. Conclusion GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA. PMID:19534746

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

PubMed

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-06-16

microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial.

PubMed

Tan, Xiao; Saarinen, Antti; Mikkola, Tuija M; Tenhunen, Jarkko; Martinmäki, Samu; Rahikainen, Aki; Cheng, Shumei; Eklund, Niklas; Pekkala, Satu; Wiklund, Petri; Munukka, Eveliina; Wen, Xinfei; Cong, Fengyu; Wang, Xi; Zhang, Yajun; Tarkka, Ina; Sun, Yining; Partinen, Markku; Alen, Markku; Cheng, Sulin

2013-07-26

Sleep is essential for normal and healthy living. Lack of good quality sleep affects physical, mental and emotional functions. Currently, the treatments of obesity-related sleep disorders focus more on suppressing sleep-related symptoms pharmaceutically and are often accompanied by side effects. Thus, there is urgent need for alternative ways to combat chronic sleep disorders. This study will investigate underlying mechanisms of the effects of exercise and diet intervention on obesity-related sleep disorders, the role of gut microbiota in relation to poor quality of sleep and day-time sleepiness, as well as the levels of hormones responsible for sleep-wake cycle regulation. Participants consist of 330 (target sample) Finnish men aged 30 to 65 years. Among them, we attempt to randomize 180 (target sample) with sleep disorders into exercise and diet intervention. After screening and physician examination, 101 men with sleep disorders are included and are randomly assigned into three groups: exercise (n = 33), diet (n = 35), and control (n = 33). In addition, we attempt to recruit a target number of 150 healthy men without sleep disorders as the reference group. The exercise group undergoes a six-month individualized progressive aerobic exercise program based on initial fitness level. The diet group follows a six month specific individualized diet program. The control group and reference group are asked to maintain their normal activity and diet during intervention. Measurements are taken before and after the intervention. Primary outcomes include objective sleep measurements by polysomnography and a home-based non-contact sleep monitoring system, and subjective sleep evaluation by questionnaires. Secondary outcome measures include anthropometry, body composition, fitness, sleep disorder-related lifestyle risk factors, composition of gut microbiota and adipose tissue metabolism, as well as specific hormone and neurotranmitter levels and inflammatory biomarkers from venous blood samples. It is expected that the improvement of sleep quality after exercise and diet intervention will be evident both in subjective and objective measures of quality of sleep. Additionally, the change of sleep quality induced by exercise and diet intervention is expected to be related to the changes in specific hormones and inflammatory biomarkers, and in the composition of gut microbiota.

HMPAS: Human Membrane Protein Analysis System

PubMed Central

2013-01-01

Background Membrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets. The significance of membrane proteins has led to the developing dozens of resources related with membrane proteins. However, most of these resources are built for specific well-known membrane protein groups, making it difficult to find common and specific features of various membrane protein groups. Methods We collected human membrane proteins from the dispersed resources and predicted novel membrane protein candidates by using ortholog information and our membrane protein classifiers. The membrane proteins were classified according to the type of interaction with the membrane, subcellular localization, and molecular function. We also made new feature dataset to characterize the membrane proteins in various aspects including membrane protein topology, domain, biological process, disease, and drug. Moreover, protein structure and ICD-10-CM based integrated disease and drug information was newly included. To analyze the comprehensive information of membrane proteins, we implemented analysis tools to identify novel sequence and functional features of the classified membrane protein groups and to extract features from protein sequences. Results We constructed HMPAS with 28,509 collected known membrane proteins and 8,076 newly predicted candidates. This system provides integrated information of human membrane proteins individually and in groups organized by 45 subcellular locations and 1,401 molecular functions. As a case study, we identified associations between the membrane proteins and diseases and present that membrane proteins are promising targets for diseases related with nervous system and circulatory system. A web-based interface of this system was constructed to facilitate researchers not only to retrieve organized information of individual proteins but also to use the tools to analyze the membrane proteins. Conclusions HMPAS provides comprehensive information about human membrane proteins including specific features of certain membrane protein groups. In this system, user can acquire the information of individual proteins and specified groups focused on their conserved sequence features, involved cellular processes, and diseases. HMPAS may contribute as a valuable resource for the inference of novel cellular mechanisms and pharmaceutical targets associated with the human membrane proteins. HMPAS is freely available at http://fcode.kaist.ac.kr/hmpas. PMID:24564858

Evaluating Vaccination Strategies for Zika Virus in the Americas.

PubMed

Durham, David P; Fitzpatrick, Meagan C; Ndeffo-Mbah, Martial L; Parpia, Alyssa S; Michael, Nelson L; Galvani, Alison P

2018-05-01

Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. 34 countries and territories in the Americas with documented Zika outbreaks. Males and females aged 9 to 49 years. Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Annual prenatal Zika infections. For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. National Institutes of Health.

Current progress of targetron technology: development, improvement and application in metabolic engineering.

PubMed

Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

2015-06-01

Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier

PubMed Central

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma. PMID:28652738

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

PubMed

Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

2015-01-01

Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells.

Inverted-U Function Relating Cortical Plasticity and Task Difficulty

PubMed Central

Engineer, Navzer D.; Engineer, Crystal T.; Reed, Amanda C.; Pandya, Pritesh K.; Jakkamsetti, Vikram; Moucha, Raluca; Kilgard, Michael P.

2012-01-01

Many psychological and physiological studies with simple stimuli have suggested that perceptual learning specifically enhances the response of primary sensory cortex to task-relevant stimuli. The aim of this study was to determine whether auditory discrimination training on complex tasks enhances primary auditory cortex responses to a target sequence relative to non-target and novel sequences. We collected responses from more than 2,000 sites in 31 rats trained on one of six discrimination tasks that differed primarily in the similarity of the target and distractor sequences. Unlike training with simple stimuli, long-term training with complex stimuli did not generate target specific enhancement in any of the groups. Instead, cortical receptive field size decreased, latency decreased, and paired pulse depression decreased in rats trained on the tasks of intermediate difficulty while tasks that were too easy or too difficult either did not alter or degraded cortical responses. These results suggest an inverted-U function relating neural plasticity and task difficulty. PMID:22249158

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

PubMed

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

PubMed

Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

2016-06-01

The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization. Copyright © 2016 Elsevier B.V. All rights reserved.

Conformational Ensembles Explored Dynamically from Disordered Peptides Targeting Chemokine Receptor CXCR4

PubMed Central

Vincenzi, Marian; Costantini, Susan; Scala, Stefania; Tesauro, Diego; Accardo, Antonella; Leone, Marilisa; Colonna, Giovanni; Guillon, Jean; Portella, Luigi; Trotta, Anna Maria; Ronga, Luisa; Rossi, Filomena

2015-01-01

This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target. PMID:26030674

DNA-aptamers binding aminoglycoside antibiotics.

PubMed

Nikolaus, Nadia; Strehlitz, Beate

2014-02-21

Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

Saccades to a remembered location elicit spatially-specific activation in human retinotopic visual cortex

PubMed Central

Geng, Joy J.; Ruff, Christian C.; Driver, Jon

2008-01-01

The possible impact upon human visual cortex from saccades to remembered target locations was investigated using fMRI. A specific location in the upper-right or upper-left visual quadrant served as the saccadic target. After a delay of 2400 msecs, an auditory signal indicated whether to execute a saccade to that location (go trial) or to cancel the saccade and remain centrally fixated (no-go). Group fMRI analysis revealed activation specific to the remembered target location for executed saccades, in contralateral lingual gyrus. No-go trials produced similar, albeit significantly reduced effects. Individual retinotopic mapping confirmed that on go trials, quadrant-specific activations arose in those parts of ventral V1, V2, and V3 that coded the target location for the saccade, whereas on no-go trials only the corresponding parts of V2 and V3 were significantly activated. These results indicate that a spatial-motor saccadic task (i.e. making an eye-movement to a remembered location) is sufficient to activate retinotopic visual cortex spatially corresponding to the target location, and that this activation is also present (though reduced) when no saccade is executed. We discuss the implications of finding that saccades to remembered locations can affect early visual cortex, not just those structures conventionally associated with eye-movements, in relation to recent ideas about attention, spatial working memory, and the notion that recently activated representations can be ‘refreshed’ when needed. PMID:18510442

Lethal violence and psychosis: a clinical profile.

PubMed

Nestor, P G; Haycock, J; Doiron, S; Kelly, J; Kelly, D

1995-01-01

To investigate the relationship between lethal violence and psychosis, the authors examined symptomatology, neuropsychological functioning, and the nature of perpetrator-victim relationships of patients with psychotic disorders who were committed to a forensic psychiatric hospital following violent, primarily criminal behavior. A severely violent group, composed primarily of psychotic patients charged with murder, was compared with a less severely violent group that was composed primarily of psychotic patients involved with property crimes. As compared with the less violent group, the severely violent group was more likely to have delusional beliefs about specific personal targets and to have delusions about significant others being replaced by impostors. These beliefs were accompanied by higher scores on neuropsychological tests of intellectual and academic abilities. A high number of their blood relatives were victims of psychotic murder. These results indicated that a higher incidence of lethal or near lethal acts of violence may characterize intellectually intact but psychotic individuals with organize delusions involving personal, accessible targets.

Signatures of DNA target selectivity by ETS transcription factors

PubMed Central

Kim, Hye Mi

2017-01-01

ABSTRACT The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation. PMID:28301293

Signatures of DNA target selectivity by ETS transcription factors.

PubMed

Poon, Gregory M K; Kim, Hye Mi

2017-05-27

The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

Drugs and Targets in Fibrosis

PubMed Central

Li, Xiaoyi; Zhu, Lixin; Wang, Beibei; Yuan, Meifei; Zhu, Ruixin

2017-01-01

Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed. PMID:29218009

Effects of task-irrelevant grouping on visual selection in partial report.

PubMed

Lunau, Rasmus; Habekost, Thomas

2017-07-01

Perceptual grouping modulates performance in attention tasks such as partial report and change detection. Specifically, grouping of search items according to a task-relevant feature improves the efficiency of visual selection. However, the role of task-irrelevant feature grouping is not clearly understood. In the present study, we investigated whether grouping of targets by a task-irrelevant feature influences performance in a partial-report task. In this task, participants must report as many target letters as possible from a briefly presented circular display. The crucial manipulation concerned the color of the elements in these trials. In the sorted-color condition, the color of the display elements was arranged according to the selection criterion, and in the unsorted-color condition, colors were randomly assigned. The distractor cost was inferred by subtracting performance in partial-report trials from performance in a control condition that had no distractors in the display. Across five experiments, we manipulated trial order, selection criterion, and exposure duration, and found that attentional selectivity was improved in sorted-color trials when the exposure duration was 200 ms and the selection criterion was luminance. This effect was accompanied by impaired selectivity in unsorted-color trials. Overall, the results suggest that the benefit of task-irrelevant color grouping of targets is contingent on the processing locus of the selection criterion.

Rockin' Readers Coordinator Handbook.

ERIC Educational Resources Information Center

Alachua County Schools, Gainesville, FL.

This coordinator's handbook describes the "Rockin' Readers" program, in which senior-citizen volunteers are matched with specifically targeted at-risk children (usually of kindergarten age or slightly older) in Alachua County, Florida, who tested below their peer group in language development and reading readiness skills. The handbook…

Age-Related Differences in Working Memory Performance in A 2-Back Task

PubMed Central

Wild-Wall, Nele; Falkenstein, Michael; Gajewski, Patrick D.

2011-01-01

The present study aimed to elucidate the neuro-cognitive processes underlying age-related differences in working memory. Young and middle-aged participants performed a two-choice task with low and a 2-back task with high working memory load. The P300, an event-related potential reflecting controlled stimulus–response processing in working memory, and the underlying neuronal sources of expected age-related differences were analyzed using sLORETA. Response speed was generally slower for the middle-aged than the young group. Under low working memory load the middle-aged participants traded speed for accuracy. The middle-aged were less efficient in the 2-back task as they responded slower while the error rates did not differ for groups. An age-related decline of the P300 amplitude and characteristic topographical differences were especially evident in the 2-back task. A more detailed analysis of the P300 in non-target trials revealed that amplitudes in the young but not middle-aged group differentiate between correctly detected vs. missed targets in the following trial. For these trials, source analysis revealed higher activation for the young vs. middle-aged group in brain areas which support working memory processes. The relationship between P300 and overt performance was validated by significant correlations. To sum up, under high working memory load the young group showed an increased neuronal activity before a successful detected target, while the middle-aged group showed the same neuronal pattern regardless of whether a subsequent target will be detected or missed. This stable memory trace before detected targets was reflected by a specific activation enhancement in brain areas which orchestrate maintenance, update, storage, and retrieval of information in working memory. PMID:21909328

Support groups for children and adolescents bereaved by suicide: Lots of interventions, little evidence.

PubMed

Journot-Reverbel, Katia; Raynaud, Jean-Philippe; Bui, Eric; Revet, Alexis

2017-04-01

Though many different interventions are proposed for suicide-bereaved children and adolescents, few data exist concerning their efficiency. This literature review focused on psychosocial interventions specifically targeting children and adolescents bereaved by suicide to try to provide some validate therapeutic guidelines propositions for clinicians. We only found two articles specifically targeting children or adolescents: both of them seemed to show some efficacy in reducing some psychosocial variables (anxiety, depression…) in suicide-bereaved children but results were limited by methodological problems. This review failed to provide evidence-based guidelines propositions for suicide-bereaved children and underline the crucial need for research in this field. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Messages about appearance, food, weight and exercise in "tween" television.

PubMed

Simpson, Courtney C; Kwitowski, Melissa; Boutte, Rachel; Gow, Rachel W; Mazzeo, Suzanne E

2016-12-01

Tweens (children ages ~8-14years) are a relatively recently defined age group, increasingly targeted by marketers. Individuals in this age group are particularly vulnerable to opinions and behaviors presented in media messages, given their level of cognitive and social development. However, little research has examined messages about appearance, food, weight, and exercise in television specifically targeting tweens, despite the popularity of this media type among this age group. This study used a content analytic approach to explore these messages in the five most popular television shows for tweens on the Disney Channel (as of 2015). Using a multiple-pass approach, relevant content in episodes from the most recently completed seasons of each show was coded. Appearance related incidents occurred in every episode; these most frequently mentioned attractiveness/beauty. Food related incidents were also present in every episode; typically, these situations were appearance and weight neutral. Exercise related incidents occurred in 53.3% of episodes; the majority expressed resistance to exercise. Weight related incidents occurred in 40.0% of the episodes; the majority praised the muscular ideal. Women were more likely to initiate appearance incidents, and men were more likely to initiate exercise incidents. These results suggest that programs specifically marketed to tweens reinforce appearance ideals, including stereotypes about female attractiveness and male athleticism, two constructs linked to eating pathology and body dissatisfaction. Given the developmental vulnerability of the target group, these findings are concerning, and highlight potential foci for prevention programming, including media literacy, for tweens. Copyright © 2016 Elsevier Ltd. All rights reserved.

An eHealth Intervention to Promote Physical Activity and Social Network of Single, Chronically Impaired Older Adults: Adaptation of an Existing Intervention Using Intervention Mapping.

PubMed

Boekhout, Janet M; Peels, Denise A; Berendsen, Brenda Aj; Bolman, Catherine Aw; Lechner, Lilian

2017-11-23

Especially for single older adults with chronic diseases, physical inactivity and a poor social network are regarded as serious threats to their health and independence. The Active Plus intervention is an automated computer-tailored eHealth intervention that has been proven effective to promote physical activity (PA) in the general population of adults older than 50 years. The aim of this study was to report on the methods and results of the systematic adaptation of Active Plus to the wishes and needs of the subgroup of single people older than 65 years who have one or more chronic diseases, as this specific target population may encounter specific challenges regarding PA and social network. The Intervention Mapping (IM) protocol was used to systematically adapt the existing intervention to optimally suit this specific target population. A literature study was performed, and quantitative as well as qualitative data were derived from health care professionals (by questionnaires, n=10) and the target population (by focus group interviews, n=14), which were then systematically integrated into the adapted intervention. As the health problems and the targeted behavior are largely the same in the original and adapted intervention, the outcome of the needs assessment was that the performance objectives remained the same. As found in the literature study and in data derived from health professionals and focus groups, the relative importance and operationalization of the relevant psychosocial determinants related to these objectives are different from the original intervention, resulting in a refinement of the change objectives to optimally fit the specific target population. This refinement also resulted in changes in the practical applications, program components, intervention materials, and the evaluation and implementation strategy for the subgroup of single, chronically impaired older adults. This study demonstrates that the adaptation of an existing intervention is an intensive process in which adopting the IM protocol is an invaluable tool. The study provides a broad insight in adapting interventions aimed at single older adults with a chronic disease. It is concluded that even when the new target population is a sizable segment of the original target population, the adapted intervention still needs considerable changes to optimally fit the needs and situational differences of the narrower target population. ©Janet M Boekhout, Denise A Peels, Brenda AJ Berendsen, Catherine AW Bolman, Lilian Lechner. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.11.2017.

Efficacy for lung metastasis induced by the allogeneic bEnd3 vaccine in mice.

PubMed

Zhao, Jun; Lu, Jing; Zhou, Lurong; Zhao, Jimin; Dong, Ziming

2018-05-04

The mouse brain microvascular endothelial cell line bEnd.3 was used to develop a vaccine and its anti-tumor effect on lung metastases was observed in immunized mice. Mouse bEnd.3 cells cultured in-vitro and then fixed with glutaraldehyde was used to immunize mice; mice were challenged with the metastatic cancer cell line U14, and changes in metastatic cancer tissues were observed through hematoxylin and eosin staining. Carboxyfluorescein succinimidyl amino ester (CSFE) and propidium iodide (PI) were used to detect cytotoxic activity of spleen T lymphocytes; the ratio of CD3 + and CD8 + T-cell sub-sets was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and immunoblot were used to examine the specific response of the antisera of immunized mice. The number of metastatic nodules in bEnd.3 and human umbilical vein endothelial cell (HUVEC) vaccine groups was less than NIH3T3 vaccine group and phosphate buffered saline (PBS) control group. The bEnd.3-induced and HUVEC-induced cytotoxic T-lymphocytes (CTLs) showed significant lytic activity against bEnd.3 and HUVEC target cells, while the antisera of mice in bEnd.3 and HUVEC vaccine groups showed specific immune responses to membrane proteins and inhibited target cell proliferation in-vitro. Immunoblot results showed specific bands at 180KD and 220KD in bEnd.3 and at 130 kD and 220 kD in HUVEC lysates. Allogeneic bEnd.3 vaccine induced an active and specific immune response to tumor vascular endothelial cells that resulted in production of antibodies against the proliferation antigens VEGF-R II, integrin, Endog etc. Immunization with this vaccine inhibited lung metastasis of cervical cancer U14 cells and prolonged the survival of these mice.

Undoing an epidemiological paradox: the tobacco industry's targeting of US Immigrants.

PubMed

Acevedo-Garcia, Dolores; Barbeau, Elizabeth; Bishop, Jennifer Anne; Pan, Jocelyn; Emmons, Karen M

2004-12-01

We sought to ascertain whether the tobacco industry has conceptualized the US immigrant population as a separate market. We conducted a content analysis of major tobacco industry documents. The tobacco industry has engaged in 3 distinct marketing strategies aimed at US immigrants: geographically based marketing directed toward immigrant communities, segmentation based on immigrants' assimilation status, and coordinated marketing focusing on US immigrant groups and their countries of origin. Public health researchers should investigate further the tobacco industry's characterization of the assimilated and non-assimilated immigrant markets, and its specific strategies for targeting these groups, in order to develop informed national and international tobacco control countermarketing strategies designed to protect immigrant populations and their countries of origin.

Proteomic Identification of Non-Gal Antibody Targets After Pig-to-Primate Cardiac Xenotransplantation

PubMed Central

Byrne, Guerard W.; Stalboerger, Paul G.; Davila, Eduardo; Heppelmann, Carrie J.; Gazi, Mozammel H.; McGregor, Hugh C. J.; LaBreche, Peter T.; Davies, William R.; Rao, Vinay P.; Oi, Keiji; Tazelaar, Henry D.; Logan, John S.; McGregor, Christopher G. A.

2008-01-01

Background Experience with non-antigenic galactose α1,3 galactose (αGal) polymers and development of αGal deficient pigs has reduced or eliminated the significance of this antigen in xenograft rejection. Despite these advances, delayed xenograft rejection (DXR) continues to occur most likely due to antibody responses to non-Gal endothelial cell (EC) antigens. Methods To gauge the diversity of the non-Gal antibody response we used antibody derived from CD46 transgenic heterotopic cardiac xenografts performed without T-cell immunosuppression, Group A (n = 4) and Gal knockout (GT-KO) heart transplants under tacrolimus and sirolimus immunosuppression, Group B (n = 8). Non-Gal antibody was measured by flow cytometry and by Western blots using GT-KO EC membrane antigens. A nanoLC/MS/MS analysis of proteins recovered from 2D gels was used to identify target antigens. Results Group A recipients exhibited a mixed cellular and humoral rejection. Group B recipients mainly exhibited classical DXR. Western blot analysis showed a non-Gal antibody response induced by GT+ and GT-KO hearts to an overlapping set of pig aortic EC membrane antigens. Proteomic analysis identified 14 potential target antigens but failed to define several immunodominant targets. Conclusions These experiments indicate that the non-Gal antibody response is directed to a number of stress response and inflammation related pig EC antigens and a few undefined targets. Further analysis of these antibody specificities using alternative methods is required to more fully define the repertoire of non-Gal antibody responses. PMID:18957049

A new method of identifying target groups for pronatalist policy applied to Australia.

PubMed

Chen, Mengni; Lloyd, Chris J; Yip, Paul S F

2018-01-01

A country's total fertility rate (TFR) depends on many factors. Attributing changes in TFR to changes of policy is difficult, as they could easily be correlated with changes in the unmeasured drivers of TFR. A case in point is Australia where both pronatalist effort and TFR increased in lock step from 2001 to 2008 and then decreased. The global financial crisis or other unobserved confounders might explain both the reducing TFR and pronatalist incentives after 2008. Therefore, it is difficult to estimate causal effects of policy using econometric techniques. The aim of this study is to instead look at the structure of the population to identify which subgroups most influence TFR. Specifically, we build a stochastic model relating TFR to the fertility rates of various subgroups and calculate elasticity of TFR with respect to each rate. For each subgroup, the ratio of its elasticity to its group size is used to evaluate the subgroup's potential cost effectiveness as a pronatalist target. In addition, we measure the historical stability of group fertility rates, which measures propensity to change. Groups with a high effectiveness ratio and also high propensity to change are natural policy targets. We applied this new method to Australian data on fertility rates broken down by parity, age and marital status. The results show that targeting parity 3+ is more cost-effective than lower parities. This study contributes to the literature on pronatalist policies by investigating the targeting of policies, and generates important implications for formulating cost-effective policies.

Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish.

PubMed

Kawahara, Atsuo; Hisano, Yu; Ota, Satoshi; Taimatsu, Kiyohito

2016-05-13

The zebrafish (Danio rerio) is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs) at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

N-terminal domain of the dual-targeted pea glutathione reductase signal peptide controls organellar targeting efficiency.

PubMed

Rudhe, Charlotta; Clifton, Rachel; Whelan, James; Glaser, Elzbieta

2002-12-06

Import of nuclear-encoded proteins into mitochondria and chloroplasts is generally organelle specific and its specificity depends on the N-terminal signal peptide. Yet, a group of proteins known as dual-targeted proteins have a targeting peptide capable of leading the mature protein to both organelles. We have investigated the domain structure of the dual-targeted pea glutathione reductase (GR) signal peptide by using N-terminal truncations. A mutant of the GR precursor (pGR) starting with the second methionine residue of the targeting peptide, pGRdelta2-4, directed import into both organelles, negating the possibility that dual import was controlled by the nature of the N terminus. The deletion of the 30 N-terminal residues (pGRdelta2-30) inhibited import efficiency into chloroplasts substantially and almost completely into mitochondria, whereas the removal of only 16 N-terminal amino acid residues (pGRdelta2-16) resulted in the strongly stimulated mitochondrial import without significantly affecting chloroplast import. Furthermore, N-terminal truncations of the signal peptide (pGRdelta2-16 and pGRdelta2-30) greatly stimulated the mitochondrial processing activity measured with the isolated processing peptidase. These results suggest a domain structure for the dual-targeting peptide of pGR and the existence of domains controlling organellar import efficiency therein.

The Ability of Narrative Communication to Address Health-related Social Norms

PubMed Central

Moran, Meghan Bridgid; Murphy, Sheila T.; Frank, Lauren; Baezconde-Garbanati, Lourdes

2013-01-01

Social norms are an important predictor of health behavior and have been targeted by a variety of health communication campaigns. However, these campaigns often encounter challenges related to the socially specific context in which norms exist: specifically, the extent to which the target population identifies with the reference group presented in the ad and the extent to which the target population believes the campaign's message. We argue that because of its capacity to effect identification among viewers, narrative communication is particularly appropriate for impacting social norms and, consequently, behavioral intention. This manuscript presents the results of a randomized trial testing the effectiveness of two films – one narrative, one non-narrative – in changing perceived social norms and behavioral intention regarding Pap testing to detect cervical cancer. Results of the study indicate that the narrative film was in fact more effective at producing positive changes in perceived norm and intention. PMID:24179677

Galactosylated magnetic nanovectors for regulation of lipid metabolism based on biomarker-specific RNAi and MR imaging.

PubMed

Heo, Dan; Lee, Chanjoo; Ku, Minhee; Haam, Seungjoo; Suh, Jin-Suck; Huh, Yong-Min; Park, Sahng Wook; Yang, Jaemoon

2015-08-21

The specific delivery of ribonucleic acid (RNA) interfering molecules to disease-related cells is still a critical blockade for in vivo systemic treatment. Here, this study suggests a robust delivery carrier for targeted delivery of RNA-interfering molecules using galactosylated magnetic nanovectors (gMNVs). gMNVs are an organic-inorganic polymeric nanomaterial composed of polycationics and magnetic nanocrystal for delivery of RNA-interfering molecules and tracking via magnetic resonance (MR) imaging. In particular, the surface of gMNVs was modified by galactosylgluconic groups for targeted delivering to asialoglycoprotein receptor (ASGPR) of hepatocytes. Moreover, the small interfering RNAs were used to regulate target proteins related with low-density lipoprotein level and in vivo MR imaging was conducted for tracking of nanovectors. The obtained results show that the prepared gMNVs demonstrate potential as a systemic theragnostic nanoplatform for RNA interference and MR imaging.

Core disgust is attenuated by ingroup relations.

PubMed

Reicher, Stephen D; Templeton, Anne; Neville, Fergus; Ferrari, Lucienne; Drury, John

2016-03-08

We present the first experimental evidence to our knowledge that ingroup relations attenuate core disgust and that this helps explain the ability of groups to coact. In study 1, 45 student participants smelled a sweaty t-shirt bearing the logo of another university, with either their student identity (ingroup condition), their specific university identity (outgroup condition), or their personal identity (interpersonal condition) made salient. Self-reported disgust was lower in the ingroup condition than in the other conditions, and disgust mediated the relationship between condition and willingness to interact with target. In study 2, 90 student participants smelled a sweaty target t-shirt bearing either the logo of their own university, another university, or no logo, with either their student identity or their specific university identity made salient. Walking time to wash hands and pumps of soap indicated that disgust was lower where the relationship between participant and target was ingroup rather than outgroup or ambivalent (no logo).

Core disgust is attenuated by ingroup relations

PubMed Central

Reicher, Stephen D.; Templeton, Anne; Neville, Fergus; Ferrari, Lucienne

2016-01-01

We present the first experimental evidence to our knowledge that ingroup relations attenuate core disgust and that this helps explain the ability of groups to coact. In study 1, 45 student participants smelled a sweaty t-shirt bearing the logo of another university, with either their student identity (ingroup condition), their specific university identity (outgroup condition), or their personal identity (interpersonal condition) made salient. Self-reported disgust was lower in the ingroup condition than in the other conditions, and disgust mediated the relationship between condition and willingness to interact with target. In study 2, 90 student participants smelled a sweaty target t-shirt bearing either the logo of their own university, another university, or no logo, with either their student identity or their specific university identity made salient. Walking time to wash hands and pumps of soap indicated that disgust was lower where the relationship between participant and target was ingroup rather than outgroup or ambivalent (no logo). PMID:26903640

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1999-10-12

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1996-01-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, C.R.; Niemeyer, C.M.; Smith, C.L.; Sano, Takeshi; Hnatowich, D.J.; Rusckowski, M.

1996-10-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products. 5 figs.

75 FR 28027 - Tobacco Products Scientific Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

.... Marketing strategies for various brands/subbrands of menthol cigarettes, including strategies targeted to particular demographic groups. 14. Marketing strategies for various brands/subbrands of menthol cigarettes... effects of menthol, biomarkers of disease risk, marketing data, and population effects. Specific areas of...

Assessment of Equine Fecal Contamination: The Search for Alternative Bacterial Source-tracking Targets

EPA Science Inventory

16S rDNA clone libraries were evaluated for detection of fecal source-identifying bacteria from a collapsed equine manure pile. Libraries were constructed using universal eubacterial primers and Bacteroides-Prevotella group-specific primers. Eubacterial sequences indicat...

Heterologous vaccine effects.

PubMed

Saadatian-Elahi, Mitra; Aaby, Peter; Shann, Frank; Netea, Mihai G; Levy, Ofer; Louis, Jacques; Picot, Valentina; Greenberg, Michael; Warren, William

2016-07-25

The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group. Copyright © 2016.

Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes

PubMed Central

Sun, Yuqi; Dai, Chunmei; Yin, Meilin; Lu, Jinghua; Hu, Haiyang; Chen, Dawei

2018-01-01

Background There are abundant glycyrrhetinic acid (GA) receptors on the cellular membrane of hepatocytes and hepatocellular carcinoma (HCC) cells. The receptor binding effect might be related to the structure of the guiding molecule. GA exists in two stereoisomers with C3-hydroxyl and C11-carbonyl active groups. Purpose The objective of this study was to investigate the relationship between the HCC-targeted effect and the configurations and groups of GA. Methods and results Different GA derivatives (18β-GA, 18α-GA, 3-acetyl-18β-GA [3-Ace-GA] and 11-deoxy-18β-GA [11-Deo-GA]) were used to investigate the targeting effect of GA’s configurations and groups on HCC cells. The EC50 values of competition to binding sites and the ratio of specific binding in HepG2 cells showed that 18β-GA and 3-Ace-GA demonstrated significant competitive effect with fluorescein isothiocyanate (FITC)-labeled GA. Then, the GA derivatives were distearoyl-phosphatidylethanolamine (DSPE)-PEGylated. 18β-GA-, 18α-GA-, 3-Ace-GA-and 11-Deo-GA-modified liposomes were prepared and characterized by size, zeta potential, encapsulation efficiency, loading capacity, leakage and membrane stability. Evaluation on the cellular location in vitro and tumor targeting in vivo was carried out. Compared to common long-circulation liposome (PEG-Lip), more 18β-GA- and 3-Ace-GA-modified liposomes aggregated around HepG2 cells in vitro in short time and transferred into HCC tumors in vivo for a longer time. Conclusion The β-configuration hydrogen atom on C18 position of GA played the most important role on the targeting effect. C11-carbonyl and C3-hydroxy groups of GA have certain and little influence on targeting action to HCC, respectively. In general, GA might be a promising targeting molecule for the research on liver diseases and hepatoma therapy. PMID:29588589

Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes.

PubMed

Sun, Yuqi; Dai, Chunmei; Yin, Meilin; Lu, Jinghua; Hu, Haiyang; Chen, Dawei

2018-01-01

There are abundant glycyrrhetinic acid (GA) receptors on the cellular membrane of hepatocytes and hepatocellular carcinoma (HCC) cells. The receptor binding effect might be related to the structure of the guiding molecule. GA exists in two stereoisomers with C3-hydroxyl and C11-carbonyl active groups. The objective of this study was to investigate the relationship between the HCC-targeted effect and the configurations and groups of GA. Different GA derivatives (18β-GA, 18α-GA, 3-acetyl-18β-GA [3-Ace-GA] and 11-deoxy-18β-GA [11-Deo-GA]) were used to investigate the targeting effect of GA's configurations and groups on HCC cells. The EC 50 values of competition to binding sites and the ratio of specific binding in HepG2 cells showed that 18β-GA and 3-Ace-GA demonstrated significant competitive effect with fluorescein isothiocyanate (FITC)-labeled GA. Then, the GA derivatives were distearoyl-phosphatidylethanolamine (DSPE)-PEGylated. 18β-GA-, 18α-GA-, 3-Ace-GA-and 11-Deo-GA-modified liposomes were prepared and characterized by size, zeta potential, encapsulation efficiency, loading capacity, leakage and membrane stability. Evaluation on the cellular location in vitro and tumor targeting in vivo was carried out. Compared to common long-circulation liposome (PEG-Lip), more 18β-GA- and 3-Ace-GA-modified liposomes aggregated around HepG2 cells in vitro in short time and transferred into HCC tumors in vivo for a longer time. The β-configuration hydrogen atom on C18 position of GA played the most important role on the targeting effect. C11-carbonyl and C3-hydroxy groups of GA have certain and little influence on targeting action to HCC, respectively. In general, GA might be a promising targeting molecule for the research on liver diseases and hepatoma therapy.

Reversibly Switchable, pH-Dependent Peptide Ligand Binding via 3,5-Diiodotyrosine Substitutions.

PubMed

Ngambenjawong, Chayanon; Sylvestre, Meilyn; Gustafson, Heather H; Pineda, Julio Marco B; Pun, Suzie H

2018-04-20

Cell type-specific targeting ligands utilized in drug delivery applications typically recognize receptors that are overexpressed on the cells of interest. Nonetheless, these receptors may also be expressed, to varying extents, on off-target cells, contributing to unintended side effects. For the selectivity profile of targeting ligands in cancer therapy to be improved, stimuli-responsive masking of these ligands with acid-, redox-, or enzyme-cleavable molecules has been reported, whereby the targeting ligands are exposed in specific environments, e.g., acidic tumor hypoxia. One possible drawback of these systems lies in their one-time, permanent trigger, which enables the "demasked" ligands to bind off-target cells if released back into the systemic circulation. A promising strategy to address the aforementioned problem is to design ligands that show selective binding based on ionization state, which may be microenvironment-dependent. In this study, we report a systematic strategy to engineer low pH-selective targeting peptides using an M2 macrophage-targeting peptide (M2pep) as an example. 3,5-Diiodotyrosine mutagenesis into native tyrosine residues of M2pep confers pH-dependent binding behavior specific to acidic environment (pH 6) when the amino acid is protonated into the native tyrosine-like state. At physiological pH of 7.4, the hydroxyl group of 3,5-diiodotyrosine on the peptide is deprotonated leading to interruption of the peptide native binding property. Our engineered pH-responsive M2pep (Ac-Y-Î-Î) binds target M2 macrophages more selectively at pH 6 than at pH 7.4. In addition, 3,5-diiodotyrosine substitutions also improve serum stability of the peptide. Finally, we demonstrate pH-dependent reversibility in target binding via a postbinding peptide elution study. The strategy presented here should be applicable for engineering pH-dependent functionality of other targeting peptides with potential applications in physiology-dependent in vivo targeting applications (e.g., targeting hypoxic tumor/inflammation) or in in vitro receptor identification.

Do smokers want to know more about the cigarettes they smoke? Results from the EDUCATE study.

PubMed

Bansal, Maansi A; Cummings, K Michael; Hyland, Andrew; Bauer, Joseph E; Hastrup, Janice L; Steger, Craig

2004-12-01

The present study (a) assessed smokers' receptivity to receiving information about the product features of their cigarette brand, (b) tested whether the use of targeted (personalized), brand-specific information affected participants' attention to the information, and (c) tested whether attention to the targeted information affected participants' beliefs about the product features and their smoking behavior. The study population included current cigarette smokers who called the New York State Smokers' Quit Line seeking assistance to stop smoking in February and March 2003. Subjects were randomized to one of three experimental groups. Group 1 received telephone counseling and the quit line's stop-smoking booklet, which included information on ingredients found in cigarettes. Group 2 received the same intervention as Group 1 plus a basic brochure with a generic cover. Group 3 received the same intervention as Group 2 except that the cover to the brochure was targeted to individual cigarette brand and type. All smokers who called the quit line were receptive to receiving information about their cigarette brand. In a 6-week follow-up interview, 60% of those who received the targeted product information brochure recalled receiving it vs. 51% of those who received the identical guide with the nontargeted cover. Recall of the material discussed in the brochure was slightly higher (not statistically significant) among subjects who received the brochure with the targeted cover compared with the same brochure with a basic cover. Regardless of whether the brochure was targeted, smokers' beliefs about different product features or their smoking behavior were not affected measurably, although those who reported reading some or all of the brochure had higher levels of awareness regarding low-tar, filtered, and no-additive cigarettes. Smokers are receptive to receiving information about their cigarette brand, but either persistent efforts or possibly more potent interventions to personalize the information are needed to ensure that they recall information about the cigarette brand they smoke.

[Ethnic origin of patients remains important].

PubMed

Stronks, Karien

2013-01-01

The ethnic diversity in medical practices is increasing rapidly. In the Netherlands, ethnic groups are predominantly defined on the basis of their geographical origin, e.g. inhabitants of Turkish, Moroccan or Surinamese origin. The prevalence of health problems and the utilisation of health care differ between ethnic groups. This ethnic variation arises, firstly, from characteristics that are inherent to these groups such as genetic profile and culture, and, secondly, from characteristics that reflect their position in Dutch society such as socio-economic position and discrimination on the other. If we could fully understand which of these specific characteristics leads to a specific pattern of health problems or health care use, the classification of patient into ethnic groups would then become redundant. As long as we do not completely understand this variation, however, ethnic origin is a good entry-point for targeting health care to groups of patients.

Face shape and face identity processing in behavioral variant fronto-temporal dementia: A specific deficit for familiarity and name recognition of famous faces.

PubMed

De Winter, François-Laurent; Timmers, Dorien; de Gelder, Beatrice; Van Orshoven, Marc; Vieren, Marleen; Bouckaert, Miriam; Cypers, Gert; Caekebeke, Jo; Van de Vliet, Laura; Goffin, Karolien; Van Laere, Koen; Sunaert, Stefan; Vandenberghe, Rik; Vandenbulcke, Mathieu; Van den Stock, Jan

2016-01-01

Deficits in face processing have been described in the behavioral variant of fronto-temporal dementia (bvFTD), primarily regarding the recognition of facial expressions. Less is known about face shape and face identity processing. Here we used a hierarchical strategy targeting face shape and face identity recognition in bvFTD and matched healthy controls. Participants performed 3 psychophysical experiments targeting face shape detection (Experiment 1), unfamiliar face identity matching (Experiment 2), familiarity categorization and famous face-name matching (Experiment 3). The results revealed group differences only in Experiment 3, with a deficit in the bvFTD group for both familiarity categorization and famous face-name matching. Voxel-based morphometry regression analyses in the bvFTD group revealed an association between grey matter volume of the left ventral anterior temporal lobe and familiarity recognition, while face-name matching correlated with grey matter volume of the bilateral ventral anterior temporal lobes. Subsequently, we quantified familiarity-specific and name-specific recognition deficits as the sum of the celebrities of which respectively only the name or only the familiarity was accurately recognized. Both indices were associated with grey matter volume of the bilateral anterior temporal cortices. These findings extent previous results by documenting the involvement of the left anterior temporal lobe (ATL) in familiarity detection and the right ATL in name recognition deficits in fronto-temporal lobar degeneration.

Estimating age-specific reproductive numbers-A comparison of methods.

PubMed

Moser, Carlee B; White, Laura F

2016-01-01

Large outbreaks, such as those caused by influenza, put a strain on resources necessary for their control. In particular, children have been shown to play a key role in influenza transmission during recent outbreaks, and targeted interventions, such as school closures, could positively impact the course of emerging epidemics. As an outbreak is unfolding, it is important to be able to estimate reproductive numbers that incorporate this heterogeneity and to use surveillance data that is routinely collected to more effectively target interventions and obtain an accurate understanding of transmission dynamics. There are a growing number of methods that estimate age-group specific reproductive numbers with limited data that build on methods assuming a homogenously mixing population. In this article, we introduce a new approach that is flexible and improves on many aspects of existing methods. We apply this method to influenza data from two outbreaks, the 2009 H1N1 outbreaks in South Africa and Japan, to estimate age-group specific reproductive numbers and compare it to three other methods that also use existing data from social mixing surveys to quantify contact rates among different age groups. In this exercise, all estimates of the reproductive numbers for children exceeded the critical threshold of one and in most cases exceeded those of adults. We introduce a flexible new method to estimate reproductive numbers that describe heterogeneity in the population.

In vivo NIRF imaging-guided delivery of a novel NGR-VEGI fusion protein for targeting tumor vasculature.

PubMed

Ma, Wenhui; Li, Guoquan; Wang, Jing; Yang, Weidong; Zhang, Yingqi; Conti, Peter S; Chen, Kai

2014-12-01

Pathological angiogenesis is crucial in tumor growth, invasion and metastasis. Previous studies demonstrated that the vascular endothelial growth inhibitor (VEGI), a member of the tumor necrosis factor superfamily, can be used as a potent endogenous inhibitor of tumor angiogenesis. Molecular probes containing the asparagine-glycine-arginine (NGR) sequence can specifically bind to CD13 receptor which is overexpressed on neovasculature and several tumor cells. Near-infrared fluorescence (NIRF) optical imaging for targeting tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The aim of this study was to develop a new NIRF imaging probe on the basis of an NGR-VEGI protein for the visualization of tumor vasculature. The NGR-VEGI fusion protein was prepared from prokaryotic expression, and its function was characterized in vitro. The NGR-VEGI protein was then labeled with a Cy5.5 fluorophore to afford Cy5.5-NGR-VEGI probe. Using the NIRF imaging technique, we visualized and quantified the specific delivery of Cy5.5-NGR-VEGI protein to subcutaneous HT-1080 fibrosarcoma tumors in mouse xenografts. The Cy5.5-NGR-VEGI probe exhibited rapid HT-1080 tumor targeting, and highest tumor-to-background contrast at 8 h post-injection (pi). Tumor specificity of Cy5.5-NGR-VEGI was confirmed by effective blocking of tumor uptake in the presence of unlabeled NGR-VEGI (20 mg/kg). Ex vivo NIRF imaging further confirmed in vivo imaging findings, demonstrating that Cy5.5-NGR-VEGI displayed an excellent tumor-to-muscle ratio (18.93 ± 2.88) at 8 h pi for the non-blocking group and significantly reduced ratio (4.92 ± 0.75) for the blocking group. In conclusion, Cy5.5-NGR-VEGI provided highly sensitive, target-specific, and longitudinal imaging of HT-1080 tumors. As a novel theranostic protein, Cy5.5-NGR-VEGI has the potential to improve cancer treatment by targeting tumor vasculature.

Use of novel species-specific PCR primers targeted to DNA gyrase subunit B (gyrB) gene for species identification of the Cronobacter sakazakii and Cronobacter dublinensis.

PubMed

Huang, Chien-Hsun; Chang, Mu-Tzu; Huang, Lina

2013-02-01

Cronobacter sakazakii and its phylogenetically closest species are considered to be an opportunistic pathogens associated with food-borne disease in neonates and infants. Neither phenotypic nor genotypic (16S ribosomal DNA sequence analysis) techniques can provide sufficient resolutions for accurately and rapidly identification of these species. The objective of this study was to develop species-specific PCR based on the gyrB gene sequence for direct species identification of the C. sakazakii and Cronobacter dublinensis within the C. sakazakii group. Two pair of species-specific primers were designed and used to specifically identify C. sakazakii and C. dublinensis, but none of the other C. sakazakii group strains. Our data indicate that the novel species-specific primers could be used to rapidly and accurately identify the species of C. sakazakii and C. dublinensis from C. sakazakii group by the PCR based assays. Copyright © 2012 Elsevier Ltd. All rights reserved.

The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions | Office of Cancer Genomics

Cancer.gov

We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children’s Oncology Group (COG) AML trials. The COG–National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases.

Targeting latent function: encouraging effective encoding for successful memory training and transfer.

PubMed

Lustig, Cindy; Flegal, Kristin E

2008-12-01

Cognitive training programs for older adults often result in improvements at the group level. However, there are typically large age and individual differences in the size of training benefits. These differences may be related to the degree to which participants implement the processes targeted by the training program. To test this possibility, we tested older adults in a memory-training procedure either under specific strategy instructions designed to encourage semantic, integrative encoding, or in a condition that encouraged time and attention to encoding but allowed participants to choose their own strategy. Both conditions improved the performance of old-old adults relative to an earlier study (D. Bissig & C. Lustig, 2007) and reduced self-reports of everyday memory errors. Performance in the strategy-instruction group was related to preexisting ability; performance in the strategy?choice group was not. The strategy-choice group performed better on a laboratory transfer test of recognition memory, and training performance was correlated with reduced everyday memory errors. Training programs that target participants' latent but inefficiently used abilities while allowing flexibility in bringing those abilities to bear may best promote effective training and transfer. Copyright (c) 2009 APA, all rights reserved.

Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus

PubMed Central

Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng

2009-01-01

In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer. PMID:19498077

Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus.

PubMed

Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng

2009-08-01

In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer.

Identification of Salmonella Typhimurium-specific DNA aptamers developed using whole-cell SELEX and FACS analysis.

PubMed

Moon, Jihea; Kim, Giyoung; Lee, Sangdae; Park, Saetbyeol

2013-11-01

Conventional methods for detection of infective organisms, such as Salmonella, are complicated and require multiple steps, and the need for rapid detection has increased. Biosensors show great potential for rapid detection of pathogens. In turn, aptamers have great potential for biosensor assay development, given their small size, ease of synthesis and labeling, lack of immunogenicity, a lower cost of production than antibodies, and high target specificity. In this study, ssDNA aptamers specific to Salmonella Typhimurium were obtained by a whole bacterium-based systematic evolution of ligands by exponential enrichment (SELEX) procedure and applied to probing S. Typhimurium. After 10 rounds of selection with S. Typhimurium as the target and Salmonella Enteritidis, Escherichia coli and Staphylococcus aureus as counter targets, the highly enriched oligonucleic acid pool was sorted using flow cytometry. In total, 12 aptamer candidates from different families were sequenced and grouped. Fluorescent analysis demonstrated that aptamer C4 had particularly high binding affinity and selectivity; this aptamer was then further characterized. © 2013 Elsevier B.V. All rights reserved.

Female-specific education, management, and lifestyle enhancement for implantable cardioverter defibrillator patients: the FEMALE-ICD study.

PubMed

Vazquez, Lauren D; Conti, Jamie B; Sears, Samuel F

2010-09-01

Significant rates of psychological distress occur in implantable cardioverter defibrillator (ICD) patients. Research has demonstrated that women are particularly at risk for developing distress and warrant psychosocial attention. The major objectives were to implement and test the effectiveness of a female-specific psychosocial group intervention on disease-specific quality of life outcomes in outpatient female ICD recipients versus a wait-list control group. Twenty-nine women were recruited for the study. Fourteen women were randomized to the intervention group and participated in a psychosocial intervention focused on female-specific issues; 15 were randomized to the wait-list control group. All women completed individual psychological batteries at baseline and at 1-month follow-up measuring shock anxiety and device acceptance. Pre-post measures of shock anxiety demonstrated a significant time by group interaction effect with the intervention group having a significantly greater decrease (Pillai's trace = 5.58, P = 0.026). A significant interaction effect (Pillai's trace = 5.05, P = 0.046) was found, such that women under the age of 50 experienced greater reduction in shock anxiety than their middle-aged cohorts. Pre-post measures of device acceptance revealed a significant time by group interaction effect with the intervention group having significantly greater increases (Pillai's trace = 5.80, P = 0.023). Structured interventions for female ICD patients involving ICD-specific education, cognitive behavioral therapy strategies, and group social support provide improvements in shock anxiety and device acceptance at 1-month re-assessment. Young women appear to be an at-risk subgroup of this population and may experience more benefit from psychosocial treatment targeting device-specific concerns. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

PubMed

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. 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.

BLISTER Regulates Polycomb-Target Genes, Represses Stress-Regulated Genes and Promotes Stress Responses in Arabidopsis thaliana.

PubMed

Kleinmanns, Julia A; Schatlowski, Nicole; Heckmann, David; Schubert, Daniel

2017-01-01

HIGHLIGHTS The PRC2 interacting protein BLISTER likely acts downstream of PRC2 to silence Polycomb target genes and is a key regulator of specific stress responses in Arabidopsis . Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes by trimethylating H3K27 (H3K27me3). Plant specific PcG components and functions are largely unknown, however, we previously identified the plant-specific protein BLISTER (BLI) as a PRC2 interactor. BLI regulates PcG target genes and promotes cold stress resistance. To further understand the function of BLI , we analyzed the transcriptional profile of bli-1 mutants. Approximately 40% of the up-regulated genes in bli are PcG target genes, however, bli-1 mutants did not show changes in H3K27me3 levels at all tested genes, indicating that BLI regulates PcG target genes downstream of or in parallel to PRC2. Interestingly, a significant number of BLI regulated H3K27me3 target genes is regulated by the stress hormone absciscic acid (ABA). We further reveal an overrepresentation of genes responding to abiotic stresses such as drought, high salinity, or heat stress among the up-regulated genes in bli mutants. Consistently, bli mutants showed reduced desiccation stress tolerance. We conclude that the PRC2 associated protein BLI is a key regulator of stress-responsive genes in Arabidopsis : it represses ABA-responsive PcG target genes, likely downstream of PRC2, and promotes resistance to several stresses such as cold and drought.

Near infrared photoimmunotherapy rapidly elicits specific host immunity against cancer cells (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kobayashi, Hisataka

2017-02-01

Near infrared photoimmunotherapy (NIR-PIT) is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (mAb) targeting cell-surface molecules. When exposed to NIR light, the conjugate induces a highly-selective necrotic/immunogenic cell death (ICD) only in target-positive, mAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent target-negative cells are unharmed. Dynamic 3D-microscopy of live tumor cells undergoing NIR-PIT showed rapid swelling in treated cells immediately after light exposure, followed by irreversible morphologic changes such as bleb formation, and rupture of vesicles within several minutes. Furthermore, biological markers of ICD including relocation of HSP70/90 and calreticulin, and release of ATP and High Mobility Group Box 1 (HMGB1), were clearly detected immediately after NIR-PIT. When NIR-PIT was performed in a mixture of cancer cells and immature dendritic cells, maturation of immature dendritic cells was strongly induced rapidly after NIR-PIT. Alternatively, NIR-PIT can also target negative regulatory immune cells such as Treg only in the tumor bed. Treg targeting NIR-PIT against CD25 can deplete >80% of Treg in tumor bed within 20 min that induces activation of tumor cell-specific CD8+-T and NK cells within 1.5 hour, and then these activated cells killed cancer cells in local tumor within 1 day and also in distant tumors of the same cell origin within 2 days. In summary, cancer cell-targeting and immuno-suppressor cell-targeting NIR-PITs effectively induce innate and acquired immunity specifically against cancer cells growing in patients, respectively.

Exploring an alternative transportation program to reduce impaired driving.

DOT National Transportation Integrated Search

2001-11-01

This study assessed the impact of an alternate ride home for persons who wanted to plan ahead for instances when they may be too impaired to drive, specifically targeting persons between the ages of 29 and 49. First, a series of focus groups was cond...

Glass wool filters for concentrating waterborne viruses and agricultural zoonotic pathogens

USDA-ARS?s Scientific Manuscript database

The key first step in evaluating pathogen levels in suspected contaminated water is concentration. Concentration methods tend to be specific for a particular pathogen group or genus, for example viruses or Cryptosporidium, requiring multiple methods if the sampling program is targeting more than on...

Ion binding compounds, radionuclide complexes, methods of making radionuclide complexes, methods of extracting radionuclides, and methods of delivering radionuclides to target locations

DOEpatents

Chen, Xiaoyuan; Wai, Chien M.; Fisher, Darrell R.

2000-01-01

The invention pertains to compounds for binding lanthanide ions and actinide ions. The invention further pertains to compounds for binding radionuclides, and to methods of making radionuclide complexes. Also, the invention pertains to methods of extracting radionuclides. Additionally, the invention pertains to methods of delivering radionuclides to target locations. In one aspect, the invention includes a compound comprising: a) a calix[n]arene group, wherein n is an integer greater than 3, the calix[n]arene group comprising an upper rim and a lower rim; b) at least one ionizable group attached to the lower rim; and c) an ion selected from the group consisting of lanthanide and actinide elements bound to the ionizable group. In another aspect, the invention includes a method of extracting a radionuclide, comprising: a) providing a sample comprising a radionuclide; b) providing a calix[n]arene compound in contact with the sample, wherein n is an integer greater than 3; and c) extracting radionuclide from the sample into the calix[n]arene compound. In yet another aspect, the invention includes a method of delivering a radionuclide to a target location, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising at least one ionizable group; b) providing a radionuclide bound to the calix[n]arene compound; and c) providing an antibody attached to the calix[n]arene compound, the antibody being specific for a material found at the target location.

Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism

PubMed Central

Yubero, Dèlia; Brandi, Núria; Ormazabal, Aida; Garcia-Cazorla, Àngels; Pérez-Dueñas, Belén; Campistol, Jaime; Ribes, Antonia; Palau, Francesc

2016-01-01

Background Next-generation sequencing (NGS) technology has allowed the promotion of genetic diagnosis and are becoming increasingly inexpensive and faster. To evaluate the utility of NGS in the clinical field, a targeted genetic panel approach was designed for the diagnosis of a set of inborn errors of metabolism (IEM). The final aim of the study was to compare the findings for the diagnostic yield of NGS in patients who presented with consistent clinical and biochemical suspicion of IEM with those obtained for patients who did not have specific biomarkers. Methods The subjects studied (n = 146) were classified into two categories: Group 1 (n = 81), which consisted of patients with clinical and biochemical suspicion of IEM, and Group 2 (n = 65), which consisted of IEM cases with clinical suspicion and unspecific biomarkers. A total of 171 genes were analyzed using a custom targeted panel of genes followed by Sanger validation. Results Genetic diagnosis was achieved in 50% of patients (73/146). In addition, the diagnostic yield obtained for Group 1 was 78% (63/81), and this rate decreased to 15.4% (10/65) in Group 2 (X2 = 76.171; p < 0.0001). Conclusions A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis. PMID:27243974

Enhanced startle responsivity 24 hours after acute stress exposure.

PubMed

Herten, Nadja; Otto, Tobias; Adolph, Dirk; Pause, Bettina M; Kumsta, Robert; Wolf, Oliver T

2016-10-01

Cortisol release in a stressful situation can be beneficial for memory encoding and memory consolidation. Stimuli, such as odors, related to the stressful episode may successfully cue memory contents of the stress experience. The current investigation aimed at testing the potency of stress to influence startle responsivity 24 hr later and to implicitly reactivate emotional memory traces triggered by an odor involved. Participants were assigned to either a stress (Trier Social Stress Test [TSST]) or control (friendly TSST [f-TSST]) condition featuring an ambient odor. On the next day, participants underwent an auditory startle paradigm while their eyeblink reflex was recorded by an electrooculogram. Three different olfactory stimuli were delivered, one being the target odor presented the day before. Additionally, negative, positive, and pictures of the committee members were included for comparing general startle responsivity and fear-potentiated startle. Participants of the stress group demonstrated an enhanced startle response across all stimuli compared to participants of the control group. There were no specific effects with regard to the target odor. The typical fear-potentiated startle response occurred. Stressed participants tended to rate the target odor more aversive than control participants. Odor recognition memory did not differ between the groups, suggesting an implicit effect on odor valence. Our results show that acute stress exposure enhances startle responsivity 24 hr later. This effect might be caused by a shift of amygdala function causing heightened sensitivity, but lower levels of specificity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

PROSPECT: Profiling of Resistance Patterns Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2011-06-01

8w DC in patients treated with erlotinib, but not sorafenib, indicating that it is not merely a prognostic signature; D) Both the 5-gene signature...disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular signatures in primary tumors...therapeutic strategies at relapse. Specific Aims: Aim 1: To define characteristic TTF/gene expression profiles of prognostically distinct

Age-specific strategies for immunization reminders and recalls: a registry-based randomized trial.

PubMed

Dombkowski, Kevin J; Costello, Lauren E; Harrington, Laura B; Dong, Shiming; Kolasa, Maureen; Clark, Sarah J

2014-07-01

Although previous studies have found reminder/recall to be effective in increasing immunization rates, little guidance exists regarding the specific ages at which it is optimal to send reminder/recall notices. To assess the relative effectiveness of centralized reminder/recall strategies targeting age-specific vaccination milestones among children in urban areas during June 2008-June 2009. Three reminder/recall strategies used capabilities of the Michigan Care Improvement Registry (MCIR), a statewide immunization information system: a 7-month recall strategy, a 12-month reminder strategy, and a 19-month recall strategy. Eligible children were randomized to notification (intervention) or no notification groups (control). Primary study outcomes included MCIR-recorded immunization activity (administration of ≥1 new dose, entry of ≥1 historic dose, entry of immunization waiver) within 60 days following each notification cycle. A total of 10,175 children were included: 2,072 for the 7-month recall, 3,502 for the 12-month reminder, and 4,601 for the 19-month recall. Immunization activity was similar between notification versus no notification groups at both 7 and 12 months. Significantly more 19-month-old children in the recall group (26%) had immunization activity compared to their counterparts who did not receive a recall notification (19%). Although recall notifications can positively affect immunization activity, the effect may vary by targeted age group. Many 7- and 12-month-olds had immunization activity following reminder/recall; however, levels of activity were similar irrespective of notification, suggesting that these groups were likely to receive medical care or immunization services without prompting. Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.

Discriminate the response of Acute Myeloid Leukemia patients to treatment by using proteomics data and Answer Set Programming.

PubMed

Chebouba, Lokmane; Miannay, Bertrand; Boughaci, Dalila; Guziolowski, Carito

2018-03-08

During the last years, several approaches were applied on biomedical data to detect disease specific proteins and genes in order to better target drugs. It was shown that statistical and machine learning based methods use mainly clinical data and improve later their results by adding omics data. This work proposes a new method to discriminate the response of Acute Myeloid Leukemia (AML) patients to treatment. The proposed approach uses proteomics data and prior regulatory knowledge in the form of networks to predict cancer treatment outcomes by finding out the different Boolean networks specific to each type of response to drugs. To show its effectiveness we evaluate our method on a dataset from the DREAM 9 challenge. The results are encouraging and demonstrate the benefit of our approach to distinguish patient groups with different response to treatment. In particular each treatment response group is characterized by a predictive model in the form of a signaling Boolean network. This model describes regulatory mechanisms which are specific to each response group. The proteins in this model were selected from the complete dataset by imposing optimization constraints that maximize the difference in the logical response of the Boolean network associated to each group of patients given the omic dataset. This mechanistic and predictive model also allow us to classify new patients data into the two different patient response groups. We propose a new method to detect the most relevant proteins for understanding different patient responses upon treatments in order to better target drugs using a Prior Knowledge Network and proteomics data. The results are interesting and show the effectiveness of our method.

From features to dimensions: cognitive and motor development in pop-out search in children and young adults.

PubMed

Grubert, Anna; Indino, Marcello; Krummenacher, Joseph

2014-01-01

In an experiment involving a total of 124 participants, divided into eight age groups (6-, 8-, 10-, 12-, 14-, 16-, 18-, and 20-year-olds) the development of the processing components underlying visual search for pop-out targets was tracked. Participants indicated the presence or absence of color or orientation feature singleton targets. Observers also solved a detection task, in which they responded to the onset of search arrays. There were two main results. First, analyses of inter-trial effects revealed differences in the search strategies of the 6-year-old participants compared to older age groups. Participants older than 8 years based target detection on feature-less dimensional salience signals (indicated by cross-trial RT costs in target dimension change relative to repetition trials), the 6-year-olds accessed the target feature to make a target present or absent decision (cross-trial RT costs in target feature change relative to feature repetition trials). The result agrees with predictions derived from the Dimension Weighting account and previous investigations of inter-trial effects in adult observers (Müller et al., 1995; Found and Müller, 1996). The results are also in line with theories of cognitive development suggesting that the ability to abstract specific visual features into feature categories is developed after the age of 7 years. Second, overall search RTs decreased with increasing age in a decelerated fashion. RT differences between consecutive age groups can be explained by sensory-motor maturation up to the age of 10 years (as indicated by RTs in the onset detection task). Expedited RTs in older age groups (10-, vs. 12-year-olds; 14- vs. 16-year-olds), but also in the 6- vs. 8-year-olds, are due to the development of search-related (cognitive) processes. Overall, the results suggest that the level of adult performance in visual search for pop-out targets is achieved by the age of 16.

From features to dimensions: cognitive and motor development in pop-out search in children and young adults

PubMed Central

Grubert, Anna; Indino, Marcello; Krummenacher, Joseph

2014-01-01

In an experiment involving a total of 124 participants, divided into eight age groups (6-, 8-, 10-, 12-, 14-, 16-, 18-, and 20-year-olds) the development of the processing components underlying visual search for pop-out targets was tracked. Participants indicated the presence or absence of color or orientation feature singleton targets. Observers also solved a detection task, in which they responded to the onset of search arrays. There were two main results. First, analyses of inter-trial effects revealed differences in the search strategies of the 6-year-old participants compared to older age groups. Participants older than 8 years based target detection on feature-less dimensional salience signals (indicated by cross-trial RT costs in target dimension change relative to repetition trials), the 6-year-olds accessed the target feature to make a target present or absent decision (cross-trial RT costs in target feature change relative to feature repetition trials). The result agrees with predictions derived from the Dimension Weighting account and previous investigations of inter-trial effects in adult observers (Müller et al., 1995; Found and Müller, 1996). The results are also in line with theories of cognitive development suggesting that the ability to abstract specific visual features into feature categories is developed after the age of 7 years. Second, overall search RTs decreased with increasing age in a decelerated fashion. RT differences between consecutive age groups can be explained by sensory-motor maturation up to the age of 10 years (as indicated by RTs in the onset detection task). Expedited RTs in older age groups (10-, vs. 12-year-olds; 14- vs. 16-year-olds), but also in the 6- vs. 8-year-olds, are due to the development of search-related (cognitive) processes. Overall, the results suggest that the level of adult performance in visual search for pop-out targets is achieved by the age of 16. PMID:24910627

Electrophysiological correlates of cross-linguistic semantic integration in hearing signers: N400 and LPC.

PubMed

Zachau, Swantje; Korpilahti, Pirjo; Hämäläinen, Jarmo A; Ervast, Leena; Heinänen, Kaisu; Suominen, Kalervo; Lehtihalmes, Matti; Leppänen, Paavo H T

2014-07-01

We explored semantic integration mechanisms in native and non-native hearing users of sign language and non-signing controls. Event-related brain potentials (ERPs) were recorded while participants performed a semantic decision task for priming lexeme pairs. Pairs were presented either within speech or across speech and sign language. Target-related ERP responses were subjected to principal component analyses (PCA), and neurocognitive basis of semantic integration processes were assessed by analyzing the N400 and the late positive complex (LPC) components in response to spoken (auditory) and signed (visual) antonymic and unrelated targets. Semantically-related effects triggered across modalities would indicate a similar tight interconnection between the signers׳ two languages like that described for spoken language bilinguals. Remarkable structural similarity of the N400 and LPC components with varying group differences between the spoken and signed targets were found. The LPC was the dominant response. The controls׳ LPC differed from the LPC of the two signing groups. It was reduced to the auditory unrelated targets and was less frontal for all the visual targets. The visual LPC was more broadly distributed in native than non-native signers and was left-lateralized for the unrelated targets in the native hearing signers only. Semantic priming effects were found for the auditory N400 in all groups, but only native hearing signers revealed a clear N400 effect to the visual targets. Surprisingly, the non-native signers revealed no semantically-related processing effect to the visual targets reflected in the N400 or the LPC; instead they appeared to rely more on visual post-lexical analyzing stages than native signers. We conclude that native and non-native signers employed different processing strategies to integrate signed and spoken semantic content. It appeared that the signers׳ semantic processing system was affected by group-specific factors like language background and/or usage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction

PubMed Central

2017-01-01

We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides such as miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3′ ends. In the presence of a target sequence, interstrand ligation is possible via the click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target strands present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and were spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10–17 moles per well (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. A similar limit of detection was found for spiked human serum samples, demonstrating the suitability of the sensor for detecting specific sequences of small oligonucleotides under real conditions. In contrast, in the presence of noncomplementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced. PMID:28332400

Controlled Retrieval of Specific Context Information in Children and Adults.

PubMed

Lorsbach, Thomas C; Friehe, Mary J; Teten, Amy Fair; Reimer, Jason F; Armendarez, Joseph J

2015-01-01

This study adapted a procedure used by Luo and Craik (2009) to examine whether developmental differences exist in the ability to use controlled retrieval processes to access the contextual details of memory representations. Participants from 3 age groups (mean ages 9, 12, and 25 years) were presented with words in 3 study contexts: with a black-and-white picture, with a color picture, or alone without a picture. Six recognition tests were then presented that varied in the demands (high or low) placed on the retrieval of specific contextual information. Each test consisted of a mixture of words that were old targets from 1 study context, distractors (i.e., previously studied words from a different context), and completely new words. A high-specificity and a low-specificity test list was paired with each test question, with high and low specificity being determined by the nature of the distractors used in a test list. High-specificity tests contained words that were studied in similar contexts: old targets (e.g., words studied with black-and-white pictures) and distractors (e.g., words studied with color pictures). In contrast, low-specificity tests contained words that were studied in dissimilar contexts: old targets (e.g., words studied with black-and-white pictures) and distractors (e.g., words previously studied without a picture). Relative to low-specificity tests, the retrieval conditions of high-specificity tests were assumed to place greater demands on the controlled access of specific contextual information. Analysis of recollection scores revealed that age differences were present on high-but not low-specificity tests, with the performance of 9-year-olds disproportionately affected by the retrieval demands of high-specificity tests.

Molecular pathways and therapeutic targets in lung cancer

PubMed Central

Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

2014-01-01

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

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

PubMed Central

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.

PubMed

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).

Haptic over visual information in the distribution of visual attention after tool-use in near and far space.

PubMed

Park, George D; Reed, Catherine L

2015-10-01

Despite attentional prioritization for grasping space near the hands, tool-use appears to transfer attentional bias to the tool's end/functional part. The contributions of haptic and visual inputs to attentional distribution along a tool were investigated as a function of tool-use in near (Experiment 1) and far (Experiment 2) space. Visual attention was assessed with a 50/50, go/no-go, target discrimination task, while a tool was held next to targets appearing near the tool-occupied hand or tool-end. Target response times (RTs) and sensitivity (d-prime) were measured at target locations, before and after functional tool practice for three conditions: (1) open-tool: tool-end visible (visual + haptic inputs), (2) hidden-tool: tool-end visually obscured (haptic input only), and (3) short-tool: stick missing tool's length/end (control condition: hand occupied but no visual/haptic input). In near space, both open- and hidden-tool groups showed a tool-end, attentional bias (faster RTs toward tool-end) before practice; after practice, RTs near the hand improved. In far space, the open-tool group showed no bias before practice; after practice, target RTs near the tool-end improved. However, the hidden-tool group showed a consistent tool-end bias despite practice. Lack of short-tool group results suggested that hidden-tool group results were specific to haptic inputs. In conclusion, (1) allocation of visual attention along a tool due to tool practice differs in near and far space, and (2) visual attention is drawn toward the tool's end even when visually obscured, suggesting haptic input provides sufficient information for directing attention along the tool.

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

PubMed Central

Li, Xian; Li, Hao; Yi, Wei; Chen, Jianyu; Liang, Biling

2013-01-01

Purpose To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N′,N′-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks’ cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors. PMID:23976852

Are All Interventions Created Equal? A Multi-Threat Approach to Tailoring Stereotype Threat Interventions

PubMed Central

Shapiro, Jenessa R.; Williams, Amy M.; Hambarchyan, Mariam

2013-01-01

To date, stereotype threat interventions have been considered interchangeable. Across 4 experiments, the present research demonstrates that stereotype threat interventions need to be tailored to the specific form of experienced stereotype threat to be effective. The Multi-Threat Framework (Shapiro & Neuberg, 2007) distinguishes between group-as-target stereotype threats—concerns that a stereotype-relevant performance will reflect poorly on the abilities of one’s group—and self-as-target stereotype threats—concerns that a stereotype-relevant performance will reflect poorly on one’s own abilities. The present experiments explored Black college students’ performance on diagnostic intelligence tests (Experiments 1 and 3) and women’s interest (Experiment 2) and performance (Experiment 4) in science, technology, engineering, and math (STEM). Across the 4 experiments, participants were randomly assigned to experience either a group-as-target or self-as-target stereotype threat. Experiments 1 and 2 revealed that role model interventions were successful at protecting only against group-as-target stereotype threats, and Experiments 3 and 4 revealed that self-affirmation interventions were successful at protecting only against self-as-target stereotype threats. The present research provides an experimental test of the Multi-Threat Framework across different negatively stereotyped groups (Black students, female students), different negatively stereotyped domains (general intelligence, STEM), and different outcomes (test performance, career interest). This research suggests that interventions should address the range of possible stereotype threats to effectively protect individuals against these threats. Through an appreciation of the distinct forms of stereotype threats and the ways in which interventions work to reduce them, this research aims to facilitate a more complete understanding of stereotype threat. PMID:23088232

The balanced ideological antipathy model: explaining the effects of ideological attitudes on inter-group antipathy across the political spectrum.

PubMed

Crawford, Jarret T; Mallinas, Stephanie R; Furman, Bryan J

2015-12-01

We introduce the balanced ideological antipathy (BIA) model, which challenges assumptions that right-wing authoritarianism (RWA) and social dominance orientation (SDO) predict inter-group antipathy per se. Rather, the effects of RWA and SDO on antipathy should depend on the target's political orientation and political objectives, the specific components of RWA, and the type of antipathy expressed. Consistent with the model, two studies (N = 585) showed that the Traditionalism component of RWA positively and negatively predicted both political intolerance and prejudice toward tradition-threatening and -reaffirming groups, respectively, whereas SDO positively and negatively predicted prejudice (and to some extent political intolerance) toward hierarchy-attenuating and -enhancing groups, respectively. Critically, the Conservatism component of RWA positively predicted political intolerance (but not prejudice) toward each type of target group, suggesting it captures the anti-democratic impulse at the heart of authoritarianism. Recommendations for future research on the relationship between ideological attitudes and inter-group antipathy are discussed. © 2015 by the Society for Personality and Social Psychology, Inc.

Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer.

PubMed

Jyotsana, Nidhi; Heuser, Michael

2018-02-01

Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development. Expert opinion: Alternative splicing is an important mechanism that controls gene expression, and hence pharmacologic and genetic control of aberrant alternative RNA splicing has been proposed as a potential therapy in cancer. To identify and validate aberrant RNA splicing patterns as therapeutic targets we need to (1) characterize the most common genetic aberrations of the spliceosome and of splice sites, (2) understand the dysregulated downstream pathways and (3) exploit in-vivo disease models of aberrant splicing. Antisense oligonucleotides show promising activity, but will benefit from improved delivery tools. Inhibitors of mutated splicing factors require improved specificity, as alternative and aberrant splicing are often intertwined like two sides of the same coin. In summary, targeting aberrant splicing is an early but emerging field in cancer treatment.

The relationship between sustained attention and aerobic fitness in a group of young adults.

PubMed

Ciria, Luis F; Perakakis, Pandelis; Luque-Casado, Antonio; Morato, Cristina; Sanabria, Daniel

2017-01-01

A growing set of studies has shown a positive relationship between aerobic fitness and a broad array of cognitive functions. However, few studies have focused on sustained attention, which has been considered a fundamental cognitive process that underlies most everyday activities. The purpose of this study was to investigate the role of aerobic fitness as a key factor in sustained attention capacities in young adults. Forty-four young adults (18-23 years) were divided into two groups as a function of the level of aerobic fitness (high-fit and low-fit). Participants completed the Psychomotor Vigilance Task (PVT) and an oddball task where they had to detect infrequent targets presented among frequent non-targets. The analysis of variance (ANOVA) showed faster responses for the high-fit group than for the low-fit group in the PVT, replicating previous accounts. In the oddball task, the high-fit group maintained their accuracy (ACC) rate of target detection over time, while the low-fit group suffered a significant decline of response ACC throughout the task. Importantly, the results show that the greater sustained attention capacity of high-fit young adults is not specific to a reaction time (RT) sustained attention task like the PVT, but it is also evident in an ACC oddball task. In sum, the present findings point to the important role of aerobic fitness on sustained attention capacities in young adults.

Measuring participant rurality in Web-based interventions.

PubMed

Danaher, Brian G; Hart, L Gary; McKay, H Garth; Severson, Herbert H

2007-08-31

Web-based health behavior change programs can reach large groups of disparate participants and thus they provide promise of becoming important public health tools. Data on participant rurality can complement other demographic measures to deepen our understanding of the success of these programs. Specifically, analysis of participant rurality can inform recruitment and social marketing efforts, and facilitate the targeting and tailoring of program content. Rurality analysis can also help evaluate the effectiveness of interventions across population groupings. We describe how the RUCAs (Rural-Urban Commuting Area Codes) methodology can be used to examine results from two Randomized Controlled Trials of Web-based tobacco cessation programs: the ChewFree.com project for smokeless tobacco cessation and the Smokers' Health Improvement Program (SHIP) project for smoking cessation. Using RUCAs methodology helped to highlight the extent to which both Web-based interventions reached a substantial percentage of rural participants. The ChewFree program was found to have more rural participation which is consistent with the greater prevalence of smokeless tobacco use in rural settings as well as ChewFree's multifaceted recruitment program that specifically targeted rural settings. Researchers of Web-based health behavior change programs targeted to the US should routinely include RUCAs as a part of analyzing participant demographics. Researchers in other countries should examine rurality indices germane to their country.

Development of a 16S rRNA-targeted fluorescence in situ hybridization probe for quantification of the ammonia-oxidizer Nitrosotalea devanaterra and its relatives.

PubMed

Restrepo-Ortiz, C X; Merbt, S N; Barrero-Canossa, J; Fuchs, B M; Casamayor, E O

2018-04-28

The Thaumarchaeota SAGMCG-1 group and, in particular, members of the genus Nitrosotalea have high occurrence in acidic soils, the rhizosphere, groundwater and oligotrophic lakes, and play a potential role in nitrogen cycling. In this study, the specific oligonucleotide fluorescence in situ hybridization probe SAG357 was designed for this Thaumarchaeota group based on the available 16S rRNA gene sequences in databases, and included the ammonia-oxidizing species Nitrosotalea devanaterra. Cell permeabilization for catalyzed reporter deposition fluorescence in situ detection and the hybridization conditions were optimized on enrichment cultures of the target species N. devanaterra, as well as the non-target ammonia-oxidizing archaeon Nitrosopumilus maritimus. Probe specificity was improved with a competitor oligonucleotide, and fluorescence intensity and cell visualization were enhanced by the design and application of two adjacent helpers. Probe performance was tested in soil samples along a pH gradient, and counting results matched the expected in situ distributions. Probe SAG357 and the CARD-FISH protocol developed in the present study will help to improve the current understanding of the ecology and physiology of N. devanaterra and its relatives in natural environments. Copyright © 2018 Elsevier GmbH. All rights reserved.

Changing the way employee benefit communications are produced: outsourcing, a more efficient, less costly process.

PubMed

Herren, K

1995-12-01

Outsourcing may offer employers an efficient, cost-effective way to produce employee benefit communications. It offers a way to utilize the latest technology to produce personalized benefit statements or to target an announcement of benefit changes to a specific group of employees.

NUL Legislative Research: General Revenue Sharing: Pygmy or Behemoth?

ERIC Educational Resources Information Center

Cooper, Maudine Rice

1976-01-01

Asserts that concern with revenue sharing "is justified on the grounds that general revenue sharing may ultimately replace existing categorical programs, those programs specifically targeted for special groups." Concludes that the potential legal influence of this program may be used to promote effective civil rights enforcement. (Author/JM)

Development and application of nanoparticles synthesized with folic acid-conjugated soy protein

USDA-ARS?s Scientific Manuscript database

In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-conjug...

Suicide Prevention in a Diverse Campus Community

ERIC Educational Resources Information Center

Shadick, Richard; Akhter, Sarah

2013-01-01

As the college population in the United States rapidly diversifies, leaders of successful campus suicide prevention programs are recognizing the importance of targeting specific groups of students. Recent estimates from the National Center for Education Statistics indicated that in 2008 more than one-third (36.7 percent) of college students…

What's (Not) Wrong with Low-Income Marriages

ERIC Educational Resources Information Center

Trail, Thomas E.; Karney, Benjamin R.

2012-01-01

In the United States, low marriage rates and high divorce rates among the poor have led policymakers to target this group for skills- and values-based interventions. The current research evaluated the assumptions underlying these interventions; specifically, the authors examined whether low-income respondents held less traditional values toward…

Analysis of Photogrammetry Data from ISIM Mockup, June 1, 2007

NASA Technical Reports Server (NTRS)

Nowak, Maria; Hill, Mike

2007-01-01

During ground testing of the Integrated Science Instrument Module (ISIM) for the James Webb Space Telescope (JWST), the ISIM Optics group plans to use a Photogrammetry Measurement System for cryogenic calibration of specific target points on the ISIM composite structure and Science Instrument optical benches and other GSE equipment. This testing will occur in the Space Environmental Systems (SES) chamber at Goddard Space Flight Center. Close range photogrammetry is a 3 dimensional metrology system using triangulation to locate custom targets in 3 coordinates via a collection of digital photographs taken from various locations and orientations. These photos are connected using coded targets, special targets that are recognized by the software and can thus correlate the images to provide a 3 dimensional map of the targets, and scaled via well calibrated scale bars. Photogrammetry solves for the camera location and coordinates of the targets simultaneously through the bundling procedure contained in the V-STARS software.

UnPAKing the class differences among p21-activated kinases.

PubMed

Eswaran, Jeyanthy; Soundararajan, Meera; Kumar, Rakesh; Knapp, Stefan

2008-08-01

The p21-activated kinases (PAKs) are signal transducers, central to many vital cellular processes, including cell morphology, motility, survival, gene transcription and hormone signalling. The mammalian PAK family contains six serine/threonine kinases divided into two subgroups, group I (PAK 1-3) and group II (PAK4-6), based on their domain architecture and regulation. PAKs functioning as dynamic signalling nodes present themselves as attractive therapeutic targets in tumours, neurological diseases and infection. The recent findings across all PAKs, including newly reported structures, shed light on the cellular functions of PAKs, highlighting molecular mechanisms of activation, catalysis and substrate specificity. We believe that a comprehensive understanding of the entire PAK family is essential for developing strategies towards PAK-targeted therapeutics.

Undoing an Epidemiological Paradox: The Tobacco Industry’s Targeting of US Immigrants

PubMed Central

Acevedo-Garcia, Dolores; Barbeau, Elizabeth; Bishop, Jennifer Anne; Pan, Jocelyn; Emmons, Karen M.

2004-01-01

Objectives. We sought to ascertain whether the tobacco industry has conceptualized the US immigrant population as a separate market. Methods. We conducted a content analysis of major tobacco industry documents. Results. The tobacco industry has engaged in 3 distinct marketing strategies aimed at US immigrants: geographically based marketing directed toward immigrant communities, segmentation based on immigrants’ assimilation status, and coordinated marketing focusing on US immigrant groups and their countries of origin. Conclusions. Public health researchers should investigate further the tobacco industry’s characterization of the assimilated and non-assimilated immigrant markets, and its specific strategies for targeting these groups, in order to develop informed national and international tobacco control countermarketing strategies designed to protect immigrant populations and their countries of origin. PMID:15569972

Drug-target interaction prediction from PSSM based evolutionary information.

PubMed

Mousavian, Zaynab; Khakabimamaghani, Sahand; Kavousi, Kaveh; Masoudi-Nejad, Ali

2016-01-01

The labor-intensive and expensive experimental process of drug-target interaction prediction has motivated many researchers to focus on in silico prediction, which leads to the helpful information in supporting the experimental interaction data. Therefore, they have proposed several computational approaches for discovering new drug-target interactions. Several learning-based methods have been increasingly developed which can be categorized into two main groups: similarity-based and feature-based. In this paper, we firstly use the bi-gram features extracted from the Position Specific Scoring Matrix (PSSM) of proteins in predicting drug-target interactions. Our results demonstrate the high-confidence prediction ability of the Bigram-PSSM model in terms of several performance indicators specifically for enzymes and ion channels. Moreover, we investigate the impact of negative selection strategy on the performance of the prediction, which is not widely taken into account in the other relevant studies. This is important, as the number of non-interacting drug-target pairs are usually extremely large in comparison with the number of interacting ones in existing drug-target interaction data. An interesting observation is that different levels of performance reduction have been attained for four datasets when we change the sampling method from the random sampling to the balanced sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

The Controlled Retrieval of Specific Context Information in Children and Adults

PubMed Central

Lorsbach, Thomas C.; Reimer, Jason F.; Friehe, Mary J.; Armendarez, Joseph J.; Teten, Amy Fair

2017-01-01

The present study adapted a procedure used recently by Luo and Craik (2009) in order to examine whether developmental differences exist in the ability to use controlled retrieval processes to access the specific contextual details of memory representations. Participants from three age groups (Mean ages: 9, 12, and 25 years) were presented with words in three study contexts: with a black-and-white picture, with a color picture, or alone without a picture. Six recognition tests were then presented that varied in the demands (high or low) placed on the retrieval of specific contextual information. Each test consisted of a mixture of words that were old targets from one study context, distractors (i.e., previously studied words from a different context), and completely new words. A “high specificity” and a “low specificity” test list was paired with each test question, with “high” and “low” specificity being determined by the nature of the distractors used in a test list. High specificity tests contained words that were studied in similar contexts: old targets (e.g., words studied with black-and-white pictures) and distractors (e.g., words studied with color pictures). In contrast, low specificity tests contained words that were studied in dissimilar contexts: old targets (e.g., words studied with black-and-white pictures) and distractors (e.g., words previously studied without a picture). Relative to low specificity tests, the retrieval conditions of high specificity tests were assumed to place greater demands on the controlled access of specific contextual information. Analysis of recollection scores revealed that age differences were present on high, but not low specificity tests, with the performance of 9-year olds being disproportionately affected by the retrieval demands of high specificity tests. PMID:26219173

Comprehension Tools for Teachers: Reading for Understanding from Prekindergarten through Fourth Grade

PubMed Central

Connor, Carol McDonald; Phillips, Beth M.; Kaschak, Michael; Apel, Kenn; Kim, Young-Suk; Al Otaiba, Stephanie; Crowe, Elizabeth C.; Thomas-Tate, Shurita; Johnson, Lakeisha Cooper; Lonigan, Christopher J.

2015-01-01

This paper describes the theoretical framework, as well as the development and testing of the intervention, Comprehension Tools for Teachers (CTT), which is composed of eight component interventions targeting malleable language and reading comprehension skills that emerging research indicates contribute to proficient reading for understanding for prekindergarteners through fourth graders. Component interventions target processes considered largely automatic as well as more reflective processes, with interacting and reciprocal effects. Specifically, we present component interventions targeting cognitive, linguistic, and text-specific processes, including morphological awareness, syntax, mental-state verbs, comprehension monitoring, narrative and expository text structure, enacted comprehension, academic knowledge, and reading to learn from informational text. Our aim was to develop a tool set composed of intensive meaningful individualized small group interventions. We improved feasibility in regular classrooms through the use of design-based iterative research methods including careful lesson planning, targeted scripting, pre- and postintervention proximal assessments, and technology. In addition to the overall framework, we discuss seven of the component interventions and general results of design and efficacy studies. PMID:26500420

Effects of target typicality on categorical search.

PubMed

Maxfield, Justin T; Stalder, Westri D; Zelinsky, Gregory J

2014-10-01

The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary. © 2014 ARVO.

The Role of Ubiquitin E3 Ligase SCF-SKP2 in Prostate Cancer Development

DTIC Science & Technology

2007-02-01

2004; 303:1371-4. 26. Nag A, Bondar T, Shiv S, Raychaudhuri P. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A...ubiquitin ligases. Nat Rev Mol Cell Biol 2005; 6:9-20. 2. Nag A, Bondar T, Shiv S, Raychaudhuri P. The xeroderma pigmentosum group E gene product DDB2 is... xeroderma pigmentosum group E patient and the subsequent inability to bind DDB1 (ref. 16). This motif is present in most of the WDR proteins we found (see

A new method of identifying target groups for pronatalist policy applied to Australia

PubMed Central

Chen, Mengni; Lloyd, Chris J.

2018-01-01

A country’s total fertility rate (TFR) depends on many factors. Attributing changes in TFR to changes of policy is difficult, as they could easily be correlated with changes in the unmeasured drivers of TFR. A case in point is Australia where both pronatalist effort and TFR increased in lock step from 2001 to 2008 and then decreased. The global financial crisis or other unobserved confounders might explain both the reducing TFR and pronatalist incentives after 2008. Therefore, it is difficult to estimate causal effects of policy using econometric techniques. The aim of this study is to instead look at the structure of the population to identify which subgroups most influence TFR. Specifically, we build a stochastic model relating TFR to the fertility rates of various subgroups and calculate elasticity of TFR with respect to each rate. For each subgroup, the ratio of its elasticity to its group size is used to evaluate the subgroup’s potential cost effectiveness as a pronatalist target. In addition, we measure the historical stability of group fertility rates, which measures propensity to change. Groups with a high effectiveness ratio and also high propensity to change are natural policy targets. We applied this new method to Australian data on fertility rates broken down by parity, age and marital status. The results show that targeting parity 3+ is more cost-effective than lower parities. This study contributes to the literature on pronatalist policies by investigating the targeting of policies, and generates important implications for formulating cost-effective policies. PMID:29425220

[Study on the hepatocytic cell targetability of liposomes].

PubMed

Hou, Xin-pu; Wang, Li; Wang, Xiang-tao; Li, Sha

2003-02-01

To target for hepatocytic cell, liposomes was modified by special ligand. Sterically stabilized liposomes (SSL) was conjugated with asialofeticin (AF), the ligand of asialoglycoprotein receptor (ASGP-R) of hepatocyte. ASGP-R-BLM is the ASGP-R reconstructed on bilayer lipid membrane (BLM). The recognition reaction between AF-SSL and ASGP-R-BLM can be monitored by the varieties of membrane electrical parameters. The targetability of AF-SSL mediated to hepatocyte was detected by radioisotopic labeled in vitro and in vivo. The therapeutic effect of antihepatocarcinoma was observed also. The lifetime of ASGP-R-BLM decreased with the added amount of AF-SSL. It was demonstrated that there was recognition reaction between AF-SSL and ASGP-R-BLM. The combination of AF-SSL with hepatocyte was significantly higher than that of SSL without AF-modified in vitro and in vivo. The survival time of rat for AF-SSL carriered ADM (adriamycin) group was much longer and the toxicities on heart, kidney and lung were lower than those SSL carried ADM group. It is possible to actively target the cell with specific receptor by ligand modified liposomes. The result prvide scientific basis of hepatocyte targeted liposomes.

Visual search in divided areas: dividers initially interfere with and later facilitate visual search.

PubMed

Nakashima, Ryoichi; Yokosawa, Kazuhiko

2013-02-01

A common search paradigm requires observers to search for a target among undivided spatial arrays of many items. Yet our visual environment is populated with items that are typically arranged within smaller (subdivided) spatial areas outlined by dividers (e.g., frames). It remains unclear how dividers impact visual search performance. In this study, we manipulated the presence and absence of frames and the number of frames subdividing search displays. Observers searched for a target O among Cs, a typically inefficient search task, and for a target C among Os, a typically efficient search. The results indicated that the presence of divider frames in a search display initially interferes with visual search tasks when targets are quickly detected (i.e., efficient search), leading to early interference; conversely, frames later facilitate visual search in tasks in which targets take longer to detect (i.e., inefficient search), leading to late facilitation. Such interference and facilitation appear only for conditions with a specific number of frames. Relative to previous studies of grouping (due to item proximity or similarity), these findings suggest that frame enclosures of multiple items may induce a grouping effect that influences search performance.

Development of Single-Stranded DNA Aptamers for Specific Bisphenol A Detection

PubMed Central

Jo, Minjoung; Ahn, Ji-Young; Lee, Joohyung; Lee, Seram; Hong, Sun Woo; Yoo, Jae-Wook; Kang, Jeehye; Dua, Pooja

2011-01-01

The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 1015 random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4′-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol–gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules. PMID:21413891

National Ignition Facility: Experimental plan

NASA Astrophysics Data System (ADS)

1994-05-01

As part of the Conceptual Design Report (CDR) for the National Ignition Facility (NIF), scientists from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), the University of Rochester's Laboratory for Laser Energetics (UR/LLE), and EG&G formed an NIF Target Diagnostics Working Group. The purpose of the Target Diagnostics Working Group is to prepare conceptual designs of target diagnostics for inclusion in the facility CDR and to determine how these specifications impact the CDR. To accomplish this, a subgroup has directed its efforts at constructing an approximate experimental plan for the ignition campaign of the NIF CDR. The results of this effort are contained in this document, the Experimental Plan for achieving fusion ignition in the NIF. This group initially concentrated on the flow-down requirements of the experimental campaign leading to ignition, which will dominate the initial efforts of the NIF. It is envisaged, however, that before ignition, there will be parallel campaigns supporting weapons physics, weapons effects, and other research. This plan was developed by analyzing the sequence of activities required to finally fire the laser at the level of power and precision necessary to achieve the conditions of an ignition hohlraum target, and to then use our experience in activating and running Nova experiments to estimate the rate of completing these activities.

Species-specific markers for the differential diagnosis of Trypanosoma cruzi and Trypanosoma rangeli and polymorphisms detection in Trypanosoma rangeli.

PubMed

Ferreira, Keila Adriana Magalhães; Fajardo, Emanuella Francisco; Baptista, Rodrigo P; Macedo, Andrea Mara; Lages-Silva, Eliane; Ramírez, Luis Eduardo; Pedrosa, André Luiz

2014-06-01

Trypanosoma cruzi and Trypanosoma rangeli are kinetoplastid parasites which are able to infect humans in Central and South America. Misdiagnosis between these trypanosomes can be avoided by targeting barcoding sequences or genes of each organism. This work aims to analyze the feasibility of using species-specific markers for identification of intraspecific polymorphisms and as target for diagnostic methods by PCR. Accordingly, primers which are able to specifically detect T. cruzi or T. rangeli genomic DNA were characterized. The use of intergenic regions, generally divergent in the trypanosomatids, and the serine carboxypeptidase gene were successful. Using T. rangeli genomic sequences for the identification of group-specific polymorphisms and a polymorphic AT(n) dinucleotide repeat permitted the classification of the strains into two groups, which are entirely coincident with T. rangeli main lineages, KP1 (+) and KP1 (-), previously determined by kinetoplast DNA (kDNA) characterization. The sequences analyzed totalize 622 bp (382 bp represent a hypothetical protein sequence, and 240 bp represent an anonymous sequence), and of these, 581 (93.3%) are conserved sites and 41 bp (6.7%) are polymorphic, with 9 transitions (21.9%), 2 transversions (4.9%), and 30 (73.2%) insertion/deletion events. Taken together, the species-specific markers analyzed may be useful for the development of new strategies for the accurate diagnosis of infections. Furthermore, the identification of T. rangeli polymorphisms has a direct impact in the understanding of the population structure of this parasite.

Descriptive Drinking Norms: For Whom Does Reference Group Matter?*

PubMed Central

Larimer, Mary E.; Neighbors, Clayton; LaBrie, Joseph W.; Atkins, David C.; Lewis, Melissa A.; Lee, Christine M.; Kilmer, Jason R.; Kaysen, Debra L.; Pedersen, Eric r.; Montoya, Heidi; Hodge, Kimberley; Desai, Sruti; Hummer, Justin F.; Walter, Theresa

2011-01-01

Objective: Perceived descriptive drinking norms often differ from actual norms and are positively related to personal consumption. However, it is not clear how normative perceptions vary with specificity of the reference group. Are drinking norms more accurate and more closely related to drinking behavior as reference group specificity increases? Do these relationships vary as a function of participant demographics? The present study examined the relationship between perceived descriptive norms and drinking behavior by ethnicity (Asian or White), sex, and fraternity/sorority status. Method: Participants were 2,699 (58% female) White (75%) or Asian (25%) undergraduates from two universities who reported their own alcohol use and perceived descriptive norms for eight reference groups: "typical student"; same sex, ethnicity, or fraternity/sorority status; and all combinations of these three factors. Results: Participants generally reported the highest perceived norms for the most distal reference group (typical student), with perceptions becoming more accurate as individuals' similarity to the reference group increased. Despite increased accuracy, participants perceived that all reference groups drank more than was actually the case. Across specific subgroups (fraternity/sorority members and men) different patterns emerged. Fraternity/sorority members reliably reported higher estimates of drinking for reference groups that included fraternity/ sorority status, and, to a lesser extent, men reported higher estimates for reference groups that included men. Conclusions: The results suggest that interventions targeting normative misperceptions may need to provide feedback based on participant demography or group membership. Although reference group-specific feedback may be important for some subgroups, typical student feedback provides the largest normative discrepancy for the majority of students. PMID:21906510

Tumor-specific novel taxoid-monoclonal antibody conjugates.

PubMed

Ojima, Iwao; Geng, Xudong; Wu, Xinyuan; Qu, Chuanxing; Borella, Christopher P; Xie, Hongsheng; Wilhelm, Sharon D; Leece, Barbara A; Bartle, Laura M; Goldmacher, Victor S; Chari, Ravi V J

2002-12-19

Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.

The Use of ICT to Support Students with Dyslexia

NASA Astrophysics Data System (ADS)

Diraä, Nadia; Engelen, Jan; Ghesquière, Pol; Neyens, Koen

The Katholieke Universiteit Leuven (K.U.Leuven) has a tradition of supporting students with a disability in order to guarantee equal opportunities to achieve their educational, personal and vocational goals. The K.U.Leuven policy is working towards inclusive education in the long term, by improving facilities and accommodation for certain target groups in the short term. Efforts have also been directed to make the learning environment more accessible for all kind of students, especially over the last few years. One of the target groups that has increasing numbers are students with learning disabilities (including dyslexia, dyscalculia, ...). To accommodate these students, the K.U.Leuven set off a project to evaluate the use of assistive technology (AT) for dyslexia. This small-scale study examined the experiences of two groups of students with dyslexia using 2 different software programs specifically developed to support this group of students. It was apparent that for students with dyslexia, reading and studying presents additional limitations which AT could facilitate to some extent.

Central neuronal motor behaviour in skilled and less skilled novices - Approaching sports-specific movement techniques.

PubMed

Vogt, Tobias; Kato, Kouki; Schneider, Stefan; Türk, Stefan; Kanosue, Kazuyuki

2017-04-01

Research on motor behavioural processes preceding voluntary movements often refers to analysing the readiness potential (RP). For this, decades of studies used laboratory setups with controlled sports-related actions. Further, recent applied approaches focus on athlete-non-athlete comparisons, omitting possible effects of training history on RP. However, RP preceding real sport-specific movements in accordance to skill acquisition remains to be elucidated. Therefore, after familiarization 16 right-handed males with no experience in archery volunteered to perform repeated sports-specific movements, i.e. 40 arrow-releasing shots at 60s rest on a 15m distant standard target. Continuous, synchronised EEG and right limb EMG recordings during arrow-releasing served to detect movement onsets for RP analyses over distinct cortical motor areas. Based on attained scores on target, archery novices were, a posteriori, subdivided into a skilled and less skilled group. EMG results for mean values revealed no significant changes (all p>0.05), whereas RP amplitudes and onsets differed between groups but not between motor areas. Arrow-releasing preceded larger RP amplitudes (p<0.05) and later RP onsets (p<0.05) in skilled compared to less skilled novices. We suggest this to reflect attentional orienting and greater effort that accompanies central neuronal preparatory states of a sports-specific movement. Copyright © 2017 Elsevier B.V. All rights reserved.

Substrate-Driven Mapping of the Degradome by Comparison of Sequence Logos

PubMed Central

Fuchs, Julian E.; von Grafenstein, Susanne; Huber, Roland G.; Kramer, Christian; Liedl, Klaus R.

2013-01-01

Sequence logos are frequently used to illustrate substrate preferences and specificity of proteases. Here, we employed the compiled substrates of the MEROPS database to introduce a novel metric for comparison of protease substrate preferences. The constructed similarity matrix of 62 proteases can be used to intuitively visualize similarities in protease substrate readout via principal component analysis and construction of protease specificity trees. Since our new metric is solely based on substrate data, we can engraft the protease tree including proteolytic enzymes of different evolutionary origin. Thereby, our analyses confirm pronounced overlaps in substrate recognition not only between proteases closely related on sequence basis but also between proteolytic enzymes of different evolutionary origin and catalytic type. To illustrate the applicability of our approach we analyze the distribution of targets of small molecules from the ChEMBL database in our substrate-based protease specificity trees. We observe a striking clustering of annotated targets in tree branches even though these grouped targets do not necessarily share similarity on protein sequence level. This highlights the value and applicability of knowledge acquired from peptide substrates in drug design of small molecules, e.g., for the prediction of off-target effects or drug repurposing. Consequently, our similarity metric allows to map the degradome and its associated drug target network via comparison of known substrate peptides. The substrate-driven view of protein-protein interfaces is not limited to the field of proteases but can be applied to any target class where a sufficient amount of known substrate data is available. PMID:24244149

Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

PubMed

Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

2018-01-01

Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2/show/NCT01115348.

Harnessing Solute Carrier Transporters for Precision Oncology.

PubMed

Nyquist, Michael D; Prasad, Bhagwat; Mostaghel, Elahe A

2017-03-28

Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions. In cancer however, there are dramatic changes in expression patterns of SLC transporters. This frequently serves to feed the increased metabolic demands of the tumor cell for amino acids, nucleotides and other metabolites, but also presents a therapeutic opportunity, as increased transporter expression may serve to increase intracellular concentrations of substrate drugs. In this review, we examine the regulation of drug transporters in cancer and how this impacts therapy response, and discuss novel approaches to targeting therapies to specific cancers via tumor-specific aberrations in transporter expression. We propose that among the oncogenic changes in SLC transporter expression there exist emergent vulnerabilities that can be exploited therapeutically, extending the application of precision medicine from tumor-specific drug targets to tumor-specific determinants of drug uptake.

Comparative study of group treatments for posttraumatic stress disorder.

PubMed

Maxwell, Kendal; Callahan, Jennifer L; Holtz, Pamela; Janis, Beth M; Gerber, Monica M; Connor, Dana R

2016-12-01

Presented herein is a comparative study of group treatments for posttraumatic stress disorder (PTSD). In this study, an emerging intervention, memory specificity training (MeST), was compared with cognitive processing therapy (CPT) using standardized outcome measures of target symptoms (i.e., anxiety and depression from client perspective; memory specificity from independent rater perspective) and global functioning (independent rater perspective), as well as a process measure of expectancy (client perspective). Clients were assessed on 3 separate occasions: at baseline, posttreatment, and 3 months posttreatment. Adherence and treatment fidelity (independent rater perspective) were monitored throughout the course of both treatment conditions. Improvement in PTSD symptoms, depressive symptoms, and global functioning were similar between MeST and CPT; an increase in ability to specify memories upon retrieval was also similar between MeST and CPT. Positive reliable change was observed in both groups on all outcome measures. With respect to the primary target of PTSD symptoms, 88% of participants in both treatment groups moved into the functional distribution by posttreatment and maintained these gains at follow-up. Notably, compared with CPT, MeST required only half the dosage (i.e., number of sessions) to accomplish these gains. Illustrative vignettes from client-therapist exchanges are provided, and results are discussed in terms of the potential mechanisms of action. Implications for both clinical practice and clinical research are also included. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Do motifs reflect evolved function?--No convergent evolution of genetic regulatory network subgraph topologies.

PubMed

Knabe, Johannes F; Nehaniv, Chrystopher L; Schilstra, Maria J

2008-01-01

Methods that analyse the topological structure of networks have recently become quite popular. Whether motifs (subgraph patterns that occur more often than in randomized networks) have specific functions as elementary computational circuits has been cause for debate. As the question is difficult to resolve with currently available biological data, we approach the issue using networks that abstractly model natural genetic regulatory networks (GRNs) which are evolved to show dynamical behaviors. Specifically one group of networks was evolved to be capable of exhibiting two different behaviors ("differentiation") in contrast to a group with a single target behavior. In both groups we find motif distribution differences within the groups to be larger than differences between them, indicating that evolutionary niches (target functions) do not necessarily mold network structure uniquely. These results show that variability operators can have a stronger influence on network topologies than selection pressures, especially when many topologies can create similar dynamics. Moreover, analysis of motif functional relevance by lesioning did not suggest that motifs were of greater importance to the functioning of the network than arbitrary subgraph patterns. Only when drastically restricting network size, so that one motif corresponds to a whole functionally evolved network, was preference for particular connection patterns found. This suggests that in non-restricted, bigger networks, entanglement with the rest of the network hinders topological subgraph analysis.

Discrimination of the Lactobacillus acidophilus group using sequencing, species-specific PCR and SNaPshot mini-sequencing technology based on the recA gene.

PubMed

Huang, Chien-Hsun; Chang, Mu-Tzu; Huang, Mu-Chiou; Wang, Li-Tin; Huang, Lina; Lee, Fwu-Ling

2012-10-01

To clearly identify specific species and subspecies of the Lactobacillus acidophilus group using phenotypic and genotypic (16S rDNA sequence analysis) techniques alone is difficult. The aim of this study was to use the recA gene for species discrimination in the L. acidophilus group, as well as to develop a species-specific primer and single nucleotide polymorphism primer based on the recA gene sequence for species and subspecies identification. The average sequence similarity for the recA gene among type strains was 80.0%, and most members of the L. acidophilus group could be clearly distinguished. The species-specific primer was designed according to the recA gene sequencing, which was employed for polymerase chain reaction with the template DNA of Lactobacillus strains. A single 231-bp species-specific band was found only in L. delbrueckii. A SNaPshot mini-sequencing assay using recA as a target gene was also developed. The specificity of the mini-sequencing assay was evaluated using 31 strains of L. delbrueckii species and was able to unambiguously discriminate strains belonging to the subspecies L. delbrueckii subsp. bulgaricus. The phylogenetic relationships of most strains in the L. acidophilus group can be resolved using recA gene sequencing, and a novel method to identify the species and subspecies of the L. delbrueckii and L. delbrueckii subsp. bulgaricus was developed by species-specific polymerase chain reaction combined with SNaPshot mini-sequencing. Copyright © 2012 Society of Chemical Industry.

Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details.

PubMed

Buffel du Vaure, Céline; Dechartres, Agnès; Battin, Constance; Ravaud, Philippe; Boutron, Isabelle

2016-09-27

To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. Systematic review of trial registration records. ClinicalTrials.gov register. All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size ≥100. From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co-occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Validation of Personal Digital Photography to Assess Dietary Quality among People with Intellectual Disabilities

ERIC Educational Resources Information Center

Elinder, L. S.; Brunosson, A.; Bergstrom, H.; Hagstromer, M.; Patterson, E.

2012-01-01

Background: Dietary assessment is a challenge in general, and specifically in individuals with intellectual disabilities (ID). This study aimed to evaluate personal digital photography as a method of assessing different aspects of dietary quality in this target group. Method: Eighteen adults with ID were recruited from community residences and…

20 CFR 1010.210 - In which Department job training programs do covered persons receive priority of service?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Any such program or service that uses technology to assist individuals to access workforce development programs (such as job and training opportunities, labor market information, career assessment tools, and... program; any workforce development program targeted to specific groups; and those programs implemented by...

20 CFR 1010.210 - In which Department job training programs do covered persons receive priority of service?

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Any such program or service that uses technology to assist individuals to access workforce development programs (such as job and training opportunities, labor market information, career assessment tools, and... program; any workforce development program targeted to specific groups; and those programs implemented by...

Warning: This Television Advertisement May Be Hazardous to Your Self-Concept.

ERIC Educational Resources Information Center

Bedore, Joan M.

A study which reviewed the research literature analyzed the relationship between television advertisements and the lowering of the self concept. Although television advertising has a relatively short history, today a person can hardly escape from it. Advertisements are specifically targeted to age-related and demographic groups. By focusing on…

34 CFR 491.21 - What selection criteria does the Secretary use?

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Support services must be designed to bring members of the target group to a state of readiness for... application to determine the extent to which— (1) The program design is tailored to the literacy and basic skills needs of the specific homeless population being served (for example, designs to address the...

Near-infrared fluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis

PubMed Central

Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Shi, Changhong; Li, Qinlong; Hu, Peizhen; Chen, Yi-Ting; Dou, Xiaoliang; Sahu, Divya; Li, Wei; Harada, Hiroshi; Zhang, Yi; Wang, Ruoxiang; Zhau, Haiyen E.; Chung, Leland W.K.

2014-01-01

Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the mechanistic properties of a specific group of NIR heptamethine carbocyanines including MHI-148 dye we identified and synthesized, and demonstrated these dyes to achieve cancer-specific imaging and targeting via a hypoxia-mediated mechanism. We found that cancer cells and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake in vitro and in vivo, which was directly mediated by hypoxia-inducible factor 1α (HIF1α). Microarray analysis and dye uptake assay further revealed a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) responsible for dye uptake, and the correlation between OATPs and HIF1α was manifested in progressive clinical cancer specimens. Finally, we demonstrated increased uptake of MHI-148 dye in situ in perfused clinical tumor samples with activated HIF1α/OATPs signaling. Our results establish these NIRF dyes as potential tumor hypoxia-dependent cancer-targeting agents and provide a mechanistic rationale for continued development of NIRF imaging agents for improved cancer detection, prognosis and therapy. PMID:24957295

Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement

PubMed Central

Graf, Christine; Beneke, Ralph; Bloch, Wilhelm; Bucksch, Jens; Dordel, Sigrid; Eiser, Stefanie; Ferrari, Nina; Koch, Benjamin; Krug, Susanne; Lawrenz, Wolfgang; Manz, Kristin; Naul, Roland; Oberhoffer, Renate; Quilling, Eike; Schulz, Henry; Stemper, Theo; Stibbe, Günter; Tokarski, Walter; Völker, Klaus; Woll, Alexander

2014-01-01

Increasing physical activity and reduction of sedentary behaviour play important roles in health promotion and prevention of lifestyle-related diseases in children and adolescents. However, the question of how much physical activity is useful for which target group is still a matter of debate. International guidelines (World Health Organization; European Association for the Study of Obesity), which are mainly based on expert opinions, recommend 60 min of physical activity every day. Age- and sex-specific features and regional differences are not taken into account. Therefore, expert consensus recommendations for promoting physical activity of children and adolescents in Germany were developed with special respect to national data, but also with respect to aspects of specific target groups, e.g., children with a lower socio-economic status (SES) or with migration background. They propose 90 min/day of physical activity, or at least 12,000 steps daily. Additionally, lifestyle factors, especially restriction of media consumption, were integrated. The recommendations provide orientation for parents and caregivers, for institutions such as schools and kindergartens as well as for communities and stakeholders. PMID:24821136

Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine.

PubMed

Belwal, Tarun; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Habtemariam, Solomon

2017-10-12

Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic β-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent hyperglycemia (diabetes), hyperinsulinemia, fatty acids and/or lipid dysregulation which are often prevalent under obesity conditions. Hence, insulin sensitizers are one class of drugs currently employed to treat diabetes and associated metabolic disorders. A number of natural products that act through multiple mechanisms have also been identified to enhance insulin sensitivity in target organs. One group of such compounds that gained interest in recent years are the dietary anthocyanins. Data from their in vitro, in vivo and clinical studies are scrutinized in this communication to show their potential health benefit through ameliorating insulin resistance. Specific mechanism of action ranging from targeting specific signal transduction receptors/enzymes to the general antioxidant and anti-inflammatory mechanisms of insulin resistance are presented.

ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage

PubMed Central

Peng, Xiaohua; Gandhi, Varsha

2013-01-01

Targeting tumor cells is an important strategy to improve the selectivity of cancer therapies. With the advanced studies in cancer biology, we know that cancer cells are usually under increased oxidative stress. The high level of reactive oxygen species in cancer cells has been exploited for developing novel therapeutic strategies to preferentially kill cancer cells. Our group, amongst others, have used boronic acids/esters as triggers for developing ROS-activated anticancer prodrugs that target cancer cells. The selectivity was achieved by combining a specific reaction between boronates and H2O2 with the efficient masking of drug toxicity in the prodrug via boronates. Prodrugs activated via ferrocene-mediated oxidation have also been developed to improve the selectivity of anticancer drugs. We describe how the strategies of ROS-activation can be used for further development of new ROS-targeting prodrugs, eventually leading to novel approaches and/or combined technology for more efficient and selective treatment of cancers. PMID:22900465

Dual-Responsive Metabolic Precursor and Light-Up AIEgen for Cancer Cell Bio-orthogonal Labeling and Precise Ablation.

PubMed

Hu, Fang; Yuan, Youyong; Wu, Wenbo; Mao, Duo; Liu, Bin

2018-06-05

Metabolic glycoengineering of unnatural glycans with bio-orthogonal chemical groups and a subsequent click reaction with fluorescent probes have been widely used in monitoring various bioprocesses. Herein, we developed a dual-responsive metabolic precursor that could specifically generate unnatural glycans with azide groups on the membrane of targeted cancer cells with high selectivity. Moreover, a water-soluble fluorescent light-up probe with aggregation-induced emission (AIE) was synthesized, which turned its fluorescence on upon a click reaction with azide groups on the cancer cell surface, enabling special cancer cell imaging with low background signal. Furthermore, the probe can generate 1 O 2 upon light irradiation, fulfilling its dual role as an imaging and therapeutic agent for cancer cells. Therefore, the concepts of the cancer-cell-specific metabolic precursor cRGD-S-Ac 3 ManNAz and the AIE light-up probe are promising in bio-orthogonal labeling and cancer-specific imaging and therapy.

A real-time polymerase chain reaction assay for the detection of Mycoplasma agalactiae.

PubMed

Fitzmaurice, J; Sewell, M; King, C M; McDougall, S; McDonald, W L; O'Keefe, J S

2008-10-01

To develop a real-time PCR for the detection of Mycoplasma agalactiae, using PCR primers targeting the ma-mp81 gene. A group of 15 M. agalactiae isolates, 21 other Mycoplasma spp. isolates and 21 other bacterial isolates was used in evaluation of the assay. All M. agalactiae isolates were detected by the assay and none of the non-target isolates was amplified. The analytical detection limit of the assay was 10 fg of purified genomic DNA and 104 cfu/ml milk inoculated with M. agalactiae. When applied to goat-milk samples collected from three herds free of M. agalactiae infection, the assay had a specificity of 100%. The assay would be useful in a diagnostic laboratory, providing specific, sensitive and rapid detection of M. agalactiae.

Enhancing Cognitive Abilities with Comprehensive Training: A Large, Online, Randomized, Active-Controlled Trial

PubMed Central

Hardy, Joseph L.; Nelson, Rolf A.; Thomason, Moriah E.; Sternberg, Daniel A.; Katovich, Kiefer; Farzin, Faraz; Scanlon, Michael

2015-01-01

Background A variety of studies have demonstrated gains in cognitive ability following cognitive training interventions. However, other studies have not shown such gains, and questions remain regarding the efficacy of specific cognitive training interventions. Cognitive training research often involves programs made up of just one or a few exercises, targeting limited and specific cognitive endpoints. In addition, cognitive training studies typically involve small samples that may be insufficient for reliable measurement of change. Other studies have utilized training periods that were too short to generate reliable gains in cognitive performance. Methods The present study evaluated an online cognitive training program comprised of 49 exercises targeting a variety of cognitive capacities. The cognitive training program was compared to an active control condition in which participants completed crossword puzzles. All participants were recruited, trained, and tested online (N = 4,715 fully evaluable participants). Participants in both groups were instructed to complete one approximately 15-minute session at least 5 days per week for 10 weeks. Results Participants randomly assigned to the treatment group improved significantly more on the primary outcome measure, an aggregate measure of neuropsychological performance, than did the active control group (Cohen’s d effect size = 0.255; 95% confidence interval = [0.198, 0.312]). Treatment participants showed greater improvements than controls on speed of processing, short-term memory, working memory, problem solving, and fluid reasoning assessments. Participants in the treatment group also showed greater improvements on self-reported measures of cognitive functioning, particularly on those items related to concentration compared to the control group (Cohen’s d = 0.249; 95% confidence interval = [0.191, 0.306]). Conclusion Taken together, these results indicate that a varied training program composed of a number of tasks targeted to different cognitive functions can show transfer to a wide range of untrained measures of cognitive performance. Trial Registration ClinicalTrials.gov NCT-02367898 PMID:26333022

A Systematic Review of Promising Strategies of Faith-Based Cancer Education and Lifestyle Interventions Among Racial/Ethnic Minority Groups.

PubMed

Hou, Su-I; Cao, Xian

2017-09-13

Church-based interventions have been used to reach racial/ethnic minorities. In order to develop effective programs, we conducted a comprehensive systematic review of faith-based cancer prevention studies (2005~2016) to examine characteristics and promising strategies. Combination terms "church or faith-based or religion," "intervention or program," and "cancer education or lifestyle" were used in searching the five major databases: CINAHL; ERIC; Health Technology Assessments; MEDLINE; and PsycInfo. A total of 20 studies met study criteria. CDC's Community Guide was used to analyze and review group interventions. Analyses were organized by two racial groups: African American (AA) and Latino/Hispanic American groups. Results showed most studies reviewed focused on breast cancer alone or in combination with other cancers. Studies of Latino/Hispanic groups targeted more on uninsured, Medicare, or Medicaid individuals, whereas AA studies generally did not include specific insurance criteria. The sample sizes of the AA studies were generally larger. The majority of these studies reviewed used pre-post, posttest only with control group, or quasi-experience designs. The Health Belief Model was the most commonly used theory in both groups. Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies. Small media and group education were the top two most popular intervention strategies in both groups. Although one-on-one strategy was used in some Latino studies, neither group used reducing client out-of-pocket costs strategy. Client reminders could also be used more in both groups as well. Current review showed church-based cancer education programs were effective in changing knowledge, but not always screening utilization. Results show faith-based cancer educational interventions are promising. To maximize intervention impact, future studies might consider using stronger study designs, incorporating a variety of proven effective strategies, including those frequently used evidence-based strategies, as well as exploring promising strategies among specific target groups.

Clinical and psychosocial predictors of exceeding target length of stay during inpatient stroke rehabilitation.

PubMed

Lai, Wesley; Buttineau, Mackenzie; Harvey, Jennifer K; Pucci, Rebecca A; Wong, Anna P M; Dell'Erario, Linda; Bosnyak, Stephanie; Reid, Shannon; Salbach, Nancy M

2017-10-01

In Ontario, Canada, patients admitted to inpatient rehabilitation hospitals post-stroke are classified into rehabilitation patient groups based on age and functional level. Clinical practice guidelines, called quality-based procedures, recommend a target length of stay (LOS) for each group. The study objective was to evaluate the extent to which patients post-stroke at an inpatient rehabilitation hospital are meeting LOS targets and to identify patient characteristics that predict exceeding target LOS. A quantitative, longitudinal study from an inpatient rehabilitation hospital was conducted. Participants included adult patients (≥18 years) with stroke, admitted to an inpatient rehabilitation hospital between 2014 and 2015. The percentage of patients exceeding the recommended target LOS was determined. Logistic regression was performed to identify clinical and psychosocial patient characteristics associated with exceeding target LOS after adjusting for stroke severity. Of 165 patients, 38.8% exceeded their target LOS. Presence of ataxia, recurrent stroke, living alone, absence of a caregiver at admission, and acquiring a caregiver during hospital LOS was each associated with significantly higher odds of exceeding target LOS in comparison to patients without these characteristics after adjusting for stroke severity (p < 0.05). Findings suggest that social and stroke-specific factors may be helpful to adjust LOS expectations and promote efficient resource allocation. This exploratory study was limited to findings from one inpatient rehabilitation hospital. Cross-validation of results using data-sets from multiple rehabilitation hospitals across Ontario is recommended.

Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder

PubMed Central

Hill, S. Kristian; Gold, James M.; Keefe, Richard S. E.; Clementz, Brett A.; Gershon, Elliot; Keshavan, Matcheri S.; Pearlson, Godfrey; Tamminga, Carol A.; Sweeney, John A.

2017-01-01

Abstract Background: Context processing may reflect a specific cognitive impairment in schizophrenia. Whether impaired context processing is observed across psychotic disorders or among relatives of affected individuals, and whether it is a deficit that is independent from the generalized neuropsychological deficits seen in psychotic disorders, are less established. Methods: Schizophrenia, schizoaffective, and psychotic bipolar probands (n = 660), their first-degree relatives (n = 741), and healthy individuals (n = 308) studied by the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium performed an expectancy task requiring use of contextual information to overcome a pre-potent response. Sensitivity for target detection and false alarm rates on trials requiring inhibition or goal maintenance were measured. Results: Proband groups and relatives with psychosis spectrum personality traits demonstrated reduced target sensitivity and elevated false alarm rates. False alarm rate was higher under inhibition vs goal maintenance conditions although this difference was attenuated in schizophrenia and schizoaffective proband groups. After accounting for global neuropsychological impairment, as reflected by the composite score from the Brief Assessment of Cognition in Schizophrenia neuropsychological battery, deficits in schizophrenia and bipolar proband groups were no longer significant. Performance measures were moderately familial. Conclusion: Reduced target detection, but not a specific deficit in context processing, is observed across psychotic disorders. Impairments in both goal maintenance and response inhibition appear to contribute comparably to deficits in schizophrenia and schizoaffective disorder, whereas greater difficulty with response inhibition underlies deficits in bipolar disorder. Yet, these deficits are not independent from the generalized neurocognitive impairment observed in schizophrenia and psychotic bipolar disorder. PMID:27306316

Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.

PubMed

Jaruratanasirikul, Sutep; Wongpoowarak, Wibul; Jullangkoon, Monchana; Samaeng, Maseetoh

2015-02-01

The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g q6h for 8 doses. A Monte Carlo simulation was performed to determine the PTA. The volume of distribution and total clearance of imipenem were 20.78 ± 1.35 l and 23.19 ± 1.34 l/h, respectively. Only a 4-h infusion of 1 g q6h regimen achieved a PTA >93% for 80% T>MIC for a MIC of 2 μg/ml. A 4-h infusion of all simulated regimens and a 0.5-h infusion of 0.5 g q6h and 1 g q6h achieved targets (CFR ≥ 90%) against Escherichia coli and Klebsiella spp. However, against Pseudomonas aeruginosa and Acinetobacter spp., no regimens achieved their targets. In conclusion, the results indicate that a higher than manufacturer's dosage recommendation is required to maximize the activity of imipenem. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

PubMed

Luscan, A; Just, P A; Briand, A; Burin des Roziers, C; Goussard, P; Nitschké, P; Vidaud, M; Avril, M F; Terris, B; Pasmant, E

2015-04-01

Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies. 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.

Using focus groups and social marketing to strengthen promotion of group prenatal care.

PubMed

Vonderheid, Susan C; Carrie, S Klima; Norr, Kathleen F; Grady, Mary Alice; Westdahl, Claire M

2013-01-01

Centering Pregnancy, an innovative group model of prenatal care, shows promise to reduce persistent adverse maternal-infant outcomes and contain costs. Because this innovation requires systemwide change, clinics reported needing support enrolling women into groups and obtaining organizational buy-in. This study used the 3-step social marketing communication strategy to help clinic staff identify key customers and customer-specific barriers to adopting or supporting Centering Pregnancy. They developed targeted information to reduce barriers and built skills in communicating with different customers through role-playing. Findings provide practical information for others to use this communication strategy to improve implementation of Centering Pregnancy.

Do children with dyslexia and/or specific language impairment compensate for place assimilation? Insight into phonological grammar and representations.

PubMed

Marshall, Chloe R; Ramus, Franck; van der Lely, Heather

2011-10-01

English speakers have to recognize, for example, that te[m] in te[m] pens is a form of ten, despite place assimilation of the nasal consonant. Children with dyslexia and specific language impairment (SLI) are commonly proposed to have a phonological deficit, and we investigate whether that deficit extends to place assimilation, as a way of probing phonological representations and phonological grammar. Children with SLI plus dyslexia, SLI only, and dyslexia only listened to sentences containing a target word in different assimilatory contexts-viable, unviable, and no change-and pressed a button to report hearing the target. The dyslexia-only group did not differ from age-matched controls, but the SLI groups showed more limited ability to accurately identify words within sentences. Once this factor was taken into account, the groups did not differ in their ability to compensate for assimilation. The results add to a growing body of evidence that phonological representations are not necessarily impaired in dyslexia. SLI children's results suggest that they too are sensitive to this aspect of phonological grammar, but are more liberal in their acceptance of alternative phonological forms of words. Furthermore, these children's ability to reject alternative phonological forms seems to be primarily limited by their vocabulary size and phonological awareness abilities.

Performance of a New Blunt-Tip Coaxial Needle for Percutaneous Biopsy and Drainage of "Hard-To-Reach" Targets.

PubMed

Cazzato, Roberto Luigi; Garnon, Julien; Shaygi, Behnam; Caudrelier, Jean; Bauones, Salem; Tsoumakidou, Georgia; Koch, Guillaume; Gangi, Afshin

2017-09-01

To present a new blunt-tip coaxial needle (SoftGuard) applied to access "hard-to-reach" targets undergoing percutaneous image-guided biopsy or drainage. All consecutive patients presenting between August and December 2016 with "hard-to-reach" (<10 mm from a critical nearby structure such as vessels, nerves, bowel or adjacent parenchymal organs) solid lesions requiring biopsy (group A) or abscesses requiring drainage for sepsis (group B) were prospectively included. The individual features of each patient and lesion as well as technical and clinical data were collected and analysed. Twenty-six patients (18 males, 8 females, mean age 59.81 ± 17.53 years) were enrolled in group A and nine (6 males, 3 females, mean age 58.33 ± 13.8 years) in group B. Technical success was achieved in 92.3% of cases from group A and 100% of cases from group B. Five (19.2%) minor complications were noted in group A (four small self-limiting pneumothoraces and one small self-limiting peri-pancreatic haematoma). There were no complications in group B. Histological results in group A accounted for 95% sensitivity, 100% specificity and 95.2% diagnostic accuracy. In group B, mean post-operative C-reactive protein was 41 ± 48.3 mg/L in comparison with 155 ± 117.5 mg/L at baseline (P = 0.004). The SoftGuard blunt-tip needle is a safe and effective tool when applied as a coaxial working cannula for percutaneous biopsy or drainage of "hard-to-reach" targets.

1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

PubMed Central

Velena, Astrida; Zarkovic, Neven; Gall Troselj, Koraljka; Bisenieks, Egils; Krauze, Aivars; Poikans, Janis; Duburs, Gunars

2016-01-01

Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry. PMID:26881016

FOAM (Functional Ontology Assignments for Metagenomes): A Hidden Markov Model (HMM) database with environmental focus

DOE PAGES

Prestat, Emmanuel; David, Maude M.; Hultman, Jenni; ...

2014-09-26

A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associatedmore » functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/.« less

Grouping and trajectory storage in multiple object tracking: impairments due to common item motions.

PubMed

Suganuma, Mutsumi; Yokosawa, Kazuhiko

2006-01-01

In our natural viewing, we notice that objects change their locations across space and time. However, there has been relatively little consideration of the role of motion information in the construction and maintenance of object representations. We investigated this question in the context of the multiple object tracking (MOT) paradigm, wherein observers must keep track of target objects as they move randomly amid featurally identical distractors. In three experiments, we observed impairments in tracking ability when the motions of the target and distractor items shared particular properties. Specifically, we observed impairments when the target and distractor items were in a chasing relationship or moved in a uniform direction. Surprisingly, tracking ability was impaired by these manipulations even when observers failed to notice them. Our results suggest that differentiable trajectory information is an important factor in successful performance of MOT tasks. More generally, these results suggest that various types of common motion can serve as cues to form more global object representations even in the absence of other grouping cues.

Biocidal Inactivation of Lactococcus lactis Bacteriophages: Efficacy and Targets of Commonly Used Sanitizers

PubMed Central

Hayes, Stephen; Murphy, James; Mahony, Jennifer; Lugli, Gabriele A.; Ventura, Marco; Noben, Jean-Paul; Franz, Charles M. A. P.; Neve, Horst; Nauta, Arjen; Van Sinderen, Douwe

2017-01-01

Lactococcus lactis strains, being intensely used in the dairy industry, are particularly vulnerable to members of the so-called 936 group of phages. Sanitization and disinfection using purpose-made biocidal solutions is a critical step in controlling phage contamination in such dairy processing plants. The susceptibility of 36 936 group phages to biocidal treatments was examined using 14 biocides and commercially available sanitizers. The targets of a number of these biocides were investigated by means of electron microscopic and proteomic analyses. The results from this study highlight significant variations in phage resistance to biocides among 936 phages. Furthermore, rather than possessing resistance to specific biocides or biocide types, biocide-resistant phages tend to possess a broad tolerance to multiple classes of antimicrobial compounds. PMID:28210242

Blood grouping based on PCR methods and agarose gel electrophoresis.

PubMed

Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

2015-01-01

The study of erythrocyte antigens continues to be an intense field of research, particularly after the development of molecular testing methods. More than 300 specificities have been described by the International Society for Blood Transfusion as belonging to 33 blood group systems. The polymerase chain reaction (PCR) is a central tool for red blood cells (RBC) genotyping. PCR and agarose gel electrophoresis are low cost, easy, and versatile in vitro methods for amplifying defined target DNA (RBC polymorphic region). Multiplex-PCR, AS-PCR (Specific Allele Polymerase Chain Reaction), and RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) techniques are usually to identify RBC polymorphisms. Furthermore, it is an easy methodology to implement. This chapter describes the PCR methodology and agarose gel electrophoresis to identify the polymorphisms of the Kell, Duffy, Kidd, and MNS blood group systems.

Single-carbon discrimination by selected peptides for individual detection of volatile organic compounds

NASA Astrophysics Data System (ADS)

Ju, Soomi; Lee, Ki-Young; Min, Sun-Joon; Yoo, Yong Kyoung; Hwang, Kyo Seon; Kim, Sang Kyung; Yi, Hyunjung

2015-03-01

Although volatile organic compounds (VOCs) are becoming increasingly recognized as harmful agents and potential biomarkers, selective detection of the organic targets remains a tremendous challenge. Among the materials being investigated for target recognition, peptides are attractive candidates because of their chemical robustness, divergence, and their homology to natural olfactory receptors. Using a combinatorial peptide library and either a graphitic surface or phenyl-terminated self-assembled monolayer as relevant target surfaces, we successfully selected three interesting peptides that differentiate a single carbon deviation among benzene and its analogues. The heterogeneity of the designed target surfaces provided peptides with varying affinity toward targeted molecules and generated a set of selective peptides that complemented each other. Microcantilever sensors conjugated with each peptide quantitated benzene, toluene and xylene to sub-ppm levels in real time. The selection of specific receptors for a group of volatile molecules will provide a strong foundation for general approach to individually monitoring VOCs.

Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study.

PubMed

Slover, Robert H; Welsh, John B; Criego, Amy; Weinzimer, Stuart A; Willi, Steven M; Wood, Michael A; Tamborlane, William V

2012-02-01

Maintenance of appropriate A1C values and minimization of hyperglycemic excursions are difficult for many pediatric patients with type 1 diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy is an alternative to multiple daily injection (MDI) therapy in this population. Sensor-augmented pump therapy for A1C reduction (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74 adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from all subjects. CGM studies were carried out at baseline, 6 months, and 12 months to quantify glycemic excursions [calculated as area under the glucose concentration-time curve (AUC)] and variability. In the SAP group, sensor compliance was recorded. Baseline A1C values were similar in subjects randomized to the SAP (8.26 ± 0.55%) and MDI groups (8.30 ± 0.53%). All subsequent A1C values showed significant (p < 0.05) treatment group differences favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were more likely to meet age-specific A1C targets and had lower AUC values for hyperglycemia with no increased risk of hypoglycemia. Glucose variability improved in the SAP group compared to the MDI group. Children wore CGM sensors more often and were more likely to reach age-specific A1C targets than adolescents. SAP therapy allows both children and adolescents with marginally or inadequately controlled type 1 diabetes to reduce A1C values, hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and safe manner. © 2011 John Wiley & Sons A/S.

Innovation in the Prevention of the Use of Child Soldiers: Women in the Security Sector

DTIC Science & Technology

2016-03-01

armed group in any capacity, including but not limited to children, boys and girls , used as fighters, cooks, porters, messengers, spies or for sexual...and girls are specifically targeted for human rights viola- tions because of their gendered roles in society. Whi le s exua l v io lence i s un...about the presence of girl soldiers in the armed groups and forces. Each time the question was posed, the response was “there are no girl sol

Docking and scoring protein interactions: CAPRI 2009.

PubMed

Lensink, Marc F; Wodak, Shoshana J

2010-11-15

Protein docking algorithms are assessed by evaluating blind predictions performed during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical assessment of predicted interactions (CAPRI). We evaluated the ability of these algorithms to sample docking poses and to single out specific association modes in 14 targets, representing 11 distinct protein complexes. These complexes play important biological roles in RNA maturation, G-protein signal processing, and enzyme inhibition and function. One target involved protein-RNA interactions not previously considered in CAPRI, several others were hetero-oligomers, or featured multiple interfaces between the same protein pair. For most targets, predictions started from the experimentally determined structures of the free (unbound) components, or from models built from known structures of related or similar proteins. To succeed they therefore needed to account for conformational changes and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking predictions of which 4420 were evaluated. Overall our assessment reveals that 67% of the groups, more than ever before, produced acceptable models or better for at least one target, with many groups submitting multiple high- and medium-accuracy models for two to six targets. Forty-one groups including four web-servers participated in the scoring experiment with 1296 evaluated models. Scoring predictions also show signs of progress evidenced from the large proportion of correct models submitted. But singling out the best models remains a challenge, which also adversely affects the ability to correctly rank docking models. With the increased interest in translating abstract protein interaction networks into realistic models of protein assemblies, the growing CAPRI community is actively developing more efficient and reliable docking and scoring methods for everyone to use. © 2010 Wiley-Liss, Inc.

Australasian Gastrointestinal Trials Group (AGITG) Contouring Atlas and Planning Guidelines for Intensity-Modulated Radiotherapy in Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Michael, E-mail: mng@radoncvic.com.au; Leong, Trevor; University of Melbourne

2012-08-01

Purpose: To develop a high-resolution target volume atlas with intensity-modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of anal cancer. Methods and Materials: A draft contouring atlas and planning guidelines for anal cancer IMRT were prepared at the Australasian Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert panel of radiation oncologists contoured an anal cancer case to generate discussion on recommendations regarding target definition for gross disease, elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV) and planning target volume (PTV) margins, dose fractionation, and other IMRT-specific issues were also addressed. A steeringmore » committee produced the final consensus guidelines. Results: Detailed contouring and planning guidelines and a high-resolution atlas are provided. Gross tumor and elective target volumes are described and pictorially depicted. All elective regions should be routinely contoured for all disease stages, with the possible exception of the inguinal and high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the elective pelvic nodal groups are recommended, while respecting anatomical boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and 45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided for OAR delineation. Conclusion: These consensus planning guidelines and high-resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG) elective nodal ano-rectal atlas and provide additional anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of IMRT for anal cancer.« less

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PubMed

De Bellis, A; Dello Iacovo, A; Bellastella, G; Savoia, A; Cozzolino, D; Sinisi, A A; Bizzarro, A; Bellastella, A; Giugliano, D

2014-10-01

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate.

PubMed

Cogan, Peter S; Koch, Tad H

2003-11-20

The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the 3'-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a (3)H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.

Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

PubMed Central

Firor, Amelia E.; Pinz, Kevin G.; Jares, Alexander; Liu, Hua; Salman, Huda; Golightly, Marc; Lan, Fengshuo; Jiang, Xun; Ma, Yupo

2016-01-01

Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target - CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs. PMID:27494836

Targeting Apoptosis for Optical Imaging of Infection

PubMed Central

Thakur, Mathew L.; Zhang, Kaijun; Paudyal, Bishnuhari; Devakumar, Devadhas; Covarrubias, Maria Y.; Cheng, Changpo; Gray, Brian D.; Wickstrom, Eric; Pak, Koon Y.

2018-01-01

Purpose Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging. Methods Bacterial infection and sterile inflammation were induced in separate groups (n=5) of mice. PS was targeted with a NIR fluorophore, PSVue®794 (2.7 pmol). Imaging was performed (ex=730 nm, em=830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity. Results Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6±0.2) were greater than those in inflammation (3.2±0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS. Conclusions Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection. PMID:21538153

Stimuli-free programmable drug release for combination chemo-therapy

NASA Astrophysics Data System (ADS)

Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

2016-06-01

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06305a

A distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-30

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

PubMed Central

2015-01-01

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

Pyropheophorbide A and c(RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy.

PubMed

Zhou, Aiguo; Wei, Yanchun; Wu, Baoyan; Chen, Qun; Xing, Da

2012-06-04

Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-RGD was developed for targeted near-infrared photodynamic therapy. The properties of UCNP-Ppa-RGD, such as morphology, stability, optical spectroscopy and singlet oxygen generation efficiency, were investigated. The results show that covalently linked pyropheophorbide a molecule not only is stable but also retains its spectroscopic and functional properties. In vitro studies confirm a stronger targeting specificity of UCNP-Ppa-RGD to integrin α(v)β(3)-positive U87-MG cells compared with that in the corresponding negative group. The photosensitizer-attached nanostructure exhibited low dark toxicity and high phototoxicity against cancer cells upon 980 nm laser irradiation at an appropriate dosage. These results represent the first demonstration of a highly stable and efficient photosensitizer modified upconversion nanostructure for targeted near-infrared photodynamic therapy of cancer cells. The novel UCNP-Ppa-RGD nanoparticle may provide a powerful alternative for near-infrared photodynamic therapy with an improved tumor targeting specificity.

A distributed computational search strategy for the identification of diagnostics targets: Application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-01

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

Bipartite networks improve understanding of effects of waterbody size and angling method on angler–fish interactions

USGS Publications Warehouse

Chizinski, Christopher J.; Martin, Dustin R.; Shizuka, Daizaburo; Pope, Kevin L.

2018-01-01

Networks used to study interactions could provide insights to fisheries. We compiled data from 27 297 interviews of anglers across waterbodies that ranged in size from 1 to 12 113 ha. Catch rates of fish species among anglers grouped by species targeted generally differed between angling methods (bank or boat). We constructed angler–catch bipartite networks (angling method specific) between anglers and fish and measured several network metrics. There was considerable variation in networks among waterbodies, with multiple metrics influenced by waterbody size. Number of species-targeting angler groups and number of fish species caught increased with increasing waterbody size. Mean number of links for species-targeting angler groups and fish species caught also increased with waterbody size. Connectance (realized proportion of possible links) of angler–catch interaction networks decreased slower for boat anglers than for bank anglers with increasing waterbody size. Network specialization (deviation of number of interactions from expected) was not significantly related to waterbody size or angling methods. Application of bipartite networks in fishery science requires careful interpretation of outputs, especially considering the numerous confounding factors prevalent in recreational fisheries.

Serving some and serving all: how providers navigate the challenges of providing racially targeted health services.

PubMed

Zhou, Amy

2017-10-01

Racially targeted healthcare provides racial minorities with culturally and linguistically appropriate health services. This mandate, however, can conflict with the professional obligation of healthcare providers to serve patients based on their health needs. The dilemma between serving a particular population and serving all is heightened when the patients seeking care are racially diverse. This study examines how providers in a multi-racial context decide whom to include or exclude from health programs. This study draws on 12 months of ethnographic fieldwork at an Asian-specific HIV organization. Fieldwork included participant observation of HIV support groups, community outreach programs, and substance abuse recovery groups, as well as interviews with providers and clients. Providers managed the dilemma in different ways. While some programs in the organization focused on an Asian clientele, others de-emphasized race and served a predominantly Latino and African American clientele. Organizational structures shaped whether services were delivered according to racial categories. When funders examined client documents, providers prioritized finding Asian clients so that their documents reflected program goals to serve the Asian population. In contrast, when funders used qualitative methods, providers could construct an image of a program that targets Asians during evaluations while they included other racial minorities in their everyday practice. Program services were organized more broadly by health needs. Even within racially targeted programs, the meaning of race fluctuates and is contested. Patients' health needs cross cut racial boundaries, and in some circumstances, the boundaries of inclusion can expand beyond specific racial categories to include racial minorities and underserved populations more generally.

DNA barcoding amphibians and reptiles.

PubMed

Vences, Miguel; Nagy, Zoltán T; Sonet, Gontran; Verheyen, Erik

2012-01-01

Only a few major research programs are currently targeting COI barcoding of amphibians and reptiles (including chelonians and crocodiles), two major groups of tetrapods. Amphibian and reptile species are typically old, strongly divergent, and contain deep conspecific lineages which might lead to problems in species assignment with incomplete reference databases. As far as known, there is no single pair of COI primers that will guarantee a sufficient rate of success across all amphibian and reptile taxa, or within major subclades of amphibians and reptiles, which means that the PCR amplification strategy needs to be adjusted depending on the specific research question. In general, many more amphibian and reptile taxa have been sequenced for 16S rDNA, which for some purposes may be a suitable complementary marker, at least until a more comprehensive COI reference database becomes available. DNA barcoding has successfully been used to identify amphibian larval stages (tadpoles) in species-rich tropical assemblages. Tissue sampling, DNA extraction, and amplification of COI is straightforward in amphibians and reptiles. Single primer pairs are likely to have a failure rate between 5 and 50% if taxa of a wide taxonomic range are targeted; in such cases the use of primer cocktails or subsequent hierarchical usage of different primer pairs is necessary. If the target group is taxonomically limited, many studies have followed a strategy of designing specific primers which then allow an easy and reliable amplification of all samples.

Improving comprehension in adolescents with severe receptive language impairments: a randomized control trial of intervention for coordinating conjunctions.

PubMed

Ebbels, Susan H; Marić, Nataša; Murphy, Aoife; Turner, Gail

2014-01-01

Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a randomized control trial with an assessor blind to group status. Fourteen participants (aged 11;3-16;1) with severe RELI (mean standard scores: CELF4 ELS = 48, CELF4 RLS = 53 and TROG-2 = 57), but higher non-verbal (Matrices = 83) and visual perceptual skills (Test of Visual Perceptual Skills (TVPS) = 86) were randomly assigned to two groups: therapy versus waiting controls. In Phase 1, the therapy group received eight 30-min individual sessions of explicit teaching with visual support (Shape Coding) with their usual SLT. In Phase 2, the waiting controls received the same therapy. The participants' comprehension was tested pre-, post-Phase 1 and post-Phase 2 therapy on (1) a specific test of the targeted conjunctions, (2) the TROG-2 and (3) a test of passives. After Phase 1, the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions (d = 1.6) and overall TROG-2 standard score (d = 1.4). The two groups did not differ on the passives test. After Phase 2, the waiting controls made similar progress to those in the original therapy group, who maintained their previous progress. Neither group showed progress on passives. When the two groups were combined, significant progress was found on the specific conjunctions (d = 1.3) and TROG-2 raw (d = 1.1) and standard scores (d = 0.9). Correlations showed no measures taken (including Matrices and TVPS) correlated significantly with progress on the targeted conjunctions or the TROG-2. Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months. Given the significant progress at a group level and the lack of reliable predictors of progress, this approach could be offered to other children with similar difficulties to the participants. However, the intervention was delivered one-to-one by speech and language therapists, thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated. © 2013 Royal College of Speech and Language Therapists.

Evidence-based intervention against bullying and cyberbullying: Evaluation of the NoTrap! program in two independent trials.

PubMed

Palladino, Benedetta E; Nocentini, Annalaura; Menesini, Ersilia

2016-01-01

The NoTrap! (Noncadiamointrappola!) program is a school-based intervention, which utilizes a peer-led approach to prevent and combat both traditional bullying and cyberbullying. The aim of the present study was to evaluate the efficacy of the third Edition of the program in accordance with the recent criteria for evidence-based interventions. Towards this aim, two quasi-experimental trials involving adolescents (age M = 14.91, SD = .98) attending their first year at different high schools were conducted. In Trial 1 (control group, n = 171; experimental group, n = 451), latent growth curve models for data from pre-, middle- and post-tests showed that intervention significantly predicted change over time in all the target variables (victimization, bullying, cybervictimization, and cyberbullying). Specifically, target variables were stable for the control group but decreased significantly over time for the experimental group. Long-term effects at the follow up 6 months later were also found. In Trial 2 (control group, n = 227; experimental group, n = 234), the moderating effect of gender was examined and there was a reported decrease in bullying and cyberbullying over time (pre- and post-test) in the experimental group but not the control group, and this decrease was similar for boys and girls. © 2016 Wiley Periodicals, Inc.

Conjugation of antibodies to gold nanorods through Fc portion: synthesis and molecular specific imaging

PubMed Central

Joshi, Pratixa P.; Yoon, Soon Joon; Hardin, William G.; Emelianov, Stanislav; Sokolov, Konstantin V.

2013-01-01

Anisotropic gold nanorods provide a convenient combination of properties, such as tunability of plasmon resonances and strong extinction cross-sections in the near-infrared to red spectral region. These properties have created significant interest in the development of antibody conjugation methods for synthesis of targeted nanorods for a number of biomedical applications, including molecular specific imaging and therapy. Previously published conjugation approaches have achieved molecular specificity. However, the current conjugation methods have several downsides including low stability and potential cytotoxicity of bioconjugates that are produced by electrostatic interactions as well as lack of control over antibody orientation during covalent conjugation. Here we addressed these shortcomings by introducing directional antibody conjugation to the gold nanorod surface. The directional conjugation is achieved through the carbohydrate moiety, which is located on one of the heavy chains of the Fc portion of most antibodies. The carbohydrate is oxidized under mild conditions to a hydrazide reactive aldehyde group. Then, a heterofunctional linker with hydrazide and dithiol groups is used to attach antibodies to gold nanorods. The directional conjugation approach was characterized using electron microscopy, zeta potential and extinction spectra. We also determined spectral changes associated with nanorod aggregation; these spectral changes can be used as a convenient quality control of nanorod bioconjugates. Molecular specificity of the synthesized antibody targeted nanorods was demonstrated using hyperspectral optical and photoacoustic imaging of cancer cell culture models. Additionally, we observed characteristic changes in optical spectra of molecular specific nanorods after their interactions with cancer cells; the observed spectral signatures can be explored for sensitive cancer detection. PMID:23631707

Influences on Adoption of Greenhouse Gas Reduction Targets among US States, 1998-2008

PubMed Central

Cale, Tabitha M.; Reams, Margaret A.

2016-01-01

While the United States has not established federal regulations for greenhouse gas (GHG) reduction targets, many US states have adopted their own standards and guidelines. In this study we examine state adoption of targets for GHG reductions during the ten-year period of 1998–2008, and identify factors that explain variation in target adoption. Potential influences are drawn from research from the public policy formulation and diffusion literature, and from studies specific to climate policy adoption. Potential influences on GHG reduction efforts among US states include socioeconomic attributes of residents, political and ideological orientations of citizens and state government, interest group activities, environmental pressures, and proximity to other states that have adopted GHG reduction targets. The findings of the multinomial logistic regression analysis indicate that states are more likely to adopt GHG reduction targets if they share a border with another state with a similar climate program and if their citizens are more ideologically liberal. Other factors including socioeconomic resources and interest group activities were not found to be associated with policy adoption. The findings yield insights into the conditions under which states are more likely to take action to reduce GHG’s, and are relevant both to state policy makers and residents with an interest in climate planning, and for researchers attempting to estimate future greenhouse gas reduction scenarios. PMID:27471657

Grouping and Read-Across Approaches for Risk Assessment of Nanomaterials.

PubMed

Oomen, Agnes G; Bleeker, Eric A J; Bos, Peter M J; van Broekhuizen, Fleur; Gottardo, Stefania; Groenewold, Monique; Hristozov, Danail; Hund-Rinke, Kerstin; Irfan, Muhammad-Adeel; Marcomini, Antonio; Peijnenburg, Willie J G M; Rasmussen, Kirsten; Jiménez, Araceli Sánchez; Scott-Fordsmand, Janeck J; van Tongeren, Martie; Wiench, Karin; Wohlleben, Wendel; Landsiedel, Robert

2015-10-26

Physicochemical properties of chemicals affect their exposure, toxicokinetics/fate and hazard, and for nanomaterials, the variation of these properties results in a wide variety of materials with potentially different risks. To limit the amount of testing for risk assessment, the information gathering process for nanomaterials needs to be efficient. At the same time, sufficient information to assess the safety of human health and the environment should be available for each nanomaterial. Grouping and read-across approaches can be utilised to meet these goals. This article presents different possible applications of grouping and read-across for nanomaterials within the broader perspective of the MARINA Risk Assessment Strategy (RAS), as developed in the EU FP7 project MARINA. Firstly, nanomaterials can be grouped based on limited variation in physicochemical properties to subsequently design an efficient testing strategy that covers the entire group. Secondly, knowledge about exposure, toxicokinetics/fate or hazard, for example via properties such as dissolution rate, aspect ratio, chemical (non-)activity, can be used to organise similar materials in generic groups to frame issues that need further attention, or potentially to read-across. Thirdly, when data related to specific endpoints is required, read-across can be considered, using data from a source material for the target nanomaterial. Read-across could be based on a scientifically sound justification that exposure, distribution to the target (fate/toxicokinetics) and hazard of the target material are similar to, or less than, the source material. These grouping and read-across approaches pave the way for better use of available information on nanomaterials and are flexible enough to allow future adaptations related to scientific developments.

Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking

PubMed Central

Iwakiri, Yasuko; Satoh, Ayano; Chatterjee, Suvro; Toomre, Derek K.; Chalouni, Cecile M.; Fulton, David; Groszmann, Roberto J.; Shah, Vijay H.; Sessa, William C.

2006-01-01

Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes. PMID:17170139

Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

PubMed Central

Minetti, Andrea; Hurtado, Northan; Grais, Rebecca F.; Ferrari, Matthew

2014-01-01

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals. PMID:24131555

The effect of targeted treatment on people with patellofemoral pain: a pragmatic, randomised controlled feasibility study.

PubMed

Drew, Benjamin T; Conaghan, Philip G; Smith, Toby O; Selfe, James; Redmond, Anthony C

2017-08-04

Targeted treatment, matched according to specific clinical criteria e.g. hip muscle weakness, may result in better outcomes for people with patellofemoral pain (PFP). However, to ensure the success of future trials, a number of questions on the feasibility of a targeted treatment need clarification. The aim of the study was to explore the feasibility of matched treatment (MT) compared to usual care (UC) management for a subgroup of people with PFP determined to have hip weakness and to explore the mechanism of effect for hip strengthening. In a pragmatic, randomised controlled feasibility study, 24 participants with PFP (58% female; mean age 29 years) were randomly allocated to receive either MT aimed specifically at hip strengthening, or UC over an eight-week period. The primary outcomes were feasibility outcomes, which included rates of adherence, attrition, eligibility, missing data and treatment efficacy. Secondary outcomes focused on the mechanistic outcomes of the intervention, which included hip kinematics. Conversion to consent (100%), missing data (0%), attrition rate (8%) and adherence to both treatment and appointments (>90%) were deemed successful endpoints. The analysis of treatment efficacy showed that the MT group reported a greater improvement for the Global Rating of Change Scale (62% vs. 9%) and the Anterior Knee Pain Scale (-5.23 vs. 1.18) but no between-group differences for either average or worst pain. Mechanistic outcomes showed a greatest reduction in peak hip internal rotation angle for the MT group (13.1% vs. -2.7%). This feasibility study indicates that a definitive randomised controlled trial investigating a targeted treatment approach is achievable. Findings suggest the mechanism of effect of hip strengthening may be to influence kinematic changes in hip function in the transverse plane. This study was registered retrospectively. ISRCTN74560952 . Registration date: 2017-02-06.

The attentional blink in typically developing and reading-disabled children.

PubMed

de Groot, Barry J A; van den Bos, Kees P; van der Meulen, Bieuwe F; Minnaert, Alexander E M G

2015-11-01

This study's research question was whether selective visual attention, and specifically the attentional blink (AB) as operationalized by a dual target rapid serial visual presentation (RSVP) task, can explain individual differences in word reading (WR) and reading-related phonological performances in typically developing children and reading-disabled subgroups. A total of 407 Dutch school children (Grades 3-6) were classified either as typically developing (n = 302) or as belonging to one of three reading-disabled subgroups: reading disabilities only (RD-only, n = 69), both RD and attention problems (RD+ADHD, n = 16), or both RD and a specific language impairment (RD+SLI, n = 20). The RSVP task employed alphanumeric stimuli that were presented in two blocks. Standardized Dutch tests were used to measure WR, phonemic awareness (PA), and alphanumeric rapid naming (RAN). Results indicate that, controlling for PA and RAN performance, general RSVP task performance contributes significant unique variance to the prediction of WR. Specifically, consistent group main effects for the parameter of AB(minimum) were found, whereas there were no AB-specific effects (i.e., AB(width) and AB(amplitude)) except for the RD+SLI group. Finally, there was a group by measurement interaction, indicating that the RD-only and comorbid groups are differentially sensitive for prolonged testing sessions. These results suggest that more general factors involved in RSVP processing may explain the group differences found. Copyright © 2015 Elsevier Inc. All rights reserved.

One size does not fit all: how the tobacco industry has altered cigarette design to target consumer groups with specific psychological and psychosocial needs.

PubMed

Cook, Benjamin Lê; Wayne, Geoffrey Ferris; Keithly, Lois; Connolly, Gregory

2003-11-01

To identify whether the tobacco industry has targeted cigarette product design towards individuals with varying psychological/psychosocial needs. Internal industry documents were identified through searches of an online archival document research tool database using relevancy criteria of consumer segmentation and needs assessment. The industry segmented consumer markets based on psychological needs (stress relief, behavioral arousal, performance enhancement, obesity reduction) and psychosocial needs (social acceptance, personal image). Associations between these segments and smoking behaviors, brand and design preferences were used to create cigarette brands targeting individuals with these needs. Cigarette brands created to address the psychological/psychosocial needs of smokers may increase the likelihood of smoking initiation and addiction. Awareness of targeted product development will improve smoking cessation and prevention efforts.

Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review.

PubMed

Turnaturi, Rita; Montenegro, Lucia; Marrazzo, Agostino; Parenti, Rosalba; Pasquinucci, Lorella; Parenti, Carmela

2018-06-07

Despite the fact that the benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

An Intensive Presentations Course in English for Aeronautical Engineering Students Using Cyclic Video Recordings

ERIC Educational Resources Information Center

Tatzl, Dietmar

2017-01-01

This article presents the design and evaluation of an intensive presentations course for aeronautical engineering students based on cyclic video recordings. The target group of this course in English for specific purposes (ESP) were undergraduate final-year students who needed to improve their presentation and foreign language skills to prepare…

Group Training in Interpersonal Problem-Solving Skills for Workplace Adaptation of Adolescents and Adults with Asperger Syndrome: A Preliminary Study

ERIC Educational Resources Information Center

Bonete, Saray; Calero, María Dolores; Fernández-Parra, Antonio

2015-01-01

Adults with Asperger syndrome show persistent difficulties in social situations which psychosocial treatments may address. Despite the multiple studies focusing on social skills interventions, only some have focused specifically on problem-solving skills and have not targeted workplace adaptation training in the adult population. This study…

Guided Learning at Workstations about Drug Prevention with Low Achievers in Science Education

ERIC Educational Resources Information Center

Thomas, Heyne; Bogner, Franz X.

2012-01-01

Our study focussed on the cognitive achievement potential of low achieving eighth graders, dealing with drug prevention (cannabis). The learning process was guided by a teacher, leading this target group towards a modified learning at workstations which is seen as an appropriate approach for low achievers. We compared this specific open teaching…

Teaching Effective Hand Raising to Children with Autism during Group Instruction

ERIC Educational Resources Information Center

Charania, Shaireen M.; LeBlanc, Linda A.; Sabanathan, Narmatha; Ktaech, Inas A.; Carr, James E.; Gunby, Kristin

2010-01-01

We taught 3 children with autism to raise a hand or keep both hands down depending on their status (e.g., having heard a target word, possessing a specific item) using modeling, prompting, and reinforcement. All 3 children acquired accurate hand-raising skills in response to progressively more difficult discrimination tasks during group…

Case Study of Chinese Exclusion Act Enforcement

ERIC Educational Resources Information Center

Dufour, Joanne, Comp.

2012-01-01

While nearly 85 percent of the U.S. population is currently made up of immigrants and their descendants, some groups were specifically targeted for exclusion and deliberately expelled. The Chinese were the first to experience this. In the 1850s, many Chinese who came to this land to search for gold or to help build the transcontinental railroad,…

The Use of Targeted Pitch Skills for Sight-Singing Instruction in the Choral Rehearsal

ERIC Educational Resources Information Center

Henry, Michele L.

2004-01-01

The purpose of this study was to determine the effectiveness of sight-singing instruction using specific pitch skills emphasizing scale degree and harmonic function. Fifteen pitch skills encompassing scalar, cadential, and chordal tasks were included in the study. Over a 12-week period, two randomly assigned groups of novice high school singers…

Using a Pattern-Centered Approach to Assess Sexual Risk-Taking in Study Abroad Students

ERIC Educational Resources Information Center

Marcantonio, Tiffany; Angelone, D. J.; Sledjeski, Eve

2016-01-01

Objectives: The purpose of this study was to examine the impact of several potential factors related to sexually risky behaviors in study abroad students. The authors utilized a pattern-centered analysis to identify specific groups that can be targeted for intervention. Participants: The sample consisted of 173 students who studied abroad in a…

Quality and Equity in the Mongolian Education Sector

ERIC Educational Resources Information Center

Steiner-Khamsi, Gita; Gerelmaa, Amgaabazar

2008-01-01

This case study identifies four targets groups that are specific to the achievement of the EFA Millennium Development Goals in Mongolia: boys, out-of-school children, vulnerable children and minorities, and children of herders. Boys from herder families in remote rural areas are at the greatest risk of drop-out or non-enrollment. The case study…

Strategies for Effective Orientation, Training, and Management of Media Center Volunteers.

ERIC Educational Resources Information Center

Dale, Carol A.

The purpose of this practicum was to develop a program for volunteers in an elementary school media center that allowed volunteers to be more independent from the media specialist. Phase I of the program, highlighting school volunteers as Target Group I, included a questionnaire, interviews, delegation of specific tasks, a posted duty roster, an…

QM/MM MD and free energy simulations of G9α-like protein (GLP) and its mutants: Understanding the factors that determine the product specificity

DOE PAGES

Chu, Yuzhuo; Yao, Jianzhuang; Guo, Hong

2012-05-18

Certain lysine residues on histone tails could be methylated by protein lysine methyltransferases (PKMTs) using S-adenosyl-L-methionine (AdoMet) as the methyl donor. Since the methylation states of the target lysines play a fundamental role in the regulation of chromatin structure and gene expression, it is important to study the property of PKMTs that allows a specific number of methyl groups (one, two or three) to be added (termed as product specificity). It has been shown that the product specificity of PKMTs may be controlled in part by the existence of specific residues at the active site. One of the best examplesmore » is a Phe/Tyr switch found in many PKMTs. Here quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed on wild type G9a-like protein (GLP) and its F1209Y and Y1124F mutants for understanding the energetic origin of the product specificity and the reasons for the change of product specificity as a result of single-residue mutations at the Phe/Tyr switch as well as other positions. The free energy barriers of the methyl transfer processes calculated from our simulations are consistent with experimental data, supporting the suggestion that the relative free energy barriers may determine, at least in part, the product specificity of PKMTs. The changes of the free energy barriers as a result of the mutations are also discussed based on the structural information obtained from the simulations. Furthermore, the results suggest that the space and active-site interactions around the -amino group of the target lysine available for methyl addition appear to among the key structural factors in controlling the product specificity and activity of PKMTs.« less

Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

PubMed

Maddula, Surekha; Ansell, Jack

2013-08-01

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

Effective identification of Lactobacillus casei group species: genome-based selection of the gene mutL as the target of a novel multiplex PCR assay.

PubMed

Bottari, Benedetta; Felis, Giovanna E; Salvetti, Elisa; Castioni, Anna; Campedelli, Ilenia; Torriani, Sandra; Bernini, Valentina; Gatti, Monica

2017-07-01

Lactobacillus casei,Lactobacillus paracasei and Lactobacillusrhamnosus form a closely related taxonomic group (the L. casei group) within the facultatively heterofermentative lactobacilli. Strains of these species have been used for a long time as probiotics in a wide range of products, and they represent the dominant species of nonstarter lactic acid bacteria in ripened cheeses, where they contribute to flavour development. The close genetic relationship among those species, as well as the similarity of biochemical properties of the strains, hinders the development of an adequate selective method to identify these bacteria. Despite this being a hot topic, as demonstrated by the large amount of literature about it, the results of different proposed identification methods are often ambiguous and unsatisfactory. The aim of this study was to develop a more robust species-specific identification assay for differentiating the species of the L. casei group. A taxonomy-driven comparative genomic analysis was carried out to select the potential target genes whose similarity could better reflect genome-wide diversity. The gene mutL appeared to be the most promising one and, therefore, a novel species-specific multiplex PCR assay was developed to rapidly and effectively distinguish L. casei, L. paracasei and L. rhamnosus strains. The analysis of a collection of 76 wild dairy isolates, previously identified as members of the L. casei group combining the results of multiple approaches, revealed that the novel designed primers, especially in combination with already existing ones, were able to improve the discrimination power at the species level and reveal previously undiscovered intraspecific biodiversity.

The effect of a couples intervention to increase breast cancer screening among korean americans.

PubMed

Lee, Eunice; Menon, Usha; Nandy, Karabi; Szalacha, Laura; Kviz, Frederick; Cho, Young; Miller, Arlene; Park, Hanjong

2014-05-01

To assess the efficacy of Korean Immigrants and Mammography-Culture-Specific Health Intervention (KIM-CHI), an educational program for Korean American (KA) couples designed to improve mammography uptake among KA women. A two-group cluster randomized, longitudinal, controlled design. 50 KA religious organizations in the Chicago area. 428 married KA women 40 years of age or older who had not had a mammogram in the past year. The women and their husbands were recruited from 50 KA religious organizations. Couples were randomly assigned to intervention or attention control groups. Those in the KIM-CHI program (n = 211 couples) were compared to an attention control group (n = 217 couples) at baseline, as well as at 6 and 15 months postintervention on mammogram uptake. Sociodemographic variables and mammography uptake were measured. Level of acculturation was measured using the Suinn-Lew Asian Self-Identity Acculturation Scale. Researchers asked questions about healthcare resources and use, health insurance status, usual source of care, physical examinations in the past two years, family history of breast cancer, and history of mammography. The KIM-CHI group showed statistically significant increases in mammography uptake compared to the attention control group at 6 months and 15 months postintervention. The culturally targeted KIM-CHI program was effective in increasing mammogram uptake among nonadherent KA women. Nurses and healthcare providers should consider specific health beliefs as well as inclusion of husbands or significant others. They also should target education to be culturally relevant for KA women to effectively improve frequency of breast cancer screening.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

PubMed

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-07-01

: L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model

PubMed Central

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-01-01

L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel–Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis. PMID:28306627

Fluorescence imaging with multifunctional polyglycerol sulfates: novel polymeric near-IR probes targeting inflammation.

PubMed

Licha, Kai; Welker, Pia; Weinhart, Marie; Wegner, Nicole; Kern, Sylvia; Reichert, Stefanie; Gemeinhardt, Ines; Weissbach, Carmen; Ebert, Bernd; Haag, Rainer; Schirner, Michael

2011-12-21

We present a highly selective approach for the targeting of inflammation with a multivalent polymeric probe. Dendritic polyglycerol was employed to synthesize a polyanionic macromolecular conjugate with a near-infrared fluorescent dye related to Indocyanine Green (ICG). On the basis of the dense assembly of sulfate groups which were generated from the polyol core, the resulting polyglycerol sulfate (molecular weight 12 kD with ~70 sulfate groups) targets factors of inflammation (IC(50) of 3-6 nM for inhibition of L-selectin binding) and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging in an animal model of rheumatoid arthritis demonstrated fast and selective uptake which enabled the differentiation of diseased joints (score 1-3) with a 3.5-fold higher fluorescence level and a signal maximum at 60 min post injection. Localization in tissues using fluorescence histology showed that the conjugates are deposited in the inflammatory infiltrate in the synovial membrane, whereas nonsulfated control was not detected in association with disease. Hence, this type of polymeric imaging probe is an alternative to current bioconjugates and provides future options for targeted imaging and drug delivery.

Targeting as a Mode of Science Communication: Principles, Issues and a Practical Example

NASA Astrophysics Data System (ADS)

Holland, G. J.; Vigh, J. L.

2011-12-01

Today's media landscape contains a rich and diverse range of communications opportunities. New media, such as the internet, blogosphere and social networks, are complementing, supplementing and also replacing the traditional mass media communications through print, radio and television. This diversification certainly contains pitfalls and difficulties as has been demonstrated in the Climategate affair. But there are also real opportunities for utilizing the diversity to provide targeted science communications that are framed in the context of the specific group of interest. That such targeting of audience attitudes and beliefs is an important key to effective science communications has been demonstrated by, for example, Leiserowitz, Maibach et al (2009). This approach does require an understanding of the audience and a careful framing of the message in terms familiar to the targeted group. Here many factors come into play, including: including immediacy, economics, culture, community leaders, emotional framing, and ideological filters. In this talk we shall elaborate on the principles, issues and opportunities. A practical example of working with the religious community on communicating the science of climate change will also be presented. This will include the approach adopted, progress to date and the lessons learnt.

Impaired preparatory re-mapping of stimulus-response associations and rule-implementation in schizophrenic patients--the role for differences in early processing.

PubMed

Finke, Mareike; Barceló, Francisco; Garolera, Maite; Cortiñas, Miriam; Garrido, Gemma; Pajares, Marta; Escera, Carles

2011-07-01

An accurate representation of task-set information is needed for successful goal directed behavior. Recent studies point to disturbances in the early processing stages as plausible causes for task-switching deficits in schizophrenia. A task-cueing protocol was administered to a group of schizophrenic patients and compared with a sample of age-matched healthy controls. Patients responded slower and less accurate compared with controls in all conditions. The concurrent recording of event-related brain potentials to contextual cues and target events revealed abnormalities in the early processing of both cue-locked and target-locked N1 potentials. Abnormally enhanced target-locked P2 amplitudes were observed in schizophrenic patients for task-switch trials only, suggesting disrupted stimulus evaluation and memory retrieval processes. The endogenous P3 potentials discriminated between task conditions but without further differences between groups. These results suggest that the observed impairments in task-switching behavior were not specifically related to anticipatory set-shifting, but derived from a deficit in the implementation of task-set representations at target onset in the presence of irrelevant and conflicting information. Copyright © 2011 Elsevier B.V. All rights reserved.

Phishing for suitable targets in the Netherlands: routine activity theory and phishing victimization.

PubMed

Leukfeldt, E Rutger

2014-08-01

This article investigates phishing victims, especially the increased or decreased risk of victimization, using data from a cybercrime victim survey in the Netherlands (n=10,316). Routine activity theory provides the theoretical perspective. According to routine activity theory, several factors influence the risk of victimization. A multivariate analysis was conducted to assess which factors actually lead to increased risk of victimization. The model included background and financial data of victims, their Internet activities, and the degree to which they were "digitally accessible" to an offender. The analysis showed that personal background and financial characteristics play no role in phishing victimization. Among eight Internet activities, only "targeted browsing" led to increased risk. As for accessibility, using popular operating systems and web browsers does not lead to greater risk, while having up-to-date antivirus software as a technically capable guardian has no effect. The analysis showed no one, clearly defined group has an increased chance of becoming a victim. Target hardening may help, but opportunities for prevention campaigns aimed at a specific target group or dangerous online activities are limited. Therefore, situational crime prevention will have to come from a different angle. Banks could play the role of capable guardian.

Impact of routine transvaginal ultrasound monitoring of cervical length in twins on administration of antenatal corticosteroids.

PubMed

Marcellin, Louis; Senat, Marie Victoire; Benachi, Alexandra; Regis, Sophie; Cabrol, Dominique; Goffinet, François

2017-05-24

To evaluate whether routine measurement of cervical length (CL) by transvaginal ultrasound (TVU) in twin pregnancies can enable identification of women who will give birth before 34 weeks and require antenatal corticosteroids (ACSs), and whether it can limit their administration to women who will give birth later. Retrospective comparative study in two tertiary referral centers in France. Women with twin gestations followed in two tertiary university hospital maternity units and who delivered from January 1, 2007 to December 31, 2009 were included. In one center, TVU was targeted to women with cases of suspected preterm labor, while the other center used it monthly for all twin pregnancies. The main outcome measure was the administration of a full course of ACS to twins delivered before 34 weeks. Two hundred and seventy women were eligible in the "targeted use" group, and 296 women in the "routine use" group. The rate of administration of at least one full course of ACS for twins born before 34 weeks did not differ between the two groups (85.0% in the targeted use group and 90.0% in the routine use group, P=0.40), but the rate of such administration for those born after 34 weeks was lower in the targeted use group (25.7% vs. 81.2%, P<0.01). On adjusting for confounders using logistic regression modeling, no significant difference in ACS administration before 34 weeks was found between the two groups [adjusted odds ratio (aOR), 0.71, 95% confidence interval (CI), 0.39-1.30]. Routine monitoring performed every month of CL with TVU does not affect the rate of administration of ACS to twins born before 34 weeks, but is associated with a higher rate of such administration for those born later in the specific center of the study.

A kinematic analysis of visually-guided movement in Williams syndrome.

PubMed

Hocking, Darren R; Rinehart, Nicole J; McGinley, Jennifer L; Moss, Simon A; Bradshaw, John L

2011-02-15

Previous studies have reported that people with the neurodevelopmental disorder Williams syndrome exhibit difficulties with visuomotor control. In the current study, we examined the extent to which visuomotor deficits were associated with movement planning or feedback-based on-line control. We used a variant of the Fitts' reciprocal aiming task on a computerized touchscreen in adults with WS, IQ-matched individuals with Down syndrome (DS), and typically developing controls. By manipulating task difficulty both as a function of target size and amplitude, we were able to vary the requirements for accuracy to examine processes associated with dorsal visual stream and cerebellar functioning. Although a greater increase in movement time as a function of task difficulty was observed in the two clinical groups with WS and DS, greater magnitude in the late kinematic components of movement-specifically, time after peak velocity-was revealed in the WS group during increased demands for accuracy. In contrast, the DS group showed a greater speed-accuracy trade-off with significantly reduced and more variable endpoint accuracy, which may be associated with cerebellar deficits. In addition, the WS group spent more time stationary in the target when task-related features reflected a higher level of difficulty, suggestive of specific deficits in movement planning. Our results indicate that the visuomotor coordination deficits in WS may reflect known impairments of the dorsal stream, but may also indicate a role for the cerebellum in dynamic feed-forward motor control. Copyright © 2010 Elsevier B.V. All rights reserved.

Environmental distribution of two widespread uncultured freshwater Euryarchaeota clades unveiled by specific primers and quantitative PCR.

PubMed

Restrepo-Ortiz, Claudia X; Casamayor, Emilio O

2013-12-01

Quantitative environmental distribution of two widely distributed uncultured freshwater Euryarchaeota with unknown functional role was explored by newly designed quantitative PCR primers targeting the 16S rRNA gene of clades Miscellaneous Euryarchaeota Group (MEG, containing the groups pMC2A384 and VALII/Eury4) and Deep-Sea Euryarchaeotal Groups (DSEG, targeting the cluster named VALIII containing the DHVE-3/DSEG, BC07-2A-27/DSEG-3 and DSEG-2 groups), respectively. The summer surface plankton of 28 lakes was analysed, and one additional dimictic deep alpine lake, Lake Redon, was temporally and vertically surveyed covering seasonal limnological variability. A trophic range between 0.2 and 5.2 μg l(-1) Chl a, and pH span from 3.8 to 9.5 was explored at altitudes between 632 and 2590 m above sea level. The primers showed to be highly selective with c. 85% coverage and 100% specificity. Only pH significantly explained the changes observed in gene abundances and environment. In Lake Redon, DSEG bloomed in deep stratified waters both in summer and early spring, and MEG at intermediate depths during the ice-cover period. Overall, MEG and DSEG showed a differential ecological distribution although correlational analyses indicated lack of coupling of both Euryarchaeota with phytoplankton (chlorophyll a). However, an intriguing positive and significant relationship was found between DSEG and putative ammonia oxidizing thaumarchaeota. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Site-specific labeling of RNA at internal ribose hydroxyl groups: terbium-assisted deoxyribozymes at work.

PubMed

Büttner, Lea; Javadi-Zarnaghi, Fatemeh; Höbartner, Claudia

2014-06-04

A general and efficient single-step method was established for site-specific post-transcriptional labeling of RNA. Using Tb(3+) as accelerating cofactor for deoxyribozymes, various labeled guanosines were site-specifically attached to 2'-OH groups of internal adenosines in in vitro transcribed RNA. The DNA-catalyzed 2',5'-phosphodiester bond formation proceeded efficiently with fluorescent, spin-labeled, biotinylated, or cross-linker-modified guanosine triphosphates. The sequence context of the labeling site was systematically analyzed by mutating the nucleotides flanking the targeted adenosine. Labeling of adenosines in a purine-rich environment showed the fastest reactions and highest yields. Overall, practically useful yields >70% were obtained for 13 out of 16 possible nucleotide (nt) combinations. Using this approach, we demonstrate preparative labeling under mild conditions for up to ~160-nt-long RNAs, including spliceosomal U6 small nuclear RNA and a cyclic-di-AMP binding riboswitch RNA.

A quasi-randomized feasibility pilot study of specific treatments to improve emotion recognition and mental-state reasoning impairments in schizophrenia.

PubMed

Marsh, Pamela Jane; Polito, Vince; Singh, Subba; Coltheart, Max; Langdon, Robyn; Harris, Anthony W

2016-10-24

Impaired ability to make inferences about what another person might think or feel (i.e., social cognition impairment) is recognised as a core feature of schizophrenia and a key determinant of the poor social functioning that characterizes this illness. The development of treatments to target social cognitive impairments as a causal factor of impaired functioning in schizophrenia is of high priority. In this study, we investigated the acceptability, feasibility, and limited efficacy of 2 programs targeted at specific domains of social cognition in schizophrenia: "SoCog" Mental-State Reasoning Training (SoCog-MSRT) and "SoCog" Emotion Recognition Training (SoCog-ERT). Thirty-one participants with schizophrenia or schizoaffective disorder were allocated to either SoCog-MSRT (n = 19) or SoCog-ERT (n = 12). Treatment comprised 12 twice-weekly sessions for 6 weeks. Participants underwent assessments of social cognition, neurocognition and symptoms at baseline, post-training and 3-months after completing training. Attendance at training sessions was high with an average of 89.29 % attendance in the SoCog-MSRT groups and 85.42 % in the SoCog-ERT groups. Participants also reported the 2 programs as enjoyable and beneficial. Both SoCog-MSRT and SoCog-ERT groups showed increased scores on a false belief reasoning task and the Reading the Mind in the Eyes test. The SoCog-MSRT group also showed reduced personalising attributional biases in a small number of participants, while the SoCog-ERT group showed improved emotion recognition. The results are promising and support the feasibility and acceptability of the 2 SoCog programs as well as limited efficacy to improve social cognitive abilities in schizophrenia. There is also some evidence that skills for the recognition of basic facial expressions need specific training. Australian New Zealand Clinical Trials Registry ACTRN12613000978763 . Retrospectively registered 3/09/2013.

Qualitative Application of the Theory of Planned Behavior to Understand Beverage Behaviors among Adults

PubMed Central

Krzeski, Erin; Harden, Samantha; Cook, Emily; Allen, Kacie; Estabrooks, Paul A.

2012-01-01

Despite strong scientific data indicating associations among sugar-sweetened beverages (SSB) and numerous adverse health outcomes, little is known about culturally specific beliefs and potential individual-level behavioral strategies to reduce SSB intake. The primary objective of this formative study targeting adults residing in rural southwest Virginia was to apply the Theory of Planned Behavior (TPB) to investigate culturally specific attitudes, subjective norms and perceived behavioral control constructs related to the consumption of SSB, water, and artificially sweetened beverages. Using a homogenous sampling strategy, eight focus groups were conducted with 54 adult participants who exceeded recommendations of <1 cup of SSB/day. An experienced moderator and co-moderator utilized a semi-structured script, grounded in the TPB, to execute the focus group. All focus groups were audio taped and transcribed verbatim. Three researchers independently coded meaning units (MU) to the major themes and subsequently met to gain consensus in coding. Important beverage specific themes emerged for attitudes, subjective norms, perceived behavioral control, and intentions. Across all beverages, the most notable themes included taste (n= 161 MU), availability/convenience (n= 95 MU), habit/addiction (n=57 MU), and cost (n= 28 MU). Health consequences associated with beverages and water quality issues also surfaced, as well as normative beliefs including the influence of doctors and peers. The identified themes and sub-themes provides critical insight into understanding culturally-relevant context and beliefs associated with beverage behaviors and helps inform the development and evaluation of future intervention efforts targeting SSB consumption in the health disparate region of southwest Virginia. PMID:23102176

Segmentation of British Sign Language (BSL): mind the gap!

PubMed

Orfanidou, Eleni; McQueen, James M; Adam, Robert; Morgan, Gary

2015-01-01

This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous signing, there are salient transitions between sign locations. We used the sign-spotting task to ask if and how BSL signers use these transitions in segmentation. A total of 96 real BSL signs were preceded by nonsense signs which were produced in either the target location or another location (with a small or large transition). Half of the transitions were within the same major body area (e.g., head) and half were across body areas (e.g., chest to hand). Deaf adult BSL users (a group of natives and early learners, and a group of late learners) spotted target signs best when there was a minimal transition and worst when there was a large transition. When location changes were present, both groups performed better when transitions were to a different body area than when they were within the same area. These findings suggest that transitions do not provide explicit sign-boundary cues in a modality-specific fashion. Instead, we argue that smaller transitions help recognition in a modality-general way by limiting lexical search to signs within location neighbourhoods, and that transitions across body areas also aid segmentation in a modality-general way, by providing a phonotactic cue to a sign boundary. We propose that sign segmentation is based on modality-general procedures which are core language-processing mechanisms.

Smoking Cessation Programs for Lesbian, Gay, Bisexual, Transgender, and Intersex People: A Content-Based Systematic Review.

PubMed

Berger, Israel; Mooney-Somers, Julie

2017-11-07

Tobacco use among lesbian, gay, bisexual, and transgender (LGBT) people is double the general population. Limited evidence suggests high smoking rates among intersex people. Lesbian, gay, bisexual, transgender, and intersex (LGBTI) people are a priority population in Australian health policy, particularly mental health and aging. Despite associations between smoking and noncommunicable diseases relevant to aging and mental health, LGBTI-targeted smoking cessation interventions in Australia have been limited to people living with HIV. Applying existing interventions to marginalized populations without modification and evaluation may fail and exacerbate inequities. To assess outcomes and characterize the populations served, cultural modifications, and behavior change techniques (BCTs) of interventions to reduce LGBTI smoking. We searched MEDLINE, six additional databases, and contacted authors to retrieve published and unpublished program evaluations. We retrieved 19 studies (3663 participants). None used control groups. Overall quit rate was 61.0% at the end of interventions and stabilized at 38.6% at 3-6 months. All studies included gay men, 13 included lesbians, 13 "LGBT," 12 bisexual people, five transgender people, and none included intersex people. Transgender people comprised 3% of participants. Of programs open to women, 27.8% of participants were women. Cultural modifications were used by 17 (89.5%) studies, commonly meeting in LGBT spaces, discussing social justice, and discussing LGBT-specific triggers. Common BCTs included providing normative information, boosting motivation/self-efficacy, relapse prevention, social support, action planning, and discussing consequences. Quit rates were high; using control groups would improve evaluation. Existing programs may fail to reach groups other than gay men. This review examines the evidence for LGBTI-targeted smoking cessation interventions. Populations within LGBTI are not proportionally represented in smoking cessation research, and no study addressed intersex smoking. Overall, LGBT-targeted interventions appear to be effective, and simply having an LGBT-specific group may be more effective than groups for the general population. More rigorous research is necessary to draw firm conclusions. Our study space analysis provides suggestions for areas of more targeted research on mechanisms underlying these complex interventions' success. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Amateur Astronomers: Secret Agents of EPO

NASA Astrophysics Data System (ADS)

Berendsen, M.; White, V.; Devore, E.; Reynolds, M.

2008-06-01

Amateur astronomers prime the public to be more interested, receptive, and excited about space science, missions, and programs. Through recent research and targeted programs, amateur astronomy outreach is being increasingly recognized by professional astronomers, educators, and other amateurs as a valued and important service. The Night Sky Network program, administered by the ASP, is the first nationwide research-based program specifically targeted to support outreach by amateur astronomers. This Network of trained and informed amateur astronomers can provide a stimulating introduction to your EPO programs as Network members share the night sky with families, students, and youth groups.

Planning an effective anti-smoking mass media campaign targeting adolescents.

PubMed

Pechmann, C; Reibling, E T

2000-05-01

This article addresses the following issues: Can an anti-smoking campaign that depends largely on mass media vehicles effectively reduce adolescent tobacco use? Why is an integrated campaign recommended and what are the steps in designing such a campaign? How should the campaign be evaluated? Specific topics include recommended campaign expenditures, target audience identification, selection of persuasive message content, executional (stylistic) considerations, media buying decisions, the use of focus group research and advertising copy-testing research, and outcome evaluations. It is concluded that comprehensive strategic planning and extensive research at all phases of the campaign are essential to success.

Research & market strategy: how choice of drug discovery approach can affect market position.

PubMed

Sams-Dodd, Frank

2007-04-01

In principal, drug discovery approaches can be grouped into target- and function-based, with the respective aims of developing either a target-selective drug or a drug that produces a specific biological effect irrespective of its mode of action. Most analyses of drug discovery approaches focus on productivity, whereas the strategic implications of the choice of drug discovery approach on market position and ability to maintain market exclusivity are rarely considered. However, a comparison of approaches from the perspective of market position indicates that the functional approach is superior for the development of novel, innovative treatments.

Targeting the Psychosexual Challenges Faced by Couples with Breast Cancer: Can Couples Group Psychotherapy Help?

PubMed Central

Lagana, Luciana; Fobair, Patricia; Spiegel, David

2016-01-01

The need for the psychosexual rehabilitation of breast cancer survivors and their intimate partners is underscored by the high prevalence of multiple psychosexual difficulties encountered by this patient population. Concerns about health, sexuality, and emotional distress are common among women with breast cancer and are often related to the side effects of cancer treatment. Additionally, both intimate relationship problems and partners’ distress are likely to influence patients’ psychosexual health. A clearer understanding of these complex clinical issues is needed in order to implement effective psychosexual rehabilitation interventions. In this article, we extended the use of the manualized and empirically validated Supportive-Expressive Group Therapy (SEGT) model to target the specific psychosexual needs of couples with breast (as well as other types of) cancer. In view of the pertinent literature in this area and based on our clinical experience utilizing this group therapy model with different patient populations, we have discussed how clinicians involved in the psychosexual care of oncology patients could apply such a model within a couples group therapy format. PMID:27239398

Contingency Operations Support to NASA Johnson Space Center Medical Operations Division

NASA Technical Reports Server (NTRS)

Stepaniak, Philip; Patlach, Bob; Swann, Mark; Adams, Adrien

2005-01-01

The Wyle Laboratories Contingency Operations Group provides support to the NASA Johnson Space Center (JSC) Medical Operations Division in the event of a space flight vehicle accident or JSC mishap. Support includes development of Emergency Medical System (EMS) requirements, procedures, training briefings and real-time support of mishap investigations. The Contingency Operations Group is compliant with NASA documentation that provides guidance in these areas and maintains contact with the United States Department of Defense (DOD) to remain current on military plans to support NASA. The contingency group also participates in Space Operations Medical Support Training Courses (SOMSTC) and represents the NASA JSC Medical Operations Division at contingency exercises conducted worldwide by the DOD or NASA. The events of September 11, 2001 have changed how this country prepares and protects itself from possible terrorist attacks on high-profile targets. As a result, JSC is now considered a high-profile target and thus, must prepare for and develop a response to a Weapons of Mass Destruction (WMD) incident. The Wyle Laboratories Contingency Operations Group supports this plan, specifically the medical response, by providing expertise and manpower.

Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.

PubMed

Ha, Byung Hak; Morse, Elizabeth M; Turk, Benjamin E; Boggon, Titus J

2015-05-22

The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Bridging evidence-practice gaps: improving use of medicines in elderly Australian veterans.

PubMed

Roughead, Elizabeth E; Kalisch Ellett, Lisa M; Ramsay, Emmae N; Pratt, Nicole L; Barratt, John D; LeBlanc, Vanessa T; Ryan, Philip; Peck, Robert; Killer, Graeme; Gilbert, Andrew L

2013-12-12

The Australian Government Department of Veterans' Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. The Veterans' MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings.

Natural variation of H3K27me3 distribution between two Arabidopsis accessions and its association with flanking transposable elements

PubMed Central

2012-01-01

Background Histone H3 lysine 27 tri-methylation and lysine 9 di-methylation are independent repressive chromatin modifications in Arabidopsis thaliana. H3K27me3 is established and maintained by Polycomb repressive complexes whereas H3K9me2 is catalyzed by SUVH histone methyltransferases. Both modifications can spread to flanking regions after initialization and were shown to be mutually exclusive in Arabidopsis. Results We analyzed the extent of natural variation of H3K27me3 in the two accessions Landsberg erecta (Ler) and Columbia (Col) and their F1 hybrids. The majority of H3K27me3 target genes in Col were unchanged in Ler and F1 hybrids. A small number of Ler-specific targets were detected and confirmed. Consistent with a cis-regulatory mechanism for establishing H3K27me3, differential targets showed allele-specific H3K27me3 in hybrids. Five Ler-specific targets showed the active mark H3K4me3 in Col and for this group, differential H3K27me3 enrichment accorded to expression variation. On the other hand, the majority of Ler-specific targets were not expressed in Col, Ler or 17 other accessions. Instead of H3K27me3, the antagonistic mark H3K9me2 and other heterochromatic features were observed at these loci in Col. These loci were frequently flanked by transposable elements, which were often missing in the Ler genome assembly. Conclusion There is little variation in H3K27me3 occupancy within the species, although H3K27me3 targets were previously shown as overrepresented among differentially expressed genes. The existing variation in H3K27me3 seems mostly explained by flanking polymorphic transposable elements. These could nucleate heterochromatin, which then spreads into neighboring H3K27me3 genes, thus converting them to H3K9me2 targets. PMID:23253144

Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer

PubMed Central

Wang, Denong; Tang, Jin; Liu, Shaoyi

2015-01-01

Using carbohydrate microarrays, we explored potential natural ligands of antitumor monoclonal antibody HAE3. This antibody was raised against a murine mammary tumor antigen but was found to cross-react with a number of human epithelial tumors in tissues. Our carbohydrate microarray analysis reveals that HAE3 is specific for an O-glycan cryptic epitope that is normally hidden in the cores of blood group substances. Using HAE3 to screen tumor cell surface markers by flow cytometry, we found that the HAE3 glycoepitope, gpHAE3, was highly expressed by a number of human breast cancer cell lines, including some triple-negative cancers that lack the estrogen, progesterone, and Her2/neu receptors. Taken together, we demonstrate that HAE3 recognizes a conserved cryptic glycoepitope of blood group precursors, which is nevertheless selectively expressed and surface-exposed in certain breast tumor cells. The potential of this class of O-glycan cryptic antigens in breast cancer subtyping and targeted immunotherapy warrants further investigation. PMID:26539555

Comparison of motives underlying food choice and barriers to healthy eating among low medium income consumers in Uruguay.

PubMed

Ares, Gastón; Machín, Leandro; Girona, Alejandra; Curutchet, María Rosa; Giménez, Ana

2017-05-18

Interventions aimed at changing dietary patterns should be designed based on the main motives underlying the food choices of specific target populations. The aim of the present study was to identify motives underlying food choice and barriers to healthy eating among consumers in two socioeconomic levels in Uruguay. Eleven focus groups were carried out with a total of 76 participants. Six of the groups involved low income participants and the others were conducted with middle income participants. Discussions were held around frequently consumed products, motives underlying food choices and barriers to healthy eating. Results confirmed the strong influence of income level on motives underlying food choice and barriers to the adoption of healthy eating. Low income participants described their choices as mainly driven by economic factors and satiety, whereas convenience was the main determinant of food selection for middle income participants. Implications for the design of public policies targeted at each group are discussed.

Developing a Multiple Caregiver Group for Caregivers of Adolescents With Disruptive Behaviors.

PubMed

Oruche, Ukamaka M; Robb, Sheri L; Aalsma, Matt; Pescosolido, Bernice; Brown-Podgorski, Brittany; Draucker, Claire Burke

2017-12-01

This article describes the development of a 6-week multiple caregiver group intervention for primary caregivers of adolescents diagnosed with Oppositional Defiant Disorder or Conduct Disorder in low-income African American families. The intervention is aimed at increasing the primary caregivers' self-efficacy in managing interactions within the family and especially with child serving educational, mental health, juvenile justice, and child welfare systems. Development of the intervention involved seven iterative activities performed in a collaborative effort between an interdisciplinary academic team, community engagement specialists, members of the targeted population, and clinical partners from a large public mental health system. The intervention development process described in this article can provide guidance for teams that aim to develop new mental health interventions that target specific outcomes in populations with unique needs. Copyright © 2017 Elsevier Inc. All rights reserved.

The impacts of fear and disgust on the perceived effectiveness of smoking warning labels: a study on Turkish university students.

PubMed

Tugrul, Tugba Orten

2015-03-01

This study investigated the perceived effectiveness of pictorial warning labels on cigarette packages on Turkish university students. In particular, the impacts of fear and disgust elicited by these labels were examined using the smoking decision process model. A survey was conducted with 344 undergraduate students at a private university in Izmir, the third largest city of Turkey. The findings showed differences in levels of fear and disgust evoked by pictorial warning labels for each stage in the smoking decision process, which in turn led to differences in the perceived effectiveness of the labels. Thus, this study underlines the importance of tailoring antismoking messages according to specific target groups and also suggests considering the smoking-decision-process model as segments and targeting groups in creating effective messages. © 2013 APJPH.

Outreach to Underrepresented Groups in Plasma Physics

NASA Astrophysics Data System (ADS)

Dominguez, A.; Zwicker, A.; Ortiz, D.; Greco, S. L.

2017-10-01

Physics, and specifically plasma physics, has a recruitment and retention problem for women and historically underrepresented minorities at all levels of their academic careers. For example, women make up approximately 8% of the APS-DPP membership while making up 13% of APS membership at large. In this presentation, we describe outreach activities we have undertaken targeting retention of these groups after their undergraduate careers. These include: Targeted recruitment visits for undergraduate research internships, as well as plasma physics workshops aimed at undergraduate women in physics, faculty members of minority serving institutions, and underrepresented undergraduates. After the first year of implementation, we have already seen results, including students reached through these programs participating in SULI undergraduate internships at PPPL. This work was support by a Grant from the DOE Office of Workforce Development for Teachers and Scientists (WDTS).

Microbial population Diversity of indigenous acidophilic bacteria for recovering the valuable resources

NASA Astrophysics Data System (ADS)

Kim, B.; Cho, K.; Lee, D.; Choi, N.; Park, C.

2011-12-01

A taxon- or group-specific PCR primer serves as a valuable tool for studying the bioleaching mechanisms of a particular group of microorganisms. Especially for an uncultured (or very difficult to isolate from their environments) group of microorganisms, the group-specific PCR primer is essential for the investigation of distribution patterns and the estimation of genetic diversity of the target microorganisms. This study investigated the Biodiversity through molecular biology method using the three different indigenous acidophilic bacteria collected from acid mine drainage in Go-seong and Yeon-hwa, Korea and acidic hot spring in Hatchnobaru, Japan. We performed the optical analysis (phase-contrast microscope and SEM), base sequencing. In the phase-contrast microscope(X 4,000) and SEM analysis, the rod-shaped bacteria with 1μm in length were observed. The results of base sequencing using EzTaxon server data revealed Acidithiobacillus ferrooxidans (Go-seong - 97.79%, Yeon-hwa - 97.90% and Hatchnobaru - 97.97%)

Sex differences in response to targeted kyphosis specific exercise and posture training in community-dwelling older adults: a randomized controlled trial.

PubMed

Katzman, Wendy B; Parimi, Neeta; Gladin, Amy; Poltavskiy, Eduard A; Schafer, Anne L; Long, Roger K; Fan, Bo; Wong, Shirley S; Lane, Nancy E

2017-12-04

Hyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis-specific exercise intervention are not known. We conducted a randomized controlled trial of a targeted kyphosis-specific exercise and postural training program on the primary outcome Cobb angle of kyphosis, and investigated whether the magnitude of change differed between men and women. One hundred twelve participants aged ≥60 years with kyphosis ≥40° were enrolled and randomized to exercise or waitlist control, and 101 participants had analyzable baseline and follow-up radiographs for Cobb angle measurements. A group intervention including 10 participants per group was delivered by a physical therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for 3 months before receiving a delayed intervention. Primary outcome was change from baseline to 3-months in Cobb angle measured from standing lateral spine radiographs. Secondary outcomes included change over 3-months in kyphometer-measured kyphosis, physical function and quality of life. Groups were combined for analysis after both received the intervention, and sex differences in response to the intervention were tested with ANOVA. Participants (60 women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD = 12.2) degrees at baseline. The active group had higher baseline modified Physical Performance Test scores than control, p = 0.03. Men had greater baseline kyphometer-measured kyphosis, p = 0.09, and higher bone mineral density (BMD), spine strength, more vertebral fractures and diffuse idiopathic skeletal hyperostosis (DISH) than women, p ≤ 0.01. There was no statistically significant difference between groups in change in Cobb at 3-months, p = 0.09, however change in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p < 0.001, favoring the active group. There were no differences between men and women in change in either kyphosis measurement after intervention, p > 0.1. A 3-month targeted spine strengthening exercise and posture training program reduced kyphometer-measured, but not radiographic-measured kyphosis. Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and DISH, sex did not affect treatment response. ClinicalTrials.gov Identifier: NCT01766674.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD.

PubMed

Ruzicka, Marcel; Quinn, Robert R; McFarlane, Phil; Hemmelgarn, Brenda; Ramesh Prasad, G V; Feber, Janusz; Nesrallah, Gihad; MacKinnon, Martin; Tangri, Navdeep; McCormick, Brendan; Tobe, Sheldon; Blydt-Hansen, Tom D; Hiremath, Swapnil

2014-06-01

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Conformational Ensembles of Calmodulin Revealed by Nonperturbing Site-Specific Vibrational Probe Groups.

PubMed

Kelly, Kristen L; Dalton, Shannon R; Wai, Rebecca B; Ramchandani, Kanika; Xu, Rosalind J; Linse, Sara; Londergan, Casey H

2018-03-22

Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound and apo calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration. The surprising lack of perturbation suggests that this probe group could be applied directly in many protein-protein binding interfaces. The infrared absorption bands for the probe groups reported many dramatic changes in the probes' local environments as CaM went from apo- to calcium-saturated to target peptide-bound conditions, including large frequency shifts and a variety of line shapes from narrow (interpreted as a rigid and invariant local environment) to symmetric to broad and asymmetric (likely from multiple coexisting and dynamically exchanging structures). The fast intrinsic time scale of infrared spectroscopy means that the line shapes report directly on site-specific details of calmodulin's variable structural distribution. Though quantitative interpretation of the probe line shapes depends on a direct connection between simulated ensembles and experimental data that does not yet exist, formation of such a connection to data such as that reported here would provide a new way to evaluate conformational ensembles from data that directly contains the structural distribution. The calmodulin probe sites developed here will also be useful in evaluating the binding mode of calmodulin with many uncharacterized regulatory targets.

Randomized Comparative Trial of a Social Cognitive Skills Group for Children With Autism Spectrum Disorder

PubMed Central

Soorya, Latha V.; Weinger, Paige M.; Beck, Todd; Soffes, Sarah; Halpern, Danielle; Gorenstein, Michelle; Kolevzon, Alexander; Buxbaum, Joseph; Wang, A. Ting

2015-01-01

Objective This study evaluated the efficacy of a targeted social skills training group in school-aged children with autism spectrum disorder (ASD). The intervention, NETT (Nonverbal communication, Emotion recognition, and Theory of mind Training), is a 12-session cognitive-behavioral intervention (CBI) for verbal, school-aged children targeting ASD-specific social behavioral impairments. Method Sixty-nine children with ASD, 8 to 11 years of age with verbal IQs greater than 70, participated in a randomized comparative trial to examine the efficacy of NETT relative to a facilitated play group. Treatment outcomes included caregiver reports of social behavior and neuropsychological assessments of social cognition conducted by blinded raters. Outcomes were collected at baseline, endpoint, and three months posttreatment. Results Significant improvements were found on social behavior outcomes such as nonverbal communication, empathic responding, and social relations in the NETT condition relative to the active control at endpoint. Verbal IQ and age moderated the interaction effect on social behavior with higher verbal IQ and older age associated with improvements in the CBI condition. No significant improvements were found on social cognitive outcomes. No significant group differences were found at three-month follow-up conducted with approximately half the sample (n=34). Conclusion These data indicate that targeted CBI social skills groups such as NETT improve social communication deficits in verbal, school-aged children with ASD. The moderating effects of high verbal IQ suggest a need to consider participant and treatment characteristics associated with outcomes in future studies. PMID:25721186

Discovering ligands for a microRNA precursor with peptoid microarrays

PubMed Central

Chirayil, Sara; Chirayil, Rachel; Luebke, Kevin J.

2009-01-01

We have screened peptoid microarrays to identify specific ligands for the RNA hairpin precursor of miR-21, a microRNA involved in cancer and heart disease. Microarrays were printed by spotting a library of 7680 N-substituted oligoglycines (peptoids) onto glass slides. Two compounds on the array specifically bind RNA having the sequence and predicted secondary structure of the miR-21 precursor hairpin and have specific affinity for the target in solution. Their binding induces a conformational change around the hairpin loop, and the most specific compound recognizes the loop sequence and a bulged uridine in the proximal duplex. Functional groups contributing affinity and specificity were identified, and by varying a critical methylpyridine group, a compound with a dissociation constant of 1.9 μM for the miR-21 precursor hairpin and a 20-fold discrimination against a closely-related hairpin was created. This work describes a systematic approach to discovery of ligands for specific pre-defined novel RNA structures. It demonstrates discovery of new ligands for an RNA for which no specific lead compounds were previously known by screening a microarray of small molecules. PMID:19561197

Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

PubMed

Hua, Susan; Cabot, Peter J

2013-01-01

The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein injection using liquid scintillation counting (LSC). Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund's Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions.

Sentence Recall by Children With SLI Across Two Nonmainstream Dialects of English

PubMed Central

McDonald, Janet L.; Seidel, Christy M.; Hegarty, Michael

2016-01-01

Purpose The inability to accurately recall sentences has proven to be a clinical marker of specific language impairment (SLI); this task yields moderate-to-high levels of sensitivity and specificity. However, it is not yet known if these results hold for speakers of dialects whose nonmainstream grammatical productions overlap with those that are produced at high rates by children with SLI. Method Using matched groups of 70 African American English speakers and 36 Southern White English speakers and dialect-strategic scoring, we examined children's sentence recall abilities as a function of their dialect and clinical status (SLI vs. typically developing [TD]). Results For both dialects, the SLI group earned lower sentence recall scores than the TD group with sensitivity and specificity values ranging from .80 to .94, depending on the analysis. Children with SLI, as compared with TD controls, manifested lower levels of verbatim recall, more ungrammatical recalls when the recall was not exact, and higher levels of error on targeted functional categories, especially those marking tense. Conclusion When matched groups are examined and dialect-strategic scoring is used, sentence recall yields moderate-to-high levels of diagnostic accuracy to identify SLI within speakers of nonmainstream dialects of English. PMID:26501934

Drilling Fluid Contamination during Riser Drilling Quantified by Chemical and Molecular Tracers

NASA Astrophysics Data System (ADS)

Inagaki, F.; Lever, M. A.; Morono, Y.; Hoshino, T.

2012-12-01

Stringent contamination controls are essential to any type of microbiological investigation, and are particularly challenging in ocean drilling, where samples are retrieved from hundreds of meters below the seafloor. In summer 2012, Integrated Ocean Drilling Expedition 337 aboard the Japanese vessel Chikyu pioneered the use of chemical tracers in riser drilling while exploring the microbial ecosystem of coalbeds 2 km below the seafloor off Shimokita, Japan. Contamination tests involving a perfluorocarbon tracer that had been successfully used during past riserless drilling expeditions were complemented by DNA-based contamination tests. In the latter, likely microbial contaminants were targeted via quantitative polymerase chain reaction assays using newly designed, group-specific primers. Target groups included potential indicators of (a) drilling mud viscosifiers (Xanthomonas, Halomonas), (b) anthropogenic wastewater (Bifidobacterium, Blautia, Methanobrevibacter), and (c) surface seawater (SAR 11, Marine Group I Archaea). These target groups were selected based on past evidence suggesting viscosifiers, wastewater, and seawater as the main sources of microbial contamination in cores retrieved by ocean drilling. Analyses of chemical and molecular tracers are in good agreement, and indicate microorganisms associated with mud viscosifiers as the main contaminants during riser drilling. These same molecular analyses are then extended to subseafloor samples obtained during riserless drilling operations. General strategies to further reduce the risk of microbial contamination during riser and riserless drilling operations are discussed.

Cy5 maleimide labelling for sensitive detection of free thiols in native protein extracts: identification of seed proteins targeted by barley thioredoxin h isoforms.

PubMed Central

Maeda, Kenji; Finnie, Christine; Svensson, Birte

2004-01-01

Barley thioredoxin h isoforms HvTrxh1 and HvTrxh2 differ in temporal and spatial distribution and in kinetic properties. Target proteins of HvTrxh1 and HvTrxh2 were identified in mature seeds and in seeds after 72 h of germination. Improvement of the established method for identification of thioredoxin-targeted proteins based on two-dimensional electrophoresis and fluorescence labelling of thiol groups was achieved by application of a highly sensitive Cy5 maleimide dye and large-format two-dimensional gels, resulting in a 10-fold increase in the observed number of labelled protein spots. The technique also provided information about accessible thiol groups in the proteins identified in the barley seed proteome. In total, 16 different putative target proteins were identified from 26 spots using tryptic in-gel digestion, matrix-assisted laser-desorption ionization-time-of-flight MS and database search. HvTrxh1 and HvTrxh2 were shown to have similar target specificity. Barley alpha-amylase/subtilisin inhibitor, previously demonstrated to be reduced by both HvTrxh1 and HvTrxh2, was among the identified target proteins, confirming the suitability of the method. Several alpha-amylase/trypsin inhibitors, some of which are already known as target proteins of thioredoxin h, and cyclophilin known as a target protein of m-type thioredoxin were also identified. Lipid transfer protein, embryospecific protein, three chitinase isoenzymes, a single-domain glyoxalase-like protein and superoxide dismutase were novel identifications of putative target proteins, suggesting new physiological roles of thioredoxin h in barley seeds. PMID:14636158

Targeted mass media interventions promoting healthy behaviours to reduce risk of non-communicable diseases in adult, ethnic minorities.

PubMed

Mosdøl, Annhild; Lidal, Ingeborg B; Straumann, Gyri H; Vist, Gunn E

2017-02-17

Physical activity, a balanced diet, avoidance of tobacco exposure, and limited alcohol consumption may reduce morbidity and mortality from non-communicable diseases (NCDs). Mass media interventions are commonly used to encourage healthier behaviours in population groups. It is unclear whether targeted mass media interventions for ethnic minority groups are more or less effective in changing behaviours than those developed for the general population. To determine the effects of mass media interventions targeting adult ethnic minorities with messages about physical activity, dietary patterns, tobacco use or alcohol consumption to reduce the risk of NCDs. We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, ERIC, SweMed+, and ISI Web of Science until August 2016. We also searched for grey literature in OpenGrey, Grey Literature Report, Eldis, and two relevant websites until October 2016. The searches were not restricted by language. We searched for individual and cluster-randomised controlled trials, controlled before-and-after studies (CBA) and interrupted time series studies (ITS). Relevant interventions promoted healthier behaviours related to physical activity, dietary patterns, tobacco use or alcohol consumption; were disseminated via mass media channels; and targeted ethnic minority groups. The population of interest comprised adults (≥ 18 years) from ethnic minority groups in the focal countries. Primary outcomes included indicators of behavioural change, self-reported behavioural change and knowledge and attitudes towards change. Secondary outcomes were the use of health promotion services and costs related to the project. Two authors independently reviewed the references to identify studies for inclusion. We extracted data and assessed the risk of bias in all included studies. We did not pool the results due to heterogeneity in comparisons made, outcomes, and study designs. We describe the results narratively and present them in 'Summary of findings' tables. We judged the quality of the evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Six studies met the inclusion criteria, including three RCTs, two cluster-RCTs and one ITS. All were conducted in the USA and comprised targeted mass media interventions for people of African descent (four studies), Spanish-language dominant Latino immigrants (one study), and Chinese immigrants (one study). The two latter studies offered the intervention in the participants' first language (Spanish, Cantonese, or Mandarin). Three interventions targeted towards women only, one pregnant women specifically. We judged all studies as being at unclear risk of bias in at least one domain and three studies as being at high risk of bias in at least one domain.We categorised the findings into three comparisons. The first comparison examined mass media interventions targeted at ethnic minorities versus an equivalent mass media intervention intended for the general population. The one study in this category (255 participants of African decent) found little or no difference in effect on self-reported behavioural change for smoking and only small differences in attitudes to change between participants who were given a culturally specific smoking cessation booklet versus a booklet intended for the general population. We are uncertain about the effect estimates, as assessed by the GRADE methodology (very low quality evidence of effect). No study provided data for indicators of behavioural change or adverse effects.The second comparison assessed targeted mass media interventions versus no intervention. One study (154 participants of African decent) reported effects for our primary outcomes. Participants in the intervention group had access to 12 one-hour live programmes on cable TV and received print material over three months regarding nutrition and physical activity to improve health and weight control. Change in body mass index (BMI) was comparable between groups 12 months after the baseline (low quality evidence). Scores on a food habits (fat behaviours) and total leisure activity scores changed favourably for the intervention group (very low quality evidence). Two other studies exposed entire populations in geographical areas to radio advertisements targeted towards African American communities. Authors presented effects on two of our secondary outcomes, use of health promotion services and project costs. The campaign message was to call smoking quit lines. The outcome was the number of calls received. After one year, one study reported 18 calls per estimated 10,000 targeted smokers from the intervention communities (estimated target population 310,500 persons), compared to 0.2 calls per estimated 10,000 targeted smokers from the control communities (estimated target population 331,400 persons) (moderate quality evidence). The ITS study also reported an increase in the number of calls from the target population during campaigns (low quality evidence). The proportion of African American callers increased in both studies (low to very low quality evidence). No study provided data on knowledge and attitudes for change and adverse effects. Information on costs were sparse.The third comparison assessed targeted mass media interventions versus a mass media intervention plus personalised content. Findings are based on three studies (1361 participants). Participants in these comparison groups received personal feedback. Two of the studies recorded weight changes over time. Neither found significant differences between the groups (low quality evidence). Evidence on behavioural changes, and knowledge and attitudes typically found some effects in favour of receiving personalised content or no significant differences between groups (very low quality evidence). No study provided data on adverse effects. Information on costs were sparse. The available evidence is inadequate for understanding whether mass media interventions targeted toward ethnic minority populations are more effective in changing health behaviours than mass media interventions intended for the population at large. When compared to no intervention, a targeted mass media intervention may increase the number of calls to smoking quit line, but the effect on health behaviours is unclear. These studies could not distinguish the impact of different components, for instance the effect of hearing a message regarding behavioural change, the cultural adaptation to the ethnic minority group, or increase reach to the target group through more appropriate mass media channels. New studies should explore targeted interventions for ethnic minorities with a first language other than the dominant language in their resident country, as well as directly compare targeted versus general population mass media interventions.

SUMO proteases as potential targets for cancer therapy.

PubMed

Bialik, Piotr; Woźniak, Katarzyna

2017-12-08

Sumoylation is one of the post-translational modifications of proteins, responsible for the regulation of many cellular processes, such as DNA replication and repair, transcription, signal transduction and nuclear transport. During sumoylation, SUMO proteins are covalently attached to the ε-amino group of lysine in target proteins via an enzymatic cascade that requires the sequential action of E1, E2 and E3 enzymes. An important aspect of sumoylation is its reversibility, which involves SUMO-specific proteases called SENPs. SENPs (sentrin/SUMO-specific proteases) catalyze the deconjugation of SUMO proteins using their isopeptidase activity. These enzymes participate through hydrolase activity in the reaction of SUMO protein maturation, which involves the removal of a short fragment on the C-terminus of SUMO inactive form and exposure two glycine residues. SENPs are important for maintaining the balance between sumoylated and desumoylated proteins required for normal cellular physiology. Six SENP isoforms (SENP1, SENP2, SENP3, SENP5, SENP6 and SENP7) have been identified in mammals. These SENPs can be divided into three subfamilies based on their sequence homology, substrate specificity and subcellular localization. Results of studies indicate the role of SUMO proteases in the development of human diseases including cancer, suggesting that these proteins may be attractive targets for new drugs.

Recollection Training and Transfer Effects in Alzheimer's Disease: Effectiveness of the Repetition-Lag Procedure

ERIC Educational Resources Information Center

Boller, Benjamin; Jennings, Janine M.; Dieudonne, Benedicte; Verny, Marc; Ergis, Anne-Marie

2012-01-01

Objective: This study was designed to extend the use of a memory training technique, known as the repetition-lag procedure, to Alzheimer patients. The specificity of this procedure is to target the process of recollection for improvement. Method: A group of 12 patients were trained individually for 6 h. The training procedure consisted of a series…

The Effects of the Use of English in Polish Product Advertisements: Implications for English for Business Purposes

ERIC Educational Resources Information Center

Planken, Brigitte; van Meurs, Frank; Radlinska, Ania

2010-01-01

English has come to be widely used for the specific purpose of advertising to reach international target groups in various countries. However, few studies to date have investigated the use--and effects of--English in advertising in Eastern European countries. This study investigated the effect of English in advertisements from Polish glossy…

Strategies for Increasing IT Enrollment: Recruiting, Retaining and Encouraging the Transfer of Women and Underrepresented Groups to Four-Year Colleges

ERIC Educational Resources Information Center

Tupper, Donna Hiestand; Leitherer, Barbara; Sorkin, Sylvia; Gore, Mary Elizabeth

2010-01-01

Through the support of the National Science Foundation,, The Community College of Baltimore County has begun two separate initiatives to increase the number of women and underrepresented minorities enrolled in technological majors. Started in 2003, the Grace Hopper Scholars Program targets specifically women interested in careers in technology,…

Presence and Image of Women in the Information Media Aimed at Adolescents Aged 10 to 16.

ERIC Educational Resources Information Center

Dansereau, Stephanie; Maranda, Jeanne

An exploratory study identified the areas of information most commonly featured in the printed and electronic media designed specifically for adolescents aged 10-16 and also identified the presence and role of women in the information targeted to this age group. A content analysis was made of both French- and English-language television programs…

South Dakota Kids Count Factbook: State and County Profiles of Child Well-Being, 1993.

ERIC Educational Resources Information Center

Haven, Terry; Dykstra, De Vee

This Kids Count factbook reports findings of a 1993 state project conducted as part of a national program designed to promote accountability of children through a nationwide profile of their condition. The data are used to encourage the private and public sectors to target specific problems and groups of children for programming and fund raising…

The Economic Benefits of Adult Learning to Low-Qualified Young Adults: Do Participation and Qualification Decrease the Risk of Unemployment?

ERIC Educational Resources Information Center

Knipprath, Heidi; De Rick, Katleen

2014-01-01

Policymakers worldwide consider participation in adult learning beneficial for employability, in particular for specific target groups. However, still little is known about the effect of adult learning pursued by low-qualified young adults on their employment prospects. On the basis of a Flemish longitudinal database, we study the determinants and…

Molecular Diversity of Bacteroidales in Fecal and Environmental Samples and Swine-Associated Subpopulations

PubMed Central

Lamendella, Regina; Li, Kent C.; Oerther, Daniel

2013-01-01

Several swine-specific microbial source tracking methods are based on PCR assays targeting Bacteroidales 16S rRNA gene sequences. The limited application of these assays can be explained by the poor understanding of their molecular diversity in fecal sources and environmental waters. In order to address this, we studied the diversity of 9,340 partial (>600 bp in length) Bacteroidales 16S rRNA gene sequences from 13 fecal sources and nine feces-contaminated watersheds. The compositions of major Bacteroidales populations were analyzed to determine which host and environmental sequences were contributing to each group. This information allowed us to identify populations which were both exclusive to swine fecal sources and detected in swine-contaminated waters. Phylogenetic and diversity analyses revealed that some markers previously believed to be highly specific to swine populations are shared by multiple hosts, potentially explaining the cross-amplification signals obtained with nontargeted hosts. These data suggest that while many Bacteroidales populations are cosmopolitan, others exhibit a preferential host distribution and may be able to survive different environmental conditions. This study further demonstrates the importance of elucidating the diversity patterns of targeted bacterial groups to develop more inclusive fecal source tracking applications. PMID:23160126

Paid advertising for AIDS prevention--would the ends justify the means?

PubMed Central

Donovan, R J; Jason, J; Gibbs, D A; Kroger, F

1991-01-01

An examination by the Centers for Disease Control and the Research Triangle Institute concluded that "hard-to-reach" populations could be reached with AIDS prevention messages through the broadcast and print media and that a study should be undertaken to assess whether paid placement of these messages could have an effect on HIV-related behaviors. The recommended target population for a study of paid advertising would be sexually active 18-24-year-old black urban dwellers. Its behavioral objectives would include abstinence and safer sex practices. For any evaluation of a paid advertising campaign to be valid, there would have to be extensive audience profiling, research into the development of the message, pretesting of the message, and involvement of the community. The proposed study would include measurement of various "dosage" levels of paid advertising, use of a no-intervention comparison group, and a novel data collection technique. Although a specific target group and specific messages would be involved, the evaluation would make a substantial contribution to resolving the broader issue of whether and how mass media should be used directly or indirectly to change or reinforce health-related behaviors. PMID:1659711

Specificity and modifiability of cognitive biases in hypochondriasis.

PubMed

Gropalis, Maria; Bleichhardt, Gaby; Hiller, Wolfgang; Witthöft, Michael

2013-06-01

According to cognitive-behavioral models of hypochondriasis (HYP), biased attentional and memory processes related to health threat stimuli are crucial for the development and maintenance of severe health anxiety. Little is known about the specificity, temporal stability, and modifiability of these biases via psychotherapy. In an emotional Stroop and subsequent recognition task, the authors compared attention and memory processes for health-related words (illnesses, bodily complaints, and panic-related words) in patients with HYP (n = 32), other somatoform disorders (SFD; n = 27), and panic disorder (PD; n = 25). A control group consisted of 31 healthy participants (CG). All patients were reexamined after 4 months of cognitive-behavioral therapy (CBT). Patients with HYP showed a significant attentional bias toward all 3 target word categories. Evidence for a specific bias was found only for the PD group. General recognition performance for health threat and neutral words was best in the HYP group. After therapy, attentional bias had clearly decreased in the HYP and SFD patients. Patients with HYP can be characterized by attentional bias and more elaborate verbal processing. These irregularities tend to disappear after psychotherapy.

Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects

PubMed Central

Lei, Yang; Nosoudi, Nasim; Vyavahare, Naren

2014-01-01

Background and aims Elastin-specific medial arterial calcification (MAC) is an arterial disease commonly referred as Monckeberg’s sclerosis. It causes significant arterial stiffness, and as yet, no clinical therapy exists to prevent or reverse it. We developed albumin nanoparticles (NPs) loaded with disodium ethylene diaminetetraacetic acid (EDTA) that were designed to target calcified elastic lamina when administrated by intravenous injection. Methods and Results We optimized NP size, charge, and EDTA-loading efficiency (150~200 nm, zeta potential of − 22.89 ~ − 31.72 mV, loading efficiency for EDTA ~20 %) for in vivo targeting in rats. These NPs released EDTA slowly for up to 5 days. In both ex-vivo study and in vivo study with injury-induced local abdominal aortic calcification, we showed that elastin antibody-coated and EDTA-loaded albumin NPs targeted the damaged elastic lamina while sparing healthy artery. Intravenous NP injections reversed elastin-specific MAC in rats after four injections over a 2-week period. EDTA-loaded albumin NPs did not cause the side effects observed in EDTA injection alone, such as decrease in serum calcium (Ca), increase in urine Ca, or toxicity to kidney. There was no bone loss in any treated groups. Conclusion We demonstrate that elastin antibody-coated and EDTA-loaded albumin NPs might be a promising nanoparticle therapy to reverse elastin-specific MAC and circumvent side effects associated with systemic EDTA chelation therapy. PMID:25285609

Novel gadopentetic acid-doped silica nanoparticles conjugated with YPSMA-1 targeting prostate cancer for MR imaging: an in vitro study.

PubMed

Jiang, Wei; He, Xiaojing; Fang, Huiying; Zhou, Xue; Ran, Haitao; Guo, Dajing

2018-05-05

The early diagnosis of prostate cancer (PCa) is particularly important for reducing its high mortality rate. With the development of molecular magnetic resonance imaging (MRI), early diagnosis via non-invasive imaging has become possible. In this study, gadopentetic acid (GA)-doped silica (Gd@SiO 2 ) was first synthesized by a reverse microemulsion method, and amino and carboxyl groups were then successively introduced onto the surface of this Gd@SiO 2 . After these steps, a monoclonal antibody (YPSMA-1) to prostate-specific membrane antigen (PSMA) was conjugated with carboxyl-modified Gd@SiO 2 (Gd@SiO 2 -COOH) nanoparticles (NPs) by the carbodiimide method. Gd@SiO 2 -Ab NPs were thus obtained as specific MR contrast agents for PCa-targeted imaging. Transmission electron microscopy showed that the Gd@SiO 2 -Ab NPs exhibited a dispersed spherical morphology with a relatively uniform size distribution. The Gd@SiO 2 -Ab NPs showed high stability and high the longitudinal relaxation rate (r 1 ). Cell-targeting experiments in vitro demonstrated the high potential of the synthesized NPs to target PSMA receptor-positive PCa cells. In vitro cytotoxicity assays showed that the Gd@SiO 2 -Ab NPs exhibited good biological safety. These results suggest that the synthesized Gd@SiO 2 -Ab NPs have great potential as specific MR contrast agents for PSMA receptor-positive PCa cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Influence of resistant starch on the SCFA production and cell counts of butyrate-producing Eubacterium spp. in the human intestine.

PubMed

Schwiertz, A; Lehmann, U; Jacobasch, G; Blaut, M

2002-01-01

The genus Eubacterium, which is the second most common genus in the human intestine, includes several known butyrate producers. We hypothesized that Eubacterium species play a role in the intestinal butyrate production and are inducible by resistant starch. In a human pilot study species-specific and group-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labelled oligonucleotide probes were used to quantify butyrogenic species of the genera Eubacterium, Clostridium and Ruminococcus. Following the intake of RS type III a significant increase in faecal butyrate but not in total SCFA was observed. However, increase in butyrate was not accompanied by a proliferation in the targeted bacteria. The tested Eubacterium species have the capacity to produce butyrate but do not appear to play a major role for butyric acid production in the human intestine. In view of the fact that the bacteria responsible for butyrate production are largely unknown, it is still difficult to devise a dietary intervention to stimulate butyrogenic bacteria in a targeted way.

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth

PubMed Central

Sengupta, Soma; Weeraratne, Shyamal Dilhan; Sun, Hongyu; Phallen, Jillian; Rallapalli, Sundari K.; Teider, Natalia; Kosaras, Bela; Amani, Vladimir; Pierre-Francois, Jessica; Tang, Yujie; Nguyen, Brian; Yu, Furong; Schubert, Simone; Balansay, Brianna; Mathios, Dimitris; Lechpammer, Mirna; Archer, Tenley C.; Tran, Phuoc; Reimer, Richard J.; Cook, James M.; Lim, Michael; Jensen, Frances E.; Pomeroy, Scott L.; Cho, Yoon-Jae

2013-01-01

Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors, and importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABR5, which encodes the α-subunit of the GABAA receptor complex, in aggressive MYC-driven, “Group 3” medulloblastomas. We hypothesized that modulation of α-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABR5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent α5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABR5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOX5 target gene expression. siRNA-mediated knockdown of HOX5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABR5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOX5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of α5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor. PMID:24196163

Specific or nonspecific? Evaluation of band, baseline, and cognitive specificity of sensorimotor rhythm- and gamma-based neurofeedback.

PubMed

Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme

2017-10-01

Neurofeedback (NF) is often criticized because of the lack of empirical evidence of its specificity. Our present study thus focused on the specificity of NF on three levels: band specificity, cognitive specificity, and baseline specificity. Ten healthy middle-aged individuals performed ten sessions of SMR (sensorimotor rhythm, 12-15Hz) NF training. A second group (N=10) received feedback of a narrow gamma band (40-43Hz). Effects of NF on EEG resting measurements (tonic EEG) and cognitive functions (memory, intelligence) were evaluated using a pre-post design. Both training groups were able to linearly increase the target training frequencies (either SMR or gamma), indicating the trainability of these EEG frequencies. Both NF training protocols led to nonspecific changes in other frequency bands during NF training. While SMR NF only led to concomitant changes in slower frequencies, gamma training affected nearly the whole power spectrum. SMR NF specifically improved memory functions. Gamma training showed only marginal effects on cognitive functions. SMR power assessed during resting measurements significantly increased after SMR NF training compared to a pre-assessment, indicating specific effects of SMR NF on baseline/tonic EEG. The gamma group did not show any pre-post changes in their EEG resting activity. In conclusion, SMR NF specifically affects cognitive functions (cognitive specificity) and tonic EEG (baseline specificity), while increasing SMR during NF training nonspecifically affects slower EEG frequencies as well (band non-specificity). Gamma NF was associated with nonspecific effects on the EEG power spectrum during training, which did not lead to considerable changes in cognitive functions or baseline EEG activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

PubMed

Kalunian, K C

2016-09-01

Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were increased in anifrolumab-treated patients. Anifrolumab is currently in pivotal phase III studies. Data appear to support the concept that targeting type I interferon in SLE patients associates with clinical efficacy and safety. Further data are forthcoming from ongoing phase III clinical trials of anifrolumab. Other drug development efforts should be considered that target plasmacytoid dendritic cells and toll like receptors given the effects these components have on interferon production. © The Author(s) 2016.

Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.

PubMed

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H P; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Calin, George A; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-07-01

The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma. First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile. These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. ©2015 American Association for Cancer Research.

Targeting interleukin-11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens

PubMed Central

Karjalainen, Katja; Jaalouk, Diana E.; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H. P.; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J.; O’Brien, Susan; Kantarjian, Hagop M.; Cortes, Jorge E.; Calin, George A.; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-01-01

Purpose The interleukin-11 receptor (IL-11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here we evaluated the IL-11R as a candidate therapeutic target in human leukemia and lymphoma. Experimental Design and Results First, we show that the IL-11R protein is expressed in a variety of human leukemia- and lymphoma derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, while expression is absent from non-malignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11) specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL-11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analog with an apparent improved anti-leukemia cell profile. Conclusion These results indicate (i) that the IL-11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. PMID:25779950

Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

PubMed Central

Son, Gyung Mo; Kim, Hyun Yul; Ryu, Je Ho; Chu, Chong Woo; Kang, Dae Hwan; Park, Su Bum; Jeong, Young-IL

2014-01-01

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting. PMID:25216338

Saccharomyces boulardii and Bacillus subtilis B10 modulate TLRs mediated signaling to induce immunity by chicken BMDCs.

PubMed

Rajput, Imran Rashid; Hussain, Altaf; Li, Ya Li; Zhang, Xiaoping; Xu, Xin; Long, Mao Yu; You, Dong Yu; Li, Wei Fen

2014-01-01

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a critical role to activate immune response. They may be targeted for immunomodulation by microbes, including probiotics. In this study, chicken bone marrow dendrite cells (chi-BMDCs) were stimulated with lipopolysachride (LPS), Saccharomyces boulardii (Sb), Bacillus subtilis B10 (Bs), co-culture of Sb + Bs and phosphate buffer saline (PBS) as a control group (Ctr) at 3, 6, and 12 h intervals. Results revealed that treatment groups modulated the phenotype and biological functions of chi-BMDCs. Scan electron microscopy showed attachment of probiotics on the surface of chi-BMDCs. Additionally transmission electron microscopy (TEM) revealed efficiently engulfing and degradation of probiotics. Gene expression levels of MHC-II, CD40, CD80 and CD86 up-regulated in stimulated groups. Furthermore, toll-like receptors TLR1, TLR2, TLR4, and chicken specific TLR15 expressions were improved and downstream associated factors MyD88, TRAF6, TAB1, and NFκ-B mRNA levels increased in all treatment groups as compared to control. Surprisingly, NFκ-B response was noted significant higher in LPS treatment among all groups. Moreover, IL-1β, IL-17, IL-4, TGF-β, and IL-10 production levels were found higher, and lower concentration of INF-γ and IL-8 were observed in Sb, Bs, and Sb + Bs treatment groups. In contrast, LPS groups showed prominent increase in IL-12, INF-γ, and IL-8 concentration levels as compared to control group. Altogether, these results emphasize a potentially important role of Saccharomyces boulardii and Bacillus subtilis B10 in modulating immunological functions of chi-BMDCs by targeting specific toll like receptors (TLRs) and associated factors. The role of probiotics on chi-BMDCs functionality in a non-mammalian species have been presented for the first time. © 2013 Wiley Periodicals, Inc.

Grouping and Read-Across Approaches for Risk Assessment of Nanomaterials

PubMed Central

Oomen, Agnes G.; Bleeker, Eric A. J.; Bos, Peter M. J.; van Broekhuizen, Fleur; Gottardo, Stefania; Groenewold, Monique; Hristozov, Danail; Hund-Rinke, Kerstin; Irfan, Muhammad-Adeel; Marcomini, Antonio; Peijnenburg, Willie J. G. M.; Rasmussen, Kirsten; Sánchez Jiménez, Araceli; Scott-Fordsmand, Janeck J.; van Tongeren, Martie; Wiench, Karin; Wohlleben, Wendel; Landsiedel, Robert

2015-01-01

Physicochemical properties of chemicals affect their exposure, toxicokinetics/fate and hazard, and for nanomaterials, the variation of these properties results in a wide variety of materials with potentially different risks. To limit the amount of testing for risk assessment, the information gathering process for nanomaterials needs to be efficient. At the same time, sufficient information to assess the safety of human health and the environment should be available for each nanomaterial. Grouping and read-across approaches can be utilised to meet these goals. This article presents different possible applications of grouping and read-across for nanomaterials within the broader perspective of the MARINA Risk Assessment Strategy (RAS), as developed in the EU FP7 project MARINA. Firstly, nanomaterials can be grouped based on limited variation in physicochemical properties to subsequently design an efficient testing strategy that covers the entire group. Secondly, knowledge about exposure, toxicokinetics/fate or hazard, for example via properties such as dissolution rate, aspect ratio, chemical (non-)activity, can be used to organise similar materials in generic groups to frame issues that need further attention, or potentially to read-across. Thirdly, when data related to specific endpoints is required, read-across can be considered, using data from a source material for the target nanomaterial. Read-across could be based on a scientifically sound justification that exposure, distribution to the target (fate/toxicokinetics) and hazard of the target material are similar to, or less than, the source material. These grouping and read-across approaches pave the way for better use of available information on nanomaterials and are flexible enough to allow future adaptations related to scientific developments. PMID:26516872

Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass-Vaccination Campaign in Mali.

PubMed

Basta, Nicole E; Borrow, Ray; Berthe, Abdoulaye; Dembélé, Awa Traoré Eps; Onwuchekwa, Uma; Townsend, Kelly; Boukary, Rahamatou M; Mabey, Lesley; Findlow, Helen; Bai, Xilian; Sow, Samba O

2015-11-15

In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide-tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%-99.7%) maintained NmA-specific rSBA titers ≥8, the accepted threshold for protection; 98.6% (95% CI, 97.8%-99.4%) had titers ≥128, and 89.5% (95% CI, 87.4%-91.6%) had titers ≥1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ≥2 µg/mL were found in 88.5% (95% CI, 86.3%-90.7%) of participants. Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Interpersonal Attraction in Dyads and Groups: Effects of the Hearts of the Beholder and the Beheld.

PubMed

Malloy, Thomas E

2018-04-01

Dyadic interpersonal attraction (IA) was studied within groups of very highly acquainted family members, friends and co-workers. IA was determined by the perceiver (i.e., the heart of the beholder), the target (i.e., the heart of the beheld), and in specific dyads, by the unique combination of the two. The consistency of one's attraction to others and others' attraction to the person across groups were addressed using the key person design . Attraction to a person in one group was independent of attraction to that person in another, although people predicted that members of different groups were similarly attracted to them. A new model (ARRMA) was specified to simultaneously study assumed reciprocity, actual reciprocity, and metaperception accuracy of attraction (i.e., accurate predictions of others' attraction to oneself). Assumed reciprocity of IA was substantial at the individual and dyadic levels. Reciprocity of attraction at the individual level, a heretofore unconfirmed "plausible hypothesis" (Newcomb, 1979), was supported; dyadic reciprocity was weak. Meta-accuracy of IA was observed among individuals but was weak in dyads. Perceived interpersonal similarity predicted IA among individuals and in specific dyads. Considering dyadic attraction within and between groups, and the use of componential analysis permitted the specification of new IA phenomena and resolved a long standing theoretical problem regarding the reciprocity of attraction.

Effect of tonic pain on motor acquisition and retention while learning to reach in a force field.

PubMed

Lamothe, Mélanie; Roy, Jean-Sébastien; Bouffard, Jason; Gagné, Martin; Bouyer, Laurent J; Mercier, Catherine

2014-01-01

Most patients receiving intensive rehabilitation to improve their upper limb function experience pain. Despite this, the impact of pain on the ability to learn a specific motor task is still unknown. The aim of this study was to determine whether the presence of experimental tonic pain interferes with the acquisition and retention stages of motor learning associated with training in a reaching task. Twenty-nine healthy subjects were randomized to either a Control or Pain Group (receiving topical capsaicin cream on the upper arm during training on Day 1). On two consecutive days, subjects made ballistic movements towards two targets (NEAR/FAR) using a robotized exoskeleton. On Day 1, the task was performed without (baseline) and with a force field (adaptation). The adaptation task was repeated on Day 2. Task performance was assessed using index distance from the target at the end of the reaching movement. Motor planning was assessed using initial angle of deviation of index trajectory from a straight line to the target. Results show that tonic pain did not affect baseline reaching. Both groups improved task performance across time (p<0.001), but the Pain group showed a larger final error (under-compensation) than the Control group for the FAR target (p = 0.030) during both acquisition and retention. Moreover, a Group x Time interaction (p = 0.028) was observed on initial angle of deviation, suggesting that subjects with Pain made larger adjustments in the feedforward component of the movement over time. Interestingly, behaviour of the Pain group was very stable from the end of Day 1 (with pain) to the beginning of Day 2 (pain-free), indicating that the differences observed could not solely be explained by the impact of pain on immediate performance. This suggests that if people learn to move differently in the presence of pain, they might maintain this altered strategy over time.

Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors.

PubMed

Kuenemann, Mélaine A; Labbé, Céline M; Cerdan, Adrien H; Sperandio, Olivier

2016-04-01

Protein-protein interactions (PPIs) play vital roles in life and provide new opportunities for therapeutic interventions. In this large data analysis, 3,300 inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively ~566,000 compounds (including natural compounds, existing drugs, active compounds on conventional targets, etc.) using a chemoinformatics approach. Using this procedure, we showed that comparable classes of PPI targets can be formed using either the similarity of their ligands or the shared properties of their binding cavities, constituting a proof-of-concept that not only can binding pockets be used to group PPI targets, but that these pockets certainly condition the properties of their corresponding ligands. These results demonstrate that matching regions in both chemical space and target space can be found. Such identified classes of targets could lead to the design of PPI-class-specific chemical libraries and therefore facilitate the development of iPPIs to the stage of drug candidates.

Making the case for change: What researchers need to consider when designing behavior change interventions aimed at improving medication dispensing.

PubMed

Cadogan, Cathal A; Ryan, Cristín; Hughes, Carmel

2016-01-01

There is a growing emphasis on behavior change in intervention development programmes aimed at improving public health and healthcare professionals' practice. A number of frameworks and methodological tools have been established to assist researchers in developing interventions seeking to change healthcare professionals' behaviors. The key features of behavior change intervention design involve specifying the target group (i.e. healthcare professional or patient cohort), the target behavior and identifying mediators (i.e. barriers and facilitators) of behavior change. Once the target behavior is clearly specified and understood, specific behavior change techniques can then be used as the basis of the intervention to target identified mediators of behavior change. This commentary outlines the challenges for pharmacy practice-based researchers in targeting dispensing as a behavior when developing behavior change interventions aimed at pharmacists and proposes a definition of dispensing to consider in future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective in vivo metabolic cell-labeling-mediated cancer targeting

PubMed Central

Wang, Hua; Wang, Ruibo; Cai, Kaimin; He, Hua; Liu, Yang; Yen, Jonathan; Wang, Zhiyu; Xu, Ming; Sun, Yiwen; Zhou, Xin; Yin, Qian; Tang, Li; Dobrucki, Iwona T; Dobrucki, Lawrence W; Chaney, Eric J; Boppart, Stephen A; Fan, Timothy M; Lezmi, Stéphane; Chen, Xuesi; Yin, Lichen; Cheng, Jianjun

2017-01-01

Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. Histone deacetylase and cathepsin L-responsive acetylated azidomannosamine, one such enzymatically activatable Ac4ManAz analog developed, mediated cancer-selective labeling in vivo, which enhanced tumor accumulation of a dibenzocyclooctyne–doxorubicin conjugate via click chemistry and enabled targeted therapy against LS174T colon cancer, MDA-MB-231 triple-negative breast cancer and 4T1 metastatic breast cancer in mice. PMID:28192414

C-STrap Sample Preparation Method--In-Situ Cysteinyl Peptide Capture for Bottom-Up Proteomics Analysis in the STrap Format.

PubMed

Zougman, Alexandre; Banks, Rosamonde E

2015-01-01

Recently we introduced the concept of Suspension Trapping (STrap) for bottom-up proteomics sample processing that is based upon SDS-mediated protein extraction, swift detergent removal and rapid reactor-type protein digestion in a quartz depth filter trap. As the depth filter surface is made of silica, it is readily modifiable with various functional groups using the silane coupling chemistries. Thus, during the digest, peptides possessing specific features could be targeted for enrichment by the functionalized depth filter material while non-targeted peptides could be collected as an unbound distinct fraction after the digest. In the example presented here the quartz depth filter surface is functionalized with the pyridyldithiol group therefore enabling reversible in-situ capture of the cysteine-containing peptides generated during the STrap-based digest. The described C-STrap method retains all advantages of the original STrap methodology and provides robust foundation for the conception of the targeted in-situ peptide fractionation in the STrap format for bottom-up proteomics. The presented data support the method's use in qualitative and semi-quantitative proteomics experiments.

Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA Group) cv. Berangan Roots

PubMed Central

Lee, Wan Sin; Gudimella, Ranganath; Wong, Gwo Rong; Tammi, Martti Tapani; Khalid, Norzulaani; Harikrishna, Jennifer Ann

2015-01-01

Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes) and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana. PMID:25993649

Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA Group) cv. Berangan Roots.

PubMed

Lee, Wan Sin; Gudimella, Ranganath; Wong, Gwo Rong; Tammi, Martti Tapani; Khalid, Norzulaani; Harikrishna, Jennifer Ann

2015-01-01

Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes) and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana.

A semi-automated image analysis procedure for in situ plankton imaging systems.

PubMed

Bi, Hongsheng; Guo, Zhenhua; Benfield, Mark C; Fan, Chunlei; Ford, Michael; Shahrestani, Suzan; Sieracki, Jeffery M

2015-01-01

Plankton imaging systems are capable of providing fine-scale observations that enhance our understanding of key physical and biological processes. However, processing the large volumes of data collected by imaging systems remains a major obstacle for their employment, and existing approaches are designed either for images acquired under laboratory controlled conditions or within clear waters. In the present study, we developed a semi-automated approach to analyze plankton taxa from images acquired by the ZOOplankton VISualization (ZOOVIS) system within turbid estuarine waters, in Chesapeake Bay. When compared to images under laboratory controlled conditions or clear waters, images from highly turbid waters are often of relatively low quality and more variable, due to the large amount of objects and nonlinear illumination within each image. We first customized a segmentation procedure to locate objects within each image and extracted them for classification. A maximally stable extremal regions algorithm was applied to segment large gelatinous zooplankton and an adaptive threshold approach was developed to segment small organisms, such as copepods. Unlike the existing approaches for images acquired from laboratory, controlled conditions or clear waters, the target objects are often the majority class, and the classification can be treated as a multi-class classification problem. We customized a two-level hierarchical classification procedure using support vector machines to classify the target objects (< 5%), and remove the non-target objects (> 95%). First, histograms of oriented gradients feature descriptors were constructed for the segmented objects. In the first step all non-target and target objects were classified into different groups: arrow-like, copepod-like, and gelatinous zooplankton. Each object was passed to a group-specific classifier to remove most non-target objects. After the object was classified, an expert or non-expert then manually removed the non-target objects that could not be removed by the procedure. The procedure was tested on 89,419 images collected in Chesapeake Bay, and results were consistent with visual counts with >80% accuracy for all three groups.

A Semi-Automated Image Analysis Procedure for In Situ Plankton Imaging Systems

PubMed Central

Bi, Hongsheng; Guo, Zhenhua; Benfield, Mark C.; Fan, Chunlei; Ford, Michael; Shahrestani, Suzan; Sieracki, Jeffery M.

2015-01-01

Plankton imaging systems are capable of providing fine-scale observations that enhance our understanding of key physical and biological processes. However, processing the large volumes of data collected by imaging systems remains a major obstacle for their employment, and existing approaches are designed either for images acquired under laboratory controlled conditions or within clear waters. In the present study, we developed a semi-automated approach to analyze plankton taxa from images acquired by the ZOOplankton VISualization (ZOOVIS) system within turbid estuarine waters, in Chesapeake Bay. When compared to images under laboratory controlled conditions or clear waters, images from highly turbid waters are often of relatively low quality and more variable, due to the large amount of objects and nonlinear illumination within each image. We first customized a segmentation procedure to locate objects within each image and extracted them for classification. A maximally stable extremal regions algorithm was applied to segment large gelatinous zooplankton and an adaptive threshold approach was developed to segment small organisms, such as copepods. Unlike the existing approaches for images acquired from laboratory, controlled conditions or clear waters, the target objects are often the majority class, and the classification can be treated as a multi-class classification problem. We customized a two-level hierarchical classification procedure using support vector machines to classify the target objects (< 5%), and remove the non-target objects (> 95%). First, histograms of oriented gradients feature descriptors were constructed for the segmented objects. In the first step all non-target and target objects were classified into different groups: arrow-like, copepod-like, and gelatinous zooplankton. Each object was passed to a group-specific classifier to remove most non-target objects. After the object was classified, an expert or non-expert then manually removed the non-target objects that could not be removed by the procedure. The procedure was tested on 89,419 images collected in Chesapeake Bay, and results were consistent with visual counts with >80% accuracy for all three groups. PMID:26010260

Energy-efficiency program for clothes washers, clothes dryers, and dishwashers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1977-11-01

The objectives of this study of dishwashers, clothes washers, and clothes dryers are: to evaluate existing energy efficiency test procedures and recommend the use of specific test procedures for each appliance group and to establish the maximum economically and technologically feasible energy-efficiency improvement goals for each appliance group. Specifically, the program requirements were to determine the energy efficiency of the 1972 models, to evaluate the feasibility improvements that could be implemented by 1980 to maximize energy efficiency, and to calculate the percentage efficiency improvement based on the 1972 baseline and the recommended 1980 targets. The test program was conducted usingmore » 5 dishwashers, 4 top-loading clothes washers, one front-loading clothes washer, 4 electric clothes dryers, and 4 gas clothes dryers. (MCW)« less

Targeting community-dwelling urinary incontinence sufferers: a multi-disciplinary community based model for conservative continence services.

PubMed

St John, Winsome; Wallis, Marianne; James, Heather; McKenzie, Shona; Guyatt, Sheridan

2004-10-01

This paper presents an argument that there is a need to provide services that target community-dwelling incontinence sufferers, and presents a demonstration case study of a multi-disciplinary, community-based conservative model of service delivery: The Waterworx Model. Rationale for approaches taken, implementation of the model, evaluation and lessons learned are discussed. In this paper community-dwelling sufferers of urinary incontinence are identified as an underserved group, and useful information is provided for those wishing to establish services for them. The Waterworx Model of continence service delivery incorporates three interrelated approaches. Firstly, client access is achieved by using community-based services via clinic and home visits, creating referral pathways and active promotion of services. Secondly, multi-disciplinary client care is provided by targeting a specific client group, multi-disciplinary assessment, promoting client self-management and developing client knowledge and health literacy. Finally, interdisciplinary collaboration and linkages is facilitated by developing multidisciplinary assessment tools, using interdisciplinary referrals, staff development, multi-disciplinary management and providing professional education. Implementation of the model achieved greater client access, improvement in urinary incontinence and client satisfaction. Our experiences suggest that those suffering urinary incontinence and living in the community are an underserved group and that continence services should be community focussed, multi-disciplinary, generalist in nature.

New and emerging targeted therapies for cystic fibrosis.

PubMed

Quon, Bradley S; Rowe, Steven M

2016-03-30

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. 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.

A systematic review on US-based community health navigator (CHN) interventions for cancer screening promotion--comparing community- versus clinic-based navigator models.

PubMed

Hou, Su-I; Roberson, Kiersten

2015-03-01

This study synthesized lessons learned from US-based community and clinic health navigator (CHN) interventions on cancer screening promotion to identify characteristics of models and approaches for addressing cancer disparities. The combination terms "cancer screening" and "community health workers or navigators" or "patient navigators" were used in searching Medline, CINAHL, and PsycInfo. A total of 27 articles published during January 2005∼April 2014 were included. Two CHN models were identified: community-based (15 studies) and clinic/hospital-based (12 studies). While both models used the term "navigators," most community-based programs referred them as community health workers/navigators/advisors, whereas clinic-based programs often called them patient navigators. Most community-based CHN interventions targeted specific racial/ethnic minority or rural groups, while clinic-based programs mostly targeted urban low income or mixed ethnic groups. Most community-based CHN programs outreached members from community networks, while clinic-based programs commonly worked with pre-identified in-service clients. Overall, regardless model type, CHNs had similar roles and responsibilities, and interventions demonstrated effective outcomes. Our review identified characteristics of CHN interventions with attention to different settings. Lessons learned have implication on the dissemination and implementation of CHN interventions for cancer screening promotion across setting and target groups.

Portable upper extremity robotics is as efficacious as upper extremity rehabilitative therapy: a randomized controlled pilot trial.

PubMed

Page, Stephen J; Hill, Valerie; White, Susan

2013-06-01

To compare the efficacy of a repetitive task-specific practice regimen integrating a portable, electromyography-controlled brace called the 'Myomo' versus usual care repetitive task-specific practice in subjects with chronic, moderate upper extremity impairment. Sixteen subjects (7 males; mean age 57.0 ± 11.02 years; mean time post stroke 75.0 ± 87.63 months; 5 left-sided strokes) exhibiting chronic, stable, moderate upper extremity impairment. Subjects were administered repetitive task-specific practice in which they participated in valued, functional tasks using their paretic upper extremities. Both groups were supervised by a therapist and were administered therapy targeting their paretic upper extremities that was 30 minutes in duration, occurring 3 days/week for eight weeks. One group participated in repetitive task-specific practice entirely while wearing the portable robotic, while the other performed the same activity regimen manually. The upper extremity Fugl-Meyer, Canadian Occupational Performance Measure and Stroke Impact Scale were administered on two occasions before intervention and once after intervention. After intervention, groups exhibited nearly identical Fugl-Meyer score increases of ≈2.1 points; the group using robotics exhibited larger score changes on all but one of the Canadian Occupational Performance Measure and Stroke Impact Scale subscales, including a 12.5-point increase on the Stroke Impact Scale recovery subscale. Findings suggest that therapist-supervised repetitive task-specific practice integrating robotics is as efficacious as manual practice in subjects with moderate upper extremity impairment.

A Binaural Grouping Model for Predicting Speech Intelligibility in Multitalker Environments

PubMed Central

Colburn, H. Steven

2016-01-01

Spatially separating speech maskers from target speech often leads to a large intelligibility improvement. Modeling this phenomenon has long been of interest to binaural-hearing researchers for uncovering brain mechanisms and for improving signal-processing algorithms in hearing-assistive devices. Much of the previous binaural modeling work focused on the unmasking enabled by binaural cues at the periphery, and little quantitative modeling has been directed toward the grouping or source-separation benefits of binaural processing. In this article, we propose a binaural model that focuses on grouping, specifically on the selection of time-frequency units that are dominated by signals from the direction of the target. The proposed model uses Equalization-Cancellation (EC) processing with a binary decision rule to estimate a time-frequency binary mask. EC processing is carried out to cancel the target signal and the energy change between the EC input and output is used as a feature that reflects target dominance in each time-frequency unit. The processing in the proposed model requires little computational resources and is straightforward to implement. In combination with the Coherence-based Speech Intelligibility Index, the model is applied to predict the speech intelligibility data measured by Marrone et al. The predicted speech reception threshold matches the pattern of the measured data well, even though the predicted intelligibility improvements relative to the colocated condition are larger than some of the measured data, which may reflect the lack of internal noise in this initial version of the model. PMID:27698261

A Binaural Grouping Model for Predicting Speech Intelligibility in Multitalker Environments.

PubMed

Mi, Jing; Colburn, H Steven

2016-10-03

Spatially separating speech maskers from target speech often leads to a large intelligibility improvement. Modeling this phenomenon has long been of interest to binaural-hearing researchers for uncovering brain mechanisms and for improving signal-processing algorithms in hearing-assistive devices. Much of the previous binaural modeling work focused on the unmasking enabled by binaural cues at the periphery, and little quantitative modeling has been directed toward the grouping or source-separation benefits of binaural processing. In this article, we propose a binaural model that focuses on grouping, specifically on the selection of time-frequency units that are dominated by signals from the direction of the target. The proposed model uses Equalization-Cancellation (EC) processing with a binary decision rule to estimate a time-frequency binary mask. EC processing is carried out to cancel the target signal and the energy change between the EC input and output is used as a feature that reflects target dominance in each time-frequency unit. The processing in the proposed model requires little computational resources and is straightforward to implement. In combination with the Coherence-based Speech Intelligibility Index, the model is applied to predict the speech intelligibility data measured by Marrone et al. The predicted speech reception threshold matches the pattern of the measured data well, even though the predicted intelligibility improvements relative to the colocated condition are larger than some of the measured data, which may reflect the lack of internal noise in this initial version of the model. © The Author(s) 2016.

Destructive disinfection of infected brood prevents systemic disease spread in ant colonies.

PubMed

Pull, Christopher D; Ugelvig, Line V; Wiesenhofer, Florian; Grasse, Anna V; Tragust, Simon; Schmitt, Thomas; Brown, Mark Jf; Cremer, Sylvia

2018-01-09

In social groups, infections have the potential to spread rapidly and cause disease outbreaks. Here, we show that in a social insect, the ant Lasius neglectus , the negative consequences of fungal infections ( Metarhizium brunneum ) can be mitigated by employing an efficient multicomponent behaviour, termed destructive disinfection, which prevents further spread of the disease through the colony. Ants specifically target infected pupae during the pathogen's non-contagious incubation period, utilising chemical 'sickness cues' emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a metazoan body that specifically targets and eliminates infected cells, ants destroy infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, in an analogous fashion, the same principles of disease defence apply at different levels of biological organisation.

Poly(malic acid) nanoconjugates containing various antibodies and oligonucleotides for multitargeting drug delivery

PubMed Central

Fujita, Manabu; Ljubimov, Alexander V; Torchilin, Vladimir P; Black, Keith L; Holler, Eggehard

2009-01-01

Nanoconjugates are emerging as promising drug-delivery vehicles because of their multimodular structure enabling them to actively target discrete cells, pass through biological barriers and simultaneously carry multiple drugs of various chemical nature. Nanoconjugates have matured from simple devices to multifunctional, biodegradable, nontoxic and nonimmunogenic constructs, capable of delivering synergistically functioning drugs in vivo. This review mainly concerns the Polycefin family of natural-derived polymeric drug-delivery devices as an example. This type of vehicle is built by hierarchic conjugation of functional groups onto the backbone of poly(malic acid), an aliphatic polyester obtained from the microorganism Physarum polycephalum. Particular Polycefin variants target human brain and breast tumors implanted into animals specifically and actively and could be detected easily by noninvasive imaging analysis. Delivery of antisense oligonucleotides to a tumor-specific angiogenic marker using Polycefin resulted in significant inhibition of tumor angiogenesis and increase of animal survival. PMID:18373429

SERS detection and targeted ablation of lymphoma cells using functionalized Ag nanoparticles

NASA Astrophysics Data System (ADS)

Yao, Qian; Cao, Fei; Feng, Chao; Zhao, Yan; Wang, Xiuhong

2016-03-01

Lymphoma is a heterogeneous group of malignancies of the lymphoid tissue, and is prevalent worldwide affecting both children and adults with a high mortality rate. There is in dire need of accurate and noninvasive approaches for early detection of the disease. Herein, we report a facile way to fabricate silver nanoparticle based nanoprobe by incorporating the corner-stone immunotherapeutic drug Rituxan for simultaneous detection and ablation of lymphoma cells in vitro. The fabricated nanoprobe can detect CD20 positive single lymphoma cell by surface enhanced Raman scattering technique with high specificity. The engineered nanoprobe retains the same antibody property as intact drug via Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) analysis. The nanoprobe efficiently eradicates lymphoma cells in vitro. By integrating the advantages of sensitive SERS detection with targeted ablation capabilities of immunotherapeutic drug through site specificity, this nanoprobe can be applied as outstanding tools in living imaging, cancer diagnosis and treatment.

Destructive disinfection of infected brood prevents systemic disease spread in ant colonies

PubMed Central

Ugelvig, Line V; Wiesenhofer, Florian; Grasse, Anna V; Tragust, Simon; Schmitt, Thomas; Brown, Mark JF

2018-01-01

In social groups, infections have the potential to spread rapidly and cause disease outbreaks. Here, we show that in a social insect, the ant Lasius neglectus, the negative consequences of fungal infections (Metarhizium brunneum) can be mitigated by employing an efficient multicomponent behaviour, termed destructive disinfection, which prevents further spread of the disease through the colony. Ants specifically target infected pupae during the pathogen’s non-contagious incubation period, utilising chemical ‘sickness cues’ emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a metazoan body that specifically targets and eliminates infected cells, ants destroy infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, in an analogous fashion, the same principles of disease defence apply at different levels of biological organisation. PMID:29310753

[Molecular pathology of pulmonary carcinomas].

PubMed

Rohan, Zdeněk; Matějčková, Milada; Matěj, Radoslav

2014-04-01

The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular has led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Therefore, pathologists closely involved in the diagnostics of lung tumors significantly contribute to the diagnostic-therapeutical algorithm. Analysis of EGFR gene mutations in lung adenocarcinomas is already routinely performed and the presence of activating mutations in EGFR is the main indication for the administration of tyrosinkinase inhibitors. Besides EGFR mutations, EML4-ALK rearrangement is also being analysed and there is potential in analysing BRAF mutations as well. The aim of this review is to summarize the role of the most relevant molecules that also serve as the therapeutic target for practicing pathologists.

Transfer of motor learning engages specific neural substrates during motor memory consolidation dependent on the practice structure.

PubMed

Kantak, Shailesh S; Sullivan, Katherine J; Fisher, Beth E; Knowlton, Barbara J; Winstein, Carolee J

2011-01-01

The authors investigated how brain activity during motor-memory consolidation contributes to transfer of learning to novel versions of a motor skill following distinct practice structures. They used 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) immediately after constant or variable practice of an arm movement skill to interfere with primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). The effect of interference was assessed through skill performance on two transfer targets: one within and one outside the range of practiced movement parameters for the variable practice group. For the control (no rTMS) group, variable practice benefited delayed transfer performance more than constant practice. The rTMS effect on delayed transfer performance differed for the two transfer targets. For the within-range target, rTMS interference had no significant affect on the delayed transfer after either practice structure. However, for the outside-range target, rTMS interference to DLPFC but not M1 attenuated delayed transfer benefit following variable practice. Additionally, for the outside-range target, rTMS interference to M1 but not DLPFC attenuated delayed transfer following constant practice. This suggests that variable practice may promote reliance on DLPFC for memory consolidation associated with outside-range transfer of learning, whereas constant practice may promote reliance on M1 for consolidation and long-term transfer.

[Identification of Clonorchis sinensis metacercariae based on PCR targeting ribosomal DNA ITS regions and COX1 gene].

PubMed

Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Yang, Yi-Chao; Li, Hong-Mei; Chen, Ying-Dan; Zhou, Xiao-Nong

2014-06-01

To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.

Near-Infrared Neodymium Tag for Quantifying Targeted Biomarker and Counting Its Host Circulating Tumor Cells.

PubMed

Liu, Chunlan; Lu, Shu; Yang, Limin; Chen, Peijie; Bai, Peiming; Wang, Qiuquan

2017-09-05

Quantitative information on a targeted analyte in a complex biological system is the most basic premise for understanding its involved mechanisms, and thus precise diagnosis of a disease if it is a so-called biomarker. Here, we designed and synthesized a neodymium (Nd)-cored tag [1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DOTA)-Nd complex together with a light-harvesting antenna aminofluorescein (AMF, λ ex/em = 494/520 nm), AMF-DOTA-Nd] with duplex signals, second near-infrared (NIR) window luminescence (λ em = 1065 nm, 2.5 μs), and stable isotopic mass ( 142 Nd). AMF-DOTA-Nd covalently linked with a urea-based peptidomimetic targeting group, 2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA)-8-Aoc-Phe-Phe-Cys (DUPAaFFC) (DUPAaFFC-AMF-DOTA-Nd), allowing us to detect and quantify prostate-specific membrane antigen (PSMA) and its splice variants (total PSMA, tPSMA), which was set as an example of targeted biomarkers in this study, using NIR and inductively coupled plasma mass spectrometry (ICPMS) with the limit of detection (LOD) (3σ) of 0.3 ng/mL. When it was applied to the analysis of 80 blood samples from prostate cancer (PCa) and benign prostatic hyperplasia (BPH) patients as well as healthy volunteers, we found that 320 and 600 ng/mL tPSMA could be recommended as the threshold values to differentiate BPH from PCa and for the diagnosis of PCa. Moreover, PSMA-positive circulating tumor cells (CTCs) were counted using ICPMS being from 134 to 773 CTCs in the PCa blood samples of the Gleason score from 6 to 9 when the cell membrane-spanning mPSMA was tagged. Such a methodology developed could be expected to be applicable to other clinic-meaningful biomolecules and their host CTCs in liquid biopsy, when other specific targeting groups are modified to the NIR Nd tag.

Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo.

PubMed

Pasqualetti, Massimo; Díaz, Carmen; Renaud, Jean-Sébastien; Rijli, Filippo M; Glover, Joel C

2007-09-05

As a step toward generating a fate map of identified neuron populations in the mammalian hindbrain, we assessed the contributions of individual rhombomeres to the vestibular nuclear complex, a major sensorimotor area that spans the entire rhombencephalon. Transgenic mice harboring either the lacZ or the enhanced green fluorescent protein reporter genes under the transcriptional control of rhombomere-specific Hoxa2 enhancer elements were used to visualize rhombomere-derived domains. We labeled functionally identifiable vestibular projection neuron groups retrogradely with conjugated dextran-amines at successive embryonic stages and obtained developmental fate maps through direct comparison with the rhombomere-derived domains in the same embryos. The fate maps show that each vestibular neuron group derives from a unique rostrocaudal domain that is relatively stable developmentally, suggesting that anteroposterior migration is not a major contributor to the rostrocaudal patterning of the vestibular system. Most of the groups are multisegmental in origin, and each rhombomere is fated to give rise to two or more vestibular projection neuron types, in a complex pattern that is not segmentally iterated. Comparison with studies in the chicken embryo shows that the rostrocaudal patterning of identified vestibular projection neuron groups is generally well conserved between avians and mammalians but that significant species-specific differences exist in the rostrocaudal limits of particular groups. This mammalian hindbrain fate map can be used as the basis for targeting genetic manipulation to specific subpopulations of vestibular projection neurons.

Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same.

PubMed

Sahu, Vishal; Nigam, Lokesh; Agnihotri, Vertica; Gupta, Abhishek; Shekhar, Shashank; Subbarao, Naidu; Bhaskar, Suman; Dey, Sharmistha

2018-05-09

The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target.p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

Evaluation of a maleimido derivative of CHX-A” DTPA for site-specific labeling of Affibody molecules

PubMed Central

Tolmachev, Vladimir; Xu, Heng; Wållberg, Helena; Ahlgren, Sara; Hjertman, Magnus; Sjöberg, Anna; Sandström, Mattias; Abrahmsén, Lars; Brechbiel, Martin W.; Orlova, Anna

2008-01-01

Affibody molecules are a new class of small targeting proteins based on a common threehelix bundle structure. Affibody molecules binding a desired target may be selected using phage-display technology. An Affibody molecule ZHER2:342 binding with subnanomolar affinity to the tumor antigen HER2 has recently been developed for radionuclide imaging in vivo. Introduction of a single cysteine into the cysteine-free Affibody scaffold provides a unique thiol group for site-specific labeling of recombinant Affibody molecules. The recently developed maleimido-CHX-A” DTPA was site-specifically conjugated at the C-terminal cysteine of ZHER2:2395-C, a variant of ZHER2:342, providing a homogenous conjugate with a dissociation constant of 56 pM. The yield of labeling with 111In was > 99% after 10 min at room temperature. In vitro cell tests demonstrated specific binding of 111In-CHX-A” DTPAZ2395-C to HER2-expressing cell-line SKOV-3 and good cellular retention of radioactivity. In normal mice, the conjugate demonstrated rapid clearance from all non-specific organs except kidney. In mice bearing SKOV-3 xenografts, the tumor uptake of 111In-CHX-A” DTPAZ2395-C was 17.3 ± 4.8 % IA/g and the tumor-to-blood ratio 86 ± 46 (4 h post-injection). HER2-exprssing xenografts were clearly visualized 1 h post-injection. In conclusion, coupling of maleimido-CHX-A” DTPA to cysteine-containing Affibody molecules provides welldefined uniform conjugate, which can be rapidly labeled at room temperature and provides high-contrast imaging of molecular targets in vivo. PMID:18620447

Trends in the Design and Development of Specific Aptamers Against Peptides and Proteins.

PubMed

Tabarzad, Maryam; Jafari, Marzieh

2016-04-01

Aptamers are single stranded oligonucleotides, comparable to monoclonal antibodies (mAbs) in selectivity and affinity and have significant strategic properties in design, development and applications more than mAbs. Ease of design and development, simple chemical modification and the attachment of functional groups, easily handling and more adaptability with analytical methods, small size and adaptation with nanostructures are the valuable characteristics of aptamers in comparison to large protein based ligands. Among a broad range of targets that their specific aptamers developed, proteins and peptides have significant position according to the number of related studies performed so far. Since proteins control many of important physiological and pathological incidents in the living organisms, particularly human beings and because of the benefits of aptamers in clinical and analytical applications, aptamer related technologies in the field of proteins and peptides are under progress, exclusively. Currently, there is only one FDA approved therapeutic aptamer in the pharmaceutical market, which is specific to vascular endothelial growth factor and is prescribed for age related macular degenerative disease. Additionally, there are several aptamers in the different phases of clinical trials. Almost all of these aptamers are specific to clinically important peptide or protein targets. In addition, the application of protein specific aptamers in the design and development of targeted drug delivery systems and diagnostic biosensors is another interesting field of aptamer technology. In this review, significant efforts related to development and applications of aptamer technologies in proteins and peptides sciences were considered to emphasis on the importance of aptamers in medicinal and clinical applications.

Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer

PubMed Central

Navarro-Teulon, Isabelle; Berthier-Vergnes, Odile; Fois, Giovanna; Zhu, Yingying; Besse, Sophie; Bawa, Olivia; Briat, Arnaud; Quintana, Mercedes; Pichard, Alexandre; Bonnet, Mathilde; Rubinstein, Eric; Pouget, Jean-Pierre; Opolon, Paule; Maigne, Lydia; Miot-Noirault, Elisabeth; Chezal, Jean-Michel

2017-01-01

Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of [111In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3; SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific absorbed dose calculations for [177Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing the feasibility of using radioimmunotherapy of CRC with this radiolabeled antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice treated with [177Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo experiments revealed specific DNA double strand breaks associated with cell apoptosis in [177Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we provide a proof-of-concept for the use of [111In/177Lu]DOTA-Ts29.2 that specifically target in vivo aggressive TSPAN8-positive cells in CRC. PMID:28423546

Implementation of Novel Design Features for qPCR-Based eDNA Assessment

PubMed Central

Veldhoen, Nik; Hobbs, Jared; Ikonomou, Georgios; Hii, Michael; Lesperance, Mary; Helbing, Caren C.

2016-01-01

Environmental stewardship requires timely, accurate information related to the status of a given ecosystem and the species that occupy it. Recent advances in the application of the highly sensitive real-time quantitative polymerase chain reaction (qPCR) towards identification of constituents within environmental DNA (eDNA) now allow targeted detection of the presence of species-specific biological material within a localized geographic region. However, as with all molecular techniques predicated on the specificity and sensitivity of the PCR assay, careful validation of each eDNA qPCR assay in development must be performed both under controlled laboratory conditions and when challenged with field-derived eDNA samples. Such a step-wise approach forms the basis for incorporation of innovative qPCR design features that strengthen the implementation and interpretation of the eDNA assay. This includes empirical determination that the qPCR assay is refractory to the presence of human DNA and the use of a tripartite assay approach comprised of 1) a primer set targeting plant chloroplast that evaluates the presence of amplifiable DNA from field samples to increase confidence in a negative result, 2) an animal group primer set to increase confidence in the assay result, and 3) a species-specific primer set to assess presence of DNA from the target species. To demonstrate this methodology, we generated eDNA assays specific for the North American bullfrog (Lithobates (Rana) catesbeiana) and the Rocky Mountain tailed frog (Ascaphus montanus) and characterized each with respect to detection sensitivity and specificity with demonstrated performance in a field survey scenario. The qPCR design features presented herein address specific challenges of eDNA assays thereby increasing their interpretative power. PMID:27802293

Molecular basis for specificity in the druggable kinome: sequence-based analysis.

PubMed

Chen, Jianping; Zhang, Xi; Fernández, Ariel

2007-03-01

Rational design of kinase inhibitors remains a challenge partly because there is no clear delineation of the molecular features that direct the pharmacological impact towards clinically relevant targets. Standard factors governing ligand affinity, such as potential for intermolecular hydrophobic interactions or for intermolecular hydrogen bonding do not provide good markers to assess cross reactivity. Thus, a core question in the informatics of drug design is what type of molecular similarity among targets promotes promiscuity and what type of molecular difference governs specificity. This work answers the question for a sizable screened sample of the human pharmacokinome including targets with unreported structure. We show that drug design aimed at promoting pairwise interactions between ligand and kinase target actually fosters promiscuity because of the high conservation of the partner groups on or around the ATP-binding site of the kinase. Alternatively, we focus on a structural marker that may be reliably determined from sequence and measures dehydration propensities mostly localized on the loopy regions of kinases. Based on this marker, we construct a sequence-based kinase classifier that enables the accurate prediction of pharmacological differences. Our indicator is a microenvironmental descriptor that quantifies the propensity for water exclusion around preformed polar pairs. The results suggest that targeting polar dehydration patterns heralds a new generation of drugs that enable a tighter control of specificity than designs aimed at promoting ligand-kinase pairwise interactions. The predictor of polar hot spots for dehydration propensity, or solvent-accessible hydrogen bonds in soluble proteins, named YAPView, may be freely downloaded from the University of Chicago website http://protlib.uchicago.edu/dloads.html. Supplementary data are available at Bioinformatics online.

Accuracy and precision of as-received implant torque wrenches.

PubMed

Britton-Vidal, Eduardo; Baker, Philip; Mettenburg, Donald; Pannu, Darshanjit S; Looney, Stephen W; Londono, Jimmy; Rueggeberg, Frederick A

2014-10-01

Previous implant torque evaluation did not determine if the target value fell within a confidence interval for the population mean of the test groups, disallowing determination of whether a specific type of wrench met a standardized goal value. The purpose of this study was to measure both the accuracy and precision of 2 different configurations (spring style and peak break) of as-received implant torque wrenches and compare the measured values to manufacturer-stated values. Ten wrenches from 4 manufacturers, representing a variety of torque-limiting mechanisms and specificity of use (with either a specific brand or universally with any brand of implant product). Drivers were placed into the wrench, and tightening torque was applied to reach predetermined values using a NIST-calibrated digital torque wrench. Five replications of measurement were made for each wrench and averaged to provide a single value from that instrument. The target torque value for each wrench brand was compared to the 95% confidence interval for the true population mean of measured values to see if it fell within the measured range. Only 1 wrench brand (Nobel Biocare) demonstrated the target torque value falling within the 95% confidence interval for the true population mean. For others, the targeted torque value fell above the 95% confidence interval (Straumann and Imtec) or below (Salvin Torq). Neither type of torque-limiting mechanism nor designation of a wrench to be used as a dedicated brand-only product or to be used as a universal product on many brands affected the ability of a wrench to deliver torque values where the true population mean included the target torque level. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery.

PubMed

Luong, Duy; Kesharwani, Prashant; Deshmukh, Rahul; Mohd Amin, Mohd Cairul Iqbal; Gupta, Umesh; Greish, Khaled; Iyer, Arun K

2016-10-01

Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers. It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

PubMed

Alden, Eva C; Cobia, Derin J; Reilly, James L; Smith, Matthew J

2015-10-01

Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (p<0.001) with CON outperforming both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF-SCZ had higher verbal working memory compared to LF-SCZ (p≤0.05, Cohen's d=0.78) but the two groups did not differ in remaining domains. The cluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted Ovarian Cancer Education for Hispanic Women: A Pilot Program in Arizona.

PubMed

Schlumbrecht, Matthew; Yarian, Ranay; Salmon, Kristine; Niven, Christine; Singh, Diljeet

2016-06-01

In disadvantaged populations, including Hispanics, there is a deficit in understanding of cancer risk factors, symptoms, prevention, and treatment. The objective of this study was to assess ovarian cancer knowledge in a population of Hispanic women in Arizona, identify deficiencies, and to evaluate the utility of an educational program developed specifically for this community's needs. A de novo questionnaire about ovarian cancer was distributed to Hispanic women enrolled in family literacy programs at Mesa Public Schools. Following this assessment, a video educational program was developed, with emphasis on areas of greatest knowledge deficits, and post-intervention assessment administered. Chi square, Wilcoxon rank sum, and Kruskal-Wallis tests were used for analysis. 167 questionnaires were completed in the pretest group and 102 in the post-intervention group. Between groups, there were no differences in age (p = 0.49), education (p = 0.68), or annual income (p = 0.26). In the pretest group, 45 % of questions were answered correctly versus 84 % in the post-test group (p < 0.01). 24.2 % of the initial respondents correctly identified ovarian cancer symptoms versus 85.6 of post-test respondents (p < 0.01). With the program, there was an increase in the number of correct post-test responses for each question and symptom (p < 0.01), except those about hereditary risk of ovarian cancer (p = 0.62) and pelvic anatomy (p = 0.16). Following identification of an ovarian cancer knowledge deficit in this cohort of Hispanic women, an educational tool targeting specific deficiencies successfully increased cancer knowledge and awareness of symptoms. Similar efforts in this and other minority populations should be continued.

Pneumocystis jirovecii (Pj) quantitative PCR to differentiate Pj pneumonia from Pj colonization in immunocompromised patients.

PubMed

Maillet, M; Maubon, D; Brion, J P; François, P; Molina, L; Stahl, J P; Epaulard, O; Bosseray, A; Pavese, P

2014-03-01

Conventional polymerase chain reaction (PCR) in respiratory samples does not differentiate between Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii (Pj) colonization. We used Pj real-time quantitative PCR (qPCR) with the objective to discriminate PCP from Pj colonization in immunocompromised patients. All positive Pj qPCR [targeting the major surface glycoprotein (MSG) gene] obtained in respiratory samples from immunocompromised patients presenting pneumonia at the Grenoble University Hospital, France, were collected between August 2009 and April 2011. Diagnoses were retrospectively determined by a multidisciplinary group of experts blinded to the Pj qPCR results. Thirty-one bronchoalveolar lavages and four broncho aspirations positive for the Pj qPCR were obtained from 35 immunocompromised patients. Diagnoses of definite, probable, and possible PCP, and pneumonia from another etiology were retrospectively made for 7, 4, 5, and 19 patients, respectively. Copy numbers were significantly higher in the "definite group" (median 465,000 copies/ml) than in the "probable group" (median 38,600 copies/ml), the "possible group" (median 1,032 copies/ml), and the "other diagnosis group" (median 390 copies/ml). With the value of 3,160 copies/ml, the sensitivity and specificity of qPCR for the diagnosis of PCP were 100 % and 70 %, respectively. With the value of 31,600 copies/ml, the sensitivity and specificity were 80 % and 100 %, respectively. The positive predictive value was 100 % for results with more than 31,600 copies/ml and the negative predictive value was 100 % for results with fewer than 3,160 copies/ml. qPCR targeting the MSG gene can be helpful to discriminate PCP from Pj colonization in immunocompromised patients, using two cut-off values, with a gray zone between them.

Tobacco drought stress responses reveal new targets for Solanaceae crop improvement.

PubMed

Rabara, Roel C; Tripathi, Prateek; Reese, R Neil; Rushton, Deena L; Alexander, Danny; Timko, Michael P; Shen, Qingxi J; Rushton, Paul J

2015-06-30

The Solanaceae are an economically important family of plants that include tobacco (Nicotiana tabacum L.), tomato, and potato. Drought is a major cause of crop losses. We have identified major changes in physiology, metabolites, mRNA levels, and promoter activities during the tobacco response to drought. We have classified these as potential components of core responses that may be common to many plant species or responses that may be family/species-specific features of the drought stress response in tobacco or the Solanaceae. In tobacco the largest increase in any metabolite was a striking 70-fold increase in 4-hydroxy-2-oxoglutaric acid (KHG) in roots that appears to be tobacco/Solanaceae specific. KHG is poorly characterized in plants but is broken down to pyruvate and glyoxylate after the E. coli SOS response to facilitate the resumption of respiration. A similar process in tobacco would represent a mechanism to restart respiration upon water availability after drought. At the mRNA level, transcription factor gene induction by drought also showed both core and species/family specific responses. Many Group IX Subgroup 3 AP2/ERF transcription factors in tobacco appear to play roles in nicotine biosynthesis as a response to herbivory, whereas their counterparts in legume species appear to play roles in drought responses. We observed apparent Solanaceae-specific drought induction of several Group IId WRKY genes. One of these, NtWRKY69, showed ABA-independent drought stress-inducible promoter activity that moved into the leaf through the vascular tissue and then eventually into the surrounding leaf cells. We propose components of a core metabolic response to drought stress in plants and also show that some major responses to drought stress at the metabolome and transcriptome levels are family specific. We therefore propose that the observed family-specific changes in metabolism are regulated, at least in part, by family-specific changes in transcription factor activity. We also present a list of potential targets for the improvement of Solanaceae drought responses.

Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Constantinou, Pamela E.; Danysh, Brian P.; Shenefelt, Derek L.; Carson, Daniel D.; Farach-Carson, Mary C.; Kulchitsky, Vladimir A.; Wu, Xiangwei; Wagner, Daniel S.; Lapotko, Dmitri O.

2012-01-01

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level. PMID:22509318

Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems.

PubMed

Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Constantinou, Pamela E; Danysh, Brian P; Shenefelt, Derek L; Carson, Daniel D; Farach-Carson, Mary C; Kulchitsky, Vladimir A; Wu, Xiangwei; Wagner, Daniel S; Lapotko, Dmitri O

2012-01-01

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level.

Comparative short-term effects of two thoracic spinal manipulation techniques in subjects with chronic mechanical neck pain: a randomized controlled trial.

PubMed

Casanova-Méndez, Amaloha; Oliva-Pascual-Vaca, Angel; Rodriguez-Blanco, Cleofás; Heredia-Rizo, Alberto Marcos; Gogorza-Arroitaonandia, Kristobal; Almazán-Campos, Ginés

2014-08-01

Spinal Manipulation (SM) has been purported to decrease pain and improve function in subjects with non-specific neck pain. Previous research has investigated which individuals with non-specific neck pain will be more likely to benefit from SM. It has not yet been proven whether or not the effectiveness of thoracic SM depends on the specific technique being used. This double-blind randomized trial has compared the short-term effects of two thoracic SM maneuvers in subjects with chronic non-specific neck pain. Sixty participants were distributed randomly into two groups. One group received the Dog technique (n = 30), with the subject in supine position, and the other group underwent the Toggle-Recoil technique (n = 30), with the participant lying prone, T4 being the targeted area in both cases. Evaluations were made of self-reported neck pain (Visual Analogue Scale); neck mobility (Cervical Range of Motion); and pressure pain threshold at the cervical and thoracic levels (C4 and T4 spinous process) and over the site described for location of tense bands of the upper trapezius muscle. Measurements were taken before intervention, immediately afterward, and 20 min later. Both maneuvers improved neck mobility and mechanosensitivity and reduced pain in the short term. No major or clinical differences were found between the groups. In the between-groups comparison slightly better results were observed in the Toggle-Recoil group only for cervical extension (p = 0.009), right lateral flexion (p = 0.004) and left rotation (p < 0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

Making Diversity Conform? An Intersectional, Longitudinal Analysis of LGBT-Specific Mainstream Media Advertisements.

PubMed

Nölke, Ana-Isabel

2018-01-01

This study introduces an intersectional analysis of explicit LGBT portrayals in mainstream advertising between 2009 and 2015. The analysis provides insights into the (in)visibility of the LGBT community over a period of significant social change. It finds that although the number of explicit representations of LGBT characters has risen dramatically, 230 out of 240 intersections of sexuality, class, age, and race remain invisible. In using a new ad format-human interest ads-advertisers move away from hypersexualization, toward real individuals' stories of love and families. Nonetheless, the analysis highlights how the erasure of multiply marginalized groups in mainstream advertising continues to perpetuate a heteronormative, domesticized version of "gayness" and discusses the adverse effects that lie herein. It is proposed that non-LGBT consumers are the underlying target group of LGBT-explicit advertising, causing non-target market effects that alienate large parts of the LGBT community despite their overt inclusion.

Theory of Prejudice and American Identity Threat Transfer for Latino and Asian Americans.

PubMed

Sanchez, Diana T; Chaney, Kimberly E; Manuel, Sara K; Remedios, Jessica D

2018-03-01

Latinos and Asian Americans confront similar stereotypes as they are often presumed to be foreigners and subjected to American identity denial. Across six studies (total N = 992), we demonstrate that Latinos and Asians anticipate ingroup prejudice and specific types of subordination (e.g., American identity threat) in the face of outgroup threats that target one another (i.e., stigma transfer). The studies explore whether stigma transfer occurred primarily when shared Latino and Asian stereotype content was a salient component of the prejudice remark (e.g., foreigner stereotypes; Study 3), or when outgroup prejudice targeted a social group with shared stereotype content (Study 4), though neither appeared to substantively moderate stigma transfer. Minority group members who conceptualize prejudiced people as holding multiple biases (i.e., a monolithic prejudice theory) were more susceptible to stigma transfer suggesting that stereotype content is not necessary for stigma transfer because people assume that prejudice is not singular.

Projection-specific visual feature encoding by layer 5 cortical subnetworks

PubMed Central

Lur, Gyorgy; Vinck, Martin A.; Tang, Lan; Cardin, Jessica A.; Higley, Michael J.

2016-01-01

Summary Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives distinct versions of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex. While there is overlap across the groups, on average corticotectal (CT) cells exhibit lower contrast thresholds and broader tuning for orientation and spatial frequency in comparison to corticostriatal (CS) cells, while corticocortical (CC) cells have intermediate properties. Noise correlational analyses support the hypothesis that CT cells integrate information across diverse layer 5 populations, whereas CS and CC cells form more selectively interconnected groups. Overall, our findings demonstrate the existence of functional subnetworks within layer 5 that may differentially route visual information to behaviorally relevant downstream targets. PMID:26972011

Sleep-Based Memory Processing Facilitates Grammatical Generalization: Evidence from Targeted Memory Reactivation

PubMed Central

Batterink, Laura J.; Paller, Ken A.

2015-01-01

Generalization — the ability to abstract regularities from specific examples and apply them to novel instances — is an essential component of language acquisition. Generalization not only depends on exposure to input during wake, but may also improve offline during sleep. Here we examined whether targeted memory reactivation during sleep can influence grammatical generalization. Participants gradually acquired the grammatical rules of an artificial language through an interactive learning procedure. Then, phrases from the language (experimental group) or stimuli from an unrelated task (control group) were covertly presented during an afternoon nap. Compared to control participants, participants re-exposed to the language during sleep showed larger gains in grammatical generalization. Sleep cues produced a bias, not necessarily a pure gain, suggesting that the capacity for memory replay during sleep is limited. We conclude that grammatical generalization was biased by auditory cueing during sleep, and by extension, that sleep likely influences grammatical generalization in general. PMID:26443322

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

PubMed

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Site-specific selfish genes as tools for the control and genetic engineering of natural populations.

PubMed

Burt, Austin

2003-05-07

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Molecular view of ligands specificity for CAG repeats in anti-Huntington therapy.

PubMed

Bochicchio, Anna; Rossetti, Giulia; Tabarrini, Oriana; Krauβ, Sybille; Carloni, Paolo

2015-10-13

Huntington's disease is a fatal and devastating neurodegenerative genetic disorder for which there is currently no cure. It is characterized by Huntingtin protein's mRNA transcripts with 36 or more CAG repeats. Inhibiting the formation of pathological complexes between these expanded transcripts and target proteins may be a valuable strategy against the disease. Yet, the rational design of molecules specifically targeting the expanded CAG repeats is limited by the lack of structural information. Here, we use well-tempered metadynamics-based free energy calculations to investigate pose and affinity of two ligands targeting CAG repeats for which affinities have been previously measured. The first consists of two 4-guanidinophenyl rings linked by an ester group. It is the most potent ligand identified so far, with Kd = 60(30) nM. The second consists of a 4-phenyl dihydroimidazole and 4-1H-indole dihydroimidazole connected by a C-C bond (Kd = 700(80) nM). Our calculations reproduce the experimental affinities and uncover the recognition pattern between ligands' and their RNA target. They also provide a molecular basis for the markedly different affinity of the two ligands for CAG repeats as observed experimentally. These findings may pave the way for a structure-based hit-to-lead optimization to further improve ligand selectivity toward CAG repeat-containing mRNAs.

Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Achilefu, Samuel I.; Dorshow, Richard B.; Rajagopalan, Raghavan

2001-04-01

We have designed, synthesized, and evaluated the efficacy of novel dye-peptide conjugates that are receptor specific. Contrary to the traditional approach of conjugating dyes to large proteins and antibodies, we used small peptide-dye conjugates that target over-expressed receptors on tumors. Despite the fact that the peptide and the dye probe have similar molecular mass, our results demonstrate that the affinity of the peptide for its receptor and the dye fluorescence properties are both retained. The use of small peptides has several advantages over large biomolecules, including ease of synthesis of a variety of compounds for potential combinatorial screening of new targets, reproducibility of high purity compounds, diffusiveness to solid tumors, and the ability to incorporate a variety of functional groups that modify the pharmacokinetics of the peptide-dye conjugates. The efficacy of these new fluorescent optical contrast agents was evaluated in vivo in well-characterized rat tumor lines expressing somatostatin (sst2) and bombesin receptors. A simple continuous wave optical imaging system was employed. The resulting optical images clearly show that successful specific tumor targeting was achieved. Thus, we have demonstrated that small peptide- dye conjugates are effective as contrast agents for optical imaging of tumors.

Birth outcomes across ethnic groups of women in Nepal.

PubMed

Acharya, Pratima Poudel; Alpass, Fiona

2004-01-01

This study was conducted at the Western Regional Hospital (WRH), Pokhara, Nepal. We investigated the relationship between selected socioeconomic variables, pregnancy indices, birth weight, and maternal health in women of different ethnic origins. In our cross-sectional data set, 29.8% of infants were born with a low birth weight. Our data analysis showed Indo-Aryan and lower caste ethnic groups had significantly lower weight babies than Tibeto-Burman and Newar groups. Further analysis showed that the Tibeto-Burman group received better care during pregnancy. Similarly, the Newar groups had significantly better nutritional intake than the Indo-Aryan and lower caste groups. The outcome of food restriction and antenatal care during pregnancy in specific ethnic groups has important implications for the health care delivery system. Health policymakers should target those ethnic groups and develop culturally based policies to reduce the incidence of low birth weight in Nepal.

Receiving social support online: implications for health education.

PubMed

White, M; Dorman, S M

2001-12-01

Online support groups are expanding as the general public becomes more comfortable using computer-mediated communication technology. These support groups have certain benefits for users who may not be able to or do not have the desire to attend face-to-face sessions. Online support groups also present challenges when compared to traditional face-to-face group communication. Communication difficulties may arise resulting from lack of visual and aural cues found in traditional face-to-face communication. Online support groups have emerged within health care as a result of the need individuals have to know more about health conditions they are confronting. The proliferation of these online communities may provide an opportunity for health educators to reach target populations with specific messages. This paper reviews the development of health-related online support groups, examines research conducted within these communities, compares their utility with traditional support groups and discusses the implications of these groups for health education.

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults.

PubMed

Lee, Ahreum; Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

2018-04-11

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.

Real-time multiplex PCR assay for detection of Yersinia pestis and Yersinia pseudotuberculosis.

PubMed

Matero, Pirjo; Pasanen, Tanja; Laukkanen, Riikka; Tissari, Päivi; Tarkka, Eveliina; Vaara, Martti; Skurnik, Mikael

2009-01-01

A multiplex real-time polymerase chain reaction (PCR) assay was developed for the detection of Yersinia pestis and Yersinia pseudotuberculosis. The assay includes four primer pairs, two of which are specific for Y. pestis, one for Y. pestis and Y. pseudotuberculosis and one for bacteriophage lambda; the latter was used as an internal amplification control. The Y. pestis-specific target genes in the assay were ypo2088, a gene coding for a putative methyltransferase, and the pla gene coding for the plasminogen activator. In addition, the wzz gene was used as a target to specifically identify both Y. pestis and the closely related Y. pseudotuberculosis group. The primer and probe sets described for the different genes can be used either in single or in multiplex PCR assays because the individual probes were designed with different fluorochromes. The assays were found to be both sensitive and specific; the lower limit of the detection was 10-100 fg of extracted Y. pestis or Y. pseudotuberculosis total DNA. The sensitivity of the tetraplex assay was determined to be 1 cfu for the ypo2088 and pla probe labelled with FAM and JOE fluorescent dyes, respectively.

Expression of the Fanconi anemia group A gene (Fanca) during mouse embryogenesis.

PubMed

Abu-Issa, R; Eichele, G; Youssoufian, H

1999-07-15

About 80% of all cases of Fanconi anemia (FA) can be accounted for by complementation groups A and C. To understand the relationship between these groups, we analyzed the expression pattern of the mouse FA group-A gene (Fanca) during embryogenesis and compared it with the known pattern of the group-C gene (Fancc). Northern analysis of RNA from mouse embryos at embryonic days 7, 11, 15, and 17 showed a predominant 4.5 kb band in all stages. By in situ hybridization, Fanca transcripts were found in the whisker follicles, teeth, brain, retina, kidney, liver, and limbs. There was also stage-specific variation in Fanca expression, particularly within the developing whiskers and the brain. Some tissues known to express Fancc (eg, gut) failed to show Fanca expression. These observations show that (1) Fanca is under both tissue- and stage-specific regulation in several tissues; (2) the expression pattern of Fanca is consistent with the phenotype of the human disease; and (3) Fanca expression is not necessarily coupled to that of Fancc. The presence of distinct tissue targets for FA genes suggests that some of the variability in the clinical phenotype can be attributed to the complementation group assignment.

Vaginismus and dyspareunia: automatic vs. deliberate disgust responsivity.

PubMed

Borg, Charmaine; de Jong, Peter J; Schultz, Willibrord Weijmar

2010-06-01

The difficulty of penetration experienced in vaginismus and dyspareunia may at least partly be due to a disgust-induced defensive response. To examine if sex stimuli specifically elicit: (i) automatic disgust-related memory associations; (ii) physiological disgust responsivity; and/or (iii) deliberate expression of disgust/threat. Two single target Implicit Association Task (st-IAT) and electromyography (EMG) were conducted on three groups: vaginismus (N = 24), dyspareunia (N = 24), and control (N = 31) group. st-IAT, to index their initial disgust-related associations and facial EMG for the m. levator labii and m. corrugator supercilii regions. Both clinical groups showed enhanced automatic sex-disgust associations. As a unique physiological expression of disgust, the levator activity was specifically enhanced for the vaginismus group, when exposed to a women-friendly SEX video clip. Also at the deliberate level, specifically the vaginismus group showed enhanced subjective disgust toward SEX pictures and the SEX clip, along with higher threat responses. Supporting the view that disgust is involved in vaginismus and dyspareunia, for both, clinical groups' sex stimuli automatically elicited associations with disgust. Particularly for the vaginismus group, these initial disgust associations persisted during subsequent validation processes and were also evident at the level of facial expression and self-report data. Findings are consistent with the notion that uncontrollable activated associations are involved in eliciting defensive reactions at the prospect of penetration seen in both conditions. Whereas deliberate attitudes, usually linked with the desire for having intercourse, possibly generate the distinction (e.g., severity) between these two conditions.

The effect of consumer incentives on Medicaid beneficiaries' compliance with well-child visit guidelines.

PubMed

Nyman, John A; Abraham, Jean M; Riley, William

2013-01-01

The Affordable Care Act of 2010 recommends that consumer incentives be employed to increase the use of preventive care by Medicaid beneficiaries, but few evaluative studies exist. This study evaluates a Target gift card incentive employed by a Minnesota health plan serving Medicaid beneficiaries over the period 2002-2003. Lacking a contemporaneous control group, the proximity between the child's residence and the nearest Target store was used as the intervention variable. Using alternative specifications for the intervention variable, results of the difference-in-differences equations suggest that the incentive program significantly increased the likelihood that a Medicaid beneficiary would have a well-child visit.

Qualitative application of the theory of planned behavior to understand beverage consumption behaviors among adults.

PubMed

Zoellner, Jamie; Krzeski, Erin; Harden, Samantha; Cook, Emily; Allen, Kacie; Estabrooks, Paul A

2012-11-01

Despite strong scientific data indicating associations among sugar-sweetened beverages (SSB) and numerous adverse health outcomes, little is known about culturally specific beliefs and potential individual-level behavioral strategies to reduce SSB intake. The primary objective of this formative study targeting adults residing in rural southwest Virginia was to apply the Theory of Planned Behavior to investigate culturally specific attitudes, subjective norms, and perceived behavioral control constructs related to the consumption of SSB, water, and artificially sweetened beverages. Using a homogenous sampling strategy, eight focus groups were conducted with 54 adult participants who exceeded recommendations of <1 cup of SSB/day. An experienced moderator and co-moderator utilized a semi-structured script, grounded in the Theory of Planned Behavior, to execute the focus group. All focus groups were audiotaped and transcribed verbatim. Three researchers independently coded meaning units to the major themes and subsequently met to gain consensus in coding. Important beverage-specific themes emerged for attitudes, subjective norms, perceived behavioral control, and intentions. Across all beverages, the most notable themes included taste (n=161 meaning units), availability/convenience (n=95 meaning units), habit/addiction (n=57 meaning units), and cost (n=28 meaning units). Health consequences associated with beverages and water-quality issues also surfaced, as well as normative beliefs, including the influence of doctors and peers. The identified themes and subthemes provide critical insight into understanding culturally relevant context and beliefs associated with beverage consumption behaviors and helps inform the development and evaluation of future intervention efforts targeting SSB consumption in the health disparate region of southwest Virginia. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

PubMed

Becker, Luis E; Siebert, Daniela; Süsal, Caner; Opelz, Gerhard; Leo, Albrecht; Waldherr, Rüdiger; Macher-Goeppinger, Stephan; Schemmer, Peter; Schaefer, Sebastian Markus; Klein, Katrin; Beimler, Jörg; Zeier, Martin; Schwenger, Vedat; Morath, Christian

2015-11-01

For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.

High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{supmore » hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.« less

Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery.

PubMed

Plichta, Michael M; Schwarz, Adam J; Grimm, Oliver; Morgen, Katrin; Mier, Daniela; Haddad, Leila; Gerdes, Antje B M; Sauer, Carina; Tost, Heike; Esslinger, Christine; Colman, Peter; Wilson, Frederick; Kirsch, Peter; Meyer-Lindenberg, Andreas

2012-04-15

Even more than in cognitive research applications, moving fMRI to the clinic and the drug development process requires the generation of stable and reliable signal changes. The performance characteristics of the fMRI paradigm constrain experimental power and may require different study designs (e.g., crossover vs. parallel groups), yet fMRI reliability characteristics can be strongly dependent on the nature of the fMRI task. The present study investigated both within-subject and group-level reliability of a combined three-task fMRI battery targeting three systems of wide applicability in clinical and cognitive neuroscience: an emotional (face matching), a motivational (monetary reward anticipation) and a cognitive (n-back working memory) task. A group of 25 young, healthy volunteers were scanned twice on a 3T MRI scanner with a mean test-retest interval of 14.6 days. FMRI reliability was quantified using the intraclass correlation coefficient (ICC) applied at three different levels ranging from a global to a localized and fine spatial scale: (1) reliability of group-level activation maps over the whole brain and within targeted regions of interest (ROIs); (2) within-subject reliability of ROI-mean amplitudes and (3) within-subject reliability of individual voxels in the target ROIs. Results showed robust evoked activation of all three tasks in their respective target regions (emotional task=amygdala; motivational task=ventral striatum; cognitive task=right dorsolateral prefrontal cortex and parietal cortices) with high effect sizes (ES) of ROI-mean summary values (ES=1.11-1.44 for the faces task, 0.96-1.43 for the reward task, 0.83-2.58 for the n-back task). Reliability of group level activation was excellent for all three tasks with ICCs of 0.89-0.98 at the whole brain level and 0.66-0.97 within target ROIs. Within-subject reliability of ROI-mean amplitudes across sessions was fair to good for the reward task (ICCs=0.56-0.62) and, dependent on the particular ROI, also fair-to-good for the n-back task (ICCs=0.44-0.57) but lower for the faces task (ICC=-0.02-0.16). In conclusion, all three tasks are well suited to between-subject designs, including imaging genetics. When specific recommendations are followed, the n-back and reward task are also suited for within-subject designs, including pharmaco-fMRI. The present study provides task-specific fMRI reliability performance measures that will inform the optimal use, powering and design of fMRI studies using comparable tasks. Copyright © 2012 Elsevier Inc. All rights reserved.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

PubMed

Winthrop, K L; Mariette, X; Silva, J T; Benamu, E; Calabrese, L H; Dumusc, A; Smolen, J S; Aguado, J M; Fernández-Ruiz, M

2018-06-01

The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Yang, Frances Fan

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved for LLY13's binding to oral cancer cells. OSCC ligands developed from this study may become potential candidates for the development of OSCC targeted theranostic agents.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells.

PubMed

Setzler, Brian P; Zhuang, Zhongbin; Wittkopf, Jarrid A; Yan, Yushan

2016-12-06

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW -1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

2016-12-01

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

PubMed Central

Naganathan, Saranga; Grunbeck, Amy; Tian, He; Huber, Thomas; Sakmar, Thomas P.

2013-01-01

To facilitate structural and dynamic studies of G protein-coupled receptor (GPCR) signaling complexes, new approaches are required to introduce informative probes or labels into expressed receptors that do not perturb receptor function. We used amber codon suppression technology to genetically-encode the unnatural amino acid, p-azido-L-phenylalanine (azF) at various targeted positions in GPCRs heterologously expressed in mammalian cells. The versatility of the azido group is illustrated here in different applications to study GPCRs in their native cellular environment or under detergent solubilized conditions. First, we demonstrate a cell-based targeted photocrosslinking technology to identify the residues in the ligand-binding pocket of GPCR where a tritium-labeled small-molecule ligand is crosslinked to a genetically-encoded azido amino acid. We then demonstrate site-specific modification of GPCRs by the bioorthogonal Staudinger-Bertozzi ligation reaction that targets the azido group using phosphine derivatives. We discuss a general strategy for targeted peptide-epitope tagging of expressed membrane proteins in-culture and its detection using a whole-cell-based ELISA approach. Finally, we show that azF-GPCRs can be selectively tagged with fluorescent probes. The methodologies discussed are general, in that they can in principle be applied to any amino acid position in any expressed GPCR to interrogate active signaling complexes. PMID:24056801

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs.

PubMed

Zhang, Chengjuan; Wei, Bing; Li, Peng; Yang, Ke; Wang, Zhizhong; Ma, Jie; Guo, Yongjun

2017-01-01

Epidermal growth factor receptor (EGFR) specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC). However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients. A total of forty-five (45) NSCLC patients who received EGFR-TKI therapy were enrolled. We identified the changes of EGFR mutations in plasma ctDNA by Amplification Refractory Mutation System (ARMS) PCR technology. In the 45 cases of NSCLC with EGFR mutations, the EGFR mutation status changed in 26 cases, in which, 12 cases (26.7%) from positive to negative, and 14 cases (31.1%) from T790M mutation negative to positive after TKI targeted therapy. The T790M occurance group had a shorter Progression -Free-Survival (PFS) than the groups of EGFR mutation undetected and EGFR mutation turned out to have no change after EGFR-TKI therapy (p < 0.05). According to this study, it's necessary to closely monitor EGFR mutations during follow-up to predict the prognosis of NSCLC patients who are to receive the TKI targeted therapy.

Libyan Former Foreign Fighters and Their Effects on the Libyan Revolution

DTIC Science & Technology

2012-03-23

Glocal organizations; Arab Spring; Sinjar Papers; CJSOTF 120; 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 52...the Libyan Islamic Fighting Group (LIFG) ........................................................................ 13 LIFG and Al Qaeda: A “ Glocal ...to be specifically targeted.(27) LIFG and Al Qaeda Connections: A “ Glocal ” Operation(28) FORMER FOREIGN FIGHTERS AND THEIR EFFECTS ON THE LIBYAN