Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.

PubMed

Kia, Azadeh; Przystal, Justyna M; Nianiaris, Nastasia; Mazarakis, Nicholas D; Mintz, Paul J; Hajitou, Amin

2012-12-01

The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications.

Discriminating crop and other canopies by overlapping binary image layers

NASA Astrophysics Data System (ADS)

Doi, Ryoichi

2013-02-01

For optimal management of agricultural fields by remote sensing, discrimination of the crop canopy from weeds and other objects is essential. In a digital photograph, a rice canopy was discriminated from a variety of weed and tree canopies and other objects by overlapping binary image layers of red-green-blue and other color components indicating the pixels with target canopy-specific (intensity) values based on the ranges of means ±(3×) standard deviations. By overlapping and merging the binary image layers, the target canopy specificity improved to 0.0015 from 0.027 for the yellow 1× standard deviation binary image layer, which was the best among all combinations of color components and means ±(3×) standard deviations. The most target rice canopy-likely pixels were further identified by limiting the pixels at different luminosity values. The discriminatory power was also visually demonstrated in this manner.

Approaches to Measuring the Effects of Wake-Promoting Drugs: A Focus on Cognitive Function

PubMed Central

Edgar, Christopher J.; Pace-Schott, Edward F.; Wesnes, Keith A.

2009-01-01

Objectives In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties. PMID:19565524

A Multi-targeted Approach to Suppress Tumor-Promoting Inflammation

PubMed Central

Samadi, Abbas K.; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Bishayee, Anupam; Lokeshwar, Bal L.; Grue, Brendan; Panis, Carolina; Boosani, Chandra S.; Poudyal, Deepak; Stafforini, Diana M.; Bhakta, Dipita; Niccolai, Elena; Guha, Gunjan; Rupasinghe, H.P. Vasantha; Fujii, Hiromasa; Honoki, Kanya; Mehta, Kapil; Aquilano, Katia; Lowe, Leroy; Hofseth, Lorne J.; Ricciardiello, Luigi; Ciriolo, Maria Rosa; Singh, Neetu; Whelan, Richard L.; Chaturvedi, Rupesh; Ashraf, S. Salman; Kumara, HMC Shantha; Nowsheen, Somaira; Mohammed, Sulma I.; Helferich, William G.; Yang, Xujuan

2015-01-01

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes. PMID:25951989

Landscape connectivity promotes plant biodiversity spillover into non-target habitats.

PubMed

Brudvig, Lars A; Damschen, Ellen I; Tewksbury, Joshua J; Haddad, Nick M; Levey, Douglas J

2009-06-09

Conservation efforts typically focus on maximizing biodiversity in protected areas. The space available for reserves is limited, however, and conservation efforts must increasingly consider how management of protected areas can promote biodiversity beyond reserve borders. Habitat corridors are considered an important feature of reserves because they facilitate movement of organisms between patches, thereby increasing species richness in those patches. Here we demonstrate that by increasing species richness inside target patches, corridors additionally benefit biodiversity in surrounding non-target habitat, a biodiversity "spillover" effect. Working in the world's largest corridor experiment, we show that increased richness extends for approximately 30% of the width of the 1-ha connected patches, resulting in 10-18% more vascular plant species around patches of target habitat connected by corridors than around unconnected but otherwise equivalent patches of habitat. Furthermore, corridor-enhanced spillover into non-target habitat can be predicted by a simple plant life-history trait: seed dispersal mode. Species richness of animal-dispersed plants in non-target habitat increased in response to connectivity provided by corridors, whereas species richness of wind-dispersed plants was unaffected by connectivity and increased in response to changes in patch shape--higher edge-to-interior ratio--created by corridors. Corridors promoted biodiversity spillover for native species of the threatened longleaf pine ecosystem being restored in our experiment, but not for exotic species. By extending economically driven spillover concepts from marine fisheries and crop pollination systems, we show how reconnecting landscapes amplifies biodiversity conservation both within and beyond reserve borders.

Epidemic spreading on complex networks with overlapping and non-overlapping community structure

NASA Astrophysics Data System (ADS)

Shang, Jiaxing; Liu, Lianchen; Li, Xin; Xie, Feng; Wu, Cheng

2015-02-01

Many real-world networks exhibit community structure where vertices belong to one or more communities. Recent studies show that community structure plays an import role in epidemic spreading. In this paper, we investigate how the extent of overlap among communities affects epidemics. In order to experiment on the characteristic of overlapping communities, we propose a rewiring algorithm that can change the community structure from overlapping to non-overlapping while maintaining the degree distribution of the network. We simulate the Susceptible-Infected-Susceptible (SIS) epidemic process on synthetic scale-free networks and real-world networks by applying our rewiring algorithm. Experiments show that epidemics spread faster on networks with higher level of overlapping communities. Furthermore, overlapping communities' effect interacts with the average degree's effect. Our work further illustrates the important role of overlapping communities in the process of epidemic spreading.

Antibodies Targeting Closely Adjacent or Minimally Overlapping Epitopes Can Displace One Another

PubMed Central

Abdiche, Yasmina Noubia; Yeung, Andy Yik; Ni, Irene; Stone, Donna; Miles, Adam; Morishige, Winse; Rossi, Andrea; Strop, Pavel

2017-01-01

Here we describe how real-time label-free biosensors can be used to identify antibodies that compete for closely adjacent or minimally overlapping epitopes on their specific antigen via a mechanism of antibody displacement. By kinetically perturbing one another’s binding towards their antigen via the formation of a transient trimolecular complex, antibodies can displace one another in a fully reversible and dose-dependent manner. Displacements can be readily identified when epitope binning assays are performed in a classical sandwich assay format whereby a solution antibody (analyte) is tested for binding to its antigen that is first captured via an immobilized antibody (ligand) because an inverted sandwiching response is observed when an analyte displaces a ligand, signifying the antigen’s unusually rapid dissociation from its ligand. In addition to classifying antibodies within a panel in terms of their ability to block or sandwich pair with one another, displacement provides a hybrid mechanism of competition. Using high-throughput epitope binning studies we demonstrate that displacements can be observed on any target, if the antibody panel contains appropriate epitope diversity. Unidirectional displacements occurring between disparate-affinity antibodies can generate apparent asymmetries in a cross-blocking experiment, confounding their interpretation. However, examining competition across a wide enough concentration range will often reveal that these displacements are reversible. Displacement provides a gentle and efficient way of eluting antigen from an otherwise high affinity binding partner which can be leveraged in designing reagents or therapeutic antibodies with unique properties. PMID:28060885

Antibodies Targeting Closely Adjacent or Minimally Overlapping Epitopes Can Displace One Another.

PubMed

Abdiche, Yasmina Noubia; Yeung, Andy Yik; Ni, Irene; Stone, Donna; Miles, Adam; Morishige, Winse; Rossi, Andrea; Strop, Pavel

2017-01-01

Here we describe how real-time label-free biosensors can be used to identify antibodies that compete for closely adjacent or minimally overlapping epitopes on their specific antigen via a mechanism of antibody displacement. By kinetically perturbing one another's binding towards their antigen via the formation of a transient trimolecular complex, antibodies can displace one another in a fully reversible and dose-dependent manner. Displacements can be readily identified when epitope binning assays are performed in a classical sandwich assay format whereby a solution antibody (analyte) is tested for binding to its antigen that is first captured via an immobilized antibody (ligand) because an inverted sandwiching response is observed when an analyte displaces a ligand, signifying the antigen's unusually rapid dissociation from its ligand. In addition to classifying antibodies within a panel in terms of their ability to block or sandwich pair with one another, displacement provides a hybrid mechanism of competition. Using high-throughput epitope binning studies we demonstrate that displacements can be observed on any target, if the antibody panel contains appropriate epitope diversity. Unidirectional displacements occurring between disparate-affinity antibodies can generate apparent asymmetries in a cross-blocking experiment, confounding their interpretation. However, examining competition across a wide enough concentration range will often reveal that these displacements are reversible. Displacement provides a gentle and efficient way of eluting antigen from an otherwise high affinity binding partner which can be leveraged in designing reagents or therapeutic antibodies with unique properties.

Radial sets: interactive visual analysis of large overlapping sets.

PubMed

Alsallakh, Bilal; Aigner, Wolfgang; Miksch, Silvia; Hauser, Helwig

2013-12-01

In many applications, data tables contain multi-valued attributes that often store the memberships of the table entities to multiple sets such as which languages a person masters, which skills an applicant documents, or which features a product comes with. With a growing number of entities, the resulting element-set membership matrix becomes very rich of information about how these sets overlap. Many analysis tasks targeted at set-typed data are concerned with these overlaps as salient features of such data. This paper presents Radial Sets, a novel visual technique to analyze set memberships for a large number of elements. Our technique uses frequency-based representations to enable quickly finding and analyzing different kinds of overlaps between the sets, and relating these overlaps to other attributes of the table entities. Furthermore, it enables various interactions to select elements of interest, find out if they are over-represented in specific sets or overlaps, and if they exhibit a different distribution for a specific attribute compared to the rest of the elements. These interactions allow formulating highly-expressive visual queries on the elements in terms of their set memberships and attribute values. As we demonstrate via two usage scenarios, Radial Sets enable revealing and analyzing a multitude of overlapping patterns between large sets, beyond the limits of state-of-the-art techniques.

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

PubMed

Potvin Kent, Monique; Velkers, Clive

2017-10-01

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

Overlap Properties of Clouds Generated by a Cloud Resolving Model

NASA Technical Reports Server (NTRS)

Oreopoulos, L.; Khairoutdinov, M.

2002-01-01

In order for General Circulation Models (GCMs), one of our most important tools to predict future climate, to correctly describe the propagation of solar and thermal radiation through the cloudy atmosphere a realistic description of the vertical distribution of cloud amount is needed. Actually, one needs not only the cloud amounts at different levels of the atmosphere, but also how these cloud amounts are related, in other words, how they overlap. Currently GCMs make some idealized assumptions about cloud overlap, for example that contiguous cloud layers overlap maximally and non-contiguous cloud layers overlap in a random fashion. Since there are difficulties in obtaining the vertical profile of cloud amount from observations, the realism of the overlap assumptions made in GCMs has not been yet rigorously investigated. Recently however, cloud observations from a relatively new type of ground radar have been used to examine the vertical distribution of cloudiness. These observations suggest that the GCM overlap assumptions are dubious. Our study uses cloud fields from sophisticated models dedicated to simulate cloud formation, maintenance, and dissipation called Cloud Resolving Models . These models are generally considered capable of producing realistic three-dimensional representation of cloudiness. Using numerous cloud fields produced by such a CRM we show that the degree of overlap between cloud layers is a function of their separation distance, and is in general described by a combination of the maximum and random overlap assumption, with random overlap dominating as separation distances increase. We show that it is possible to parameterize this behavior in a way that can eventually be incorporated in GCMs. Our results seem to have a significant resemblance to the results from the radar observations despite the completely different nature of the datasets. This consistency is encouraging and will promote development of new radiative transfer codes that will

saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.

PubMed

Portnoy, Victoria; Lin, Szu Hua Sharon; Li, Kathy H; Burlingame, Alma; Hu, Zheng-Hui; Li, Hao; Li, Long-Cheng

2016-03-01

Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.

MiR-32 promotes gastric carcinoma tumorigenesis by targeting Kruppel-like factor 4

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

Yan, Chao; Yu, Jianchun, E-mail: yu_jchpumch@163.com; Liu, Yuqin

Gastric cancer (GC) is a prevalent malignant cancer worldwide and is highly lethal because of its fast growth. Currently, the clinical therapy options for GC remain limited. MiR-32 has been reported as an oncogenic microRNA in many cancers, but its role in GC is unclear. Here, we found that miR-32 was overexpressed in GC tissues compared with adjacent normal tissue, and miR-32 was higher in GC patients' plasma compared with healthy individuals. Furthermore, we have identified miR-32 to be oncogenic, by promoting gastric cell proliferation, migration and invasion. We also identified Kruppel-like factor 4 (KLF4) as a direct target ofmore » miR-32. Knockdown of KLF4 promoted proliferation, migration and invasion of GC cells. We conclude that miR-32 promotes GC cell proliferation, migration and invasion by targeting KLF4, suggesting that the miR-32-KLF4 pathway may be useful in clinical diagnosis and therapeutics. - Highlights: • miR-32 was overexpression in GC tissues than adjacent normal tissue. • miR-32 was higher in GC patients' plasma compared with healthy people. • miR-32 promotes GC cell proliferation, migration and invasion by targeting KLF4.« less

The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

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

Moretto, A.; Nicolli, A.; Lotti, M.

2007-03-15

Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crudemore » homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC{sub 50} of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds.« less

Targeting Promoter-Associated Noncoding RNA In Vivo.

PubMed

Civenni, Gianluca

2017-01-01

There are many classes of noncoding RNAs (ncRNAs), with wide-ranging functionalities (e.g., RNA editing, mediation of mRNA splicing, ribosomal function). MicroRNAs (miRNAs) and long ncRNAs (lncRNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. Incorrect expression or mutation of lncRNAs has been reported to be associated with several disease conditions, such a malignant transformation in humans. Importantly, pivotal players in tumorigenesis and cancer progression, such as c-Myc, may be regulated by lncRNA at promoter level. The function of lncRNA can be reduced with antisense oligonucleotides that sequester or degrade mature lncRNAs. In alternative, lncRNA transcription can be blocked by small interference RNA (RNAi), which had acquired, recently, broad interested in clinical applications. In vivo-jetPEI™ is a linear polyethylenimine mediating nucleic acid (DNA, shRNA, siRNA, oligonucelotides) delivery with high efficiency. Different in vivo delivery routes have been validated: intravenous (IV), intraperitoneal (IP), intratumoral, subcutaneous, topical, and intrathecal. High levels of nucleic acid delivery are achieved into a broad range of tissues, such as lung, salivary glands, heart, spleen, liver, and prostate upon systemic administration. In addition, in vivo-jetPEI™ is also an efficient carrier for local gene and siRNA delivery such as intratumoral or topical application on the skin. After systemic injection, siRNA can be detected and the levels can be validated in target tissues by qRT-PCR. Targeting promoter-associated lncRNAs with siRNAs (small interfering RNAs) in vivo is becoming an exciting breakthrough for the treatment of human disease.

Developing, implementing, and evaluating a condom promotion program targeting sexually active adolescents.

PubMed

Alstead, M; Campsmith, M; Halley, C S; Hartfield, K; Goldbaum, G; Wood, R W

1999-12-01

This article describes the development, implementation, and evaluation of the Condom Campaign, a 1995 HIV prevention program promoting condom use among sexually active adolescents in three King County, Washington, urban communities. This program employed three main strategies: (a) mobilizing all levels of the target communities to support and guide program development and implementation; (b) creating and implementing a mass media campaign targeting sexually active teenagers that promoted correct condom use and favorable attitudes toward condoms; and (c) recruiting public agencies, community organizations, and businesses to distribute condoms from bins and vending machines. We evaluated the program through a series of cross-sectional interviews conducted in the three communities chosen for their elevated levels of adolescent sexual risk behavior. Overall, 73% of target youth reported exposure to the Condom Campaign; exposure did not differ by age, gender, race, or level of sexual experience. Levels of sexual activity remained stable throughout the media campaign.

Understanding COPD-overlap syndromes.

PubMed

Poh, Tuang Yeow; Mac Aogáin, Micheál; Chan, Adrian Kwok Wai; Yii, Anthony Chau Ang; Yong, Valerie Fei Lee; Tiew, Pei Yee; Koh, Mariko Siyue; Chotirmall, Sanjay Haresh

2017-04-01

Chronic obstructive pulmonary disease accounts for a large burden of lung disease. It can 'overlap' with other respiratory diseases including bronchiectasis, fibrosis and obstructive sleep apnea (OSA). While COPD alone confers morbidity and mortality, common features with contrasting clinical outcomes can occur in COPD 'overlap syndromes'. Areas covered: Given the large degree of heterogeneity in COPD, individual variation to treatment is adopted based on its observed phenotype, which in turn overlaps with features of other respiratory disease states such as asthma. This is coined asthma-COPD overlap syndrome ('ACOS'). Other examples of such overlapping clinical states include bronchiectasis-COPD ('BCOS'), fibrosis-COPD ('FCOS') and OSA-COPD ('OCOS'). The objective of this review is to highlight similarities and differences between the COPD-overlap syndromes in terms of risk factors, pathophysiology, diagnosis and potential treatment differences. Expert commentary: As a consequence of COPD overlap syndromes, a transition from the traditional 'one size fits all' treatment approach is necessary. Greater treatment stratification according to clinical phenotype using a precision medicine approach is now required. In this light, it is important to recognize and differentiate COPD overlap syndromes as distinct disease states compared to individual diseases such as asthma, COPD, fibrosis or bronchiectasis.

The Escherichia coli cAMP receptor protein bound at a single target can activate transcription initiation at divergent promoters: a systematic study that exploits new promoter probe plasmids.

PubMed Central

El-Robh, Mohamed Samir; Busby, Stephen J W

2002-01-01

We report the first detailed quantitative study of divergent promoters dependent on the Escherichia coli cAMP receptor protein (CRP), a factor known to activate transcription initiation at target promoters by making direct interactions with the RNA polymerase holoenzyme. In this work, we show that CRP bound at a single target site is able to activate transcription at two divergently organized promoters. Experiments using promoter probe plasmids, designed to study divergent promoters in vivo and in vitro, show that the divergent promoters function independently. Further in vitro experiments show that two holo RNA polymerase molecules cannot be accommodated simultaneously at the divergent promoters. PMID:12350222

EBF factors drive expression of multiple classes of target genes governing neuronal development.

PubMed

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Identification of HMX1 target genes: A predictive promoter model approach

PubMed Central

Boulling, Arnaud; Wicht, Linda

2013-01-01

Purpose A homozygous mutation in the H6 family homeobox 1 (HMX1) gene is responsible for a new oculoauricular defect leading to eye and auricular developmental abnormalities as well as early retinal degeneration (MIM 612109). However, the HMX1 pathway remains poorly understood, and in the first approach to better understand the pathway’s function, we sought to identify the target genes. Methods We developed a predictive promoter model (PPM) approach using a comparative transcriptomic analysis in the retina at P15 of a mouse model lacking functional Hmx1 (dmbo mouse) and its respective wild-type. This PPM was based on the hypothesis that HMX1 binding site (HMX1-BS) clusters should be more represented in promoters of HMX1 target genes. The most differentially expressed genes in the microarray experiment that contained HMX1-BS clusters were used to generate the PPM, which was then statistically validated. Finally, we developed two genome-wide target prediction methods: one that focused on conserving PPM features in human and mouse and one that was based on the co-occurrence of HMX1-BS pairs fitting the PPM, in human or in mouse, independently. Results The PPM construction revealed that sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) (Sgcg), teashirt zinc finger homeobox 2 (Tshz2), and solute carrier family 6 (neurotransmitter transporter, glycine) (Slc6a9) genes represented Hmx1 targets in the mouse retina at P15. Moreover, the genome-wide target prediction revealed that mouse genes belonging to the retinal axon guidance pathway were targeted by Hmx1. Expression of these three genes was experimentally validated using a quantitative reverse transcription PCR approach. The inhibitory activity of Hmx1 on Sgcg, as well as protein tyrosine phosphatase, receptor type, O (Ptpro) and Sema3f, two targets identified by the PPM, were validated with luciferase assay. Conclusions Gene expression analysis between wild-type and dmbo mice allowed us to develop a PPM

Bar and club tobacco promotions in the alternative press: targeting young adults.

PubMed

Sepe, Edward; Glantz, Stanton A

2002-01-01

This study examined changes in tobacco promotions in the alternative press in San Francisco and Philadelphia from 1994 to 1999. A random sample of alternative newspapers was analyzed, and a content analysis was conducted. Between 1994 and 1999, numbers of tobacco advertisements increased from 8 to 337 in San Francisco and from 8 to 351 in Philadelphia. Product advertisements represented only 45% to 50% of the total; the remaining advertisements were entertainment-focused promotions, mostly bar-club and event promotions. The tobacco industry has increased its use of bars and clubs as promotional venues and has used the alternative press to reach the young adults who frequent these establishments. This increased targeting of young adults may be associated with an increase in smoking among this group.

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting.

PubMed

Farokhimanesh, Samila; Rahbarizadeh, Fatemeh; Rasaee, Mohammad J; Kamali, Abbas; Mashkani, Baratali

2010-01-01

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl-2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual-specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia-responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT-PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase-3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low-potential toxicity for normal tissues.

Underwater Laser Micromilling of Commercially-Pure Titanium Using Different Scan Overlaps

NASA Astrophysics Data System (ADS)

Charee, Wisan; Tangwarodomnukun, Viboon

2018-01-01

Underwater laser milling process is a technique for minimizing the thermal damage and gaining a higher material removal rate than processing in air. This paper presents the effect of laser scan overlap on cavity width, depth and surface roughness in the laser milling of commercially-pure titanium in water. The effects of laser pulse energy and pulse repetition rate were also examined, in which a nanosecond pulse laser emitting a 1064-nm wavelength was used in this study. The experimental results indicated that a wide and deep cavity was achievable under high laser energy and large scan overlap. According to the surface roughness, the use of high pulse repetition rate together with low laser energy can promote a smooth laser-milled surface particularly at 50% scan overlap. These findings can further suggest a suitable laser micromilling condition for titanium in roughing and finishing operations.

Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

PubMed Central

Javan, Bita; Shahbazi, Majid

2017-01-01

Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

Aberrant N400 responses to phonological overlap during rhyme judgements in children at risk for dyslexia.

PubMed

Noordenbos, Mark W; Segers, Eliane; Wagensveld, Barbara; Verhoeven, Ludo

2013-11-06

It is widely accepted that dyslexia is associated with difficulties in phonological awareness and that rhyme awareness in young children can predict later reading success. However, little is known regarding the underlying phonological mechanisms of rhyme awareness in dyslexia, as rhyme awareness is typically assessed using explicit behavioural measures that represent only the endpoint of processing and often lack phonological distracters. We examined event-related potentials (ERPs) in response to auditory word pairs that differed in phonological overlap during a rhyme judgement task given to 6-year-old beginning readers who were at risk for dyslexia (n=30) and typical-reading age-matched controls (n=29). ERPs were recorded in response to word pairs with various types of phonological overlap, including rhyming (e.g., wall-ball), non-rhyming overlapping (e.g., bell-ball) and non-rhyming unrelated (e.g., sock-ball) word pairs. Both groups of participants exhibited N400 responses for basic rhyme judgements vs. unrelated targets. In the typical-reading controls, the neural responses also differed between the rhyming targets and the non-rhyming overlapping targets, whereas neural responses to these targets were similar in the group of children at risk for dyslexia, indicating difficulties in their ability to process similar-sounding, non-rhyming targets. These findings suggest that typical-reading children solve the rhyme judgement task using a more analytical approach, whereas children who are at risk for dyslexia base their judgments on a comparison of overall sound similarity. © 2013 Elsevier B.V. All rights reserved.

CUP promotes deadenylation and inhibits decapping of mRNA targets

PubMed Central

Igreja, Catia; Izaurralde, Elisa

2011-01-01

CUP is an eIF4E-binding protein (4E-BP) that represses the expression of specific maternal mRNAs prior to their posterior localization. Here, we show that CUP employs multiple mechanisms to repress the expression of target mRNAs. In addition to inducing translational repression, CUP maintains mRNA targets in a repressed state by promoting their deadenylation and protects deadenylated mRNAs from further degradation. Translational repression and deadenylation are independent of eIF4E binding and require both the middle and C-terminal regions of CUP, which collectively we termed the effector domain. This domain associates with the deadenylase complex CAF1–CCR4–NOT and decapping activators. Accordingly, in isolation, the effector domain is a potent trigger of mRNA degradation and promotes deadenylation, decapping and decay. However, in the context of the full-length CUP protein, the decapping and decay mediated by the effector domain are inhibited, and target mRNAs are maintained in a deadenylated, repressed form. Remarkably, an N-terminal regulatory domain containing a noncanonical eIF4E-binding motif is required to protect CUP-associated mRNAs from decapping and further degradation, suggesting that this domain counteracts the activity of the effector domain. Our findings indicate that the mode of action of CUP is more complex than previously thought and provide mechanistic insight into the regulation of mRNA expression by 4E-BPs. PMID:21937713

An analysis of health promotion materials for Dutch truck drivers: Off target and too complex?

PubMed

Boeijinga, Anniek; Hoeken, Hans; Sanders, José

2017-01-01

Despite various health promotion initiatives, unfavorable figures regarding Dutch truck drivers' eating behaviors, exercise behaviors, and absenteeism have not improved. The aim was to obtain a better understanding of the low level of effectiveness of current health interventions for Dutch truck drivers by examining to what extent these are tailored to the target group's particular mindset (focus of content) and health literacy skills (presentation of content). The article analyzes 21 health promotion materials for Dutch truck drivers using a two-step approach: (a) an analysis of the materials' focus, guided by the Health Action Process Approach; and (b) an argumentation analysis, guided by pragma-dialectics. The corpus analysis revealed: (a) a predominant focus on the motivation phase; and (b) in line with the aim of motivating the target group, a consistent use of pragmatic arguments, which were typically presented in an implicit way. The results indicate that existing health promotion materials for Dutch truck drivers are not sufficiently tailored to the target group's mindset and health literacy skills. Recommendations are offered to develop more tailored/effective health interventions targeting this high-risk, underserved occupational group.

Deadly targeting of women in promoting cigarettes.

PubMed

O'Keefe, A M; Pollay, R W

1996-01-01

The history of tobacco marketing portrays a strong relationship between cigarette advertising targeted to women and the rise in the prevalence of women smoking. This article describes how tobacco companies crafted their marketing strategies to obfuscate the growing evidence of the health hazards of tobacco and to circumvent attempts to regulate cigarette advertising. It shows how the tobacco industry understood and capitalized on the women's liberation movement to sell cigarettes as symbols of freedom and emancipation, tracing the creation and promotion of Virginia Slims as a case study. And it documents the unfortunate success of these marketing strategies as reflected in the trends of tobacco use, especially among underage girls, and the commensurate increase in tobacco-related disease and death among women.

STITCHER: A web resource for high-throughput design of primers for overlapping PCR applications.

PubMed

O'Halloran, Damien M

2015-06-01

Overlapping PCR is routinely used in a wide number of molecular applications. These include stitching PCR fragments together, generating fluorescent transcriptional and translational fusions, inserting mutations, making deletions, and PCR cloning. Overlapping PCR is also used for genotyping by traditional PCR techniques and in detection experiments using techniques such as loop-mediated isothermal amplification (LAMP). STITCHER is a web tool providing a central resource for researchers conducting all types of overlapping PCR experiments with an intuitive interface for automated primer design that's fast, easy to use, and freely available online (http://ohalloranlab.net/STITCHER.html). STITCHER can handle both single sequence and multi-sequence input, and specific features facilitate numerous other PCR applications, including assembly PCR, adapter PCR, and primer walking. Field PCR, and in particular, LAMP, offers promise as an on site tool for pathogen detection in underdeveloped areas, and STITCHER includes off-target detection features for pathogens commonly targeted using LAMP technology.

Exploring Polypharmacology Using a ROCS-Based Target Fishing Approach

DTIC Science & Technology

2012-01-01

target representatives. Target profiles were then generated for a given query molecule by computing maximal shape/ chemistry overlap between the query...molecule and the drug sets assigned to each protein target. The overlap was computed using the program ROCS (Rapid Overlay of Chemical Structures ). We...approaches in off-target prediction has been reviewed.9,10 Many structure -based target fishing (SBTF) approaches, such as INVDOCK11 and Target Fishing Dock

[Health targets for health promotion in an area of conflict between individual freedom, state paternalism and common welfare].

PubMed

Michelsen, K

2010-01-01

In Germany, a growing number of health targets has been adopted in the last years by various actors. While health targets are a useful instrument of governance, the priority setting and a respective redistribution of resources have to be legitimised in the cause of their advantages and disadvantages for population groups. The involved sciences including ethics can support decision-making, but not fully justify decisions. Therefore, decisions on health targets must be made in a transparent and participative process. In spite of a growing number of health targets, the lack of targets in health policies is to be criticised. Within the health targets, those measures assigned to curative medicine and prevention have a greater weight than health promotion. Health promotion should follow the WHO Ottawa-Charter and be embedded in the concept of "capabilities". Under these conditions, a stronger consideration of health promotion in the health target process would be desirable. However, the present actor constellations within health target processes make such a direction improbable. The struggle around capabilities and individual freedom occurs through, in and about institutions of the civil society as well as political and legal institutions. To restrict the discussion about public health and health promotions to an juxtaposition of individual freedom and state paternalism minimises societal and social restrictions of individual freedom as well as the possibility of a safeguard and enlargement of individual freedoms through political and legal institutions.

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B

PubMed Central

Jackson, Kasey L.; Dayton, Robert D.; Deverman, Benjamin E.; Klein, Ronald L.

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats. PMID:27867348

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

PubMed

Jackson, Kasey L; Dayton, Robert D; Deverman, Benjamin E; Klein, Ronald L

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

The overlap between cyberbullying and traditional bullying.

PubMed

Waasdorp, Tracy E; Bradshaw, Catherine P

2015-05-01

Cyberbullying appears to be on the rise among adolescents due in part to increased access to electronic devices and less online supervision. Less is known about how cyberbullying differs from traditional bullying which occurs in person and the extent to which these two forms overlap. Our first aim was to examine the overlap of traditional bullying (relational, verbal, and physical) with cyberbullying. The second aim examined student- and school-level correlates of cyber victimization as compared to traditional victims. The final aim explored details of the cyberbullying experience (e.g., who sent the message, how was the message sent, and what was the message about). Data came from 28,104 adolescents (grades, 9-12) attending 58 high schools. Approximately 23% of the youth reported being victims of any form of bullying (cyber, relational, physical, and verbal) within the last month, with 25.6% of those victims reporting being cyberbullied. The largest proportion (50.3%) of victims reported they were victimized by all four forms, whereas only 4.6% reported being only cyberbullied. Multilevel analyses indicated that as compared to those who were only traditionally bullied, those who were cyberbullied were more likely to have externalizing (odds ratio = 1.44) and internalizing symptoms (odds ratio = 1.25). Additional analyses examined detailed characteristics of the cyberbullying experiences, indicating a relatively high level of overlap between cyber and traditional bullying. Implications for preventive interventions targeting youth involved with cyberbullying and its overlap with other forms of bullying are discussed. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Marketing health promotion: hitting or missing the target in occupational health.

PubMed

Fontana, S A

1993-10-01

1. Occupational health nurses can use marketing strategies to plan, offer, and manage health promotion programs; and to conduct research aimed at better understanding the health needs of workers. 2. By applying a social marketing orientation to health promotion planning, occupational health nurses can tailor programs to fit employees' needs, and deliver health messages that are readily understandable to worker groups. 3. A priority in implementing any occupational health program or service is learning about the needs, desires, and health habits of employees. 4. Greater benefits to employee health may occur by targeting change in structures and systems at the workplace rather than solely focusing on lifestyle issues.

Measuring the extent of overlaps in protected area designations

PubMed Central

Arnell, Andy; Juffe-Bignoli, Diego; Shi, Yichuan; Bingham, Heather; MacSharry, Brian; Kingston, Naomi

2017-01-01

Over the past decades, a number of national policies and international conventions have been implemented to promote the expansion of the world’s protected area network, leading to a diversification of protected area strategies, types and designations. As a result, many areas are protected by more than one convention, legal instrument, or other effective means which may result in a lack of clarity around the governance and management regimes of particular locations. We assess the degree to which different designations overlap at global, regional and national levels to understand the extent of this phenomenon at different scales. We then compare the distribution and coverage of these multi-designated areas in the terrestrial and marine realms at the global level and among different regions, and we present the percentage of each county’s protected area extent that is under more than one designation. Our findings show that almost a quarter of the world’s protected area network is protected through more than one designation. In fact, we have documented up to eight overlapping designations. These overlaps in protected area designations occur in every region of the world, both in the terrestrial and marine realms, but are more common in the terrestrial realm and in some regions, notably Europe. In the terrestrial realm, the most common overlap is between one national and one international designation. In the marine realm, the most common overlap is between any two national designations. Multi-designations are therefore a widespread phenomenon but its implications are not well understood. This analysis identifies, for the first time, multi-designated areas across all designation types. This is a key step to understand how these areas are managed and governed to then move towards integrated and collaborative approaches that consider the different management and conservation objectives of each designation. PMID:29176888

Measuring the extent of overlaps in protected area designations.

PubMed

Deguignet, Marine; Arnell, Andy; Juffe-Bignoli, Diego; Shi, Yichuan; Bingham, Heather; MacSharry, Brian; Kingston, Naomi

2017-01-01

Over the past decades, a number of national policies and international conventions have been implemented to promote the expansion of the world's protected area network, leading to a diversification of protected area strategies, types and designations. As a result, many areas are protected by more than one convention, legal instrument, or other effective means which may result in a lack of clarity around the governance and management regimes of particular locations. We assess the degree to which different designations overlap at global, regional and national levels to understand the extent of this phenomenon at different scales. We then compare the distribution and coverage of these multi-designated areas in the terrestrial and marine realms at the global level and among different regions, and we present the percentage of each county's protected area extent that is under more than one designation. Our findings show that almost a quarter of the world's protected area network is protected through more than one designation. In fact, we have documented up to eight overlapping designations. These overlaps in protected area designations occur in every region of the world, both in the terrestrial and marine realms, but are more common in the terrestrial realm and in some regions, notably Europe. In the terrestrial realm, the most common overlap is between one national and one international designation. In the marine realm, the most common overlap is between any two national designations. Multi-designations are therefore a widespread phenomenon but its implications are not well understood. This analysis identifies, for the first time, multi-designated areas across all designation types. This is a key step to understand how these areas are managed and governed to then move towards integrated and collaborative approaches that consider the different management and conservation objectives of each designation.

Inter-sigmulon communication through topological promoter coupling

PubMed Central

del Peso Santos, Teresa; Shingler, Victoria

2016-01-01

Divergent transcription from within bacterial intergenic regions frequently involves promoters dependent on alternative σ-factors. This is the case for the non-overlapping σ70- and σ54-dependent promoters that control production of the substrate-responsive regulator and enzymes for (methyl)phenol catabolism. Here, using an array of in vivo and in vitro assays, we identify transcription-driven supercoiling arising from the σ54-promoter as the mechanism underlying inter-promoter communication that results in stimulation of the activity of the σ70-promoter. The non-overlapping ‘back-to-back’ configuration of a powerful σ54-promoter and weak σ70-promoter within this system offers a previously unknown means of inter-sigmulon communication that renders the σ70-promoter subservient to signals that elicit σ54-dependent transcription without it possessing a cognate binding site for the σ54-RNA polymerase holoenzyme. This mode of control has the potential to be a prevalent, but hitherto unappreciated, mechanism by which bacteria adjust promoter activity to gain appropriate transcriptional control. PMID:27422872

MicroRNA-21 promotes proliferation of rat hepatocyte BRL-3A by targeting FASLG.

PubMed

Li, J J; Chan, W H; Leung, W Y; Wang, Y; Xu, C S

2015-04-27

Rat liver regeneration (RLR) induced by partial hepatectomy involves cell proliferation regulated by numerous factors, including microRNAs (miRNAs). miRNA high-throughput sequencing has been established and used to analyze miRNA expression profiles. This study showed that 39 miRNAs were related to RLR through the analysis of miRNA high-throughput sequencing. Their role toward rat normal hepatocyte line BRL-3A was studied by gain- and loss-of-function analyses, and one of them, microRNA-21 (miR-21), obviously upregulated and promoted BRL-3A cell proliferation. Using bioinformatics to search for miR-21 targets revealed that Fas ligand (FASLG) is one of miR-21's target genes. A dual-luciferase report assay and Western blot assay showed that miR-21 directly targeted the 3'-untranslated region of FASLG and inhibited the expression of FASLG, which suggests that miR-21 promoted BRL-3A cell proliferation by reducing FASLG expression.

Overlapping clusters for distributed computation.

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

Mirrokni, Vahab; Andersen, Reid; Gleich, David F.

2010-11-01

Scalable, distributed algorithms must address communication problems. We investigate overlapping clusters, or vertex partitions that intersect, for graph computations. This setup stores more of the graph than required but then affords the ease of implementation of vertex partitioned algorithms. Our hope is that this technique allows us to reduce communication in a computation on a distributed graph. The motivation above draws on recent work in communication avoiding algorithms. Mohiyuddin et al. (SC09) design a matrix-powers kernel that gives rise to an overlapping partition. Fritzsche et al. (CSC2009) develop an overlapping clustering for a Schwarz method. Both techniques extend an initialmore » partitioning with overlap. Our procedure generates overlap directly. Indeed, Schwarz methods are commonly used to capitalize on overlap. Elsewhere, overlapping communities (Ahn et al, Nature 2009; Mishra et al. WAW2007) are now a popular model of structure in social networks. These have long been studied in statistics (Cole and Wishart, CompJ 1970). We present two types of results: (i) an estimated swapping probability {rho}{infinity}; and (ii) the communication volume of a parallel PageRank solution (link-following {alpha} = 0.85) using an additive Schwarz method. The volume ratio is the amount of extra storage for the overlap (2 means we store the graph twice). Below, as the ratio increases, the swapping probability and PageRank communication volume decreases.« less

The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs.

PubMed

Ning, Qianqian; Li, Yixue; Wang, Zhen; Zhou, Songwen; Sun, Hong; Yu, Guangjun

2017-03-27

Long non-coding RNA overlapping with protein-coding gene (lncRNA-coding pair) is a special type of overlapping genes. Protein-coding overlapping genes have been well studied and increasing attention has been paid to lncRNAs. By studying lncRNA-coding pairs in human genome, we showed that lncRNA-coding pairs were more likely to be generated by overprinting and retaining genes in lncRNA-coding pairs were given higher priority than non-overlapping genes. Besides, the preference of overlapping configurations preserved during evolution was based on the origin of lncRNA-coding pairs. Further investigations showed that lncRNAs promoting the splicing of their embedded protein-coding partners was a unilateral interaction, but the existence of overlapping partners improving the gene expression was bidirectional and the effect was decreased with the increased evolutionary age of genes. Additionally, the expression of lncRNA-coding pairs showed an overall positive correlation and the expression correlation was associated with their overlapping configurations, local genomic environment and evolutionary age of genes. Comparison of the expression correlation of lncRNA-coding pairs between normal and cancer samples found that the lineage-specific pairs including old protein-coding genes may play an important role in tumorigenesis. This work presents a systematically comprehensive understanding of the evolution and the expression pattern of human lncRNA-coding pairs.

Illusion induced overlapped optics.

PubMed

Zang, XiaoFei; Shi, Cheng; Li, Zhou; Chen, Lin; Cai, Bin; Zhu, YiMing; Zhu, HaiBin

2014-01-13

The traditional transformation-based cloak seems like it can only hide objects by bending the incident electromagnetic waves around the hidden region. In this paper, we prove that invisible cloaks can be applied to realize the overlapped optics. No matter how many in-phase point sources are located in the hidden region, all of them can overlap each other (this can be considered as illusion effect), leading to the perfect optical interference effect. In addition, a singular parameter-independent cloak is also designed to obtain quasi-overlapped optics. Even more amazing of overlapped optics is that if N identical separated in-phase point sources covered with the illusion media, the total power outside the transformation region is N2I0 (not NI0) (I0 is the power of just one point source, and N is the number point sources), which seems violating the law of conservation of energy. A theoretical model based on interference effect is proposed to interpret the total power of these two kinds of overlapped optics effects. Our investigation may have wide applications in high power coherent laser beams, and multiple laser diodes, and so on.

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

PubMed

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

2014-06-01

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

How do associative and phonemic overlap interact to boost illusory recollection?

PubMed

Hutchison, Keith A; Meade, Michelle L; Williams, Nikolas S; Manley, Krista D; McNabb, Jaimie C

2018-05-01

This project investigated the underlying mechanisms that boost false remember responses when participants receive study words that are both semantically and phonologically similar to a critical lure. Participants completed a memory task in which they were presented with a list of words all associated with a critical lure. Included within the list of semantic associates was a target that was either semantically associated (e.g., yawn) to the critical lure (e.g., sleep) or shared the initial (e.g., slam) or final (e.g., beep) phoneme(s) with the critical lure. After hearing the list, participants recalled each list item and indicated whether they just knew it was on the list or if they instead recollected specific contextual details of that item's presentation. We found that inserting an initial phonemic overlap target boosted experiences of recollection, but only when semantically related associates were presented beforehand. The results are consistent with models of spoken word recognition and show that established semantic context plus initial phonemic overlap play important roles in boosting false recollection.

Combined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasis.

PubMed

Torres, Sofía; Garcia-Palmero, Irene; Bartolomé, Rubén A; Fernandez-Aceñero, María Jesús; Molina, Elena; Calviño, Eva; Segura, Miguel F; Casal, J Ignacio

2017-05-01

The process of liver colonization in colorectal cancer remains poorly characterized. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value. We found that 38 miRNAs were differentially expressed between highly metastatic (KM12SM/SW620) and poorly metastatic (KM12C/SW480) cancer cell lines. After initial validation, we determined that three miRNAs (miR-424-3p, -503, and -1292) were overexpressed in metastatic colorectal cancer cell lines and human samples. Stable transduction of non-metastatic cells with each of the three miRNAs promoted metastatic properties in culture and increased liver colonization in vivo. Moreover, miR-424-3p and miR-1292 were associated with poor prognosis in human patients. A quantitative proteomic analysis of colorectal cancer cells transfected with miR-424-3p, miR-503, or miR-1292 identified alterations in 149, 129, or 121 proteins, respectively, with an extensive overlap of the target proteins of the three miRNAs. Importantly, down-regulation of two of these shared target proteins, CKB and UBA2, increased cell adhesion and proliferation in colorectal cancer cells. The capacity of distinct miRNAs to regulate the same mRNAs boosts the capacity of miRNAs to regulate cancer metastasis and underscores the necessity of targeting multiple miRNAs for effective cancer therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity

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

Zhang, XueLi, E-mail: zhangxueli.200010@yahoo.com.cn; Zhu, WeiYing; Zhang, JiFa

2010-04-30

MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in human gastric cancer progression has been reported; however, the role of miR-650 in gastric cancer is poorly understood. In this study, we show that miR-650 is involved in lymphatic and distant metastasis in human gastric cancer, and we find that ectopic expression of miR-650 promotes tumorigenesis and proliferation of gastric cancer cells. A luciferase reporter assay demonstrates that Inhibitor of Growth 4 (ING4) is a direct target of miR-650. Collectively, our study demonstrates that over-expression of miR-650 in gastric cancer may promotemore » proliferation and growth of cancer cells, at least partially through directly targeting ING4. These findings help clarify the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-650 modulation may be a bona fide miRNA-based treatment of gastric cancer.« less

Norm overlap between many-body states: Uncorrelated overlap between arbitrary Bogoliubov product states

NASA Astrophysics Data System (ADS)

Bally, B.; Duguet, T.

2018-02-01

Background: State-of-the-art multi-reference energy density functional calculations require the computation of norm overlaps between different Bogoliubov quasiparticle many-body states. It is only recently that the efficient and unambiguous calculation of such norm kernels has become available under the form of Pfaffians [L. M. Robledo, Phys. Rev. C 79, 021302 (2009), 10.1103/PhysRevC.79.021302]. Recently developed particle-number-restored Bogoliubov coupled-cluster (PNR-BCC) and particle-number-restored Bogoliubov many-body perturbation (PNR-BMBPT) ab initio theories [T. Duguet and A. Signoracci, J. Phys. G 44, 015103 (2017), 10.1088/0954-3899/44/1/015103] make use of generalized norm kernels incorporating explicit many-body correlations. In PNR-BCC and PNR-BMBPT, the Bogoliubov states involved in the norm kernels differ specifically via a global gauge rotation. Purpose: The goal of this work is threefold. We wish (i) to propose and implement an alternative to the Pfaffian method to compute unambiguously the norm overlap between arbitrary Bogoliubov quasiparticle states, (ii) to extend the first point to explicitly correlated norm kernels, and (iii) to scrutinize the analytical content of the correlated norm kernels employed in PNR-BMBPT. Point (i) constitutes the purpose of the present paper while points (ii) and (iii) are addressed in a forthcoming paper. Methods: We generalize the method used in another work [T. Duguet and A. Signoracci, J. Phys. G 44, 015103 (2017), 10.1088/0954-3899/44/1/015103] in such a way that it is applicable to kernels involving arbitrary pairs of Bogoliubov states. The formalism is presently explicated in detail in the case of the uncorrelated overlap between arbitrary Bogoliubov states. The power of the method is numerically illustrated and benchmarked against known results on the basis of toy models of increasing complexity. Results: The norm overlap between arbitrary Bogoliubov product states is obtained under a closed

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

PubMed Central

Ruderfer, Douglas M; Charney, Alexander W; Readhead, Ben; Kidd, Brian A; Kähler, Anna K; Kenny, Paul J; Keiser, Michael J; Moran, Jennifer L; Hultman, Christina M; Scott, Stuart A; Sullivan, Patrick F; Purcell, Shaun M; Dudley, Joel T; Sklar, Pamela

2016-01-01

Summary Background Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia. Methods We defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance. Findings We combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0·00046, pcorrected =0·024) and antipsychotics (347 genes, p=0·00078, pcorrected=0·046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in

An Aphid Effector Targets Trafficking Protein VPS52 in a Host-Specific Manner to Promote Virulence.

PubMed

Rodriguez, Patricia A; Escudero-Martinez, Carmen; Bos, Jorunn I B

2017-03-01

Plant- and animal-feeding insects secrete saliva inside their hosts, containing effectors, which may promote nutrient release and suppress immunity. Although for plant pathogenic microbes it is well established that effectors target host proteins to modulate host cell processes and promote disease, the host cell targets of herbivorous insects remain elusive. Here, we show that the existing plant pathogenic microbe effector paradigm can be extended to herbivorous insects in that effector-target interactions inside host cells modify critical host processes to promote plant susceptibility. We showed that the effector Mp1 from Myzus persicae associates with the host Vacuolar Protein Sorting Associated Protein52 (VPS52). Using natural variants, we provide a strong link between effector virulence activity and association with VPS52, and show that the association is highly specific to M persicae -host interactions. Also, coexpression of Mp1, but not Mp1-like variants, specifically with host VPS52s resulted in effector relocalization to vesicle-like structures that associate with prevacuolar compartments. We show that high VPS52 levels negatively impact virulence, and that aphids are able to reduce VPS52 levels during infestation, indicating that VPS52 is an important virulence target. Our work is an important step forward in understanding, at the molecular level, how a major agricultural pest promotes susceptibility during infestation of crop plants. We give evidence that an herbivorous insect employs effectors that interact with host proteins as part of an effective virulence strategy, and that these effectors likely function in a species-specific manner. © 2017 American Society of Plant Biologists. All Rights Reserved.

Tobacco Industry Promotional Strategies Targeting American Indians/Alaska Natives and Exploiting Tribal Sovereignty.

PubMed

Lempert, Lauren K; Glantz, Stanton A

2018-03-12

American Indians/Alaska Natives have the highest commercial tobacco use in the United States, resulting in higher tobacco-caused deaths and diseases than the general population. Some American Indians/Alaska Natives use commercial tobacco for ceremonial as well as recreational uses. Because federally-recognized Tribal lands are sovereign, they are not subject to state cigarette taxes and smokefree laws. This study analyzes tobacco industry promotional efforts specifically targeting American Indians/Alaska Natives and exploiting Tribal lands to understand appropriate policy responses in light of American Indians'/Alaska Natives' unique sovereign status and culture. We analyzed previously secret tobacco industry documents available at the Truth Tobacco Documents Library (https://industrydocuments.library.ucsf.edu/tobacco/). Tobacco companies used promotional strategies targeting American Indians/Alaska Natives and exploiting Tribal lands that leveraged the federally-recognized Tribes' unique sovereign status exempting them from state cigarette taxes and smokefree laws, and exploited some Tribes' existing traditional uses of ceremonial tobacco and poverty. Tactics included price reductions, coupons, giveaways, gaming promotions, charitable contributions and sponsorships. Additionally, tobacco companies built alliances with Tribal leaders to help improve their corporate image, advance ineffective "youth smoking prevention" programs, and defeat tobacco control policies. The industry's promotional tactics likely contribute to disparities in smoking prevalence and smoking-related diseases among American Indians//Alaska Natives. Proven policy interventions to address these disparities including tobacco price increases, cigarette taxes, comprehensive smokefree laws, and industry denormalization campaigns to reduce smoking prevalence and smoking-related disease could be considered by Tribal communities. The sovereign status of federally-recognized Tribes does not prevent them

Cost-effectiveness of targeted versus tailored interventions to promote mammography screening among women military veterans in the United States.

PubMed

Lairson, David R; Chan, Wen; Chang, Yu-Chia; del Junco, Deborah J; Vernon, Sally W

2011-05-01

We conducted an economic evaluation of mammography promotion interventions in a population-based, nationally representative sample of 5500 women veterans. Women 52 years and older were randomly selected from the National Registry of Women Veterans and randomly assigned to a survey-only control group and two intervention groups that varied in the extent of personalization (tailored vs. targeted). Effectiveness measures were the prevalence of at least one self-reported post-intervention mammogram and two post-intervention mammograms 6-15 months apart. Incremental cost-effectiveness ratios (ICERs) were the incremental cost per additional person screened. Uncertainty was examined with sensitivity analysis and bootstrap simulation. The targeted intervention cost $25 per person compared to $52 per person for the tailored intervention. About 27% of the cost was incurred in identifying and recruiting the eligible population. The percent of women reporting at least one mammogram were .447 in the control group, .469 in the targeted group, and .460 in the tailored group. The ICER was $1116 comparing the targeted group to the control group (95% confidence interval (CI)=$493 to dominated). The tailored intervention was dominated (more costly and less effective) by the targeted intervention. Decision-makers should consider effectiveness evidence and the full recruitment and patient time costs associated with the implementation of screening interventions when making investments in mammography screening promotion programs. Identification and recruitment of eligible participants add substantial costs to outreach screening promotion interventions. Tailoring adds substantial cost to the targeted mammography promotion strategy without a commensurate increase in effectiveness. Although cost-effectiveness has been reported to be higher for some in-reach screening promotion interventions, a recent meta-analysis revealed significant heterogeneity in the effect sizes of published health

Efficient methods for overlapping group lasso.

PubMed

Yuan, Lei; Liu, Jun; Ye, Jieping

2013-09-01

The group Lasso is an extension of the Lasso for feature selection on (predefined) nonoverlapping groups of features. The nonoverlapping group structure limits its applicability in practice. There have been several recent attempts to study a more general formulation where groups of features are given, potentially with overlaps between the groups. The resulting optimization is, however, much more challenging to solve due to the group overlaps. In this paper, we consider the efficient optimization of the overlapping group Lasso penalized problem. We reveal several key properties of the proximal operator associated with the overlapping group Lasso, and compute the proximal operator by solving the smooth and convex dual problem, which allows the use of the gradient descent type of algorithms for the optimization. Our methods and theoretical results are then generalized to tackle the general overlapping group Lasso formulation based on the l(q) norm. We further extend our algorithm to solve a nonconvex overlapping group Lasso formulation based on the capped norm regularization, which reduces the estimation bias introduced by the convex penalty. We have performed empirical evaluations using both a synthetic and the breast cancer gene expression dataset, which consists of 8,141 genes organized into (overlapping) gene sets. Experimental results show that the proposed algorithm is more efficient than existing state-of-the-art algorithms. Results also demonstrate the effectiveness of the nonconvex formulation for overlapping group Lasso.

Lymphatic-targeted cationic liposomes: a robust vaccine adjuvant for promoting long-term immunological memory.

PubMed

Wang, Ce; Liu, Peng; Zhuang, Yan; Li, Ping; Jiang, Boling; Pan, Hong; Liu, Lanlan; Cai, Lintao; Ma, Yifan

2014-09-22

Although retaining antigens at the injection site (the so-called "depot effect") is an important strategy for vaccine development, increasing evidence showed that lymphatic-targeted vaccine delivery with liposomes could be a promising approach for improving vaccine efficacy. However, it remains unclear whether antigen depot or lymphatic targeting would benefit long-term immunological memory, a major determinant of vaccine efficacy. In the present study, OVA antigen was encapsulated with DOTAP cationic liposomes (LP) or DOTAP-PEG-mannose liposomes (LP-Man) to generate depot or lymphatic-targeted liposome vaccines, respectively. The result of in vivo imaging showed that LP mostly accumulated near the injection site, whereas LP-Man not only effectively accumulated in draining lymph nodes (LNs) and the spleen, but also enhanced the uptake by resident antigen-presenting cells. Although LP vaccines with depot effect induced anti-OVA IgG more potently than LP-Man vaccines did on day 40 after priming, they failed to mount an effective B-cell memory response upon OVA re-challenge after three months. In contrast, lymphatic-targeted LP-Man vaccines elicited sustained antibody production and robust recall responses three months after priming, suggesting lymphatic targeting rather than antigen depot promoted the establishment of long-term memory responses. The enhanced long-term immunological memory by LP-Man was attributed to vigorous germinal center responses as well as increased Tfh cells and central memory CD4(+) T cells in the secondary lymphoid organs. Hence, lymphatic-targeted vaccine delivery with LP-Man could be an effective strategy to promote long-lasting immunological memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overlap of movement planning and movement execution reduces reaction time.

PubMed

Orban de Xivry, Jean-Jacques; Legrain, Valéry; Lefèvre, Philippe

2017-01-01

Motor planning is the process of preparing the appropriate motor commands in order to achieve a goal. This process has largely been thought to occur before movement onset and traditionally has been associated with reaction time. However, in a virtual line bisection task we observed an overlap between movement planning and execution. In this task performed with a robotic manipulandum, we observed that participants (n = 30) made straight movements when the line was in front of them (near target) but often made curved movements when the same target was moved sideways (far target, which had the same orientation) in such a way that they crossed the line perpendicular to its orientation. Unexpectedly, movements to the far targets had shorter reaction times than movements to the near targets (mean difference: 32 ms, SE: 5 ms, max: 104 ms). In addition, the curvature of the movement modulated reaction time. A larger increase in movement curvature from the near to the far target was associated with a larger reduction in reaction time. These highly curved movements started with a transport phase during which accuracy demands were not taken into account. We conclude that an accuracy demand imposes a reaction time penalty if processed before movement onset. This penalty is reduced if the start of the movement consists of a transport phase and if the movement plan can be refined with respect to accuracy demands later in the movement, hence demonstrating an overlap between movement planning and execution. In the planning of a movement, the brain has the opportunity to delay the incorporation of accuracy requirements of the motor plan in order to reduce the reaction time by up to 100 ms (average: 32 ms). Such shortening of reaction time is observed here when the first phase of the movement consists of a transport phase. This forces us to reconsider the hypothesis that motor plans are fully defined before movement onset. Copyright © 2017 the American Physiological Society.

Overlap of movement planning and movement execution reduces reaction time

PubMed Central

Legrain, Valéry; Lefèvre, Philippe

2016-01-01

Motor planning is the process of preparing the appropriate motor commands in order to achieve a goal. This process has largely been thought to occur before movement onset and traditionally has been associated with reaction time. However, in a virtual line bisection task we observed an overlap between movement planning and execution. In this task performed with a robotic manipulandum, we observed that participants (n = 30) made straight movements when the line was in front of them (near target) but often made curved movements when the same target was moved sideways (far target, which had the same orientation) in such a way that they crossed the line perpendicular to its orientation. Unexpectedly, movements to the far targets had shorter reaction times than movements to the near targets (mean difference: 32 ms, SE: 5 ms, max: 104 ms). In addition, the curvature of the movement modulated reaction time. A larger increase in movement curvature from the near to the far target was associated with a larger reduction in reaction time. These highly curved movements started with a transport phase during which accuracy demands were not taken into account. We conclude that an accuracy demand imposes a reaction time penalty if processed before movement onset. This penalty is reduced if the start of the movement consists of a transport phase and if the movement plan can be refined with respect to accuracy demands later in the movement, hence demonstrating an overlap between movement planning and execution. NEW & NOTEWORTHY In the planning of a movement, the brain has the opportunity to delay the incorporation of accuracy requirements of the motor plan in order to reduce the reaction time by up to 100 ms (average: 32 ms). Such shortening of reaction time is observed here when the first phase of the movement consists of a transport phase. This forces us to reconsider the hypothesis that motor plans are fully defined before movement onset. PMID:27733598

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

PubMed

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-10

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

NASA Astrophysics Data System (ADS)

Sau, Samaresh; Agarwalla, Pritha; Mukherjee, Sudip; Bag, Indira; Sreedhar, Bojja; Pal-Bhadra, Manika; Patra, Chitta Ranjan; Banerjee, Rajkumar

2014-05-01

Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

PubMed

Javierre, Biola M; Burren, Oliver S; Wilder, Steven P; Kreuzhuber, Roman; Hill, Steven M; Sewitz, Sven; Cairns, Jonathan; Wingett, Steven W; Várnai, Csilla; Thiecke, Michiel J; Burden, Frances; Farrow, Samantha; Cutler, Antony J; Rehnström, Karola; Downes, Kate; Grassi, Luigi; Kostadima, Myrto; Freire-Pritchett, Paula; Wang, Fan; Stunnenberg, Hendrik G; Todd, John A; Zerbino, Daniel R; Stegle, Oliver; Ouwehand, Willem H; Frontini, Mattia; Wallace, Chris; Spivakov, Mikhail; Fraser, Peter

2016-11-17

Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

miR-543 promotes gastric cancer cell proliferation by targeting SIRT1

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

Li, Juan; Dong, Guoying; Wang, Bo

SIRT1, a class III histone deacetylase, exerts inhibitory effects on tumorigenesis and is downregulated in gastric cancer. However, the role of microRNAs in the regulation of SIRT1 in gastric cancer is still largely unknown. Here, we identified miR-543 as a predicted upstream regulator of SIRT1 using 3 different bioinformatics databases. Mimics of miR-543 significantly inhibited the expression of SIRT1, whereas an inhibitor of miR-543 increased SIRT1 expression. MiR-543 directly targeted the 3′-UTR of SIRT1, and both of the two binding sites contributed to the inhibitory effects. In gastric epithelium-derived cell lines, miR-543 promoted cell proliferation and cell cycle progression, andmore » overexpression of SIRT1 rescued the above effects of miR-543. The inhibitory effects of miR-543 on SIRT1 were also validated using clinical gastric cancer samples. Moreover, we found that miR-543 expression was positively associated with tumor size, clinical grade, TNM stage and lymph node metastasis in gastric cancer patients. Our results identify a new regulatory mechanism of miR-543 on SIRT1 expression in gastric cancer, and raise the possibility that the miR-543/SIRT1 pathway may serve as a potential target for the treatment of gastric cancer. - Highlights: • SIRT1 is a novel target of miR-543. • miR-543 promotes gastric cancer cell proliferation and cell cycle progression by targeting SIRT1. • miR-543 is upregulated in GC and positively associated with tumor size, clinical grade, TNM stage and lymph node metastasis. • miR-543 is negatively correlated with SIRT1 expression in gastric cancer tissues.« less

New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

PubMed

Qi, Jingjing; Yu, Yong; Akilli Öztürk, Özlem; Holland, Jane D; Besser, Daniel; Fritzmann, Johannes; Wulf-Goldenberg, Annika; Eckert, Klaus; Fichtner, Iduna; Birchmeier, Walter

2016-10-01

We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. 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/

How Long Do Satellites Need to Overlap? Evaluation of Climate Data Stability from Overlapping Satellite Records

NASA Technical Reports Server (NTRS)

Weatherhead, Elizabeth C.; Harder, Jerald; Araujo-Pradere, Eduardo A.; Bodeker, Greg; English, Jason M.; Flynn, Lawrence E.; Frith, Stacey M.; Lazo, Jeffrey K.; Pilewskie, Peter; Weber, Mark;

How long do satellites need to overlap? Evaluation of climate data stability from overlapping satellite records

NASA Astrophysics Data System (ADS)

Weatherhead, Elizabeth C.; Harder, Jerald; Araujo-Pradere, Eduardo A.; Bodeker, Greg; English, Jason M.; Flynn, Lawrence E.; Frith, Stacey M.; Lazo, Jeffrey K.; Pilewskie, Peter; Weber, Mark; Woods, Thomas N.

2017-12-01

Sensors on satellites provide unprecedented understanding of the Earth's climate system by measuring incoming solar radiation, as well as both passive and active observations of the entire Earth with outstanding spatial and temporal coverage. A common challenge with satellite observations is to quantify their ability to provide well-calibrated, long-term, stable records of the parameters they measure. Ground-based intercomparisons offer some insight, while reference observations and internal calibrations give further assistance for understanding long-term stability. A valuable tool for evaluating and developing long-term records from satellites is the examination of data from overlapping satellite missions. This paper addresses how the length of overlap affects the ability to identify an offset or a drift in the overlap of data between two sensors. Ozone and temperature data sets are used as examples showing that overlap data can differ by latitude and can change over time. New results are presented for the general case of sensor overlap by using Solar Radiation and Climate Experiment (SORCE) Spectral Irradiance Monitor (SIM) and Solar Stellar Irradiance Comparison Experiment (SOLSTICE) solar irradiance data as an example. To achieve a 1 % uncertainty in estimating the offset for these two instruments' measurement of the Mg II core (280 nm) requires approximately 5 months of overlap. For relative drift to be identified within 0.1 % yr-1 uncertainty (0.00008 W m-2 nm-1 yr-1), the overlap for these two satellites would need to be 2.5 years. Additional overlap of satellite measurements is needed if, as is the case for solar monitoring, unexpected jumps occur adding uncertainty to both offsets and drifts; the additional length of time needed to account for a single jump in the overlap data may be as large as 50 % of the original overlap period in order to achieve the same desired confidence in the stability of the merged data set. Results presented here are directly

Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

PubMed Central

Kuo, Cheng-Hsiang; Leon, Lorraine; Chung, Eun Ji; Huang, Ru-Ting; Sontag, Timothy J.; Reardon, Catherine A.; Getz, Godfrey S.; Tirrell, Matthew; Fang, Yun

2015-01-01

Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation. Furthermore, to enhance specificity and transfection efficiency, polyelectrolyte complex micelles can be modified to include targeting capabilities. Here, we describe the design of targeted polyelectrolyte complex micelles containing inhibitors against dys-regulated microRNAs (miRNAs) that promote atherosclerosis, a leading cause of human mortality and morbidity. Inhibition of dys-regulated miRNAs in diseased cells associated with atherosclerosis has resulted in therapeutic efficacy in animal models and has been proposed to treat human diseases. However, the non-specific targeting of microRNA inhibitors via systemic delivery has remained an issue that may cause unwanted side effects. For this reason, we incorporated two different peptide sequences to our miRNA inhibitor containing polyelectrolyte complex micelles. One of the peptides (Arginine-Glutamic Acid-Lysine-Alanine or REKA) was used in another micellar system that demonstrated lesion-specific targeting in a mouse model of atherosclerosis. The other peptide (Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine or VHPKQHR) was identified via phage display and targets vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1). In this study we have tested the in vitro efficacy and efficiency of lesion- and cell-specific delivery of microRNA inhibitors to the cells associated with atherosclerotic lesions via peptide-targeted polyelectrolyte complex micelles. Our results show that REKA-containing micelles (fibrin-targeting) and VHPKQHR-containing micelles (VCAM-1 targeting) can be used to carry and deliver microRNA inhibitors into macrophages and human endothelial cells, respectively

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

PubMed

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

2017-05-01

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

Modification of the hTERT promoter by heat shock elements enhances the efficiency and specificity of cancer targeted gene therapy.

PubMed

Wang, Xiaolong; Zhou, PeiHua; Sun, XueJun; Wei, GuangBing; Zhang, Li; Wang, Hui; Yao, JianFeng; Jia, PengBo; Zheng, JianBao

2016-05-01

One of the current challenges facing cancer gene therapy is the tumour-specific targeting of therapeutic genes. Effective targeting in gene therapy requires accurate spatial and temporal control of gene expression. To develop a sufficient and accurate tumour-targeting method for cancer gene therapy, we have investigated the use of hyperthermia to control the expression of a transgene under the control of the human telomerase reverse transcriptase (hTERT) promoter and eight heat shock elements (8HSEs). Luciferase reporters were constructed by inserting eight HSEs and the hTERT promoter (8HSEs-hTERTp) upstream of the pGL4.20 vector luciferase gene. The luciferase activity of the hTERT promoter and 8HSEs-hTERT promoter were then compared in the presence and absence of heat. The differences in luciferase activity were analysed using dual luciferase assays in SW480 (high hTERT expression), MKN28 and MRC-5 cells (low hTERT expression). The luciferase activity of the Hsp70B promoter was also compared to the 8HSEs-hTERT promoter in the above listed cell lines. Lentiviral vector and heat-induced expression of EGFP expression under the control of the 8HSEs-hTERT promoter in cultured cells and mouse tumour xenografts was measured by reverse transcription polymerase (RT-PCR), Western blot and immunofluorescence assays. hTERT promoter activity was higher in SW480 cells than in MKN28 or MRC-5 cells. At 43 °C, the luciferase activity of the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN28 or MRC-5 cells. Importantly, the differences in luciferase activity were much more obvious in both high (SW480) and low (MKN28 and MRC-5) hTERT expressing cells when the activity of the 8HSEs-hTERT promoter was compared to the Hsp70B promoter. Moreover, under the control of 8HSEs-hTERT promoter in vitro and in vivo, EGFP expression was obviously increased by heat treatment in SW480 cells but not in MKN28 or MRC-5 cells, nor was expression increased under

Information-optimal genome assembly via sparse read-overlap graphs.

PubMed

Shomorony, Ilan; Kim, Samuel H; Courtade, Thomas A; Tse, David N C

2016-09-01

In the context of third-generation long-read sequencing technologies, read-overlap-based approaches are expected to play a central role in the assembly step. A fundamental challenge in assembling from a read-overlap graph is that the true sequence corresponds to a Hamiltonian path on the graph, and, under most formulations, the assembly problem becomes NP-hard, restricting practical approaches to heuristics. In this work, we avoid this seemingly fundamental barrier by first setting the computational complexity issue aside, and seeking an algorithm that targets information limits In particular, we consider a basic feasibility question: when does the set of reads contain enough information to allow unambiguous reconstruction of the true sequence? Based on insights from this information feasibility question, we present an algorithm-the Not-So-Greedy algorithm-to construct a sparse read-overlap graph. Unlike most other assembly algorithms, Not-So-Greedy comes with a performance guarantee: whenever information feasibility conditions are satisfied, the algorithm reduces the assembly problem to an Eulerian path problem on the resulting graph, and can thus be solved in linear time. In practice, this theoretical guarantee translates into assemblies of higher quality. Evaluations on both simulated reads from real genomes and a PacBio Escherichia coli K12 dataset demonstrate that Not-So-Greedy compares favorably with standard string graph approaches in terms of accuracy of the resulting read-overlap graph and contig N50. Available at github.com/samhykim/nsg courtade@eecs.berkeley.edu or dntse@stanford.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Automatic prevention of label overlap

DOT National Transportation Integrated Search

1976-03-01

The project comprised a number of simulation exercises : designed to evaluate methods of either preventing or : resolving the problems likely to be caused by label overlap on : Labelled Plan Displays (LPD). The automatic prevention of : label overlap...

Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila.

PubMed

Matthews, Benjamin J; Grueber, Wesley B

2011-09-13

Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and nonoverlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3-11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B-expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counters extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

An Oomycete CRN Effector Reprograms Expression of Plant HSP Genes by Targeting their Promoters

PubMed Central

Song, Tianqiao; Ma, Zhenchuan; Shen, Danyu; Li, Qi; Li, Wanlin; Su, Liming; Ye, Tingyue; Zhang, Meixiang; Wang, Yuanchao; Dou, Daolong

2015-01-01

Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters. PMID:26714171

An Oomycete CRN Effector Reprograms Expression of Plant HSP Genes by Targeting their Promoters.

PubMed

Song, Tianqiao; Ma, Zhenchuan; Shen, Danyu; Li, Qi; Li, Wanlin; Su, Liming; Ye, Tingyue; Zhang, Meixiang; Wang, Yuanchao; Dou, Daolong

2015-12-01

Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters.

Expansion of the CRISPR-Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs.

PubMed

Ranganathan, Vinod; Wahlin, Karl; Maruotti, Julien; Zack, Donald J

2014-08-08

The repurposed CRISPR-Cas9 system has recently emerged as a revolutionary genome-editing tool. Here we report a modification in the expression of the guide RNA (gRNA) required for targeting that greatly expands the targetable genome. gRNA expression through the commonly used U6 promoter requires a guanosine nucleotide to initiate transcription, thus constraining genomic-targeting sites to GN19NGG. We demonstrate the ability to modify endogenous genes using H1 promoter-expressed gRNAs, which can be used to target both AN19NGG and GN19NGG genomic sites. AN19NGG sites occur ~15% more frequently than GN19NGG sites in the human genome and the increase in targeting space is also enriched at human genes and disease loci. Together, our results enhance the versatility of the CRISPR technology by more than doubling the number of targetable sites within the human genome and other eukaryotic species.

Restoration and reconstruction from overlapping images

NASA Technical Reports Server (NTRS)

Reichenbach, Stephen E.; Kaiser, Daniel J.; Hanson, Andrew L.; Li, Jing

1997-01-01

This paper describes a technique for restoring and reconstructing a scene from overlapping images. In situations where there are multiple, overlapping images of the same scene, it may be desirable to create a single image that most closely approximates the scene, based on all of the data in the available images. For example, successive swaths acquired by NASA's planned Moderate Imaging Spectrometer (MODIS) will overlap, particularly at wide scan angles, creating a severe visual artifact in the output image. Resampling the overlapping swaths to produce a more accurate image on a uniform grid requires restoration and reconstruction. The one-pass restoration and reconstruction technique developed in this paper yields mean-square-optimal resampling, based on a comprehensive end-to-end system model that accounts for image overlap, and subject to user-defined and data-availability constraints on the spatial support of the filter.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

PubMed Central

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-01

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

Automated treatment planning for a dedicated multi-source intra-cranial radiosurgery treatment unit accounting for overlapping structures and dose homogeneity

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

Ghobadi, Kimia; Ghaffari, Hamid R.; Aleman, Dionne M.

2013-09-15

Purpose: The purpose of this work is to advance the two-step approach for Gamma Knife{sup ®} Perfexion™ (PFX) optimization to account for dose homogeneity and overlap between the planning target volume (PTV) and organs-at-risk (OARs).Methods: In the first step, a geometry-based algorithm is used to quickly select isocentre locations while explicitly accounting for PTV-OARs overlaps. In this approach, the PTV is divided into subvolumes based on the PTV-OARs overlaps and the distance of voxels to the overlaps. Only a few isocentres are selected in the overlap volume, and a higher number of isocentres are carefully selected among voxels that aremore » immediately close to the overlap volume. In the second step, a convex optimization is solved to find the optimal combination of collimator sizes and their radiation duration for each isocentre location.Results: This two-step approach is tested on seven clinical cases (comprising 11 targets) for which the authors assess coverage, OARs dose, and homogeneity index and relate these parameters to the overlap fraction for each case. In terms of coverage, the mean V{sub 99} for the gross target volume (GTV) was 99.8% while the V{sub 95} for the PTV averaged at 94.6%, thus satisfying the clinical objectives of 99% for GTV and 95% for PTV, respectively. The mean relative dose to the brainstem was 87.7% of the prescription dose (with maximum 108%), while on average, 11.3% of the PTV overlapped with the brainstem. The mean beam-on time per fraction per dose was 8.6 min with calibration dose rate of 3.5 Gy/min, and the computational time averaged at 205 min. Compared with previous work involving single-fraction radiosurgery, the resulting plans were more homogeneous with average homogeneity index of 1.18 compared to 1.47.Conclusions: PFX treatment plans with homogeneous dose distribution can be achieved by inverse planning using geometric isocentre selection and mathematical modeling and optimization techniques. The quality of

Hmo1 directs pre-initiation complex assembly to an appropriate site on its target gene promoters by masking a nucleosome-free region

PubMed Central

Kasahara, Koji; Ohyama, Yoshifumi; Kokubo, Tetsuro

2011-01-01

Saccharomyces cerevisiae Hmo1 binds to the promoters of ∼70% of ribosomal protein genes (RPGs) at high occupancy, but is observed at lower occupancy on the remaining RPG promoters. In Δhmo1 cells, the transcription start site (TSS) of the Hmo1-enriched RPS5 promoter shifted upstream, while the TSS of the Hmo1-limited RPL10 promoter did not shift. Analyses of chimeric RPS5/RPL10 promoters revealed a region between the RPS5 upstream activating sequence (UAS) and core promoter, termed the intervening region (IVR), responsible for strong Hmo1 binding and an upstream TSS shift in Δhmo1 cells. Chromatin immunoprecipitation analyses showed that the RPS5-IVR resides within a nucleosome-free region and that pre-initiation complex (PIC) assembly occurs at a site between the IVR and a nucleosome overlapping the TSS (+1 nucleosome). The PIC assembly site was shifted upstream in Δhmo1 cells on this promoter, indicating that Hmo1 normally masks the RPS5-IVR to prevent PIC assembly at inappropriate site(s). This novel mechanism ensures accurate transcriptional initiation by delineating the 5′- and 3′-boundaries of the PIC assembly zone. PMID:21288884

Leveraging disjoint communities for detecting overlapping community structure

NASA Astrophysics Data System (ADS)

Chakraborty, Tanmoy

2015-05-01

Network communities represent mesoscopic structure for understanding the organization of real-world networks, where nodes often belong to multiple communities and form overlapping community structure in the network. Due to non-triviality in finding the exact boundary of such overlapping communities, this problem has become challenging, and therefore huge effort has been devoted to detect overlapping communities from the network. In this paper, we present PVOC (Permanence based Vertex-replication algorithm for Overlapping Community detection), a two-stage framework to detect overlapping community structure. We build on a novel observation that non-overlapping community structure detected by a standard disjoint community detection algorithm from a network has high resemblance with its actual overlapping community structure, except the overlapping part. Based on this observation, we posit that there is perhaps no need of building yet another overlapping community finding algorithm; but one can efficiently manipulate the output of any existing disjoint community finding algorithm to obtain the required overlapping structure. We propose a new post-processing technique that by combining with any existing disjoint community detection algorithm, can suitably process each vertex using a new vertex-based metric, called permanence, and thereby finds out overlapping candidates with their community memberships. Experimental results on both synthetic and large real-world networks show that PVOC significantly outperforms six state-of-the-art overlapping community detection algorithms in terms of high similarity of the output with the ground-truth structure. Thus our framework not only finds meaningful overlapping communities from the network, but also allows us to put an end to the constant effort of building yet another overlapping community detection algorithm.

Identification of the Downstream Promoter Targets of Smad Tumor Suppressors in Human Breast Cancer Cells

DTIC Science & Technology

2004-10-01

signaling mediator Smad2, Smad3 and Smad4 which form oligomeric complexes and migrate into nucleus to function as transcription factors to modulate... Smad3 and Smad4. 2. Identification of the downstream promoter targets of Smad3 or Smad4 in breast cancer cells. 3. Identify Smad4 regulated downstream...Development of a novel chromatin immunoprecipitation assay (CHIPS) using a TAP-TAG system to isolate in vivo binding targets of Smad3 and Smad4

Trophic overlap between expanding and contracting fish predators in a range margin undergoing change.

PubMed

Westerbom, Mats; Lappalainen, Antti; Mustonen, Olli; Norkko, Alf

2018-05-21

Climate change is predicted to cause a freshening of the Baltic Sea, facilitating range expansions of freshwater species and contractions of marine. Resident marine flounders (Platichthys flesus) and expansive freshwater roach (Rutilus rutilus) are dominant consumers in the Baltic Sea sublittoral where they occur in partial sympatry. By comparing patterns of resource use by flounders and roach along a declining resource gradient of blue mussels (Mytilus trossulus) our aim was to explore predator functional responses and the degree of trophic overlap. Understanding the nature of density-dependent prey acquisition has important implications for predicting population dynamics of both predators and their shared prey. Results showed a highly specialized diet for both species, high reliance on blue mussels throughout the range, similar prey size preference and high trophic overlap. Highest overlap occurred where blue mussels were abundant but overlap was also high where they were scarce. Our results highlight the importance of a single food item - the blue mussel - for both species, likely promoting high population size and range expansion of roach. Findings also suggest that range expansion of roach may have a top-down structuring force on mussels that differ in severity and location from that originating from resident flounders.

An Aphid Effector Targets Trafficking Protein VPS52 in a Host-Specific Manner to Promote Virulence1[OPEN

PubMed Central

2017-01-01

Plant- and animal-feeding insects secrete saliva inside their hosts, containing effectors, which may promote nutrient release and suppress immunity. Although for plant pathogenic microbes it is well established that effectors target host proteins to modulate host cell processes and promote disease, the host cell targets of herbivorous insects remain elusive. Here, we show that the existing plant pathogenic microbe effector paradigm can be extended to herbivorous insects in that effector-target interactions inside host cells modify critical host processes to promote plant susceptibility. We showed that the effector Mp1 from Myzus persicae associates with the host Vacuolar Protein Sorting Associated Protein52 (VPS52). Using natural variants, we provide a strong link between effector virulence activity and association with VPS52, and show that the association is highly specific to M. persicae-host interactions. Also, coexpression of Mp1, but not Mp1-like variants, specifically with host VPS52s resulted in effector relocalization to vesicle-like structures that associate with prevacuolar compartments. We show that high VPS52 levels negatively impact virulence, and that aphids are able to reduce VPS52 levels during infestation, indicating that VPS52 is an important virulence target. Our work is an important step forward in understanding, at the molecular level, how a major agricultural pest promotes susceptibility during infestation of crop plants. We give evidence that an herbivorous insect employs effectors that interact with host proteins as part of an effective virulence strategy, and that these effectors likely function in a species-specific manner. PMID:28100451

Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis.

PubMed

Andersson, Camilla M; Bjärås, Gunilla E M; Tillgren, Per; Ostenson, Claes-Göran

2003-09-01

This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.

Solving Partial Differential Equations on Overlapping Grids

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

Henshaw, W D

2008-09-22

We discuss the solution of partial differential equations (PDEs) on overlapping grids. This is a powerful technique for efficiently solving problems in complex, possibly moving, geometry. An overlapping grid consists of a set of structured grids that overlap and cover the computational domain. By allowing the grids to overlap, grids for complex geometries can be more easily constructed. The overlapping grid approach can also be used to remove coordinate singularities by, for example, covering a sphere with two or more patches. We describe the application of the overlapping grid approach to a variety of different problems. These include the solutionmore » of incompressible fluid flows with moving and deforming geometry, the solution of high-speed compressible reactive flow with rigid bodies using adaptive mesh refinement (AMR), and the solution of the time-domain Maxwell's equations of electromagnetism.« less

Targeted advertising, promotion, and price for menthol cigarettes in California high school neighborhoods.

PubMed

Henriksen, Lisa; Schleicher, Nina C; Dauphinee, Amanda L; Fortmann, Stephen P

2012-01-01

To describe advertising, promotions, and pack prices for the leading brands of menthol and nonmenthol cigarettes near California high schools and to examine their associations with school and neighborhood demographics. In stores (n = 407) within walking distance (0.8 km [1/2 mile]) of California high schools (n = 91), trained observers counted ads for menthol and nonmenthol cigarettes and collected data about promotions and prices for Newport and Marlboro, the leading brand in each category. Multilevel modeling examined the proportion of all cigarette advertising for any menthol brand, the proportion of stores with sales promotions, and the lowest advertised pack price in relation to store types and school/neighborhood demographics. For each 10 percentage point increase in the proportion of Black students, the proportion of menthol advertising increased by 5.9 percentage points (e.g., from an average of 25.7%-31.6%), the odds of a Newport promotion were 50% higher (95% CI = 1.01, 2.22), and the cost of Newport was 12 cents lower (95% CI = -0.18, -0.06). By comparison, the odds of a promotion and the price for Marlboro, the leading brand of nonmenthol cigarettes, were unrelated to any school or neighborhood demographics. In high school neighborhoods, targeted advertising exposes Blacks to more promotions and lower prices for the leading brand of menthol cigarettes. This evidence contradicts the manufacturer's claims that the availability of its promotions is not based on race/ethnicity. It also highlights the need for tobacco control policies that would limit disparities in exposure to retail marketing for cigarettes.

An extension to artifact-free projection overlaps

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

Lin, Jianyu, E-mail: jianyulin@hotmail.com

2015-05-15

Purpose: In multipinhole single photon emission computed tomography, the overlapping of projections has been used to increase sensitivity. Avoiding artifacts in the reconstructed image associated with projection overlaps (multiplexing) is a critical issue. In our previous report, two types of artifact-free projection overlaps, i.e., projection overlaps that do not lead to artifacts in the reconstructed image, were formally defined and proved, and were validated via simulations. In this work, a new proposition is introduced to extend the previously defined type-II artifact-free projection overlaps so that a broader range of artifact-free overlaps is accommodated. One practical purpose of the new extensionmore » is to design a baffle window multipinhole system with artifact-free projection overlaps. Methods: First, the extended type-II artifact-free overlap was theoretically defined and proved. The new proposition accommodates the situation where the extended type-II artifact-free projection overlaps can be produced with incorrectly reconstructed portions in the reconstructed image. Next, to validate the theory, the extended-type-II artifact-free overlaps were employed in designing the multiplexing multipinhole spiral orbit imaging systems with a baffle window. Numerical validations were performed via simulations, where the corresponding 1-pinhole nonmultiplexing reconstruction results were used as the benchmark for artifact-free reconstructions. The mean square error (MSE) was the metric used for comparisons of noise-free reconstructed images. Noisy reconstructions were also performed as part of the validations. Results: Simulation results show that for noise-free reconstructions, the MSEs of the reconstructed images of the artifact-free multiplexing systems are very similar to those of the corresponding 1-pinhole systems. No artifacts were observed in the reconstructed images. Therefore, the testing results for artifact-free multiplexing systems designed using

Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states.

PubMed

Li, Wei Vivian; Razaee, Zahra S; Li, Jingyi Jessica

2016-01-11

The dynamics of epigenomic marks in their relevant chromatin states regulate distinct gene expression patterns, biological functions and phenotypic variations in biological processes. The availability of high-throughput epigenomic data generated by next-generation sequencing technologies allows a data-driven approach to evaluate the similarities and differences of diverse tissue and cell types in terms of epigenomic features. While ChromImpute has allowed for the imputation of large-scale epigenomic information to yield more robust data to capture meaningful relationships between biological samples, widely used methods such as hierarchical clustering and correlation analysis cannot adequately utilize epigenomic data to accurately reveal the distinction and grouping of different tissue and cell types. We utilize a three-step testing procedure-ANOVA, t test and overlap test to identify tissue/cell-type- associated enhancers and promoters and to calculate a newly defined Epigenomic Overlap Measure (EPOM). EPOM results in a clear correspondence map of biological samples from different tissue and cell types through comparison of epigenomic marks evaluated in their relevant chromatin states. Correspondence maps by EPOM show strong capability in distinguishing and grouping different tissue and cell types and reveal biologically meaningful similarities between Heart and Muscle, Blood & T-cell and HSC & B-cell, Brain and Neurosphere, etc. The gene ontology enrichment analysis both supports and explains the discoveries made by EPOM and suggests that the associated enhancers and promoters demonstrate distinguishable functions across tissue and cell types. Moreover, the tissue/cell-type-associated enhancers and promoters show enrichment in the disease-related SNPs that are also associated with the corresponding tissue or cell types. This agreement suggests the potential of identifying causal genetic variants relevant to cell-type-specific diseases from our identified

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.

Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new molecular targets for breast cancer therapeutics.

PubMed

Brown, Robert V; Gaerig, Vanessa C; Simmons, Taesha; Brooks, Tracy A

2013-12-05

ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics.

A Potent, Imaging Adenoviral Vector Driven by the Cancer-selective Mucin-1 Promoter That Targets Breast Cancer Metastasis

PubMed Central

Huyn, Steven T.; Burton, Jeremy B.; Sato, Makoto; Carey, Michael; Gambhir, Sanjiv S.; Wu, Lily

2009-01-01

Purpose With breast cancer, early detection and proper staging are critical, and will often influence both the treatment regimen and the therapeutic outcome for those affected with this disease. Improvements in these areas will play a profound role in reducing mortality from breast cancer. Experimental Design In this work we developed a breast cancer – targeted serotype 5 adenoviral vector, utilizing the tumor-specific mucin-1 promoter in combination with the two-step transcriptional amplification system, a system used to augment the activity of weak tissue – specific promoters. Results We showed the strong specificity of this tumor-selective adenovirus to express the luciferase optical imaging gene, leading to diagnostic signals that enabled detection of sentinel lymph node metastasis of breast cancer. Furthermore, we were able to target hepatic metastases following systemic administration of this mucin-1 selective virus. Conclusions Collectively, we showed that the amplified mucin-1 promoter – driven vector is able to deliver to and selectively express a desirable transgene in metastatic lesions of breast tumors. This work has strong clinical relevance to current diagnostic staging approaches, and could add to targeted therapeutic strategies to advance the fight against breast cancer. PMID:19366829

Seeding for pervasively overlapping communities

NASA Astrophysics Data System (ADS)

Lee, Conrad; Reid, Fergal; McDaid, Aaron; Hurley, Neil

2011-06-01

In some social and biological networks, the majority of nodes belong to multiple communities. It has recently been shown that a number of the algorithms specifically designed to detect overlapping communities do not perform well in such highly overlapping settings. Here, we consider one class of these algorithms, those which optimize a local fitness measure, typically by using a greedy heuristic to expand a seed into a community. We perform synthetic benchmarks which indicate that an appropriate seeding strategy becomes more important as the extent of community overlap increases. We find that distinct cliques provide the best seeds. We find further support for this seeding strategy with benchmarks on a Facebook network and the yeast interactome.

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

PubMed

Vickers, Timothy A; Crooke, Stanley T

2012-07-01

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

Overlapping ETS and CRE Motifs (G/CCGGAAGTGACGTCA) Preferentially Bound by GABPα and CREB Proteins

PubMed Central

Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Shlyakhtenko, Andrey; Mann, Ishminder; Waterfall, Joshua J.; Meltzer, Paul; Sathyanarayana, B. K.; FitzGerald, Peter C.; Vinson, Charles

2012-01-01

Previously, we identified 8-bps long DNA sequences (8-mers) that localize in human proximal promoters and grouped them into known transcription factor binding sites (TFBS). We now examine split 8-mers consisting of two 4-mers separated by 1-bp to 30-bps (X4-N1-30-X4) to identify pairs of TFBS that localize in proximal promoters at a precise distance. These include two overlapping TFBS: the ETS⇔ETS motif (C/GCCGGAAGCGGAA) and the ETS⇔CRE motif (C/GCGGAAGTGACGTCAC). The nucleotides in bold are part of both TFBS. Molecular modeling shows that the ETS⇔CRE motif can be bound simultaneously by both the ETS and the B-ZIP domains without protein-protein clashes. The electrophoretic mobility shift assay (EMSA) shows that the ETS protein GABPα and the B-ZIP protein CREB preferentially bind to the ETS⇔CRE motif only when the two TFBS overlap precisely. In contrast, the ETS domain of ETV5 and CREB interfere with each other for binding the ETS⇔CRE. The 11-mer (CGGAAGTGACG), the conserved part of the ETS⇔CRE motif, occurs 226 times in the human genome and 83% are in known regulatory regions. In vivo GABPα and CREB ChIP-seq peaks identified the ETS⇔CRE as the most enriched motif occurring in promoters of genes involved in mRNA processing, cellular catabolic processes, and stress response, suggesting that a specific class of genes is regulated by this composite motif. PMID:23050235

Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function.

PubMed

Storm, Elaine E; Durinck, Steffen; de Sousa e Melo, Felipe; Tremayne, Jarrod; Kljavin, Noelyn; Tan, Christine; Ye, Xiaofen; Chiu, Cecilia; Pham, Thinh; Hongo, Jo-Anne; Bainbridge, Travis; Firestein, Ron; Blackwood, Elizabeth; Metcalfe, Ciara; Stawiski, Eric W; Yauch, Robert L; Wu, Yan; de Sauvage, Frederic J

2016-01-07

Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.

Targeted Advertising, Promotion, and Price For Menthol Cigarettes in California High School Neighborhoods

PubMed Central

Schleicher, Nina C.; Dauphinee, Amanda L.; Fortmann, Stephen P.

2012-01-01

Objectives: To describe advertising, promotions, and pack prices for the leading brands of menthol and nonmenthol cigarettes near California high schools and to examine their associations with school and neighborhood demographics. Methods: In stores (n = 407) within walking distance (0.8 km [1/2 mile]) of California high schools (n = 91), trained observers counted ads for menthol and nonmenthol cigarettes and collected data about promotions and prices for Newport and Marlboro, the leading brand in each category. Multilevel modeling examined the proportion of all cigarette advertising for any menthol brand, the proportion of stores with sales promotions, and the lowest advertised pack price in relation to store types and school/neighborhood demographics. Results: For each 10 percentage point increase in the proportion of Black students, the proportion of menthol advertising increased by 5.9 percentage points (e.g., from an average of 25.7%–31.6%), the odds of a Newport promotion were 50% higher (95% CI = 1.01, 2.22), and the cost of Newport was 12 cents lower (95% CI = −0.18, −0.06). By comparison, the odds of a promotion and the price for Marlboro, the leading brand of nonmenthol cigarettes, were unrelated to any school or neighborhood demographics. Conclusions: In high school neighborhoods, targeted advertising exposes Blacks to more promotions and lower prices for the leading brand of menthol cigarettes. This evidence contradicts the manufacturer’s claims that the availability of its promotions is not based on race/ethnicity. It also highlights the need for tobacco control policies that would limit disparities in exposure to retail marketing for cigarettes. PMID:21705460

Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7

PubMed Central

Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

2015-01-01

Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression. PMID:26010572

Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7.

PubMed

Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

2015-01-01

Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression.

miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5

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

Wang, Yongfang; Xu, Lianhong; Jiang, Lixin, E-mail: jianglx66766@163.com

2015-03-13

MicroRNAs (miRNAs) are short, non-coding RNAs (∼22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating numerous target genes at posttranscriptional level. However, the role of microRNAs in lung cancer, particularly non-small-cell lung cancer (NSCLC), has remained elusive. In this study, two microRNAs, miR-1271 and miR-628, and their predicted target genes were identified differentially expressed in NSCLC by analyzing the miRNA and mRNA expression data from NSCLC tissues and their matching normal controls. miR-1271 and its target gene HOXA5 were selected for further investigation. CCK-8 proliferation assay showed that the cell proliferation was promoted by miR-1271more » in NSCLC cells, while miR-1271 inhibitor could significantly inhibited the proliferation of NSCLC cells. Interestingly, migration and invasion assay indicated that overexpression of miR-1271 could significantly promoted the migration and invasion of NSCLC cells, whereas miR-1271 inhibitor could inhibited both cell migration and invasion of NSCLC cells. Western blot showed that miR-1271 suppressed the protein level of HOXA5, and luciferase assays confirmed that miR-1271 directly bound to the 3'untranslated region of HOXA5. This study indicated indicate that miR-1271 regulates NSCLC cell proliferation and invasion, via the down-regulation of HOXA5. Thus, miR-1271 may represent a potential therapeutic target for NSCLC intervention. - Highlights: • Overexpression of miR-1271 promoted proliferation and invasion of NSCLC cells. • miR-1271 inhibitor inhibited the proliferation and invasion of NSCLC cells. • miR-1271 targets 3′ UTR of HOXA5 in NSCLC cells. • miR-1271 negatively regulates HOXA5 in NSCLC cells.« less

Vertical overlap of probability density functions of cloud and precipitation hydrometeors: CLOUD AND PRECIPITATION PDF OVERLAP

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

Ovchinnikov, Mikhail; Lim, Kyo-Sun Sunny; Larson, Vincent E.

Coarse-resolution climate models increasingly rely on probability density functions (PDFs) to represent subgrid-scale variability of prognostic variables. While PDFs characterize the horizontal variability, a separate treatment is needed to account for the vertical structure of clouds and precipitation. When sub-columns are drawn from these PDFs for microphysics or radiation parameterizations, appropriate vertical correlations must be enforced via PDF overlap specifications. This study evaluates the representation of PDF overlap in the Subgrid Importance Latin Hypercube Sampler (SILHS) employed in the assumed PDF turbulence and cloud scheme called the Cloud Layers Unified By Binormals (CLUBB). PDF overlap in CLUBB-SILHS simulations of continentalmore » and tropical oceanic deep convection is compared with overlap of PDF of various microphysics variables in cloud-resolving model (CRM) simulations of the same cases that explicitly predict the 3D structure of cloud and precipitation fields. CRM results show that PDF overlap varies significantly between different hydrometeor types, as well as between PDFs of mass and number mixing ratios for each species, - a distinction that the current SILHS implementation does not make. In CRM simulations that explicitly resolve cloud and precipitation structures, faster falling species, such as rain and graupel, exhibit significantly higher coherence in their vertical distributions than slow falling cloud liquid and ice. These results suggest that to improve the overlap treatment in the sub-column generator, the PDF correlations need to depend on hydrometeor properties, such as fall speeds, in addition to the currently implemented dependency on the turbulent convective length scale.« less

HIV-Related Stigma and Overlapping Stigmas Towards People Living With HIV Among Health Care Trainees in Canada.

PubMed

Wagner, Anne C; Girard, Todd; McShane, Kelly E; Margolese, Shari; Hart, Trevor A

2017-08-01

HIV continues to be a stigmatized disease, despite significant advances in care and concerted effort to reduce discrimination, stereotypes, and prejudice. Living with HIV is often associated with a multitude of overlapping and intersecting experiences which can, in and of themselves, also be stigmatized, and which may exacerbate HIV-related stigma. The consequences of these stigmatizing experiences are particularly impactful when the stigmatizing individual is a health care provider, as this can influence access to and quality of care. The current study empirically investigates a model of overlapping stigmas (homophobia, racism, sexism, stigma against injection drug use and stigma against sex work) potentially held by health care provider trainees in Canada to determine how these constructs overlap and intersect, and to assess whether HIV-related stigma may have unique attributes. Understanding overlapping stigmas can help inform targeted, stigma-informed training for health care trainees in order to provide effective, compassionate care for people living with HIV.

Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes.

PubMed

Garcia-Lopez, Amparo; Tessaro, Francesca; Jonker, Hendrik R A; Wacker, Anna; Richter, Christian; Comte, Arnaud; Berntenis, Nikolaos; Schmucki, Roland; Hatje, Klas; Petermann, Olivier; Chiriano, Gianpaolo; Perozzo, Remo; Sciarra, Daniel; Konieczny, Piotr; Faustino, Ignacio; Fournet, Guy; Orozco, Modesto; Artero, Ruben; Metzger, Friedrich; Ebeling, Martin; Goekjian, Peter; Joseph, Benoît; Schwalbe, Harald; Scapozza, Leonardo

2018-05-23

Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5' splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformations of TSL2 and promotes a shift to triloop conformations that display enhanced E7 splicing. Collectively, our study validates TSL2 as a target for small-molecule drug discovery in SMA, identifies a novel mechanism of action for an E7 splicing modifier, and sets a precedent for other splicing-mediated diseases where RNA structure could be similarly targeted.

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

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

Li, Zhi; Li, Youjun, E-mail: liyoujunn@126.com; Wang, Nan

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and proteinmore » exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.« less

Doing Televised Rhetorical Analysis as a Means of Promoting College Awareness in a Target Market.

ERIC Educational Resources Information Center

Schnell, Jim

This paper describes aspects of doing televised rhetorical analysis as they relate to the promotion of college awareness in a particular target market. Considerations in the paper include variables that most professors encounter in their efforts to address the "service" expectations of their employment and how these variables can be…

miR-101a targeting EZH2 promotes the differentiation of goat skeletal muscle satellite cells.

PubMed

Li, Jun-Tao; Zhao, Wei; Li, Dan-Dan; Feng, Jing; Ba, Gui; Song, Tian-Zeng; Zhang, Hong-Ping

2017-09-20

miR-101a promotes the differentiation of goat skeletal muscle satellite cells (SMSCs), as we previously reported, but the underpinning mechanism remains to be illuminated. In this study, we predicted the target gene of miR-101a by employing online softwares PicTar, TargetScan and miRanda, and found that enhancer of zeste homologue 2 (EZH2) was targeted by miR-101a. Further we identified that EZH2 contained miR-101a binding sites at its 3'UTR by using the dual-luciferase reporter assay system. In addition, we showed that during SMSC differentiation, the downregulated levels of EZH2 mRNA and protein were accompanied by increasing miR-101a expression via qRT-PCR and Western blot. Additionally, the expression of EZH2 significantly increased (P<0.01) when miR-101a was suppressed, whereas overexpressing miR-101a almost had no effect on EZH2 expression (P>0.05). These data demonstrated that miR-101a promotes SMSC differentiation directly through EZH2, which provides a theoretical reference for further elucidating the mechanism of miR-101a in SMSC differentiation.

A model for evolution of overlapping community networks

NASA Astrophysics Data System (ADS)

Karan, Rituraj; Biswal, Bibhu

2017-05-01

A model is proposed for the evolution of network topology in social networks with overlapping community structure. Starting from an initial community structure that is defined in terms of group affiliations, the model postulates that the subsequent growth and loss of connections is similar to the Hebbian learning and unlearning in the brain and is governed by two dominant factors: the strength and frequency of interaction between the members, and the degree of overlap between different communities. The temporal evolution from an initial community structure to the current network topology can be described based on these two parameters. It is possible to quantify the growth occurred so far and predict the final stationary state to which the network is likely to evolve. Applications in epidemiology or the spread of email virus in a computer network as well as finding specific target nodes to control it are envisaged. While facing the challenge of collecting and analyzing large-scale time-resolved data on social groups and communities one faces the most basic questions: how do communities evolve in time? This work aims to address this issue by developing a mathematical model for the evolution of community networks and studying it through computer simulation.

Pyviko: an automated Python tool to design gene knockouts in complex viruses with overlapping genes.

PubMed

Taylor, Louis J; Strebel, Klaus

2017-01-07

Gene knockouts are a common tool used to study gene function in various organisms. However, designing gene knockouts is complicated in viruses, which frequently contain sequences that code for multiple overlapping genes. Designing mutants that can be traced by the creation of new or elimination of existing restriction sites further compounds the difficulty in experimental design of knockouts of overlapping genes. While software is available to rapidly identify restriction sites in a given nucleotide sequence, no existing software addresses experimental design of mutations involving multiple overlapping amino acid sequences in generating gene knockouts. Pyviko performed well on a test set of over 240,000 gene pairs collected from viral genomes deposited in the National Center for Biotechnology Information Nucleotide database, identifying a point mutation which added a premature stop codon within the first 20 codons of the target gene in 93.2% of all tested gene-overprinted gene pairs. This shows that Pyviko can be used successfully in a wide variety of contexts to facilitate the molecular cloning and study of viral overprinted genes. Pyviko is an extensible and intuitive Python tool for designing knockouts of overlapping genes. Freely available as both a Python package and a web-based interface ( http://louiejtaylor.github.io/pyViKO/ ), Pyviko simplifies the experimental design of gene knockouts in complex viruses with overlapping genes.

Neural overlap in processing music and speech

PubMed Central

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

2015-01-01

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

High-Order Moving Overlapping Grid Methodology in a Spectral Element Method

NASA Astrophysics Data System (ADS)

Merrill, Brandon E.

A moving overlapping mesh methodology that achieves spectral accuracy in space and up to second-order accuracy in time is developed for solution of unsteady incompressible flow equations in three-dimensional domains. The targeted applications are in aerospace and mechanical engineering domains and involve problems in turbomachinery, rotary aircrafts, wind turbines and others. The methodology is built within the dual-session communication framework initially developed for stationary overlapping meshes. The methodology employs semi-implicit spectral element discretization of equations in each subdomain and explicit treatment of subdomain interfaces with spectrally-accurate spatial interpolation and high-order accurate temporal extrapolation, and requires few, if any, iterations, yet maintains the global accuracy and stability of the underlying flow solver. Mesh movement is enabled through the Arbitrary Lagrangian-Eulerian formulation of the governing equations, which allows for prescription of arbitrary velocity values at discrete mesh points. The stationary and moving overlapping mesh methodologies are thoroughly validated using two- and three-dimensional benchmark problems in laminar and turbulent flows. The spatial and temporal global convergence, for both methods, is documented and is in agreement with the nominal order of accuracy of the underlying solver. Stationary overlapping mesh methodology was validated to assess the influence of long integration times and inflow-outflow global boundary conditions on the performance. In a turbulent benchmark of fully-developed turbulent pipe flow, the turbulent statistics are validated against the available data. Moving overlapping mesh simulations are validated on the problems of two-dimensional oscillating cylinder and a three-dimensional rotating sphere. The aerodynamic forces acting on these moving rigid bodies are determined, and all results are compared with published data. Scaling tests, with both methodologies

Phase-space overlap measures. I. Fail-safe bias detection in free energies calculated by molecular simulation

NASA Astrophysics Data System (ADS)

Wu, Di; Kofke, David A.

2005-08-01

We consider ways to quantify the overlap of the parts of phase space important to two systems, labeled A and B. Of interest is how much of the A-important phase space lies in that important to B, and how much of B lies in A. Two measures are proposed. The first considers four total-energy distributions, formed from all combinations made by tabulating either the A-system or the B-system energy when sampling either the A or B system. Measures for A in B and B in A are given by two overlap integrals defined on pairs of these distributions. The second measure is based on information theory, and defines two relative entropies which are conveniently expressed in terms of the dissipated work for free-energy perturbation (FEP) calculations in the A →B and B →A directions, respectively. Phase-space overlap is an important consideration in the performance of free-energy calculations. To demonstrate this connection, we examine bias in FEP calculations applied to a system of independent particles in a harmonic potential. Systems are selected to represent a range of overlap situations, including extreme subset, subset, partial overlap, and nonoverlap. The magnitude and symmetry of the bias (A →B vs B →A) are shown to correlate well with the overlap, and consequently with the overlap measures. The relative entropies are used to scale the amount of sampling to obtain a universal bias curve. This result leads to develop a simple heuristic that can be applied to determine whether a work-based free-energy measurement is free of bias. The heuristic is based in part on the measured free energy, but we argue that it is fail-safe inasmuch as any bias in the measurement will not promote a false indication of accuracy.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription.

PubMed

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-27

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4(+) T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription

PubMed Central

Suzuki, Kazuo; Ahlenstiel, Chantelle; Marks, Katherine; Kelleher, Anthony D

2015-01-01

In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4+ T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection. PMID:25625613

Targeting human c-Myc promoter duplex DNA with actinomycin D by use of multi-way analysis of quantum-dot-mediated fluorescence resonance energy transfer.

PubMed

Gholami, Somayeh; Kompany-Zareh, Mohsen

2013-07-01

Actinomycin D (Act D), an oncogenic c-Myc promoter binder, interferes with the action of RNA polymerase. There is great demand for high-throughput technology able to monitor the activity of DNA-binding drugs. To this end, binding of 7-aminoactinomycin D (7AAD) to the duplex c-Myc promoter was investigated by use of 2D-photoluminescence emission (2D-PLE), and the resulting data were subjected to analysis by use of convenient and powerful multi-way approaches. Fluorescence measurements were performed by use of the quantum dot (QD)-conjugated c-Myc promoter. Intercalation of 7AAD within duplex base pairs resulted in efficient energy transfer from drug to QD via fluorescence resonance energy transfer (FRET). Multi-way analysis of the three-way data array obtained from titration experiments was performed by use of restricted Tucker3 and hard trilinear decomposition (HTD). These techniques enable analysis of high-dimensional and complex data from nanobiological systems which include several spectrally overlapped structures. It was almost impossible to obtain robust and meaningful information about the FRET process for such high overlap data by use of classical analysis. The soft approach had the important advantage over univariate classical methods of enabling us to investigate the source of variance in the fluorescence signal of the DNA-drug complex. It was established that hard trilinear decomposition analysis of FRET-measured data overcomes the problem of rank deficiency, enabling calculation of concentration profiles and pure spectra for all species, including non-fluorophores. The hard modeling approach was also used for determination of equilibrium constants for the hybridization and intercalation equilibria, using nonlinear fit data analysis. The intercalation constant 3.6 × 10(6) mol(-1) L and hybridization stability 1.0 × 10(8) mol(-1) L obtained were in good agreement with values reported in the literature. The analytical concentration of the QD-labeled DNA

SAGE: String-overlap Assembly of GEnomes.

PubMed

Ilie, Lucian; Haider, Bahlul; Molnar, Michael; Solis-Oba, Roberto

2014-09-15

De novo genome assembly of next-generation sequencing data is one of the most important current problems in bioinformatics, essential in many biological applications. In spite of significant amount of work in this area, better solutions are still very much needed. We present a new program, SAGE, for de novo genome assembly. As opposed to most assemblers, which are de Bruijn graph based, SAGE uses the string-overlap graph. SAGE builds upon great existing work on string-overlap graph and maximum likelihood assembly, bringing an important number of new ideas, such as the efficient computation of the transitive reduction of the string overlap graph, the use of (generalized) edge multiplicity statistics for more accurate estimation of read copy counts, and the improved use of mate pairs and min-cost flow for supporting edge merging. The assemblies produced by SAGE for several short and medium-size genomes compared favourably with those of existing leading assemblers. SAGE benefits from innovations in almost every aspect of the assembly process: error correction of input reads, string-overlap graph construction, read copy counts estimation, overlap graph analysis and reduction, contig extraction, and scaffolding. We hope that these new ideas will help advance the current state-of-the-art in an essential area of research in genomics.

Cost-effectiveness of health promotion targeting physical activity and healthy eating in mental health care.

PubMed

Verhaeghe, Nick; De Smedt, Delphine; De Maeseneer, Jan; Maes, Lea; Van Heeringen, Cornelis; Annemans, Lieven

2014-08-18

There is a higher prevalence of obesity in individuals with mental disorders compared to the general population. The results of several studies suggested that weight reduction in this population is possible following psycho-educational and/or behavioural weight management interventions. Evidence of the effectiveness alone is however inadequate for policy making. The aim of the current study was to evaluate the cost-effectiveness of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. A Markov decision-analytic model using a public payer perspective was applied, projecting the one-year results of a 10-week intervention over a time horizon of 20 years, assuming a repeated yearly implementation of the programme. Scenario analysis was applied evaluating the effects on the results of alternative modelling assumptions. One-way sensitivity analysis was performed to assess the effects on the results of varying key input parameters. An incremental cost-effectiveness ratio of 27,096€/quality-adjusted life years (QALY) in men, and 40,139€/QALY in women was found in the base case. Scenario analysis assuming an increase in health-related quality of life as a result of the body mass index decrease resulted in much better cost-effectiveness in both men (3,357€/QALY) and women (3,766€/QALY). The uncertainty associated with the intervention effect had the greatest impact on the model. As far as is known to the authors, this is the first health economic evaluation of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. Such research is important as it provides payers and governments with better insights how to spend the available resources in the most efficient way. Further research examining the cost-effectiveness of health promotion targeting physical activity and healthy eating in individuals with mental disorders is required.

Neural overlap in processing music and speech.

PubMed

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L

2015-03-19

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Finite Element Analysis of the Implantation Process of Overlapping Stents

PubMed Central

Xu, Jiang; Yang, Jie; Sohrabi, Salman; Zhou, Yihua; Liu, Yaling

2017-01-01

Overlapping stents are widely used in vascular stent surgeries. However, the rate of stent fractures (SF) and in-stent restenosis (ISR) after using overlapping stents is higher than that of single stent implantations. Published studies investigating the nature of overlapping stents rely primarily on medical images, which can only reveal the effect of the surgery without providing insights into how stent overlap influences the implantation process. In this paper, a finite element analysis of the overlapping stent implantation process was performed to study the interaction between overlapping stents. Four different cases, based on three typical stent overlap modes and two classical balloons, were investigated. The results showed that overlapping contact patterns among struts were edge-to-edge, edge-to-surface, and noncontact. These were mainly induced by the nonuniform deformation of the stent in the radial direction and stent tubular structures. Meanwhile, the results also revealed that the contact pressure was concentrated in the edge of overlapping struts. During the stent overlap process, the contact pattern was primarily edge-to-edge contact at the beginning and edge-to-surface contact as the contact pressure increased. The interactions between overlapping stents suggest that the failure of overlapping stents frequently occurs along stent edges, which agrees with the previous experimental research regarding the safety of overlapping stents. This paper also provides a fundamental understanding of the mechanical properties of overlapping stents. PMID:28690712

Overexpression of miR169o, an Overlapping microRNA in Response to Both Nitrogen Limitation and Bacterial Infection, Promotes Nitrogen Use Efficiency and Susceptibility to Bacterial Blight in Rice.

PubMed

Chao, Yu; Chen, Yutong; Cao, Yaqian; Chen, Huamin; Wang, Jichun; Bi, Yong-Mei; Tian, Fang; Yang, Fenghuan; Rothstein, Steven J; Zhou, Xueping; He, Chenyang

2018-03-15

Limiting nitrogen (N) supply contributes to improved resistance to bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice (Oryza sativa). To understand the regulatory roles of microRNAs in this phenomenon, sixty-three differentially-expressed overlapping miRNAs in response to Xoo infection and N-limitation stress in rice were identified through deep RNA-sequence and stem loop qRT-PCR. Among these, miR169o was further assessed as a typical overlapping miRNA through the overexpression of the miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass accumulation with significantly increased nitrate and total amino acid contents in roots than wild type (WT). Transcript level assays showed that under different N supply conditions miR169o opposite regulated NRT2 which is reduced under normal N supply condition but remarkably induced under N limiting stress. On the other hand, osa-miR169o-OX plants also displayed increased disease lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a, PR10b and PAL) compared with WT after inoculation with Xoo. In addition, miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping miR169o contributes to increase N use efficiency and negatively regulates the resistance to bacterial blight in rice. Consistently, transient expression of NF-YAs in rice protoplast promoted the transcripts of PR genes and NRT2 genes, while reduced the transcripts of NRT1 genes. Our results provide novel and additional insights into the coordinated regulatory mechanisms of crosstalk between Xoo infection and N-deficiency responses in rice.

Influence of slice overlap on positron emission tomography image quality

NASA Astrophysics Data System (ADS)

McKeown, Clare; Gillen, Gerry; Dempsey, Mary Frances; Findlay, Caroline

2016-02-01

PET scans use overlapping acquisition beds to correct for reduced sensitivity at bed edges. The optimum overlap size for the General Electric (GE) Discovery 690 has not been established. This study assesses how image quality is affected by slice overlap. Efficacy of 23% overlaps (recommended by GE) and 49% overlaps (maximum possible overlap) were specifically assessed. European Association of Nuclear Medicine (EANM) guidelines for calculating minimum injected activities based on overlap size were also reviewed. A uniform flood phantom was used to assess noise (coefficient of variation, (COV)) and voxel accuracy (activity concentrations, Bq ml-1). A NEMA (National Electrical Manufacturers Association) body phantom with hot/cold spheres in a background activity was used to assess contrast recovery coefficients (CRCs) and signal to noise ratios (SNR). Different overlap sizes and sphere-to-background ratios were assessed. COVs for 49% and 23% overlaps were 9% and 13% respectively. This increased noise was difficult to visualise on the 23% overlap images. Mean voxel activity concentrations were not affected by overlap size. No clinically significant differences in CRCs were observed. However, visibility and SNR of small, low contrast spheres (⩽13 mm diameter, 2:1 sphere to background ratio) may be affected by overlap size in low count studies if they are located in the overlap area. There was minimal detectable influence on image quality in terms of noise, mean activity concentrations or mean CRCs when comparing 23% overlap with 49% overlap. Detectability of small, low contrast lesions may be affected in low count studies—however, this is a worst-case scenario. The marginal benefits of increasing overlap from 23% to 49% are likely to be offset by increased patient scan times. A 23% overlap is therefore appropriate for clinical use. An amendment to EANM guidelines for calculating injected activities is also proposed which better reflects the effect overlap size has

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

PubMed

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

A mixed methods evaluation of televised health promotion advertisements targeted at older adults

PubMed Central

Berry, Tanya R.; Spence, John C.; Plotnikoff, Ronald C.; Bauman, Adrian; McCargar, Linda; Witcher, Chad; Clark, Marianne; Stolp, Sean

2016-01-01

The purpose of this research was to evaluate television advertisements targeted at 55–70-year olds that promoted physical activity and fruit and vegetable consumption. Awareness of the campaign, perceived credibility of the source, intentions to visit a promoted website, and intentions to perform the healthy behaviors were evaluated using mixed methods research. Results from a population level survey (n = 1600) showed low unprompted and prompted awareness of the campaign and no differences in intentions or behaviors among those who were aware of the campaign. Unprompted recall resulted in a very wide range of responses including the citation of many commercial advertisers. Qualitative themes that emerged from the focus groups included neutral, positive, and negative comments about the advertisements, source credibility, website considerations specific to seniors, and suggestions about appropriate advertising for older adults. This research showed that the increased attention paid to the advertisements was due in a large part to negative reactions to the character used in the advertisements. Another important finding was the government was not considered to be a credible source of health information. Finally, health promoters should be cautious about websites as the primary source of information, particularly for older adults. PMID:19493572

Iterative Overlap FDE for Multicode DS-CDMA

NASA Astrophysics Data System (ADS)

Takeda, Kazuaki; Tomeba, Hiromichi; Adachi, Fumiyuki

Recently, a new frequency-domain equalization (FDE) technique, called overlap FDE, that requires no GI insertion was proposed. However, the residual inter/intra-block interference (IBI) cannot completely be removed. In addition to this, for multicode direct sequence code division multiple access (DS-CDMA), the presence of residual interchip interference (ICI) after FDE distorts orthogonality among the spreading codes. In this paper, we propose an iterative overlap FDE for multicode DS-CDMA to suppress both the residual IBI and the residual ICI. In the iterative overlap FDE, joint minimum mean square error (MMSE)-FDE and ICI cancellation is repeated a sufficient number of times. The bit error rate (BER) performance with the iterative overlap FDE is evaluated by computer simulation.

The chromodomain of Tf1 integrase promotes binding to cDNA and mediates target site selection.

PubMed

Chatterjee, Atreyi Ghatak; Leem, Young Eun; Kelly, Felice D; Levin, Henry L

2009-03-01

The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDDelta, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDDelta caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting.

Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens

PubMed Central

Niu, Jun; Wang, Jia; Hu, Huiwen; Chen, Yinlei; An, Jiyong; Cai, Jian; Sun, Runze; Sheng, Zhongting; Liu, Xieping; Lin, Shanzhi

2016-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5′ deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process. PMID:26853706

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

PubMed Central

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

2016-01-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

PubMed

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

2016-02-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

[More] evidence to support oral health promotion services targeted to smokers calling tobacco quitlines in the United States.

PubMed

McClure, Jennifer B; Riggs, Karin; St John, Jackie; Catz, Sheryl L

2013-04-11

Prior research demonstrated a need and opportunity to target smokers calling a free, state-funded tobacco quitline to provide behavioral counseling for oral health promotion; however, it is unclear whether these results generalize to tobacco quitline callers of higher socioeconomic status receiving services through commercially-funded quitlines. This knowledge will inform planning for a future public oral health promotion program targeted to tobacco quitline callers. We surveyed smokers (n = 455) who had recently received tobacco quitline services through their medical insurance. Participants were asked about their self-reported oral health indicators, key behavioral risk factors for oral disease, motivation for changing their oral self-care behavior, and interest in future oral health promotion services. Where applicable, results were compared against those from a representative sample of callers to a free, state-funded quitline (n = 816) in the same geographic region. Callers to a commercially-funded quitline had higher socioeconomic status, were more likely to have dental insurance, and reported better overall oral health indicators and routine self-care (oral hygiene, dental visits) than callers to a state-funded quitline. Nevertheless opportunities for oral health promotion were identified. Nearly 80% of commercial quitline callers failed to meet basic daily hygiene recommendations, 32.8% had not visited the dentist in more than a year, and 63.3% reported daily alcohol consumption (which reacts synergistically with tobacco to increase oral cancer risk). Nearly half (44%) were interested in learning how to improve their oral health status and, on average, moderately high levels of motivation for oral health care were reported. Many participants also had dental insurance, eliminating an important barrier to professional dental care. Future public oral health promotion efforts should focus on callers to both free state-supported and commercially

MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor.

PubMed

Bao, Qinxue; Zhao, Mingyue; Chen, Li; Wang, Yu; Wu, Siyuan; Wu, Wenchao; Liu, Xiaojing

2017-04-15

Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy. Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R. Transverse aortic constriction (TAC) model and neonatal rat cardiomyocytes (NCMs) stimulated with angiotensin II (AngII) were used to explore the relationship between miR-297 and Sig-1R. Additionally, the function of miR-297 in cardiomyocyte hypertrophy and ER stress/unfolded protein response (UPR) signaling pathway was investigated by transfecting miR-297 mimics/inhibitor. miR-297 levels were increased in both TAC-induced hypertrophic heart tissue and AngII-induced cardiomyocyte hypertrophy. Up-regulation of miR-297 by specific mimics exacerbated AngII-induced cardiomyocyte hypertrophy, whereas inhibition of miR-297 suppressed the process. During cardiomyocyte hypertrophy, Sig-1R expression, which was negatively regulated by miR-297 by directly targeting its 3'untranslated region (UTR), was decreased. Furthermore, attenuation of miR-297 inhibited the activation of X-box binding protein 1 (Xbp1) and activating transcriptional factor 4 (ATF4) signaling pathways in NCMs. Our data demonstrate that miR-297 promotes cardiomyocyte hypertrophy by inhibiting the expression of Sig-1R and activation of ER stress signaling, which provides a novel interpretation for cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Sub-Plate Overlap Code Documentation

NASA Technical Reports Server (NTRS)

Taff, L. G.; Bucciarelli, B.; Zarate, N.

1997-01-01

An expansion of the plate overlap method of astrometric data reduction to a single plate has been proposed and successfully tested. Each plate is (artificially) divided into sub-plates which can then be overlapped. This reduces the area of a 'plate' over which a plate model needs to accurately represent the relationship between measured coordinates and standard coordinates. Application is made to non-astrographic plates such as Schmidt plates and to wide-field astrographic plates. Indeed, the method is completely general and can be applied to any type of recording media.

Finding overlapping communities in multilayer networks.

PubMed

Liu, Weiyi; Suzumura, Toyotaro; Ji, Hongyu; Hu, Guangmin

2018-01-01

Finding communities in multilayer networks is a vital step in understanding the structure and dynamics of these layers, where each layer represents a particular type of relationship between nodes in the natural world. However, most community discovery methods for multilayer networks may ignore the interplay between layers or the unique topological structure in a layer. Moreover, most of them can only detect non-overlapping communities. In this paper, we propose a new community discovery method for multilayer networks, which leverages the interplay between layers and the unique topology in a layer to reveal overlapping communities. Through a comprehensive analysis of edge behaviors within and across layers, we first calculate the similarities for edges from the same layer and the cross layers. Then, by leveraging these similarities, we can construct a dendrogram for the multilayer networks that takes both the unique topological structure and the important interplay into consideration. Finally, by introducing a new community density metric for multilayer networks, we can cut the dendrogram to get the overlapping communities for these layers. By applying our method on both synthetic and real-world datasets, we demonstrate that our method has an accurate performance in discovering overlapping communities in multilayer networks.

How Does Target Duration Affect Object Substitution Masking?

ERIC Educational Resources Information Center

Gellatly, Angus; Pilling, Michael; Carter, Wakefield; Guest, Duncan

2010-01-01

Object substitution masking (OSM) is typically studied using a brief search display. The target item may be indicated by a cue/mask surrounding but not overlapping it. Report of the target is reduced when mask offset trails target offset rather than being simultaneous with it. We report 5 experiments investigating whether OSM can be obtained if…

Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment.

PubMed

Charpentier, Monica S; Whipple, Rebecca A; Vitolo, Michele I; Boggs, Amanda E; Slovic, Jana; Thompson, Keyata N; Bhandary, Lekhana; Martin, Stuart S

2014-02-15

Cancer stem-like cells (CSC) and circulating tumor cells (CTC) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTN), a type of tubulin-based protrusion of the plasma cell membrane that forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the human mammary epithelial (HMLE) cell line presents increased McTNs compared with its isogenic non-stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTNs in stem cell reattachment. Moreover, live-cell confocal microscopy showed that McTNs persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. Although exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTNs can mediate attachment and metastasis but might be targeted by curcumin as an antimetastatic strategy. ©2013 AACR.

Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment

PubMed Central

Charpentier, Monica S.; Whipple, Rebecca A.; Vitolo, Michele I.; Boggs, Amanda E.; Slovic, Jana; Thompson, Keyata N.; Bhandary, Lekhana; Martin, Stuart S.

2014-01-01

Cancer stem-like cells (CSC) and circulating tumor cells (CTCs) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTNs), a type of tubulin-based protrusion of the plasma cell membrane which forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the HMLE breast cell line presents increased McTNs compared to its isogenic non-stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTN in stem cell reattachment. Moreover, live cell confocal microscopy showed that McTN persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. While exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTN can mediate attachment and metastasis but might be targeted by curcumin as an anti-metastatic strategy. PMID:24371229

Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter

PubMed Central

Chen, Hui; Kazemier, Hinke G; de Groote, Marloes L.; Ruiters, Marcel H. J.; Xu, Guo-Liang; Rots, Marianne G.

2014-01-01

Increasing evidence indicates that active DNA demethylation is involved in several processes in mammals, resulting in developmental stage-specificity and cell lineage-specificity. The recently discovered Ten-Eleven Translocation (TET) dioxygenases are accepted to be involved in DNA demethylation by initiating 5-mC oxidation. Aberrant DNA methylation profiles are associated with many diseases. For example in cancer, hypermethylation results in silencing of tumor suppressor genes. Such silenced genes can be re-expressed by epigenetic drugs, but this approach has genome-wide effects. In this study, fusions of designer DNA binding domains to TET dioxygenase family members (TET1, -2 or -3) were engineered to target epigenetically silenced genes (ICAM-1, EpCAM). The effects on targeted CpGs’ methylation and on expression levels of the target genes were assessed. The results indicated demethylation of targeted CpG sites in both promoters for targeted TET2 and to a lesser extent for TET1, but not for TET3. Interestingly, we observed re-activation of transcription of ICAM-1. Thus, our work suggests that we provided a mechanism to induce targeted DNA demethylation, which facilitates re-activation of expression of the target genes. Furthermore, this Epigenetic Editing approach is a powerful tool to investigate functions of epigenetic writers and erasers and to elucidate consequences of epigenetic marks. PMID:24194590

UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

PubMed Central

Binkert, Melanie; Kozma-Bognár, László; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

2014-01-01

In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap.

PubMed

Wiest, Matheus J; Bergquist, Austin J; Schimidt, Helen L; Jones, Kelvin E; Collins, David F

2017-04-01

In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017. © 2016 Wiley Periodicals, Inc.

The Chromodomain of Tf1 Integrase Promotes Binding to cDNA and Mediates Target Site Selection▿ †

PubMed Central

Chatterjee, Atreyi Ghatak; Leem, Young Eun; Kelly, Felice D.; Levin, Henry L.

2009-01-01

The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDΔ, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDΔ caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting. PMID:19109383

Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

PubMed Central

Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

2011-01-01

The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

Finding overlapping communities in multilayer networks

PubMed Central

Liu, Weiyi; Suzumura, Toyotaro; Ji, Hongyu; Hu, Guangmin

2018-01-01

Finding communities in multilayer networks is a vital step in understanding the structure and dynamics of these layers, where each layer represents a particular type of relationship between nodes in the natural world. However, most community discovery methods for multilayer networks may ignore the interplay between layers or the unique topological structure in a layer. Moreover, most of them can only detect non-overlapping communities. In this paper, we propose a new community discovery method for multilayer networks, which leverages the interplay between layers and the unique topology in a layer to reveal overlapping communities. Through a comprehensive analysis of edge behaviors within and across layers, we first calculate the similarities for edges from the same layer and the cross layers. Then, by leveraging these similarities, we can construct a dendrogram for the multilayer networks that takes both the unique topological structure and the important interplay into consideration. Finally, by introducing a new community density metric for multilayer networks, we can cut the dendrogram to get the overlapping communities for these layers. By applying our method on both synthetic and real-world datasets, we demonstrate that our method has an accurate performance in discovering overlapping communities in multilayer networks. PMID:29694387

IAOseq: inferring abundance of overlapping genes using RNA-seq data.

PubMed

Sun, Hong; Yang, Shuang; Tun, Liangliang; Li, Yixue

2015-01-01

Overlapping transcription constitutes a common mechanism for regulating gene expression. A major limitation of the overlapping transcription assays is the lack of high throughput expression data. We developed a new tool (IAOseq) that is based on reads distributions along the transcribed regions to identify the expression levels of overlapping genes from standard RNA-seq data. Compared with five commonly used quantification methods, IAOseq showed better performance in the estimation accuracy of overlapping transcription levels. For the same strand overlapping transcription, currently existing high-throughput methods are rarely available to distinguish which strand was present in the original mRNA template. The IAOseq results showed that the commonly used methods gave an average of 1.6 fold overestimation of the expression levels of same strand overlapping genes. This work provides a useful tool for mining overlapping transcription levels from standard RNA-seq libraries. IAOseq could be used to help us understand the complex regulatory mechanism mediated by overlapping transcripts. IAOseq is freely available at http://lifecenter.sgst.cn/main/en/IAO_seq.jsp.

miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells

PubMed Central

Fei, Xiubin; Zhang, Jingang; Zhao, Yunwei; Sun, Meijia; Zhao, Haifeng; Li, Shuang

2018-01-01

Lung cancer is a major cause of death worldwide, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The aim of this study was to investigate whether miR-96 mediated the invasion and metastasis of NSCLC by targeting glypican-3 (GPC3). Reverse transcription-quantitative PCR (RT-qPCR) was employed to detect the level of miR-96 and GPC3 mRNA. We applied western blot analysis to measure the protein expression level of GPC3 gene. The luciferase reporter assay was employed to confirm that GPC3 was a target gene of miR-96. The Transwell assay was used to detect migration and invasion. The results revealed that miR-96 was upregulated in NSCLC tissues and lung cancer cells (A549 and H460) compared with corresponding paracancerous tissues and normal epidermic MRC-5 cells. Overexpression of miR-96 promoted invasion and migration in A549 cells. GPC3 was a direct target of miR-96 and regulated by miR-96. GPC3 could reverse partial fuction of miR-96 on proliferation. In conclusion, miR-96 was able to promote the migration and invasion of lung cancer cells by targeting GPC3 gene. The newly identified miR-96/GPC3 axis may provide a therapeutic method for the treatment of NSCLC. PMID:29805640

Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death.

PubMed

Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jeong, Yoo Kyung; Jo, Jae-Cheol; Choi, Yunsuk; Koh, SuJin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk

2017-11-10

Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90β (HSP90β) expression and release Apaf-1 in c-KIT-positive AML cells. Finally, this activates a caspase-dependent apoptotic pathway in c-KIT-positive AML cells. Moreover, the inhibition of c-KIT endocytosis by dynamin inhibitor (DY) reversed cell viability and c-KIT expression by dasatinib and radotinib. HSP90β expression was recovered by DY in c-KIT-positive AML cells as well. Furthermore, the effect of radotinib on c-KIT and HSP90β showed the same pattern in a xenograft animal model using HEL92.1.7 cells. Therefore, dasatinib and radotinib promote AML cell death by targeting c-KIT. Taken together, these results indicate that dasatinib and radotinib treatment have a potential role in anti-leukemic therapy on c-KIT-positive AML cells.

The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis

PubMed Central

Sechler, Marybeth; Parrish, Janet K.; Birks, Diane K.; Jedlicka, Paul

2017-01-01

Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the Melanoma Cell Adhesion Molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Lastly, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components. PMID:28319067

Dual DNA binding property of ABA insensitive 3 like factors targeted to promoters responsive to ABA and auxin.

PubMed

Nag, Ronita; Maity, Manas Kanti; Dasgupta, Maitrayee

2005-11-01

The ABA responsive ABI3 and the auxin responsive ARF family of transcription factors bind the CATGCATG (Sph) and TGTCTC core motifs in ABA and auxin response elements (ABRE and AuxRE), respectively. Several evidences indicate ABI3s to act downstream to auxin too. Because DNA binding domain of ABI3s shows significant overlap with ARFs we enquired whether auxin responsiveness through ABI3s could be mediated by their binding to canonical AuxREs. Investigations were undertaken through in vitro gel mobility shift assays (GMSA) using the DNA binding domain B3 of PvAlf (Phaseolus vulgaris ABI3 like factor) and upstream regions of auxin responsive gene GH3 (-267 to -141) and ABA responsive gene Em (-316 to -146) harboring AuxRE and ABRE, respectively. We demonstrate that B3 domain of PvAlf could bind AuxRE only when B3 was associated with its flanking domain B2 (B2B3). Such strict requirement of B2 domain was not observed with ABRE, where B3 could bind with or without being associated with B2. This dual specificity in DNA binding of ABI3s was also demonstrated with nuclear extracts of cultured cells of Arachis hypogea. Supershift analysis of ABRE and AuxRE bound nuclear proteins with antibodies raised against B2B3 domains of PvAlf revealed that ABI3 associated complexes were detectable in association with both cis elements. Competition GMSA confirmed the same complexes to bind ABRE and AuxRE. This dual specificity of ABI3 like factors in DNA binding targeted to natural promoters responsive to ABA and auxin suggests them to have a potential role in conferring crosstalk between these two phytohormones.

Insulation and wiring specificity of BceR-like response regulators and their target promoters in Bacillus subtilis.

PubMed

Fang, Chong; Nagy-Staroń, Anna; Grafe, Martin; Heermann, Ralf; Jung, Kirsten; Gebhard, Susanne; Mascher, Thorsten

2017-04-01

BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, P bceA or P psdA , resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of P bceA and P psdA that ensure the insulation of these two paralogous pathways at the RR-promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities. © 2016 John Wiley & Sons Ltd.

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... select agent or toxin to APHIS or CDC. (i) The seizure of any of the following overlap select agents and.... This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after seizure of the overlap select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form...

PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

PubMed

Yan, Chen; Chen, Yaqing; Kong, Weiwei; Fu, Liya; Liu, Yunde; Yao, Qingjuan; Yuan, Yuhua

2017-05-01

Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Health promotion, environmental health and Agenda 21.

PubMed

Scriven, A; Young, S

1998-04-01

In 1992, at the Rio Earth Summit, many governments, including our own, committed themselves to developing local strategies for sustainable development in the form of Local Agenda 21. Sustainable development is discussed, as is the philosophy and practice of health promotion and environmental health. Common approaches are identified and the links in relation to key areas of activities, strategies, values and principles are outlined. Finally, recommendations are made and conclusions drawn in relation to the overlap between environmental health action, Agenda 21 strategies and health promotion practice.

Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion.

PubMed

Otto, Michael W; Eastman, Abraham; Lo, Stephen; Hearon, Bridget A; Bickel, Warren K; Zvolensky, Michael; Smits, Jasper A J; Doan, Stacey N

2016-11-01

Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors-anxiety sensitivity (AS) and working memory capacity (WMC)-for enhancing risk for the initiation and/or maintenance of a range of negative health behaviors. AS is a distress-related risk factor that potentiates avoidance/coping motivations for negative health behaviors. Stress provides the conditions for negative somatic and affective states, and AS amplifies the aversiveness of these experiences and correspondingly hinders adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by decreasing the capacity to filter out current temptations, attenuating a focus on longer-term goals and impairing the application of relevant coping skills at times of stress. In this review, we provide conceptual models for the separate roles of high AS and low WMC in negative health behaviors, review the influence of these factors on specific health behavior exemplars (eating behaviors/obesity, physical activity, smoking, alcohol use, and sleep promotion), provide preliminary evidence for their value as independent treatment targets for health-behavior promotion, and encourage specific research directions in relation to these variables. Copyright © 2016. Published by Elsevier Ltd.

Does segmental overlap help or hurt? Evidence from blocked cyclic naming in spoken and written production.

PubMed

Breining, Bonnie; Nozari, Nazbanou; Rapp, Brenda

2016-04-01

Past research has demonstrated interference effects when words are named in the context of multiple items that share a meaning. This interference has been explained within various incremental learning accounts of word production, which propose that each attempt at mapping semantic features to lexical items induces slight but persistent changes that result in cumulative interference. We examined whether similar interference-generating mechanisms operate during the mapping of lexical items to segments by examining the production of words in the context of others that share segments. Previous research has shown that initial-segment overlap amongst a set of target words produces facilitation, not interference. However, this initial-segment facilitation is likely due to strategic preparation, an external factor that may mask underlying interference. In the present study, we applied a novel manipulation in which the segmental overlap across target items was distributed unpredictably across word positions, in order to reduce strategic response preparation. This manipulation led to interference in both spoken (Exp. 1) and written (Exp. 2) production. We suggest that these findings are consistent with a competitive learning mechanism that applies across stages and modalities of word production.

Targeting G-quadruplex DNA structures in the telomere and oncogene promoter regions by benzimidazole‒carbazole ligands.

PubMed

Kaulage, Mangesh H; Maji, Basudeb; Pasadi, Sanjeev; Ali, Asfa; Bhattacharya, Santanu; Muniyappa, K

2018-03-25

Recent studies support the idea that G-quadruplex structures in the promoter regions of oncogenes and telomere DNA can serve as potential therapeutic targets in the treatment of cancer. Accordingly, several different types of organic small molecules that stabilize G-quadruplex structures and inhibit telomerase activity have been discerned. Here, we describe the binding of benzimidazole-carbazole ligands to G-quadruplex structures formed in G-rich DNA sequences containing the promoter regions of human c-MYC, c-KIT1, c-KIT2, VEGF and BCL2 proto-oncogenes. The fluorescence spectroscopic data indicate that benzimidazole-carbazole ligands bind and stabilize the G-quadruplexes in the promoter region of oncogenes. The molecular docking studies provide insights into the mode and extent of binding of this class of ligands to the G-quadruplexes formed in oncogene promoters. The high stability of these G-quadruplex structures was validated by thermal denaturation and telomerase-catalyzed extension of the 3' end. Notably, benzimidazole-carbazole ligands suppress the expression of oncogenes in cancer cells in a dose-dependent manner. We anticipate that benzimidazole-carbazole ligands, by virtue of their ability to stabilize G-quadruplex structures in the promoter regions of oncogenes, might reduce the risk of cancer through the loss of function in the proteins encoded by these genes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication

PubMed Central

Singh, Shilpa; Vaughan, Catherine A.; Frum, Rebecca A.; Grossman, Steven R.; Deb, Sumitra

2017-01-01

Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 leads to decreased origin firing and a higher frequency of fork collapse in isogenic cells, explaining their poorer proliferation rate. Following genome-wide analyses utilizing ChIP-Seq and RNA-Seq, GOF p53–induced origin firing, micronuclei formation, and fork protection were traced to the ability of GOF p53 to transactivate cyclin A and CHK1. Highlighting the therapeutic potential of CHK1’s role in GOF p53 dependency, experiments in cell culture and mouse xenografts demonstrated that inhibition of CHK1 selectively blocked proliferation of cells and tumors expressing GOF p53. Our data suggest the possibility that checkpoint inhibitors could efficiently and selectively target cancers expressing GOF p53 alleles. PMID:28394262

Impact of a targeted direct marketing price promotion intervention (Buywell) on food-purchasing behaviour by low income consumers: a randomised controlled trial.

PubMed

Stead, M; MacKintosh, A M; Findlay, A; Sparks, L; Anderson, A S; Barton, K; Eadie, D

2017-08-01

Price promotions are a promising intervention for encouraging healthier food purchasing. We aimed to assess the impact of a targeted direct marketing price promotion combined with healthy eating advice and recipe suggestions on the purchase of selected healthier foods by low income consumers. We conducted a randomised controlled trial (n = 53 367) of a direct marketing price promotion (Buywell) combined with healthy eating advice and recipe suggestions for low income consumers identified as 'less healthy' shoppers. Impact was assessed using electronic point of sale data for UK low income shoppers before, during and after the promotion. The proportion of customers buying promoted products in the intervention month increased by between 1.4% and 2.8% for four of the five products. There was significantly higher uptake in the promotion month (P < 0.001) for the intervention group than would have been expected on the basis of average uptake in the other months. When product switching was examined for semi-skimmed/skimmed milk, a modest increase (1%) was found in the intervention month of customers switching from full-fat to low-fat milk. This represented 8% of customers who previously bought only full-fat milk. The effects were generally not sustained after the promotion period. Short-term direct marketing price promotions combined with healthy eating advice and recipe suggestions targeted at low income consumers are feasible and can have a modest impact on short-term food-purchasing behaviour, although further approaches are needed to help sustain these changes. © 2017 The British Dietetic Association Ltd.

Burnout-depression overlap: a review.

PubMed

Bianchi, Renzo; Schonfeld, Irvin Sam; Laurent, Eric

2015-03-01

Whether burnout is a form of depression or a distinct phenomenon is an object of controversy. The aim of the present article was to provide an up-to-date review of the literature dedicated to the question of burnout-depression overlap. A systematic literature search was carried out in PubMed, PsycINFO, and IngentaConnect. A total of 92 studies were identified as informing the issue of burnout-depression overlap. The current state of the art suggests that the distinction between burnout and depression is conceptually fragile. It is notably unclear how the state of burnout (i.e., the end stage of the burnout process) is conceived to differ from clinical depression. Empirically, evidence for the distinctiveness of the burnout phenomenon has been inconsistent, with the most recent studies casting doubt on that distinctiveness. The absence of consensual diagnostic criteria for burnout and burnout research's insufficient consideration of the heterogeneity of depressive disorders constitute major obstacles to the resolution of the raised issue. In conclusion, the epistemic status of the seminal, field-dominating definition of burnout is questioned. It is suggested that systematic clinical observation should be given a central place in future research on burnout-depression overlap. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectors of root sedentary nematodes target diverse plant cell compartments to manipulate plant functions and promote infection.

PubMed

Jaouannet, Maëlle; Rosso, Marie-Noëlle

2013-09-01

Sedentary plant-parasitic nematodes maintain a biotrophic relationship with their hosts over a period of several weeks and induce the differentiation of root cells into specialized feeding cells. Nematode effectors, which are synthesized in the esophageal glands and injected into the plant tissue through the syringe-like stylet, play a central role in these processes. Previous work on nematode effectors has shown that the apoplasm is targeted during invasion of the host while the cytoplasm is targeted during the induction and the maintenance of the feeding site. A large number of candidate effectors potentially secreted by the nematode into the plant tissues to promote infection have now been identified. This work has shown that the targeting and the role of effectors are more complex than previously thought. This review will not cover the prolific recent findings in nematode effector function but will instead focus on recent selected examples that illustrate the variety of plant cell compartments that effectors are addressed to in order reach their plant targets.

Prevention of overlapping prescriptions of psychotropic drugs by community pharmacists.

PubMed

Shimane, Takuya; Matsumoto, Toshihiko; Wada, Kiyoshi

2012-10-01

The nonmedical use or abuse of prescription drugs, including psychotropic medicines, is a growing health problem in Japan. Patient access to psychotropic drugs, specifically from the oversupply of medications due to overlapping prescriptions, may increase the risk of drug abuse and dependence. However, very little is known about such overlapping prescriptions. Today, the dispensing of prescriptions is generally moving from inside to outside of hospitals, with psychotropic drugs mainly dispensed at community pharmacies. In this study, we used health insurance claims (i.e., receipts) for dispensing as the main source of information in an investigation of overlapping prescriptions of psychotropic drugs. A total of 119 patients were found to have received overlapping prescriptions, as identified by community pharmacists who were members of the Saitama Pharmaceutical Association, using patient medication records, followed by medication counseling and prescription notes for the patient. According to our findings, the most frequently overlapping medication was etizolam. Etizolam can be prescribed for more than 30 days since it is not regulated under Japanese law as a "psychotropic drug." Generally, when a drug can be prescribed for a greater number of days, it increases the likelihood of an overlapping prescription during the same period. As a result, the long-term prescription of etizolam increases the risk of overlapping prescriptions. We also found that the patients who received overlapping prescriptions of etizolam were mostly elderly and the most common pattern was prescription from both internal medicine and orthopedics physicians. Etizolam has wide range of indications that are covered by health insurance. Our results suggest that patients who received overlapping prescriptions of etizolam may receive prescriptions from different prescribers for different purposes. Therefore, it may be appropriate to regulate etizolam as a "psychotropic drug" under Japanese law

Overlapping Community Detection based on Network Decomposition

NASA Astrophysics Data System (ADS)

Ding, Zhuanlian; Zhang, Xingyi; Sun, Dengdi; Luo, Bin

2016-04-01

Community detection in complex network has become a vital step to understand the structure and dynamics of networks in various fields. However, traditional node clustering and relatively new proposed link clustering methods have inherent drawbacks to discover overlapping communities. Node clustering is inadequate to capture the pervasive overlaps, while link clustering is often criticized due to the high computational cost and ambiguous definition of communities. So, overlapping community detection is still a formidable challenge. In this work, we propose a new overlapping community detection algorithm based on network decomposition, called NDOCD. Specifically, NDOCD iteratively splits the network by removing all links in derived link communities, which are identified by utilizing node clustering technique. The network decomposition contributes to reducing the computation time and noise link elimination conduces to improving the quality of obtained communities. Besides, we employ node clustering technique rather than link similarity measure to discover link communities, thus NDOCD avoids an ambiguous definition of community and becomes less time-consuming. We test our approach on both synthetic and real-world networks. Results demonstrate the superior performance of our approach both in computation time and accuracy compared to state-of-the-art algorithms.

RNAi Experiments in D. melanogaster: Solutions to the Overlooked Problem of Off-Targets Shared by Independent dsRNAs

PubMed Central

Seinen, Erwin; Burgerhof, Johannes G. M.; Jansen, Ritsert C.; Sibon, Ody C. M.

2010-01-01

Background RNAi technology is widely used to downregulate specific gene products. Investigating the phenotype induced by downregulation of gene products provides essential information about the function of the specific gene of interest. When RNAi is applied in Drosophila melanogaster or Caenorhabditis elegans, often large dsRNAs are used. One of the drawbacks of RNAi technology is that unwanted gene products with sequence similarity to the gene of interest can be down regulated too. To verify the outcome of an RNAi experiment and to avoid these unwanted off-target effects, an additional non-overlapping dsRNA can be used to down-regulate the same gene. However it has never been tested whether this approach is sufficient to reduce the risk of off-targets. Methodology We created a novel tool to analyse the occurance of off-target effects in Drosophila and we analyzed 99 randomly chosen genes. Principal Findings Here we show that nearly all genes contain non-overlapping internal sequences that do show overlap in a common off-target gene. Conclusion Based on our in silico findings, off-target effects should not be ignored and our presented on-line tool enables the identification of two RNA interference constructs, free of overlapping off-targets, from any gene of interest. PMID:20957038

Window and Overlap Processing Effects on Power Estimates from Spectra

NASA Astrophysics Data System (ADS)

Trethewey, M. W.

2000-03-01

Fast Fourier transform (FFT) spectral processing is based on the assumption of stationary ergodic data. In engineering practice, the assumption is often violated and non-stationary data processed. Data windows are commonly used to reduce leakage by decreasing the signal amplitudes near the boundaries of the discrete samples. With certain combinations of non-stationary signals and windows, the temporal weighting may attenuate important signal characteristics to adversely affect any subsequent processing. In other words, the window artificially reduces a significant section of the time signal. Consequently, spectra and overall power estimated from the affected samples are unreliable. FFT processing can be particularly problematic when the signal consists of randomly occurring transients superimposed on a more continuous signal. Overlap processing is commonly used in this situation to improve the estimates. However, the results again depend on the temporal character of the signal in relation to the window weighting. A worst-case scenario, a short-duration half sine pulse, is used to illustrate the relationship between overlap percentage and resulting power estimates. The power estimates are shown to depend on the temporal behaviour of the square of overlapped window segments. An analysis shows that power estimates may be obtained to within 0.27 dB for the following windows and overlap combinations: rectangular (0% overlap), Hanning (62.5% overlap), Hamming (60.35% overlap) and flat-top (82.25% overlap).

Neutron Spectroscopy for pulsed beams with frame overlap using a double time-of-flight technique

NASA Astrophysics Data System (ADS)

Harrig, K. P.; Goldblum, B. L.; Brown, J. A.; Bleuel, D. L.; Bernstein, L. A.; Bevins, J.; Harasty, M.; Laplace, T. A.; Matthews, E. F.

2018-01-01

A new double time-of-flight (dTOF) neutron spectroscopy technique has been developed for pulsed broad spectrum sources with a duty cycle that results in frame overlap, where fast neutrons from a given pulse overtake slower neutrons from previous pulses. Using a tunable beam at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory, neutrons were produced via thick-target breakup of 16 MeV deuterons on a beryllium target in the cyclotron vault. The breakup spectral shape was deduced from a dTOF measurement using an array of EJ-309 organic liquid scintillators. Simulation of the neutron detection efficiency of the scintillator array was performed using both GEANT4 and MCNP6. The efficiency-corrected spectral shape was normalized using a foil activation technique to obtain the energy-dependent flux of the neutron beam at zero degrees with respect to the incoming deuteron beam. The dTOF neutron spectrum was compared to spectra obtained using HEPROW and GRAVEL pulse height spectrum unfolding techniques. While the unfolding and dTOF results exhibit some discrepancies in shape, the integrated flux values agree within two standard deviations. This method obviates neutron time-of-flight spectroscopy challenges posed by pulsed beams with frame overlap and opens new opportunities for pulsed white neutron source facilities.

Gene network interconnectedness and the generalized topological overlap measure

PubMed Central

Yip, Andy M; Horvath, Steve

2007-01-01

Background Network methods are increasingly used to represent the interactions of genes and/or proteins. Genes or proteins that are directly linked may have a similar biological function or may be part of the same biological pathway. Since the information on the connection (adjacency) between 2 nodes may be noisy or incomplete, it can be desirable to consider alternative measures of pairwise interconnectedness. Here we study a class of measures that are proportional to the number of neighbors that a pair of nodes share in common. For example, the topological overlap measure by Ravasz et al. [1] can be interpreted as a measure of agreement between the m = 1 step neighborhoods of 2 nodes. Several studies have shown that two proteins having a higher topological overlap are more likely to belong to the same functional class than proteins having a lower topological overlap. Here we address the question whether a measure of topological overlap based on higher-order neighborhoods could give rise to a more robust and sensitive measure of interconnectedness. Results We generalize the topological overlap measure from m = 1 step neighborhoods to m ≥ 2 step neighborhoods. This allows us to define the m-th order generalized topological overlap measure (GTOM) by (i) counting the number of m-step neighbors that a pair of nodes share and (ii) normalizing it to take a value between 0 and 1. Using theoretical arguments, a yeast co-expression network application, and a fly protein network application, we illustrate the usefulness of the proposed measure for module detection and gene neighborhood analysis. Conclusion Topological overlap can serve as an important filter to counter the effects of spurious or missing connections between network nodes. The m-th order topological overlap measure allows one to trade-off sensitivity versus specificity when it comes to defining pairwise interconnectedness and network modules. PMID:17250769

Overlap among Environmental Databases.

ERIC Educational Resources Information Center

Miller, Betty

1981-01-01

Describes the methodology and results of a study comparing the overlap of Enviroline, Pollution, and the Environmental Periodicals Bibliography files through searches on acid rain, asbestos and water, diesel, glass recycling, Lake Erie, Concorde, reverse osmosis wastewater treatment cost, and Calspan. Nine tables are provided. (RBF)

Selective Inhibition of the Human tie-1 Promoter with Triplex-Forming Oligonucleotides Targeted to Ets Binding Sites

PubMed Central

Hewett, Peter W; Daft, Emma L; Laughton, Charles A; Ahmad, Shakil; Ahmed, Asif; Murray, J Clifford

2006-01-01

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21–22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (Kd ~10−7 M) at 37 °C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction. PMID:16838069

Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to Ets binding sites.

PubMed

Hewett, Peter W; Daft, Emma L; Laughton, Charles A; Ahmad, Shakil; Ahmed, Asif; Murray, J Clifford

2006-01-01

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction.

High-Throughput Analysis of Promoter Occupancy Reveals Direct Neural Targets of FOXP2, a Gene Mutated in Speech and Language Disorders

PubMed Central

Vernes, Sonja C. ; Spiteri, Elizabeth ; Nicod, Jérôme ; Groszer, Matthias ; Taylor, Jennifer M. ; Davies, Kay E. ; Geschwind, Daniel H. ; Fisher, Simon E. 

2007-01-01

We previously discovered that mutations of the human FOXP2 gene cause a monogenic communication disorder, primarily characterized by difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech. Affected people have deficits in expressive and receptive linguistic processing and display structural and/or functional abnormalities in cortical and subcortical brain regions. FOXP2 provides a unique window into neural processes involved in speech and language. In particular, its role as a transcription factor gene offers powerful functional genomic routes for dissecting critical neurogenetic mechanisms. Here, we employ chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip) to successfully identify genomic sites that are directly bound by FOXP2 protein in native chromatin of human neuron-like cells. We focus on a subset of downstream targets identified by this approach, showing that altered FOXP2 levels yield significant changes in expression in our cell-based models and that FOXP2 binds in a specific manner to consensus sites within the relevant promoters. Moreover, we demonstrate significant quantitative differences in target expression in embryonic brains of mutant mice, mediated by specific in vivo Foxp2-chromatin interactions. This work represents the first identification and in vivo verification of neural targets regulated by FOXP2. Our data indicate that FOXP2 has dual functionality, acting to either repress or activate gene expression at occupied promoters. The identified targets suggest roles in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance and represent novel entry points into in vivo pathways that may be disturbed in speech and language disorders. PMID:17999362

Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines

PubMed Central

Cheung, Hannah C.; Hai, Tao; Zhu, Wen; Baggerly, Keith A.; Tsavachidis, Spiridon; Krahe, Ralf

2009-01-01

Polypyrimidine tract-binding protein 1 (PTBP1) is a multi-functional RNA-binding protein that is aberrantly overexpressed in glioma. PTBP1 and its brain-specific homologue polypyrimidine tract-binding protein 2 (PTBP2) regulate neural precursor cell differentiation. However, the overlapping and non-overlapping target transcripts involved in this process are still unclear. To determine why PTBP1 and not PTBP2 would promote glial cell-derived tumours, both PTBP1 and PTBP2 were knocked down in the human glioma cell lines U251 and LN229 to determine the role of these proteins in cell proliferation, migration, and adhesion. Surprisingly, removal of both PTBP1 and PTBP2 slowed cell proliferation, with the double knockdown having no additive effects. Decreased expression of both proteins individually and in combination inhibited cell migration and increased adhesion of cells to fibronectin and vitronectin. A global survey of differential exon expression was performed following PTBP1 knockdown in U251 cells using the Affymetrix Exon Array to identify PTBP1-specific splicing targets that enhance gliomagenesis. In the PTBP1 knockdown, previously determined targets were unaltered in their splicing patterns. A single gene, RTN4 (Nogo) had significantly enhanced inclusion of exon 3 when PTBP1 was removed. Overexpression of the splice isoform containing exon 3 decreased cell proliferation to a similar degree as the removal of PTBP1. These results provide the first evidence that RNA-binding proteins affect the invasive and rapid growth characteristics of glioma cell lines. Its actions on proliferation appear to be mediated, in part, through alternative splicing of RTN4. PMID:19506066

Wheat Chloroplast Targeted sHSP26 Promoter Confers Heat and Abiotic Stress Inducible Expression in Transgenic Arabidopsis Plants

PubMed Central

Khurana, Neetika; Chauhan, Harsh; Khurana, Paramjit

2013-01-01

The small heat shock proteins (sHSPs) have been found to play a critical role in physiological stress conditions in protecting proteins from irreversible aggregation. To characterize the hloroplast targeted sHSP26 promoter in detail, deletion analysis of the promoter is carried out and analysed via transgenics in Arabidopsis. In the present study, complete assessment of the importance of CCAAT-box elements along with Heat shock elements (HSEs) in the promoter of sHSP26 was performed. Moreover, the importance of 5′ untranslated region (UTR) has also been established in the promoter via Arabidopsis transgenics. An intense GUS expression was observed after heat stress in the transgenics harbouring a full-length promoter, confirming the heat-stress inducibility of the promoter. Transgenic plants without UTR showed reduced GUS expression when compared to transgenic plants with UTR as was confirmed at the RNA and protein levels by qRT-PCR and GUS histochemical assays, thus suggesting the possible involvement of some regulatory elements present in the UTR in heat-stress inducibility of the promoter. Promoter activity was also checked under different abiotic stresses and revealed differential expression in different deletion constructs. Promoter analysis based on histochemical assay, real-time qPCR and fluorimetric analysis revealed that HSEs alone could not transcribe GUS gene significantly in sHSP26 promoter and CCAAT box elements contribute synergistically to the transcription. Our results also provide insight into the importance of 5`UTR of sHsp26 promoter thus emphasizing the probable role of imperfect CCAAT-box element or some novel cis-element with respect to heat stress. PMID:23349883

Characteristics and self-rated health of overlap syndrome.

PubMed

Chung, Jung Wha; Kong, Kyoung Ae; Lee, Jin Hwa; Lee, Seok Jeong; Ryu, Yon Ju; Chang, Jung Hyun

2014-01-01

Overlap syndrome shares features of both asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate characteristics of overlap syndrome and their effect on self-rated health (SRH). We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey of 2007-2009. Subjects with acceptable spirometry and available wheezing history were included. Subjects were classified into four groups based on forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) results and the presence or absence of self-reported wheezing for the previous 12 months: 1) COPD group, defined as having FEV1/FVC <0.7 without self-reported wheezing history; 2) asthma group, defined as having self-reported wheezing history without FEV1/FVC <0.7; 3) overlap syndrome group, having both FEV1/FVC <0.7 and wheezing history; and 4) non-obstructive disease (NOD) group, having neither FEV1/FVC <0.7 nor self-reported wheezing. SRH was categorized as better or lower based on responses to a questionnaire. From a total 9,104 subjects, 700 were assigned to the COPD group, 560 to the asthma group, 210 to the overlap syndrome group, and 7,634 to the NOD group. Compared to the other groups, subjects in the overlap syndrome group were more likely to have low lung function, a high proportion of smokers, low socioeconomic status, short education duration, lower SRH, and past diagnosis of pulmonary tuberculosis or bronchiectasis. Multiple logistic regression analysis revealed that both overlap syndrome and asthma groups were independently associated with lower SRH after adjustment for age, sex, socioeconomic status, education level, smoking status, comorbidities, and lung function. Female, old age, low education level, low economic status, smoker and other comorbidities were also associated with lower SRH. Overlap syndrome was accompanied by high morbidity and was associated with lower SRH, which needs more appropriate care.

An Exposition of Fischer's Model of Overlapping Contracts.

ERIC Educational Resources Information Center

Fields, T. Windsor; Hart, William R.

1992-01-01

Suggests how the classic model of overlapping contracts can be incorporated into the contract wage model of aggregate supply. Illustrates dynamics of macroeconomic adjustment following a shock to aggregate demand. Concludes that overlapping contracts do not prolong the adjustment process; rather, the longest remaining contract determines the time…

Word and face processing engage overlapping distributed networks: Evidence from RSVP and EEG investigations.

PubMed

Robinson, Amanda K; Plaut, David C; Behrmann, Marlene

2017-07-01

Words and faces have vastly different visual properties, but increasing evidence suggests that word and face processing engage overlapping distributed networks. For instance, fMRI studies have shown overlapping activity for face and word processing in the fusiform gyrus despite well-characterized lateralization of these objects to the left and right hemispheres, respectively. To investigate whether face and word perception influences perception of the other stimulus class and elucidate the mechanisms underlying such interactions, we presented images using rapid serial visual presentations. Across 3 experiments, participants discriminated 2 face, word, and glasses targets (T1 and T2) embedded in a stream of images. As expected, T2 discrimination was impaired when it followed T1 by 200 to 300 ms relative to longer intertarget lags, the so-called attentional blink. Interestingly, T2 discrimination accuracy was significantly reduced at short intertarget lags when a face was followed by a word (face-word) compared with glasses-word and word-word combinations, indicating that face processing interfered with word perception. The reverse effect was not observed; that is, word-face performance was no different than the other object combinations. EEG results indicated the left N170 to T1 was correlated with the word decrement for face-word trials, but not for other object combinations. Taken together, the results suggest face processing interferes with word processing, providing evidence for overlapping neural mechanisms of these 2 object types. Furthermore, asymmetrical face-word interference points to greater overlap of face and word representations in the left than the right hemisphere. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Analysis of Surface Roughness at Overlapping Laser Shock Peening

NASA Astrophysics Data System (ADS)

Dai, F. Z.; Zhang, Z. D.; Zhou, J. Z.; Lu, J. Z.; Zhang, Y. K.

2016-02-01

The overlapping effects on surface roughness are studied when samples are treated by laser shock peening (LSP). Surface roughness of overlapped circular laser spot is calculated by ISO 25178 height parameters. The usually used overlapping styles namely isosceles-right-triangle-style (AAP) and equilateral-triangle-style (AAA) are carefully investigated when the overlapping degree in x-axis (ηx) is below 50%. Surface roughness of isosceles-right-triangle-style attains its minimum value at ηx of 29.3%, and attains its maximum value at ηx of 43.6%. Surface roughness of equilateral-triangle-style attains its minimum value at ηx of 42.3%, and attains its maximum value at ηx of 32%. Experimental results are well consistent with theoretical analysis.

Long non-coding RNA CASC15 promotes tongue squamous carcinoma progression through targeting miR-33a-5p.

PubMed

Zuo, Zhibin; Ma, Long; Gong, Zuode; Xue, Lande; Wang, Qibao

2018-05-26

Long non-coding RNAs (lncRNAs) have gained a lot of attention because they participate in several human disorders, including tumors. This study determined the role of LncRNA CASC15 (cancer susceptibility candidate 15) in the development of tongue squamous cell carcinoma (TSCC). Here, we identified that CASC15 expression was upregulated in TSCC samples and cell lines. We showed that overexpression of CASC15 promoted cell proliferation, cycle, and migration in TSCC. In addition, we revealed that miR-33a-5p expression was downregulated in TSCC tissues and cell lines. Moreover, we showed that the expression of CASC15 was negatively related with miR-33a-5p expression in TSCC tissues. Ectopic expression of miR-33a-5p suppressed cell proliferation, cycle, and migration in TSCC. Elevated expression of CASC15 suppressed miR-33a-5p expression and promoted ZEB1 expression in SCC4 cell. Ectopic expression of CASC15 promoted TSCC cell proliferation, cycle, and migration through targeting miR-33a-5p. These results suggested that lncRNA CASC15 and miR-33a-5p might be exploited as new markers of TSCC and were potential treatment targets for TSCC patients.

Circular RNA GLI2 promotes osteosarcoma cell proliferation, migration, and invasion by targeting miR-125b-5p.

PubMed

Li, Ji-Feng; Song, Yu-Ze

2017-07-01

Circular RNAs are novel identified type of endogenous non-coding RNAs, which exert vital functions in human and animals. However, the in-depth role of circular RNAs in the progression of tumorigenesis, especially osteosarcoma, is still undefined. Our preliminary study had found that cir-GLI2 was significantly upregulated in osteosarcoma tissues compared to adjacent non-tumor tissue. Moreover, cir-GLI2 silencing could effectively suppress the proliferation, migration, and invasion capacity of osteosarcoma cells, indicating the tumor-promoting role. Besides, bioinformatics analysis and luciferase reporter assay predicted the direct binding to miR-125b-5p, which has been reported to function as a tumor suppressor in osteosarcoma. Furthermore, functional experiments validated that cir-GLI2 exerted the tumor-promoting effects on osteosarcoma cells via negatively targeting miR-125b-5p. In conclusion, our study demonstrated that cir-GLI2 acts as an oncogenic circular RNA in osteosarcoma genesis, providing a novel diagnostic and therapeutic target for osteosarcoma.

Chemical Structural Novelty: On-Targets and Off-Targets

PubMed Central

Yera, Emmanuel R.; Cleves, Ann. E.; Jain, Ajay N.

2011-01-01

Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation. PMID:21916467

Extracting protein dynamics information from overlapped NMR signals using relaxation dispersion difference NMR spectroscopy.

PubMed

Konuma, Tsuyoshi; Harada, Erisa; Sugase, Kenji

2015-12-01

Protein dynamics plays important roles in many biological events, such as ligand binding and enzyme reactions. NMR is mostly used for investigating such protein dynamics in a site-specific manner. Recently, NMR has been actively applied to large proteins and intrinsically disordered proteins, which are attractive research targets. However, signal overlap, which is often observed for such proteins, hampers accurate analysis of NMR data. In this study, we have developed a new methodology called relaxation dispersion difference that can extract conformational exchange parameters from overlapped NMR signals measured using relaxation dispersion spectroscopy. In relaxation dispersion measurements, the signal intensities of fluctuating residues vary according to the Carr-Purcell-Meiboon-Gill pulsing interval, whereas those of non-fluctuating residues are constant. Therefore, subtraction of each relaxation dispersion spectrum from that with the highest signal intensities, measured at the shortest pulsing interval, leaves only the signals of the fluctuating residues. This is the principle of the relaxation dispersion difference method. This new method enabled us to extract exchange parameters from overlapped signals of heme oxygenase-1, which is a relatively large protein. The results indicate that the structural flexibility of a kink in the heme-binding site is important for efficient heme binding. Relaxation dispersion difference requires neither selectively labeled samples nor modification of pulse programs; thus it will have wide applications in protein dynamics analysis.

Plant targets for Pseudomonas syringae type III effectors: virulence targets or guarded decoys?

PubMed

Block, Anna; Alfano, James R

2011-02-01

The phytopathogenic bacterium Pseudomonas syringae can suppress both pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) by the injection of type III effector (T3E) proteins into host cells. T3Es achieve immune suppression using a variety of strategies including interference with immune receptor signaling, blocking RNA pathways and vesicle trafficking, and altering organelle function. T3Es can be recognized indirectly by resistance proteins monitoring specific T3E targets resulting in ETI. It is presently unclear whether the monitored targets represent bona fide virulence targets or guarded decoys. Extensive overlap between PTI and ETI signaling suggests that T3Es may suppress both pathways through common targets and by possessing multiple activities. Copyright © 2010 Elsevier Ltd. All rights reserved.

Reduced OSM for Long Duration Targets: Individuation or Items Loaded into VSTM?

ERIC Educational Resources Information Center

Guest, Duncan; Gellatly, Angus; Pilling, Michael

2012-01-01

Typical studies of object substitution masking (OSM) employ a briefly presented search array. The target item is indicated by a cue/mask that surrounds but does not overlap the target and, compared to a common offset control condition, report of the target is reduced when the mask remains present after target offset. Given how little observers are…

Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.

PubMed

Su, Zhao-Zhong; Sarkar, Devanand; Emdad, Luni; Duigou, Gregory J; Young, Charles S H; Ware, Joy; Randolph, Aaron; Valerie, Kristoffer; Fisher, Paul B

2005-01-25

One impediment to effective cancer-specific gene therapy is the rarity of regulatory sequences targeting gene expression selectively in tumor cells. Although many tissue-specific promoters are recognized, few cancer-selective gene promoters are available. Progression-elevated gene-3 (PEG-3) is a rodent gene identified by subtraction hybridization that displays elevated expression as a function of transformation by diversely acting oncogenes, DNA damage, and cancer cell progression. The promoter of PEG-3, PEG-Prom, displays robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Whereas GFP expression, when under the control of a CMV promoter, is detected in both normal and cancer cells, when GFP is expressed under the control of the PEG-Prom, cancer-selective expression is evident. Mutational analysis identifies the AP-1 and PEA-3 transcription factors as primary mediators of selective, cancer-specific expression of the PEG-Prom. Synthesis of apoptosis-inducing genes, under the control of the CMV promoter, inhibits the growth of both normal and cancer cells, whereas PEG-Prom-mediated expression of these genes kills only cancer cells and spares normal cells. The efficacy of the PEG-Prom as part of a cancer gene therapeutic regimen is further documented by in vivo experiments in which PEG-Prom-controlled expression of an apoptosis-inducing gene completely inhibited prostate cancer xenograft growth in nude mice. These compelling observations indicate that the PEG-Prom, with its cancer-specific expression, provides a means of selectively delivering genes to cancer cells, thereby providing a crucial component in developing effective cancer gene therapies.

Phytophthora effector targets a novel component of small RNA pathway in plants to promote infection.

PubMed

Qiao, Yongli; Shi, Jinxia; Zhai, Yi; Hou, Yingnan; Ma, Wenbo

2015-05-05

A broad range of parasites rely on the functions of effector proteins to subvert host immune response and facilitate disease development. The notorious Phytophthora pathogens evolved effectors with RNA silencing suppression activity to promote infection in plant hosts. Here we report that the Phytophthora Suppressor of RNA Silencing 1 (PSR1) can bind to an evolutionarily conserved nuclear protein containing the aspartate-glutamate-alanine-histidine-box RNA helicase domain in plants. This protein, designated PSR1-Interacting Protein 1 (PINP1), regulates the accumulation of both microRNAs and endogenous small interfering RNAs in Arabidopsis. A null mutation of PINP1 causes embryonic lethality, and silencing of PINP1 leads to developmental defects and hypersusceptibility to Phytophthora infection. These phenotypes are reminiscent of transgenic plants expressing PSR1, supporting PINP1 as a direct virulence target of PSR1. We further demonstrate that the localization of the Dicer-like 1 protein complex is impaired in the nucleus of PINP1-silenced or PSR1-expressing cells, indicating that PINP1 may facilitate small RNA processing by affecting the assembly of dicing complexes. A similar function of PINP1 homologous genes in development and immunity was also observed in Nicotiana benthamiana. These findings highlight PINP1 as a previously unidentified component of RNA silencing that regulates distinct classes of small RNAs in plants. Importantly, Phytophthora has evolved effectors to target PINP1 in order to promote infection.

NF-Y Binding Site Architecture Defines a C-Fos Targeted Promoter Class

PubMed Central

Haubrock, Martin; Hartmann, Fabian; Wingender, Edgar

2016-01-01

ChIP-seq experiments detect the chromatin occupancy of known transcription factors in a genome-wide fashion. The comparisons of several species-specific ChIP-seq libraries done for different transcription factors have revealed a complex combinatorial and context-specific co-localization behavior for the identified binding regions. In this study we have investigated human derived ChIP-seq data to identify common cis-regulatory principles for the human transcription factor c-Fos. We found that in four different cell lines, c-Fos targeted proximal and distal genomic intervals show prevalences for either AP-1 motifs or CCAAT boxes as known binding motifs for the transcription factor NF-Y, and thereby act in a mutually exclusive manner. For proximal regions of co-localized c-Fos and NF-YB binding, we gathered evidence that a characteristic configuration of repeating CCAAT motifs may be responsible for attracting c-Fos, probably provided by a nearby AP-1 bound enhancer. Our results suggest a novel regulatory function of NF-Y in gene-proximal regions. Specific CCAAT dimer repeats bound by the transcription factor NF-Y define this novel cis-regulatory module. Based on this behavior we propose a new enhancer promoter interaction model based on AP-1 motif defined enhancers which interact with CCAAT-box characterized promoter regions. PMID:27517874

Chironomidae larvae (Diptera) of Neotropical floodplain: overlap niche in different habitats.

PubMed

Butakka, C M M; Ragonha, F H; Takeda, A M

2014-05-01

The niche overlap between trophic groups of Chironomidae larvae in different habitats was observed between trophic groups and between different environments in Neotropical floodplain. For the evaluation we used the index of niche overlap (CXY) and analysis of trophic networks, both from the types and amount of food items identified in the larval alimentary canal. In all environments, the larvae fed on mainly organic matter such as plants fragments and algae, but there were many omnivore larvae. Species that have high values of food items occurred in diverse environments as generalists with great overlap niche and those with a low amount of food items with less overlap niche were classified as specialists. The largest number of trophic niche overlap was observed among collector-gatherers in connected floodplain lakes. The lower values of index niche overlap were predators. The similarity in the diet of different taxa in the same niche does not necessarily imply competition between them, but coexistence when the food resource is not scarce in the environment even in partially overlapping niches.

Research on Some Bus Transport Networks with Random Overlapping Clique Structure

NASA Astrophysics Data System (ADS)

Yang, Xu-Hua; Wang, Bo; Wang, Wan-Liang; Sun, You-Xian

2008-11-01

On the basis of investigating the statistical data of bus transport networks of three big cities in China, we propose that each bus route is a clique (maximal complete subgraph) and a bus transport network (BTN) consists of a lot of cliques, which intensively connect and overlap with each other. We study the network properties, which include the degree distribution, multiple edges' overlapping time distribution, distribution of the overlap size between any two overlapping cliques, distribution of the number of cliques that a node belongs to. Naturally, the cliques also constitute a network, with the overlapping nodes being their multiple links. We also research its network properties such as degree distribution, clustering, average path length, and so on. We propose that a BTN has the properties of random clique increment and random overlapping clique, at the same time, a BTN is a small-world network with highly clique-clustered and highly clique-overlapped. Finally, we introduce a BTN evolution model, whose simulation results agree well with the statistical laws that emerge in real BTNs.

SU-F-I-57: Evaluate and Optimize PET Acquisition Overlap in 18F-FDG Oncology Wholebody PET/CT: Can We Scan PET Faster?

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

Zhang, J; Natwa, M; Hall, NC

Purpose: The longer patient has to remain on the table during PET imaging, the higher the likelihood of motion artifacts due to patient discomfort. This study was to investigate and optimize PET acquisition overlap in 18F-FDG oncology wholebody PET/CT to speed up PET acquisition and improve patient comfort. Methods: Wholebody 18F-FDG PET/CT of phantoms, 8 pre-clinical patients (beagles) and 5 clinical oncology patients were performed in 90s/bed on a time-of-flight Gemini TF 64 system. Imaging of phantoms and beagles was acquired with reduced PET overlaps (40%, 33%, 27%, 20%, 13% and no overlap) in addition to the system default (53%).more » In human studies, 1 or 2 reduced overlaps from the listed options were used to acquire PET/CT sweeps right after the default standard of care imaging. Image quality was blindly reviewed using visual scoring criteria and quantitative SUV assessment. NEMA PET sensitivity was performed under different overlaps. Results: All PET exams demonstrated no significant impact on the visual grades for overlaps >20%. Blinded reviews assigned the best visual scores to PET using overlaps 53%–27%. Reducing overlap to 27% for oncology patients (12-bed) saved an average of ∼40% acquisition time (11min) compared to using the default overlap (18min). No significant SUV variances were found when reducing overlap to half of default for cerebellum, lung, heart, aorta, liver, fat, muscle, bone marrow, thighs and target lesions (p>0.05), except expected variability in urinary system. Conclusion: This study demonstrated by combined phantom, pre-clinical and clinical PET/CT scans that PET acquisition overlap in axial of today’s systems can be reduced and optimized. It showed that a reduction of PET acquisition overlap to 27% (half of system default) can be implemented to reduce table time by ∼40% to improve patient comfort and minimize potential motion artifacts, without prominently degrading image quality or compromising PET quantification.« less

Overlap syndrome of COPD and OSA in Koreans.

PubMed

Choi, Kyung-Mee; Thomas, Robert J; Kim, Jinkwan; Lee, Seung Ku; Yoon, Dae Wui; Shin, Chol

2017-07-01

Overlap syndrome of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) leads to increased morbidity and mortality. There have been no reports available on the overlap syndrome for Koreans. Our primary aim was to identify prevalence and predictors of the overlap syndrome in Koreans.This is a cross-sectional study with a community-based sample of 1298 participants (mean age, 59.7 ± 6.7) from the cohort of Korean Genomic and Epidemiologic Study during 2013 to 2014. OSA and COPD were assessed by apnea-hypopnea index (AHI) and the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC < 70%), respectively, based on polysomnography and spirometry measurements. Using logistic regression with adjustment for the confounders identified by univariate analysis, odds ratio (OR) was estimated with 95% confidence interval (CI) of COPD among those with OSA.The prevalence rate of OSA was 45.8%, of which 32.8% were moderate-to-severe (AHI ≥ 15); 10.8% of those having OSA also had COPD, that is, the overlap syndrome. The prevalence of COPD remained the same as 10.8% regardless of the presence of OSA. The mean ratio of FEV1/FVC for those with COPD was 0.77, regardless of OSA. The OR increased for age (OR, 1.1; 95% CI, 1.0-1.1) and smokers (OR, 3.6; 95% CI, 2.0-6.4), but decreased for body mass index (BMI) (OR, 0.84; 95% CI, 0.8-0.9) and overweight state (OR, 0.4; 95% CI, 0.2-0.7). Risk factors of the overlap syndrome differed by OSA severity, that is, BMI in those with moderate-to-severe OSA, whereas sex (OR, 4.7; 95% CI, 2.1-10.6) and age (OR, 1.1; 95% CI, 1.0-1.1) in those with mild OSA.In a population study from Korea, 10.8% of OSA patients had an overlap syndrome with COPD. Although BMI is a well-known risk factor of OSA, it is likely that being overweight may be protective for moderate-to-severe OSA patients from the risk of COPD (i.e., overlap syndrome).

miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis.

PubMed

Sun, Xiaojuan; Charbonneau, Cherie; Wei, Lei; Chen, Qian; Terek, Richard M

2015-09-01

Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis; however, its role in chondrosarcoma is undetermined. miR-181a is overexpressed in high-grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine whether miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is a regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis; however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the antiangiogenic and antimetastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. Targeting miR-181a can inhibit tumor angiogenesis, growth, and metastasis, thus suggesting the possibility of antagomir-based therapy in chondrosarcoma. ©2015 American Association for Cancer Research.

Percolation in multiplex networks with overlap.

PubMed

Cellai, Davide; López, Eduardo; Zhou, Jie; Gleeson, James P; Bianconi, Ginestra

2013-11-01

From transportation networks to complex infrastructures, and to social and communication networks, a large variety of systems can be described in terms of multiplexes formed by a set of nodes interacting through different networks (layers). Multiplexes may display an increased fragility with respect to the single layers that constitute them. However, so far the overlap of the links in different layers has been mostly neglected, despite the fact that it is an ubiquitous phenomenon in most multiplexes. Here, we show that the overlap among layers can improve the robustness of interdependent multiplex systems and change the critical behavior of the percolation phase transition in a complex way.

Compression of Flow Can Reveal Overlapping-Module Organization in Networks

NASA Astrophysics Data System (ADS)

Viamontes Esquivel, Alcides; Rosvall, Martin

2011-10-01

To better understand the organization of overlapping modules in large networks with respect to flow, we introduce the map equation for overlapping modules. In this information-theoretic framework, we use the correspondence between compression and regularity detection. The generalized map equation measures how well we can compress a description of flow in the network when we partition it into modules with possible overlaps. When we minimize the generalized map equation over overlapping network partitions, we detect modules that capture flow and determine which nodes at the boundaries between modules should be classified in multiple modules and to what degree. With a novel greedy-search algorithm, we find that some networks, for example, the neural network of the nematode Caenorhabditis elegans, are best described by modules dominated by hard boundaries, but that others, for example, the sparse European-roads network, have an organization of highly overlapping modules.

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

Glucose Induces Protein Targeting to Glycogen in Hepatocytes by Fructose 2,6-Bisphosphate-Mediated Recruitment of MondoA to the Promoter

PubMed Central

Petrie, John L.; Al-Oanzi, Ziad H.; Arden, Catherine; Tudhope, Susan J.; Mann, Jelena; Kieswich, Julius; Yaqoob, Muhammad M.; Towle, Howard C.

2013-01-01

In the liver, a high glucose concentration activates transcription of genes encoding glucose 6-phosphatase and enzymes for glycolysis and lipogenesis by elevation in phosphorylated intermediates and recruitment of the transcription factor ChREBP (carbohydrate response element binding protein) and its partner, Mlx, to gene promoters. A proposed function for this mechanism is intracellular phosphate homeostasis. In extrahepatic tissues, MondoA, the paralog of ChREBP, partners with Mlx in transcriptional induction by glucose. We tested for glucose induction of regulatory proteins of the glycogenic pathway in hepatocytes and identified the glycogen-targeting proteins, GL and PTG (protein targeting to glycogen), as being encoded by Mlx-dependent glucose-inducible genes. PTG induction by glucose was MondoA dependent but ChREBP independent and was enhanced by forced elevation of fructose 2,6-bisphosphate and by additional xylitol-derived metabolites. It was counteracted by selective depletion of fructose 2,6-bisphosphate with a bisphosphatase-active kinase-deficient variant of phosphofructokinase 2/fructosebisphosphatase 2, which prevented translocation of MondoA to the nucleus and recruitment to the PTG promoter. We identify a novel role for MondoA in the liver and demonstrate that elevated fructose 2,6-bisphosphate is essential for recruitment of MondoA to the PTG promoter. Phosphometabolite activation of MondoA and ChREBP and their recruitment to target genes is consistent with a mechanism for gene regulation to maintain intracellular phosphate homeostasis. PMID:23207906

miR-300 promotes proliferation and EMT-mediated colorectal cancer migration and invasion by targeting p53.

PubMed

Wang, Lin; Yu, Peiwu

2016-12-01

p53 mutations in tumors can induce the loss of wild-type tumor-suppressing p53 function, which results in the increase in proliferation, migration and invasion ability in cancer cells. Studies have shown that the expression of p53 is regulated by several microRNAs (miRNAs). In the present study, we found that miR-300 and p53 were significantly increased in colorectal cancer (CRC) tissues when compared with levels noted in adjacent colorectal tissues. Both miR-300 and p53 were significantly correlated with lymphatic metastasis and TNM stage. Both miR-300 and p53 promoted CRC cell (SW480 and HT29) proliferation, migration, and invasion, respectively, in vitro. In addition, we found that miR-300 is a direct positive regulator of p53 through binding to the binding site in the 3'UTR of the p53 gene in human CRC cells. Moreover, both miR-300 and p53 induced CRC cell epithelial‑mesenchymal transition (EMT) respectively. Taken together, we demonstrated that miR-300 promoted proliferation and EMT-mediated CRC migration and invasion by targeting p53. These findings provide a new theoretical basis and potential therapeutic targets, and thus lays the foundation for exploring the pathogenesis of CRC.

Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy.

PubMed

Danda, Ravikanth; Krishnan, Gopinath; Ganapathy, Kalaivani; Krishnan, Uma Maheswari; Vikas, Khetan; Elchuri, Sailaja; Chatterjee, Nivedita; Krishnakumar, Subramanian

2013-01-01

In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus-thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3'UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM (+ve)/let-7b(down-regulated)), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM (-ve)/let-7b(up-regulated)), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM (+ve)/let-7b(up-regulated)) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells.

Calculation of the overlap factor for scanning LiDAR based on the tridimensional ray-tracing method.

PubMed

Chen, Ruiqiang; Jiang, Yuesong; Wen, Luhong; Wen, Donghai

2017-06-01

The overlap factor is used to evaluate the LiDAR light collection ability. Ranging LiDAR is mainly determined by the optical configuration. However, scanning LiDAR, equipped with a scanning mechanism to acquire a 3D coordinate points cloud for a specified target, is essential in considering the scanning effect at the same time. Otherwise, scanning LiDAR will reduce the light collection ability and even cannot receive any echo. From this point of view, we propose a scanning LiDAR overlap factor calculation method based on the tridimensional ray-tracing method, which can be applied to scanning LiDAR with any special laser intensity distribution, any type of telescope (reflector, refractor, or mixed), and any shape obstruction (i.e., the reflector of a coaxial optical system). A case study for our LiDAR with a scanning mirror is carried out, and a MATLAB program is written to analyze the laser emission and reception process. Sensitivity analysis is carried out as a function of scanning mirror rotation speed and detector position, and the results guide how to optimize the overlap factor for our LiDAR. The results of this research will have a guiding significance in scanning LiDAR design and assembly.

Sample-based engine noise synthesis using an enhanced pitch-synchronous overlap-and-add method.

PubMed

Jagla, Jan; Maillard, Julien; Martin, Nadine

2012-11-01

An algorithm for the real time synthesis of internal combustion engine noise is presented. Through the analysis of a recorded engine noise signal of continuously varying engine speed, a dataset of sound samples is extracted allowing the real time synthesis of the noise induced by arbitrary evolutions of engine speed. The sound samples are extracted from a recording spanning the entire engine speed range. Each sample is delimitated such as to contain the sound emitted during one cycle of the engine plus the necessary overlap to ensure smooth transitions during the synthesis. The proposed approach, an extension of the PSOLA method introduced for speech processing, takes advantage of the specific periodicity of engine noise signals to locate the extraction instants of the sound samples. During the synthesis stage, the sound samples corresponding to the target engine speed evolution are concatenated with an overlap and add algorithm. It is shown that this method produces high quality audio restitution with a low computational load. It is therefore well suited for real time applications.

On the optimization of mitred overlaps in transformer cores

NASA Astrophysics Data System (ADS)

Bengtsson, C.; Pfützner, H.; Schönhuber, P.

1989-05-01

The influence of the overlap length a on the no-load loss P and excitation power S of single phase model cores was measured for different sheet widths w. It was found that the optimum overlap length a0 shows a non-linear increase with w. The appearance of such minima, however, was irregular, and in many cases, the lowest no-load loss was obtained at the smallest investigated overlap length, an effect which may result from the assembling conditions. Minima in P will appear as a consequence of a balance between loss contributions resulting from normal flux in the overlap region, from increased longitudinal flux due to flux transfer between sheets, and from the triangular cut-outs at the inner corners of the cores. However, the dependence of a0 on w is attributed only to the triangular cut-outs. The flatness of the minima in combination with their irregular appearance, makes the effect difficult to be used in practice. It is concluded that in power transformers, the overlap length should be chosen as small as possible within the limitations set by stability requirements of the core. This is especially important in cores with a high operating flux density.

Communication Avoiding and Overlapping for Numerical Linear Algebra

DTIC Science & Technology

2012-05-08

future exascale systems, communication cost must be avoided or overlapped. Communication-avoiding 2.5D algorithms improve scalability by reducing...linear algebra problems to future exascale systems, communication cost must be avoided or overlapped. Communication-avoiding 2.5D algorithms improve...will continue to grow relative to the cost of computation. With exascale computing as the long-term goal, the community needs to develop techniques

A genetically encoded and gate for cell-targeted metabolic labeling of proteins.

PubMed

Mahdavi, Alborz; Segall-Shapiro, Thomas H; Kou, Songzi; Jindal, Granton A; Hoff, Kevin G; Liu, Shirley; Chitsaz, Mohsen; Ismagilov, Rustem F; Silberg, Jonathan J; Tirrell, David A

2013-02-27

We describe a genetic AND gate for cell-targeted metabolic labeling and proteomic analysis in complex cellular systems. The centerpiece of the AND gate is a bisected methionyl-tRNA synthetase (MetRS) that charges the Met surrogate azidonorleucine (Anl) to tRNA(Met). Cellular protein labeling occurs only upon activation of two different promoters that drive expression of the N- and C-terminal fragments of the bisected MetRS. Anl-labeled proteins can be tagged with fluorescent dyes or affinity reagents via either copper-catalyzed or strain-promoted azide-alkyne cycloaddition. Protein labeling is apparent within 5 min after addition of Anl to bacterial cells in which the AND gate has been activated. This method allows spatial and temporal control of proteomic labeling and identification of proteins made in specific cellular subpopulations. The approach is demonstrated by selective labeling of proteins in bacterial cells immobilized in the center of a laminar-flow microfluidic channel, where they are exposed to overlapping, opposed gradients of inducers of the N- and C-terminal MetRS fragments. The observed labeling profile is predicted accurately from the strengths of the individual input signals.

A Genetically Encoded AND Gate for Cell-Targeted Metabolic Labeling of Proteins

PubMed Central

Mahdavi, Alborz; Segall-Shapiro, Thomas H.; Kou, Songzi; Jindal, Granton A.; Hoff, Kevin G.; Liu, Shirley; Chitsaz, Mohsen; Ismagilov, Rustem F.; Silberg, Jonathan J.; Tirrell, David A.

2013-01-01

We describe a genetic AND gate for cell-targeted metabolic labeling and proteomic analysis in complex cellular systems. The centerpiece of the AND gate is a bisected methionyl-tRNA synthetase (MetRS) that charges the Met surrogate azidonorleucine (Anl) to tRNAMet. Cellular protein labeling occurs only upon activation of two different promoters that drive expression of the N- and C-terminal fragments of the bisected MetRS. Anl-labeled proteins can be tagged with fluorescent dyes or affinity reagents via either copper-catalyzed or strain-promoted azide-alkyne cycloaddition. Protein labeling is apparent within five minutes after addition of Anl to bacterial cells in which the AND gate has been activated. This method allows spatial and temporal control of proteomic labeling and identification of proteins made in specific cellular subpopulations. The approach is demonstrated by selective labeling of proteins in bacterial cells immobilized in the center of a laminar-flow microfluidic channel, where they are exposed to overlapping, opposed gradients of inducers of the N- and C-terminal MetRS fragments. The observed labeling profile is predicted accurately from the strengths of the individual input signals. PMID:23406315

Spatial analysis of ecosystem service relationships to improve targeting of payments for hydrological services

PubMed Central

Manson, Robert H.; Ricketts, Taylor H.; Geissert, Daniel

2018-01-01

Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México’s National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003–2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico’s PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and

Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions

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

MacArthur, Stewart; Li, Xiao-Yong; Li, Jingyi

2009-05-15

BACKGROUND: We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional. RESULTS: Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of functionmore » and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors. CONCLUSIONS: It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo, with specificity achieved by modulating the amount, rather than the identity, of bound factor.« less

AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription.

PubMed

Takai, Hideki; Araki, Shouta; Mezawa, Masaru; Kim, Dong-Soon; Li, Xinyue; Yang, Li; Li, Zhengyang; Wang, Zhitao; Nakayama, Youhei; Ogata, Yorimasa

2008-02-29

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. We previously reported that fibroblast growth factor 2 (FGF2) regulates BSP gene transcription via FGF2 response element (FRE) in the proximal promoter of rat BSP gene. We here report that activator protein 1 (AP1) binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2. Using the osteoblastic cell line ROS17/2.8, we determined that BSP mRNA levels increased by 10 ng/ml FGF2 at 6 and 12 h. Runx2 protein levels increased by FGF2 (10 ng/ml) at 3 h. Treatment of ROS17/2.8 cells with FGF2 (10 ng/ml, 12 h) increased luciferase activities of constructs including -116 to +60 and -938 to +60 of the rat BSP gene promoter. Effects of FGF2 abrogated in constructs included 2 bp mutations in the FRE and AP1/GRE elements. Luciferase activities induced by FGF2 were blocked by tyrosine kinase inhibitor herbimycin A, src-tyrosine kinase inhibitor PP1 and MAP kinase kinase inhibitor U0126. Gel shift analyses showed that FGF2 increased binding of FRE and AP1/GRE elements. Notably, the AP1/GRE-protein complexes were supershifted by Smad1 and c-Fos antibodies, c-Jun and Dlx5 antibodies disrupted the complexes formation, on the other hand AP1/GRE-protein complexes did not change by Runx2 antibody. These studies demonstrate that FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter.

Some new results on the central overlap problem in astrometry

NASA Astrophysics Data System (ADS)

Rapaport, M.

1998-07-01

The central overlap problem in astrometry has been revisited in the recent last years by Eichhorn (1988) who explicitly inverted the matrix of a constrained least squares problem. In this paper, the general explicit solution of the unconstrained central overlap problem is given. We also give the explicit solution for an other set of constraints; this result is a confirmation of a conjecture expressed by Eichhorn (1988). We also consider the use of iterative methods to solve the central overlap problem. A surprising result is obtained when the classical Gauss Seidel method is used; the iterations converge immediately to the general solution of the equations; we explain this property writing the central overlap problem in a new set of variables.

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis.

PubMed

Lee, Seung Joon; Langhans, Sigrid A

2012-01-26

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin.

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

PubMed Central

2012-01-01

Background Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Methods Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. Results We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. Conclusions We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin. PMID:22280307

Defining risk of prescription opioid overdose: pharmacy shopping and overlapping prescriptions among long-term opioid users in medicaid.

PubMed

Yang, Zhuo; Wilsey, Barth; Bohm, Michele; Weyrich, Meghan; Roy, Kakoli; Ritley, Dominique; Jones, Christopher; Melnikow, Joy

2015-05-01

Use of multiple pharmacies concurrently (pharmacy shopping) and overlapping prescriptions may be indicators of potential misuse or abuse of prescription opioid medications. To evaluate strategies for identifying patients at high risk, we first compared different definitions of pharmacy shopping and then added the indicator of overlapping opioid prescriptions. We identified a cohort of 90,010 Medicaid enrollees who used ≥ 3 opioid prescriptions for ≥ 90 days during 2008 to 2010 from a multistate Medicaid claims database. We compared the diagnostic odds ratios for opioid overdose events of 9 pharmacy shopping definitions. Within a 90-day interval, a threshold of 4 pharmacies had the highest diagnostic odds ratio and was used to define pharmacy shopping. The overdose rate was higher in the subgroup with overlapping prescriptions (18.5 per 1,000 person-years [PYs]) than in the subgroup with pharmacy shopping as the sole indicator (10.7 per 1,000 PYs). Among the subgroup with both conditions, the overdose rate was 26.3 per 1,000 PYs, compared with 4.3 per 1,000 PYs for those with neither condition. Overlapping opioid prescriptions and pharmacy shopping measures had adjusted hazard ratios of 3.0 and 1.8, respectively, for opioid overdose. Using these measures will improve accurate identification of patients at highest risk of opioid overdose, the first step in implementing targeted prevention policies. Long-term prescription opioid use may lead to adverse events, including overdose. Both pharmacy shopping and overlapping opioid prescriptions are associated with adverse outcomes. This study demonstrates that using both indicators will better identify those at high risk of overdose. Published by Elsevier Inc.

A High-Resolution Study of Hippocampal and Medial Temporal Lobe Correlates of Spatial Context and Prospective Overlapping Route Memory

PubMed Central

Brown, Thackery I.; Hasselmo, Michael E.; Stern, Chantal E.

2015-01-01

When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high-resolution functional magnetic resonance imaging (hr-fMRI) in humans to test whether the CA3/DG hippocampal subfield and para-hippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr-fMRI scanning, participants navigated virtual mazes that were well-learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre-scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non-overlapping Cue periods. Trial-by-trial Cue period responses in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL

Separation and sequence detection of overlapped fingerprints: experiments and first results

NASA Astrophysics Data System (ADS)

Kärgel, Rainer; Giebel, Sascha; Leich, Marcus; Dittmann, Jana

2011-11-01

Latent fingerprints provide vital information in modern crime scene investigation. On frequently touched surfaces the fingerprints may overlap which poses a major problem for forensic analysis. In order to make such overlapping fingerprints available for analysis, they have to be separated. An additional evaluation of the sequence in which the fingerprints were brought onto the surface can help to reconstruct the progression of events. Advances in both tasks can considerably aid crime investigation agencies and are the subject of this work. Here, a statistical approach, initially devised for the separation of overlapping text patterns by Tonazzini et al.,1 is employed to separate overlapping fingerprints. The method involves a maximum a posteriori estimation of the single fingerprints and the mixing coefficients, computed by an expectation-maximization algorithm. A fingerprint age determination feature based on corrosion is evaluated for sequence estimation. The approaches are evaluated using 30 samples of overlapping latent fingerprints on two different substrates. The fingerprint images are acquired with a non-destructive chromatic white light surface measurement device, each sample containing exactly two fingerprints that overlap in the center of the image. Since forensic investigations rely on manual assessment of acquired fingerprints by forensics experts, a subjective scale ranging from 0 to 8 is used to rate the separation results. Our results indicate that the chosen method can separate overlapped fingerprints which exhibit strong differences in contrast, since results gradually improve with the growing contrast difference of the overlapping fingerprints. Investigating the effects of corrosion leads to a reliable determination of the fingerprints' sequence as the timespan between their leaving increases.

MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2

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

Zhu, Haigang; Hou, Liyue; Liu, Jingjing

MiR-217 is a well-known tumor suppressor, and its down-regulation has been shown in a wide range of solid and leukaemic cancers. However, the biological role of miR-217 in psoriasis pathogenesis, especially in keratinocyte hyperproliferation and differentiation, is not clearly understood. In this study, we found the expression of miR-217 was markedly down-regulated in psoriasis keratinocytes of psoriatic patients. In addition, overexpression of miR-217 inhibited the proliferation and promoted the differentiation of primary human keratinocytes. On the contrary, inhibition of endogenous miR-217 increased cell proliferation and delayed differentiation. Furthermore, Grainyhead-like 2 (GRHL2) was identified as a direct target of miR-217 bymore » luciferase reporter assay. The expression of miR-217 and GRHL2 was inversely correlated in both transfected keratinocytes and in psoriasis lesional skin. Moreover, knocking down GRHL2 expression by siRNA enhanced keratinocyte differentiation. Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. - Highlights: • miR-217 is down-regulated in psoriasis skin lesions. • miR-217 inhibits the proliferation and promotes differentiation of keratinocytes. • GRHL2 is a novel target of miR-217 in keratinocytes. • GRHL2 is up-regulated and inversely correlated with miR-217 in psoriasis skin lesions.« less

Optical filter selection for high confidence discrimination of strongly overlapping infrared chemical spectra.

PubMed

Major, Kevin J; Poutous, Menelaos K; Ewing, Kenneth J; Dunnill, Kevin F; Sanghera, Jasbinder S; Aggarwal, Ishwar D

2015-09-01

Optical filter-based chemical sensing techniques provide a new avenue to develop low-cost infrared sensors. These methods utilize multiple infrared optical filters to selectively measure different response functions for various chemicals, dependent on each chemical's infrared absorption. Rather than identifying distinct spectral features, which can then be used to determine the identity of a target chemical, optical filter-based approaches rely on measuring differences in the ensemble response between a given filter set and specific chemicals of interest. Therefore, the results of such methods are highly dependent on the original optical filter choice, which will dictate the selectivity, sensitivity, and stability of any filter-based sensing method. Recently, a method has been developed that utilizes unique detection vector operations defined by optical multifilter responses, to discriminate between volatile chemical vapors. This method, comparative-discrimination spectral detection (CDSD), is a technique which employs broadband optical filters to selectively discriminate between chemicals with highly overlapping infrared absorption spectra. CDSD has been shown to correctly distinguish between similar chemicals in the carbon-hydrogen stretch region of the infrared absorption spectra from 2800-3100 cm(-1). A key challenge to this approach is how to determine which optical filter sets should be utilized to achieve the greatest discrimination between target chemicals. Previous studies used empirical approaches to select the optical filter set; however this is insufficient to determine the optimum selectivity between strongly overlapping chemical spectra. Here we present a numerical approach to systematically study the effects of filter positioning and bandwidth on a number of three-chemical systems. We describe how both the filter properties, as well as the chemicals in each set, affect the CDSD results and subsequent discrimination. These results demonstrate the

Modeling of chromosome intermingling by partially overlapping uniform random polygons.

PubMed

Blackstone, T; Scharein, R; Borgo, B; Varela, R; Diao, Y; Arsuaga, J

2011-03-01

During the early phase of the cell cycle the eukaryotic genome is organized into chromosome territories. The geometry of the interface between any two chromosomes remains a matter of debate and may have important functional consequences. The Interchromosomal Network model (introduced by Branco and Pombo) proposes that territories intermingle along their periphery. In order to partially quantify this concept we here investigate the probability that two chromosomes form an unsplittable link. We use the uniform random polygon as a crude model for chromosome territories and we model the interchromosomal network as the common spatial region of two overlapping uniform random polygons. This simple model allows us to derive some rigorous mathematical results as well as to perform computer simulations easily. We find that the probability that one uniform random polygon of length n that partially overlaps a fixed polygon is bounded below by 1 − O(1/√n). We use numerical simulations to estimate the dependence of the linking probability of two uniform random polygons (of lengths n and m, respectively) on the amount of overlapping. The degree of overlapping is parametrized by a parameter [Formula: see text] such that [Formula: see text] indicates no overlapping and [Formula: see text] indicates total overlapping. We propose that this dependence relation may be modeled as f (ε, m, n) = [Formula: see text]. Numerical evidence shows that this model works well when [Formula: see text] is relatively large (ε ≥ 0.5). We then use these results to model the data published by Branco and Pombo and observe that for the amount of overlapping observed experimentally the URPs have a non-zero probability of forming an unsplittable link.

Overlapping of duties and technical autonomy among nurses of the Family Health Strategy.

PubMed

Feliciano, Katia Virginia de Oliveira; Kovacs, Maria Helena; Sarinho, Silvia Wanick

2010-06-01

To understand how Estratégia Saúde da Família (Family Health Strategy) nurses experience the overlapping of duties and building of technical autonomy. This was a qualitative study performed with 22 nurses, in the city of Recife, Northeastern Brazil, between August 2005 and November 2006. Based on management evaluation (geographic access; conflicts in the team, between team and district and between team and community; and public violence in the area), four teams were selected in each of the six health districts. Semi-structured interviews were conducted. The main themes in the interview guide were about work expectations and relevance, its organization and process, and feelings towards these practices. The results were interpreted under the perspective of burnout. The nurses' opinion on the excessive number of families, insufficient organizational support and pressures from user demands that had not been met was recurrent. Overlapping of health care and management caused work overload, creating anxiety, impotence, frustration and the feeling of being treated unfairly when tasks were divided among team members. The clinical dimension of practice led to a feeling of insecurity of a technical and ethical nature, in addition to the satisfaction for the power and prestige achieved by the professional category. Specialized medical training represented an obstacle to autonomy and responsibility becoming interdependent. Stress, dissatisfaction, becoming physically and mentally ill, recognition of the relevance of work and importance of one's performance, and low work involvement were reported. In view of the lack of expectation of changes in the short term, the overlapping of low professional satisfaction and work overload causes negative attitudes, indicating the importance of health promotion to increase the possibility of influencing and changing work conditions.

Overlap Spectrum Fiber Bragg Grating Sensor Based on Light Power Demodulation

PubMed Central

Zhang, Hao; Jiang, Junzhen; Liu, Shuang; Chen, Huaixi; Zheng, Xiaoqian; Qiu, Yishen

2018-01-01

Demodulation is a bottleneck for applications involving fiber Bragg gratings (FBGs). An overlap spectrum FBG sensor based on a light power demodulation method is presented in this paper. The demodulation method uses two chirp FBGs (cFBGs) of which the reflection spectra partially overlap each other. The light power variation of the overlap spectrum can be linked to changes in the measurand, and the sensor function can be realized via this relationship. A temperature experiment showed that the relationship between the overlap power spectrum of the FBG sensor and temperature had good linearity and agreed with the theoretical analysis. PMID:29772793

Detection and Evaluation of Pre-Preg Gaps and Overlaps in Glare Laminates

NASA Astrophysics Data System (ADS)

Nardi, Davide; Abouhamzeh, Morteza; Leonard, Rob; Sinke, Jos

2018-03-01

Gaps and overlaps between pre-preg plies represent common flaws in composite materials that can be introduced easily in an automated fibre placement manufacturing process and are potentially detrimental for the mechanical performances of the final laminates. Whereas gaps and overlaps have been addressed for full composite material, the topic has not been extended to a hybrid composite material such as Glare, a member of the family of Fibre Metal Laminates (FMLs). In this paper/research, the manufacturing, the detection, and the optical evaluation of intraply gaps and overlaps in Glare laminates are investigated. As part of an initial assessment study on the effect of gaps and overlaps on Glare, only the most critical lay-up has been considered. The experimental investigation started with the manufacturing of specimens having gaps and overlaps with different widths, followed by a non-destructive ultrasonic-inspection. An optical evaluation of the gaps and overlaps was performed by means of microscope image analysis of the cross sections of the specimens. The results from the non-destructive evaluations show the effectiveness of the ultrasonic detection of gaps and overlaps both in position, shape, width, and severity. The optical inspections confirm the accuracy of the non-destructive evaluation also adding useful insights about the geometrical features due to the presence of gaps and overlaps in the final Glare laminates. All the results justify the need for a further investigation on the effect of gaps and overlaps on the mechanical properties.

A network approach to the comorbidity between posttraumatic stress disorder and major depressive disorder: The role of overlapping symptoms.

PubMed

Afzali, Mohammad H; Sunderland, Matthew; Teesson, Maree; Carragher, Natacha; Mills, Katherine; Slade, Tim

2017-01-15

The role of symptom overlap between major depressive disorder and posttraumatic stress disorder in comorbidity between two disorders is unclear. The current study applied network analysis to map the structure of symptom associations between these disorders. Data comes from a sample of 909 Australian adults with a lifetime history of trauma and depressive symptoms. Data analysis consisted of the construction of two comorbidity networks of PTSD/MDD with and without overlapping symptoms, identification of the bridging symptoms, and computation of the centrality measures. The prominent bridging role of four overlapping symptoms (i.e., sleep problems, irritability, concentration problems, and loss of interest) and five non-overlapping symptoms (i.e., feeling sad, feelings of guilt, psychomotor retardation, foreshortened future, and experiencing flashbacks) is highlighted. The current study uses DSM-IV criteria for PTSD and does not take into consideration significant changes made to PTSD criteria in DSM-5. Moreover, due to cross-sectional nature of the data, network estimates do not provide information on whether a symptom actively triggers other symptoms or whether a symptom mostly is triggered by other symptoms. The results support the role of dysphoria-related symptoms in PTSD/MDD comorbidity. Moreover, Identification of central symptoms and bridge symptoms will provide useful targets for interventions that seek to intervene early in the development of comorbidity. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-E-T-294: Dosimetric Analysis of Planning Phase Using Overlap Volume Histogram for Respiratory Gated Radiotherapy

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

Kang, S; Kim, D; Kim, T

2015-06-15

Purpose: End-of-exhale (EOE) phase is generally preferred for gating window because tumor position is more reproducible. However, other gating windows might be more appropriate for dose distribution perspective. In this pilot study, we proposed to utilize overlap volume histogram (OVH) to search optimized gating window and demonstrated its feasibility. Methods: We acquired 4DCT of 10 phases for 3 lung patients (2 with a target at right middle lobe and 1 at right upper lobe). After structures were defined in every phase, the OVH of each OAR was generated to quantify the three dimensional spatial relationship between the PTV and OARsmore » (bronchus, esophagus, heart and cord etc.) at each phase. OVH tells the overlap volume of an OAR according to outward distance from the PTV. Relative overlap volume at 20 mm outward distance from the PTV (ROV-20) was also defined as a metric for measuring overlap volume and obtained. For dose calculation, 3D CRT plans were made for all phases under the same beam angles and objectives (e.g., 95% of the PTV coverage with at least 100% of the prescription dose of 50 Gy). The gating window phase was ranked according to ROV-20, and the relationship between the OVH and dose distribution at each phase was evaluated by comparing the maximum dose, mean dose, and equivalent uniform dose of OAR. Results: OVHs showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. For 2 out of 3 patients (both with a target at RML), maximum dose, mean dose, and EUD increased as ROV-20 increased. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist and OVH can be a useful tool for determining such phases without performing dose optimization calculations in all phases. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2012-007883) through the National Research

Aspects and the Overlap Function.

ERIC Educational Resources Information Center

Levine, Marilyn M.; Levine, Leonard P.

1984-01-01

Presents system for automatic handling of ordered sets, states based on these sets, and differing points of view regarding Universe of Discourse. Aspects are represented by new logical "overlap" function with examples taken from Ranganathan's horse and carriage parable and several books involving four main concepts (history, geography,…

A Guide to Using STITCHER for Overlapping Assembly PCR Applications.

PubMed

O'Halloran, Damien M

2017-01-01

Overlapping PCR is commonly used in many molecular applications that include stitching PCR fragments together, generating fluorescent transcriptional and translational fusions, inserting mutations, making deletions, and PCR cloning. Overlapping PCR is also used for genotyping and in detection experiments using techniques such as loop-mediated isothermal amplification (LAMP). STITCHER is a web tool providing a central resource for researchers conducting all types of overlapping assembly PCR experiments with an intuitive interface for automated primer design that's fast, easy to use, and freely available online.

Overlaps among phenological phases in flood plain forest ecosystem

NASA Astrophysics Data System (ADS)

Bartošová, Lenka; Bauer, Zdeněk; Trnka, Miroslav; Možný, Martin; Štěpánek, Petr; Žalud, Zdeněk

2015-04-01

There is a growing concern that climate change has significant impacts on species phenology, seasonal population dynamics, and thus interaction (a)synchrony between species. Species that have historically undergone life history events on the same seasonal calendar may lose synchrony and therefore lose the ability to interact as they have in the past. In view of the match/mismatch hypothesis, the different extents or directions of the phenological shifts among interacting species may have significant implications for community structure and dynamics. That's why our principal goal of the study is to determine the phenological responses within the ecosystem of flood plain forest and analyzed the phenological overlapping among each phenological periods of given species. The phenological observations were done at flood-plain forest experimental site during the period 1961-2012. The whole ecosystem in this study create 17 species (15 plants and 2 bird species) and each species is composed of 2 phenological phases. Phenological periods of all species of ecosystem overlap each other and 43 of these overlapping were chosen and the length, trend and correlation with temperature were elaborated. The analysis of phenophases overlapping of chosen species showed that the length of overlay is getting significantly shorter in 1 case. On the other hand the situation when the length of overlaps is getting significantly longer arose in 4 cases. Remaining overlaps (38) of all phenological periods among various species is getting shorter or longer but with no significance or have not changed anyhow. This study was funded by project "Building up a multidisciplinary scientific team focused on drought" No. CZ.1.07/2.3.00/20.0248. and of projects no. LD13030 supporting participation of the Czech Republic in the COST action ES1106.

Segmenting overlapping nano-objects in atomic force microscopy image

NASA Astrophysics Data System (ADS)

Wang, Qian; Han, Yuexing; Li, Qing; Wang, Bing; Konagaya, Akihiko

2018-01-01

Recently, techniques for nanoparticles have rapidly been developed for various fields, such as material science, medical, and biology. In particular, methods of image processing have widely been used to automatically analyze nanoparticles. A technique to automatically segment overlapping nanoparticles with image processing and machine learning is proposed. Here, two tasks are necessary: elimination of image noises and action of the overlapping shapes. For the first task, mean square error and the seed fill algorithm are adopted to remove noises and improve the quality of the original image. For the second task, four steps are needed to segment the overlapping nanoparticles. First, possibility split lines are obtained by connecting the high curvature pixels on the contours. Second, the candidate split lines are classified with a machine learning algorithm. Third, the overlapping regions are detected with the method of density-based spatial clustering of applications with noise (DBSCAN). Finally, the best split lines are selected with a constrained minimum value. We give some experimental examples and compare our technique with two other methods. The results can show the effectiveness of the proposed technique.

Comparison of Patient Outcomes and Cost of Overlapping Versus Nonoverlapping Spine Surgery.

PubMed

Zygourakis, Corinna C; Sizdahkhani, Saman; Keefe, Malla; Lee, Janelle; Chou, Dean; Mummaneni, Praveen V; Ames, Christopher P

2017-04-01

Overlapping surgery recently has gained significant media attention, but there are limited data on its safety and efficacy. To date, there has been no analysis of overlapping surgery in the field of spine. Our goal was to compare overlapping versus nonoverlapping spine surgery patient outcomes and cost. A retrospective review was undertaken of 2319 spine surgeries (n = 848 overlapping; 1471 nonoverlapping) performed by 3 neurosurgery attendings from 2012 to 2015 at the University of California San Francisco. Collected variables included patient age, sex, insurance, American Society of Anesthesiology score, severity of illness, risk of mortality, procedure type, surgeon, day of surgery, source of transfer, admission type, overlapping versus nonoverlapping surgery (≥1 minute of overlapping procedure time), Medicare-Severity Diagnosis-Related Group, osteotomy, and presence of another attending/fellow/resident. Univariate, then multivariate mixed-effect models were used to evaluate the effect of the collected variables on the following outcomes: procedure time, estimated blood loss, length of stay, discharge status, 30-day mortality, 30-day unplanned readmission, unplanned return to OR, and total hospital cost. Urgent spine cases were more likely to be done in an overlapping fashion (all P < 0.01). After we adjusted for patient demographics, clinical indicators, and procedure characteristics, overlapping surgeries had longer procedure times (estimate = 26.17; P < 0.001) and lower rates of discharge to home (odds ratio 0.65; P < 0.001), but equivalent rates of 30-day mortality, readmission, return to the operating room, estimated blood loss, length of stay, and total hospital cost (all P = ns). Overlapping spine surgery may be performed safely at our institution, although continued monitoring of patient outcomes is necessary. Overlapping surgery does not lead to greater hospital costs. Copyright © 2017 Elsevier Inc. All rights reserved.

Overlapping communities detection based on spectral analysis of line graphs

NASA Astrophysics Data System (ADS)

Gui, Chun; Zhang, Ruisheng; Hu, Rongjing; Huang, Guoming; Wei, Jiaxuan

2018-05-01

Community in networks are often overlapping where one vertex belongs to several clusters. Meanwhile, many networks show hierarchical structure such that community is recursively grouped into hierarchical organization. In order to obtain overlapping communities from a global hierarchy of vertices, a new algorithm (named SAoLG) is proposed to build the hierarchical organization along with detecting the overlap of community structure. SAoLG applies the spectral analysis into line graphs to unify the overlap and hierarchical structure of the communities. In order to avoid the limitation of absolute distance such as Euclidean distance, SAoLG employs Angular distance to compute the similarity between vertices. Furthermore, we make a micro-improvement partition density to evaluate the quality of community structure and use it to obtain the more reasonable and sensible community numbers. The proposed SAoLG algorithm achieves a balance between overlap and hierarchy by applying spectral analysis to edge community detection. The experimental results on one standard network and six real-world networks show that the SAoLG algorithm achieves higher modularity and reasonable community number values than those generated by Ahn's algorithm, the classical CPM and GN ones.

How does the 'rest-self overlap' mediate the qualitative and automatic features of self-reference?

PubMed

Northoff, Georg

2016-01-01

The target article points out the qualitative and automatic features of self-reference while leaving open the underlying neural mechanisms. Based on empirical evidence about rest-self overlap and rest-stimulus interaction being special for self-related stimuli, I postulate that the resting state shows self-specific organization. The resting state's self-specific organization may be encoded by activity balances between different networks which in turn predispose the qualitative features of subsequent self-related stimulus-induced activity in, for instance, SAN as well as the automatic features of self-reference effects.

Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo

PubMed Central

Uprety, Bhawana; Sen, Rwik

2015-01-01

NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions. PMID:26100014

Two distinct cellular proteins interact with the EIa-responsive element of an adenovirus early promoter.

PubMed Central

Jansen-Durr, P; Wintzerith, M; Reimund, B; Hauss, C; Kédinger, C

1990-01-01

EIa-dependent transactivation of the adenovirus EIIa early (EIIaE) promoter is correlated with the activation of the cellular transcription factor E2F. In this study we identified a cellular protein, C alpha, that is distinct from E2F and that binds two sites in the EIIaE promoter, one of which overlaps with the proximal E2F binding site of the EIIaE promoter. The possible involvement of C alpha in the EIa responsiveness of this promoter is discussed. Images PMID:2139142

Non-overlap subaperture interferometric testing for large optics

NASA Astrophysics Data System (ADS)

Wu, Xin; Yu, Yingjie; Zeng, Wenhan; Qi, Te; Chen, Mingyi; Jiang, Xiangqian

2017-08-01

It has been shown that the number of subapertures and the amount of overlap has a significant influence on the stitching accuracy. In this paper, a non-overlap subaperture interferometric testing method (NOSAI) is proposed to inspect large optical components. This method would greatly reduce the number of subapertures and the influence of environmental interference while maintaining the accuracy of reconstruction. A general subaperture distribution pattern of NOSAI is also proposed for the large rectangle surface. The square Zernike polynomial is employed to fit such wavefront. The effect of the minimum fitting terms on the accuracy of NOSAI and the sensitivities of NOSAI to subaperture's alignment error, power systematic error, and random noise are discussed. Experimental results validate the feasibility and accuracy of the proposed NOSAI in comparison with wavefront obtained by a large aperture interferometer and stitching surface by multi-aperture overlap-scanning technique (MAOST).

Overlapping bio-absorbable scaffolds: Aim for D2D technique?

PubMed

Khan, Asaad A; Dangas, George D

2018-06-01

The results of overlapping metallic stents have been concerning but this practice is often unavoidable in the setting of long or tortuous lesions, diameter discrepancy of proximal and distal vessel, and for residual dissections. Theoretically, bio-absorbable scaffolds may carry an advantage over metallic stents due to the progressive resorption of the scaffold theoretically rendering the overlap a non-issue; this has not been clinically evident. Since stent/scaffold overlap cannot be entirely avoided, improved stent delivery/deployment and scaffold design modification may reduce complications in this complex patient subset. © 2018 Wiley Periodicals, Inc.

Arginine deiminase expressed in vivo, driven by human telomerase reverse transcriptase promoter, displays high hepatoma targeting and oncolytic efficiency.

PubMed

Jiang, Hui; Guo, Song; Xiao, Dan; Bian, Xuzhao; Wang, Jie; Wang, Ying; Zhou, Huiting; Cai, Jun; Zheng, Zhongliang

2017-06-06

Arginine starvation has the potential to selectively treat both primary tumor and (micro) metastatic tissue with very low side effects. Arginine deiminase (ADI; EC 3.5.3.6), an arginine-degrading enzyme, has been studied as a potential anti-tumor drug for the treatment of arginine-auxotrophic tumors. Though ADI-PEG20 (pegylated ADI by PEG 20,000) already passed the phase I/II clinical trials [1], it is just used as adjuvant therapy because of its low efficiency and less targeting. Then, this paper discussed the efficiency of arginine starvation mediated by ADI expressed in cytoplasm for liver cancers. In order to guarantee the tumor targeting, human telomerase reverse transcriptase (hTERT) promoter was used to drive the expression of ADI in vivo. To access the anti-tumor efficiency of ADI, p53 gene was used as the positive control. Thus, ADI displayed obvious cytotoxicity to BEL7402 and HUH7 cell lines in cytoplasm. The apoptosis rates rose from 15% to nearly 60% after changing the expression vectors from pcDNA4 plasmid to adenovirus. Compared with p53-adenovirus, ADI-adenovirus showed the higher oncolytic activity in the intratumoral injection model of mice. Tumor disappeared after the treatment of ADI-adenovirus for two weeks, and the mice pulled through all. Therefore, ADI is an ideal anti-tumor gene for caner targeting therapy with the help of hTERT promoter.

An ant colony based algorithm for overlapping community detection in complex networks

NASA Astrophysics Data System (ADS)

Zhou, Xu; Liu, Yanheng; Zhang, Jindong; Liu, Tuming; Zhang, Di

2015-06-01

Community detection is of great importance to understand the structures and functions of networks. Overlap is a significant feature of networks and overlapping community detection has attracted an increasing attention. Many algorithms have been presented to detect overlapping communities. In this paper, we present an ant colony based overlapping community detection algorithm which mainly includes ants' location initialization, ants' movement and post processing phases. An ants' location initialization strategy is designed to identify initial location of ants and initialize label list stored in each node. During the ants' movement phase, the entire ants move according to the transition probability matrix, and a new heuristic information computation approach is redefined to measure similarity between two nodes. Every node keeps a label list through the cooperation made by ants until a termination criterion is reached. A post processing phase is executed on the label list to get final overlapping community structure naturally. We illustrate the capability of our algorithm by making experiments on both synthetic networks and real world networks. The results demonstrate that our algorithm will have better performance in finding overlapping communities and overlapping nodes in synthetic datasets and real world datasets comparing with state-of-the-art algorithms.

Mitigating fluorescence spectral overlap in wide-field endoscopic imaging

PubMed Central

Hou, Vivian; Nelson, Leonard Y.; Seibel, Eric J.

2013-01-01

Abstract. The number of molecular species suitable for multispectral fluorescence imaging is limited due to the overlap of the emission spectra of indicator fluorophores, e.g., dyes and nanoparticles. To remove fluorophore emission cross-talk in wide-field multispectral fluorescence molecular imaging, we evaluate three different solutions: (1) image stitching, (2) concurrent imaging with cross-talk ratio subtraction algorithm, and (3) frame-sequential imaging. A phantom with fluorophore emission cross-talk is fabricated, and a 1.2-mm ultrathin scanning fiber endoscope (SFE) is used to test and compare these approaches. Results show that fluorophore emission cross-talk could be successfully avoided or significantly reduced. Near term, the concurrent imaging method of wide-field multispectral fluorescence SFE is viable for early stage cancer detection and localization in vivo. Furthermore, a means to enhance exogenous fluorescence target-to-background ratio by the reduction of tissue autofluorescence background is demonstrated. PMID:23966226

Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation.

PubMed

Yuan, Y; Zhang, G Q; Chai, W; Ni, M; Xu, C; Chen, J Y

2016-10-01

Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1. MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13. miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1.Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J

MiRNA-133b promotes the proliferation of human Sertoli cells through targeting GLI3

PubMed Central

Yao, Chencheng; Sun, Min; Yuan, Qingqing; Niu, Minghui; Chen, Zheng; Hou, Jingmei; Wang, Hong; Wen, Liping; Liu, Yun; Li, Zheng; He, Zuping

2016-01-01

Sertoli cells play critical roles in regulating spermatogenesis and they can be reprogrammed to the cells of other lineages, highlighting that they have significant applications in reproductive and regenerative medicine. The fate determinations of Sertoli cells are regulated precisely by epigenetic factors. However, the expression, roles, and targets of microRNA (miRNA) in human Sertoli cells remain unknown. Here we have for the first time revealed that 174 miRNAs were distinctly expressed in human Sertoli cells between Sertoli-cell-only syndrome (SCOS) patients and obstructive azoospermia (OA) patients with normal spermatogenesis using miRNA microarrays and real time PCR, suggesting that these miRNAs may be associated with the pathogenesis of SCOS. MiR-133b is upregulated in Sertoli cells of SCOS patients compared to OA patients. Proliferation assays with miRNA mimics and inhibitors showed that miR-133b enhanced the proliferation of human Sertoli cells. Moreover, we demonstrated that GLI3 was a direct target of miR-133b and the expression of Cyclin B1 and Cyclin D1 was enhanced by miR-133b mimics but decreased by its inhibitors. Gene silencing of GLI3 using RNA inference stimulated the growth of human Sertoli cells. Collectively, miR-133b promoted the proliferation of human Sertoli cells by targeting GLI3. This study thus sheds novel insights into epigenetic regulation of human Sertoli cells and the etiology of azoospermia and offers new targets for treating male infertility PMID:26755652

Specific surface area of overlapping spheres in the presence of obstructions

NASA Astrophysics Data System (ADS)

Jenkins, D. R.

2013-02-01

This study considers the random placement of uniform sized spheres, which may overlap, in the presence of another set of randomly placed (hard) spheres, which do not overlap. The overlapping spheres do not intersect the hard spheres. It is shown that the specific surface area of the collection of overlapping spheres is affected by the hard spheres, such that there is a minimum in the specific surface area as a function of the relative size of the two sets of spheres. The occurrence of the minimum is explained in terms of the break-up of pore connectivity. The configuration can be considered to be a simple model of the structure of a porous composite material. In particular, the overlapping particles represent voids while the hard particles represent fillers. Example materials are pervious concrete, metallurgical coke, ice cream, and polymer composites. We also show how the material properties of such composites are affected by the void structure.

Specific surface area of overlapping spheres in the presence of obstructions.

PubMed

Jenkins, D R

2013-02-21

This study considers the random placement of uniform sized spheres, which may overlap, in the presence of another set of randomly placed (hard) spheres, which do not overlap. The overlapping spheres do not intersect the hard spheres. It is shown that the specific surface area of the collection of overlapping spheres is affected by the hard spheres, such that there is a minimum in the specific surface area as a function of the relative size of the two sets of spheres. The occurrence of the minimum is explained in terms of the break-up of pore connectivity. The configuration can be considered to be a simple model of the structure of a porous composite material. In particular, the overlapping particles represent voids while the hard particles represent fillers. Example materials are pervious concrete, metallurgical coke, ice cream, and polymer composites. We also show how the material properties of such composites are affected by the void structure.

The effect of relatedness and pack size on territory overlap in African wild dogs.

PubMed

Jackson, Craig R; Groom, Rosemary J; Jordan, Neil R; McNutt, J Weldon

2017-01-01

Spacing patterns mediate competitive interactions between conspecifics, ultimately increasing fitness. The degree of territorial overlap between neighbouring African wild dog ( Lycaon pictus ) packs varies greatly, yet the role of factors potentially affecting the degree of overlap, such as relatedness and pack size, remain unclear. We used movement data from 21 wild dog packs to calculate the extent of territory overlap (20 dyads). On average, unrelated neighbouring packs had low levels of overlap restricted to the peripheral regions of their 95% utilisation kernels. Related neighbours had significantly greater levels of peripheral overlap. Only one unrelated dyad included overlap between 75%-75% kernels, but no 50%-50% kernels overlapped. However, eight of 12 related dyads overlapped between their respective 75% kernels and six between the frequented 50% kernels. Overlap between these more frequented kernels confers a heightened likelihood of encounter, as the mean utilisation intensity per unit area within the 50% kernels was 4.93 times greater than in the 95% kernels, and 2.34 times greater than in the 75% kernels. Related packs spent significantly more time in their 95% kernel overlap zones than did unrelated packs. Pack size appeared to have little effect on overlap between related dyads, yet among unrelated neighbours larger packs tended to overlap more onto smaller packs' territories. However, the true effect is unclear given that the model's confidence intervals overlapped zero. Evidence suggests that costly intraspecific aggression is greatly reduced between related packs. Consequently, the tendency for dispersing individuals to establish territories alongside relatives, where intensively utilised portions of ranges regularly overlap, may extend kin selection and inclusive fitness benefits from the intra-pack to inter-pack level. This natural spacing system can affect survival parameters and the carrying capacity of protected areas, having important

Community-Engaged Strategies to Promote Relevance of Research Capacity-Building Efforts Targeting Community Organizations.

PubMed

Cunningham, Jennifer; Miller, Stephania T; Joosten, Yvonne; Elzey, Jared D; Israel, Tiffany; King, Christine; Luther, Patrick; Vaughn, Yolanda; Wilkins, Consuelo H

2015-10-01

The study goal is to highlight strategies for promoting relevance of research capacity-building efforts targeting community organizations (CO)s. Two community partners, representing two COs, were invited to participate in CO research development trainings, Community Research Forums (Forum)s. Their contributions were documented via Forum document review. Forum participants, representatives from other COs, completed post-Forum surveys to identify additional training needs and rate Forum impact relative to their training expectations. A content-based analysis and descriptive statistics were used to summarize needs assessment- and impact-related survey responses, respectively. Community partners were involved in eight Forum-related activities including marketing (planning), facilitation (implementation), and manuscript coauthorship (dissemination). Eighty-one individuals, representing 55 COs, attended the Forums. Needs assessment responses revealed a desire for additional assistance with existing Forum topics (e.g., defining research priorities) and a need for new ones (e.g., promoting organizational buy in for research). Ninety-one percent of participants agreed that the Forum demonstrated the value of research to COs and how to create a research agenda. Including community partners in all Forum phases ensured that CO perspectives were integrated throughout. Post-Forum needs and impact assessment results will help in tailoring, where needed, future training topics and strategies, respectively. © 2015 Wiley Periodicals, Inc.

Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens

PubMed Central

Gubin, Matthew M.; Zhang, Xiuli; Schuster, Heiko; Caron, Etienne; Ward, Jeffrey P.; Noguchi, Takuro; Ivanova, Yulia; Hundal, Jasreet; Arthur, Cora D.; Krebber, Willem-Jan; Mulder, Gwenn E.; Toebes, Mireille; Vesely, Matthew D.; Lam, Samuel S.K.; Korman, Alan J.; Allison, James P.; Freeman, Gordon J.; Sharpe, Arlene H.; Pearce, Erika L.; Schumacher, Ton N.; Aebersold, Ruedi; Rammensee, Hans-Georg; Melief, Cornelis J. M.; Mardis, Elaine R.; Gillanders, William E.; Artyomov, Maxim N.; Schreiber, Robert D.

2014-01-01

The immune system plays key roles in determining the fate of developing cancers by not only functioning as a tumour promoter facilitating cellular transformation, promoting tumour growth and sculpting tumour cell immunogenicity1–6, but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion1,2,7. Yet clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer induced immunosuppression. In many individuals, immunosuppression is mediated by Cytotoxic T-Lymphocyte Associated Antigen-4 (CTLA-4) and Programmed Death-1 (PD-1), two immunomodulatory receptors expressed on T cells8,9. Monoclonal antibody (mAb) based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits—including durable responses—to patients with different malignancies10–13. However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Herein, we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T cell rejection antigens following αPD-1 and/or αCTLA-4 therapy of mice bearing progressively growing sarcomas and show that therapeutic synthetic long peptide (SLP) vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Whereas, mutant tumour antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with αPD-1- and/or αCTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens (TSMA) are not only important targets of checkpoint blockade therapy but also can be

p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy.

PubMed

Tsuchiya, Megumi; Ogawa, Hidesato; Koujin, Takako; Mori, Chie; Osakada, Hiroko; Kobayashi, Shouhei; Hiraoka, Yasushi; Haraguchi, Tokuko

2018-03-01

Autophagy is a bulk degradation pathway, and selective autophagy to remove foreign entities is called xenophagy. The conjugation of ubiquitin to target pathogens is an important process in xenophagy but when and where this ubiquitination occurs remains unclear. Here, we analyzed the temporal sequence and subcellular location of ubiquitination during xenophagy using time-lapse observations, with polystyrene beads mimicking invading pathogens. Results revealed accumulation of a ubiquitination marker around the beads within 3 min after endosome rupture. Recruitment of ubiquitin to the beads was significantly delayed in p62-knockout murine embryonic fibroblast cells, and this delay was rescued by ectopic p62 expression. Ectopic expression of a phosphorylation-mimicking p62 mutated at serine residue 405 (equivalent to human serine residue 403) rescued this delay, but its unphosphorylated form did not. These results indicate that ubiquitination mainly occurs after endosome rupture and suggest that p62, specifically the phosphorylated form, promotes ubiquitin conjugation to target proteins in xenophagy.

[miR-25 promotes cell proliferation by targeting RECK in human cervical carcinoma HeLa cells].

PubMed

Qiu, Gang; Fang, Baoshuan; Xin, Guohong; Wei, Qiang; Yuan, Xiaoye; Wu, Dayong

2015-01-01

To investigate the effect of miR-25 on the proliferation of human cervical carcinoma HeLa cells and its association with reversion-inducing cysteine-rich protein with Kazal motifs (RECK). The recombinant plasmids of pcDNATM6.2-GW-pre-miR-25, pmirGLO-RECK-WT, pmirGLO-RECK-MT and anti-miR-25 were constructed, and their transfection efficiencies into HeLa cells were identified by real-time quantitative PCR (qRT-PCR). The potential proliferation-stimulating function of miR-25 was analyzed by MTT assay in HeLa cells. Furthermore, the target effect of miR-25 on the RECK was determined by dual-luciferase reporter assay system, qRT-PCR and Western blotting. Sequence analysis demonstrated that the recombinant plasmids of pcDNATM6.2-GW-pre-miR-25 and pmirGLO-RECK-WT, pmirGLO-RECK-MT were successfully constructed, and qRT-PCR revealed that the transfection efficiencies of pre-miR-25 and anti-miR-25 were desirable in HeLa cells. MTT assay showed that miR-25 over-expression promoted the proliferation of HeLa cells. In addition, the luciferase activity was significantly reduced in HeLa cells cotransfected with pre-miR-25 and RECK-WT. The qRT-PCR and Western blotting indicated that the expression level of RECK was up-regulated in HeLa cells transfected with anti-miR-25 at the transcriptional and posttranscriptional levels. miR-25 could promote cell proliferation by targeting RECK in HeLa cells.

The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to promote RNAi in C. elegans.

PubMed

Shirayama, Masaki; Stanney, William; Gu, Weifeng; Seth, Meetu; Mello, Craig C

2014-04-14

Argonaute (AGO) proteins are key nuclease effectors of RNAi. Although purified AGOs can mediate a single round of target RNA cleavage in vitro, accessory factors are required for small interfering RNA (siRNA) loading and to achieve multiple-target turnover. To identify AGO cofactors, we immunoprecipitated the C. elegans AGO WAGO-1, which engages amplified small RNAs during RNAi. These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12. rde-12 mutants are deficient in RNAi, including viral suppression, and fail to produce amplified secondary siRNAs and certain endogenous siRNAs (endo-siRNAs). RDE-12 colocalizes with WAGO-1 in germline P granules and in cytoplasmic and perinuclear foci in somatic cells. These findings and our genetic studies suggest that RDE-12 is first recruited to target mRNA by upstream AGOs (RDE-1 and ERGO-1), where it promotes small RNA amplification and/or WAGO-1 loading. Downstream of these events, RDE-12 forms an RNase-resistant (target mRNA-independent) complex with WAGO-1 and may thus have additional functions in target mRNA surveillance and silencing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hospital mergers and market overlap.

PubMed Central

Brooks, G R; Jones, V G

1997-01-01

OBJECTIVE: To address two questions: What are the characteristics of hospitals that affect the likelihood of their being involved in a merger? What characteristics of particular pairs of hospitals affect the likelihood of the pair engaging in a merger? DATA SOURCES/STUDY SETTING: Hospitals in the 12 county region surrounding the San Francisco Bay during the period 1983 to 1992 were the focus of the study. Data were drawn from secondary sources, including the Lexis/Nexis database, the American Hospital Association, and the Office of Statewide Health Planning and Development of the State of California. STUDY DESIGN: Seventeen hospital mergers during the study period were identified. A random sample of pairs of hospitals that did not merge was drawn to establish a statistically efficient control set. Models constructed from hypotheses regarding hospital and market characteristics believed to be related to merger likelihood were tested using logistic regression analysis. DATA COLLECTION: See Data Sources/Study Setting. PRINCIPAL FINDINGS: The analysis shows that the likelihood of a merger between a particular pair of hospitals is positively related to the degree of market overlap that exists between them. Furthermore, market overlap and performance difference interact in their effect on merger likelihood. In an analysis of individual hospitals, conditions of rivalry, hospital market share, and hospital size were not found to influence the likelihood that a hospital will engage in a merger. CONCLUSIONS: Mergers between hospitals are not driven directly by considerations of market power or efficiency as much as by the existence of specific merger opportunities in the hospitals' local markets. Market overlap is a condition that enables a merger to occur, but other factors, such as the relative performance levels of the hospitals in question and their ownership and teaching status, also play a role in influencing the likelihood that a merger will in fact take place. PMID

An Economical Analytical Equation for the Integrated Vertical Overlap of Cumulus and Stratus

NASA Astrophysics Data System (ADS)

Park, Sungsu

2018-03-01

By extending the previously proposed heuristic parameterization, the author derived an analytical equation computing the overlap areas between the precipitation (or radiation) areas and the cloud areas in a cloud system consisting of cumulus and stratus. The new analytical equation is accurate and much more efficient than the previous heuristic equation, which suffers from the truncation error in association with the digitalization of the overlap areas. Global test simulations with the new analytical formula in an offline mode showed that the maximum cumulus overlap simulates more surface precipitation flux than the random cumulus overlap. On the other hand, the maximum stratus overlap simulates less surface precipitation flux than random stratus overlap, which is due to the increase in the evaporation rate of convective precipitation from the random to maximum stratus overlap. The independent precipitation approximation (IPA) marginally decreases the surface precipitation flux, implying that IPA works well with other parameterizations. In contrast to the net production rate of precipitation and surface precipitation flux that increase when the cumulus and stratus are maximally and randomly overlapped, respectively, the global mean net radiative cooling and longwave cloud radiative forcing (LWCF) increase when the cumulus and stratus are randomly overlapped. On the global average, the vertical cloud overlap exerts larger impacts on the precipitation flux than on the radiation flux. The radiation scheme taking the subgrid variability of water vapor between the cloud and clear portions into account substantially increases the global mean LWCF in tropical deep convection and midlatitude storm track regions.

Overlapping sphincteroplasty and posterior repair.

PubMed

Crane, Andrea K; Myers, Erinn M; Lippmann, Quinn K; Matthews, Catherine A

2014-12-01

Knowledge of how to anatomically reconstruct extensive posterior-compartment defects is variable among gynecologists. The objective of this video is to demonstrate an effective technique of overlapping sphincteroplasty and posterior repair. In this video, a scripted storyboard was constructed that outlines the key surgical steps of a comprehensive posterior compartment repair: (1) surgical incision that permits access to posterior compartment and perineal body, (2) dissection of the rectovaginal space up to the level of the cervix, (3) plication of the rectovaginal muscularis, (4) repair of internal and external anal sphincters, and (5) reconstruction of the perineal body. Using a combination of graphic illustrations and live video footage, tips on repair are highlighted. The goals at the end of repair are to: (1) have improved vaginal caliber, (2) increase rectal tone along the entire posterior vaginal wall, (3) have the posterior vaginal wall at a perpendicular plane to the perineal body, (4) reform the hymenal ring, and (5) not have an overly elongated perineal body. This video provides a step-by-step guide on how to perform an overlapping sphincteroplasty and posterior repair.

Interference of Overlapping Insect Vibratory Communication Signals: An Eushistus heros Model

PubMed Central

Čokl, Andrej; Laumann, Raul Alberto; Žunič Kosi, Alenka; Blassioli-Moraes, Maria Carolina; Virant-Doberlet, Meta; Borges, Miguel

2015-01-01

Plants limit the range of insect substrate-borne vibratory communication by their architecture and mechanical properties that change transmitted signal time, amplitude and frequency characteristics. Stinkbugs gain higher signal-to-noise ratio and increase communication distance by emitting narrowband low frequency vibratory signals that are tuned with transmission properties of plants. The objective of the present study was to investigate hitherto overlooked consequences of duetting with mutually overlapped narrowband vibratory signals. The overlapped vibrations of the model stinkbug species Eushistus heros, produced naturally or induced artificially on different plants, have been analysed. They represent female and male strategies to preserve information within a complex masked signal. The brown stinkbugs E. heros communicate with species and gender specific vibratory signals that constitute characteristic duets in the calling, courtship and rivalry phases of mating behaviour. The calling female pulse overlaps the male vibratory response when the latency of the latter is shorter than the duration of the female triggering signal or when the male response does not inhibit the following female pulse. Overlapping of signals induces interference that changes their amplitude pattern to a sequence of regularly repeated pulses in which their duration and the difference between frequencies of overlapped vibrations are related inversely. Interference does not occur in overlapped narrow band female calling pulses and broadband male courtship pulse trains. In a duet with overlapped signals females and males change time parameters and increase the frequency difference between signals by changing the frequency level and frequency modulation pattern of their calls. PMID:26098637

Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification.

PubMed

Maixner, William; Fillingim, Roger B; Williams, David A; Smith, Shad B; Slade, Gary D

2016-09-01

There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs. This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Overlap in drug-disease associations between clinical practice guidelines and drug structured product label indications.

PubMed

Leung, Tiffany I; Dumontier, Michel

2016-06-08

Clinical practice guidelines (CPGs) recommend pharmacologic treatments for clinical conditions, and drug structured product labels (SPLs) summarize approved treatment indications. Both resources are intended to promote evidence-based medical practices and guide clinicians' prescribing decisions. However, it is unclear how well CPG recommendations about pharmacologic therapies match SPL indications for recommended drugs. In this study, we perform text mining of CPG summaries to examine drug-disease associations in CPG recommendations and in SPL treatment indications for 15 common chronic conditions. We constructed an initial text corpus of guideline summaries from the National Guideline Clearinghouse (NGC) from a set of manually selected ICD-9 codes for each of the 15 conditions. We obtained 377 relevant guideline summaries and their Major Recommendations section, which excludes guidelines for pediatric patients, pregnant or breastfeeding women, or for medical diagnoses not meeting inclusion criteria. A vocabulary of drug terms was derived from five medical taxonomies. We used named entity recognition, in combination with dictionary-based and ontology-based methods, to identify drug term occurrences in the text corpus and construct drug-disease associations. The ATC (Anatomical Therapeutic Chemical Classification) was utilized to perform drug name and drug class matching to construct the drug-disease associations from CPGs. We then obtained drug-disease associations from SPLs using conditions mentioned in their Indications section in SIDER. The primary outcomes were the frequency of drug-disease associations in CPGs and SPLs, and the frequency of overlap between the two sets of drug-disease associations, with and without using taxonomic information from ATC. Without taxonomic information, we identified 1444 drug-disease associations across CPGs and SPLs for 15 common chronic conditions. Of these, 195 drug-disease associations overlapped between CPGs and SPLs, 917

Conserved Role of Intragenic DNA Methylation in Regulating Alternative Promoters

PubMed Central

Maunakea, Alika K.; Nagarajan, Raman P.; Bilenky, Mikhail; Ballinger, Tracy J.; D’Souza, Cletus; Fouse, Shaun D.; Johnson, Brett E.; Hong, Chibo; Nielsen, Cydney; Zhao, Yongjun; Turecki, Gustavo; Delaney, Allen; Varhol, Richard; Thiessen, Nina; Shchors, Ksenya; Heine, Vivi M.; Rowitch, David H.; Xing, Xiaoyun; Fiore, Chris; Schillebeeckx, Maximiliaan; Jones, Steven J.M.; Haussler, David; Marra, Marco A.; Hirst, Martin; Wang, Ting; Costello, Joseph F.

2014-01-01

While the methylation of DNA in 5′ promoters suppresses gene expression, the role of DNA methylation in gene bodies is unclear1–5. In mammals, tissue- and cell type-specific methylation is present in a small percentage of 5′ CpG island (CGI) promoters, while a far greater proportion occurs across gene bodies, coinciding with highly conserved sequences5–10. Tissue-specific intragenic methylation might reduce,3 or, paradoxically, enhance transcription elongation efficiency1,2,4,5. Capped analysis of gene expression (CAGE) experiments also indicate that transcription commonly initiates within and between genes11–15. To investigate the role of intragenic methylation, we generated a map of DNA methylation from human brain encompassing 24.7 million of the 28 million CpG sites. From the dense, high-resolution coverage of CpG islands, the majority of methylated CpG islands were revealed to be in intragenic and intergenic regions, while less than 3% of CpG islands in 5′ promoters were methylated. The CpG islands in all three locations overlapped with RNA markers of transcription initiation, and unmethylated CpG islands also overlapped significantly with trimethylation of H3K4, a histone modification enriched at promoters16. The general and CpG-island-specific patterns of methylation are conserved in mouse tissues. An in-depth investigation of the human SHANK3 locus17,18 and its mouse homologue demonstrated that this tissue-specific DNA methylation regulates intragenic promoter activity in vitro and in vivo. These methylation-regulated, alternative transcripts are expressed in a tissue and cell type-specific manner, and are expressed differentially within a single cell type from distinct brain regions. These results support a major role for intragenic methylation in regulating cell context-specific alternative promoters in gene bodies. PMID:20613842

Partially Overlapping Brain Networks for Singing and Cello Playing.

PubMed

Segado, Melanie; Hollinger, Avrum; Thibodeau, Joseph; Penhune, Virginia; Zatorre, Robert J

2018-01-01

This research uses an MR-Compatible cello to compare functional brain activation during singing and cello playing within the same individuals to determine the extent to which arbitrary auditory-motor associations, like those required to play the cello, co-opt functional brain networks that evolved for singing. Musical instrument playing and singing both require highly specific associations between sounds and movements. Because these are both used to produce musical sounds, it is often assumed in the literature that their neural underpinnings are highly similar. However, singing is an evolutionarily old human trait, and the auditory-motor associations used for singing are also used for speech and non-speech vocalizations. This sets it apart from the arbitrary auditory-motor associations required to play musical instruments. The pitch range of the cello is similar to that of the human voice, but cello playing is completely independent of the vocal apparatus, and can therefore be used to dissociate the auditory-vocal network from that of the auditory-motor network. While in the MR-Scanner, 11 expert cellists listened to and subsequently produced individual tones either by singing or cello playing. All participants were able to sing and play the target tones in tune (<50C deviation from target). We found that brain activity during cello playing directly overlaps with brain activity during singing in many areas within the auditory-vocal network. These include primary motor, dorsal pre-motor, and supplementary motor cortices (M1, dPMC, SMA),the primary and periprimary auditory cortices within the superior temporal gyrus (STG) including Heschl's gyrus, anterior insula (aINS), anterior cingulate cortex (ACC), and intraparietal sulcus (IPS), and Cerebellum but, notably, exclude the periaqueductal gray (PAG) and basal ganglia (Putamen). Second, we found that activity within the overlapping areas is positively correlated with, and therefore likely contributing to, both

Partially Overlapping Brain Networks for Singing and Cello Playing

PubMed Central

Segado, Melanie; Hollinger, Avrum; Thibodeau, Joseph; Penhune, Virginia; Zatorre, Robert J.

2018-01-01

This research uses an MR-Compatible cello to compare functional brain activation during singing and cello playing within the same individuals to determine the extent to which arbitrary auditory-motor associations, like those required to play the cello, co-opt functional brain networks that evolved for singing. Musical instrument playing and singing both require highly specific associations between sounds and movements. Because these are both used to produce musical sounds, it is often assumed in the literature that their neural underpinnings are highly similar. However, singing is an evolutionarily old human trait, and the auditory-motor associations used for singing are also used for speech and non-speech vocalizations. This sets it apart from the arbitrary auditory-motor associations required to play musical instruments. The pitch range of the cello is similar to that of the human voice, but cello playing is completely independent of the vocal apparatus, and can therefore be used to dissociate the auditory-vocal network from that of the auditory-motor network. While in the MR-Scanner, 11 expert cellists listened to and subsequently produced individual tones either by singing or cello playing. All participants were able to sing and play the target tones in tune (<50C deviation from target). We found that brain activity during cello playing directly overlaps with brain activity during singing in many areas within the auditory-vocal network. These include primary motor, dorsal pre-motor, and supplementary motor cortices (M1, dPMC, SMA),the primary and periprimary auditory cortices within the superior temporal gyrus (STG) including Heschl's gyrus, anterior insula (aINS), anterior cingulate cortex (ACC), and intraparietal sulcus (IPS), and Cerebellum but, notably, exclude the periaqueductal gray (PAG) and basal ganglia (Putamen). Second, we found that activity within the overlapping areas is positively correlated with, and therefore likely contributing to, both

Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.

PubMed

Li, Wen-Yuan; Zhang, Wei-Ting; Cheng, Yong-Xia; Liu, Yan-Cui; Zhai, Feng-Guo; Sun, Ping; Li, Hui-Ting; Deng, Ling-Xiao; Zhu, Xiao-Feng; Wang, Ying

2018-06-01

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

Overlap Areas of a Square Box on a Square Mesh

DTIC Science & Technology

2017-04-01

ARL-TN-0818 ● APR 2017 US Army Research Laboratory Overlap Areas of a Square Box on a Square Mesh by James U Cazamias...originator. ARL-TN-0818 ● APR 2017 US Army Research Laboratory Overlap Areas of a Square Box on a Square Mesh by James U Cazamias...

T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

PubMed

de Melo, Andréa Barbosa; Nascimento, Eduardo J M; Braga-Neto, Ulisses; Dhalia, Rafael; Silva, Ana Maria; Oelke, Mathias; Schneck, Jonathan P; Sidney, John; Sette, Alessandro; Montenegro, Silvia M L; Marques, Ernesto T A

2013-01-01

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+) and CD8(+) T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

PubMed Central

de Melo, Andréa Barbosa; Nascimento, Eduardo J. M.; Braga-Neto, Ulisses; Dhalia, Rafael; Silva, Ana Maria; Oelke, Mathias; Schneck, Jonathan P.; Sidney, John; Sette, Alessandro; Montenegro, Silvia M. L.; Marques, Ernesto T. A.

2013-01-01

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, “promiscuous” T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. PMID:23383350

Biodiversity Areas under Threat: Overlap of Climate Change and Population Pressures on the World's Biodiversity Priorities.

PubMed

Aukema, Juliann E; Pricope, Narcisa G; Husak, Gregory J; Lopez-Carr, David

2017-01-01

Humans and the ecosystem services they depend on are threatened by climate change. Places with high or growing human population as well as increasing climate variability, have a reduced ability to provide ecosystem services just as the need for these services is most critical. A spiral of vulnerability and ecosystem degradation often ensues in such places. We apply different global conservation schemes as proxies to examine the spatial relation between wet season precipitation, population change over three decades, and natural resource conservation. We pose two research questions: 1) Where are biodiversity and ecosystem services vulnerable to the combined effects of climate change and population growth? 2) Where are human populations vulnerable to degraded ecosystem services? Results suggest that globally only about 20% of the area between 50 degrees latitude North and South has experienced significant change-largely wetting-in wet season precipitation. Approximately 40% of rangelands and 30% of rainfed agriculture lands have experienced significant precipitation changes, with important implications for food security. Over recent decades a number of critical conservation areas experienced high population growth concurrent with significant wetting or drying (e.g. the Horn of Africa, Himalaya, Western Ghats, and Sri Lanka), posing challenges not only for human adaptation but also to the protection and sustenance of biodiversity and ecosystem services. Identifying areas of climate and population risk and their overlap with conservation priorities can help to target activities and resources that promote biodiversity and ecosystem services while improving human well-being.

LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway.

PubMed

Ji, Jie; Tang, Junwei; Deng, Lei; Xie, Yu; Jiang, Runqiu; Li, Guoqiang; Sun, Beicheng

2015-12-15

Hepatocellular carcinoma (HCC) is well known as the sixth most common malignant tumor and the third leading cause of cancer-related deaths globally. LINC00152 was documented as an important long non-coding RNA (lncRNA) involved in the pathogenesis of gastric cancer; however, the detailed mechanism of action of LINC00152 remains unknown. Here, based on the increased level of LINC00152 in HCC tissues, we found that LINC00152 could promote cell proliferation in vitro and tumor growth in vivo. Furthermore, microarray-based analysis indicated that LINC00152 could activate the mechanistic target of rapamycin(mTOR) pathway by binding to the promoter of EpCAM through a cis-regulation, as confirmed by Gal4-λN/BoxB reporter system. Thus, LINC00152 might be involved in the oncogenesis of HCC by activating the mTOR signaling pathway and might be a novel index for clinical diagnosis in the future.

Shake for Sigma, Pray for Pi: Classroom Orbital Overlap Analogies

ERIC Educational Resources Information Center

Dicks, Andrew P.

2011-01-01

An introductory organic classroom demonstration is discussed where analogies are made between common societal hand contact and covalent bond formation. A handshake signifies creation of a [sigma] bond ("head-on" orbital overlap), whereas the action of praying illustrates "sideways" overlap and generation of a [pi] bond. The nature of orbital and…

Radiative Impacts of Cloud Heterogeneity and Overlap in an Atmospheric General Circulation Model

NASA Technical Reports Server (NTRS)

Oreopoulos, L.; Lee, D.; Sud, Y. C.; Suarez, M. J.

2012-01-01

The radiative impacts of introducing horizontal heterogeneity of layer cloud condensate, and vertical overlap of condensate and cloud fraction are examined with the aid of a new radiation package operating in the GEOS-5 Atmospheric General Circulation Model. The impacts are examined in terms of diagnostic top-of-the-atmosphere shortwave (SW) and longwave (LW) cloud radiative effect (CRE) calculations for a range of assumptions and parameter specifications about the overlap. The investigation is conducted for two distinct cloud schemes, the one that comes with the standard GEOS-5 distribution, and another which has been recently used experimentally for its enhanced GEOS-5 distribution, and another which has been recently used experimentally for its enhanced cloud microphysical capabilities; both are coupled to a cloud generator allowing arbitrary cloud overlap specification. We find that cloud overlap radiative impacts are significantly stronger for the operational cloud scheme for which a change of cloud fraction overlap from maximum-random to generalized results to global changes of SW and LW CRE of approximately 4 Watts per square meter, and zonal changes of up to approximately 10 Watts per square meter. This is because of fewer occurrences compared to the other scheme of large layer cloud fractions and of multi-layer situations with large numbers of atmospheric being simultaneously cloudy, conditions that make overlap details more important. The impact on CRE of the details of condensate distribution overlap is much weaker. Once generalized overlap is adopted, both cloud schemes are only modestly sensitive to the exact values of the overlap parameters. We also find that if one of the CRE components is overestimated and the other underestimated, both cannot be driven towards observed values by adjustments to cloud condensate heterogeneity and overlap alone.

Development of a frontal small overlap crashworthiness evaluation test.

PubMed

Sherwood, Christopher P; Mueller, Becky C; Nolan, Joseph M; Zuby, David S; Lund, Adrian K

2013-01-01

Small overlap frontal crashes are those in which crash forces are applied outboard of the vehicle's longitudinal frame rails. In-depth analyses of crashes indicate that such crashes account for a significant proportion of frontal crashes with seriously injured occupants. The objective of this research was to evaluate possible barrier crash tests that could be used to evaluate the crashworthiness of vehicles across a spectrum of small overlap crash types. Sixteen full-scale vehicle tests were conducted using 3 midsize passenger vehicles in up to 6 different test configurations, including vehicle-to-vehicle and barrier tests. All vehicles were tested at 64 km/h with an instrumented Hybrid III midsize male driver dummy. All test configurations resulted in primary loading of the wheel, suspension system, and hinge pillar. Vehicles underwent substantial lateral movement during the crash, which varied by crash configuration. The occupant compartments had significant intrusion, particularly to the most outboard structures. Inboard movement of the steering wheel in combination with outboard movement of the dummies (due to the lateral vehicle motion) caused limited interaction with the frontal air bag in most cases. When assessing overall crashworthiness (based on injury measures, structural deformation, and occupant kinematics), one vehicle had superior performance in each crash configuration. This was confirmation that the countermeasures benefiting performance in a single small overlap test also will provide a benefit in other crash configurations. Based on these test results, the Insurance Institute for Highway Safety has developed a small overlap crashworthiness evaluation with the following characteristics: a rigid flat barrier with a 150-mm corner radius, 25 percent overlap, 64 km/h test speed, and a Hybrid III midsize male driver dummy.

Comparisons of Satellite-Deduced Overlapping Cloud Properties and CALIPSO CloudSat Data

NASA Technical Reports Server (NTRS)

Chang, Fu-Lung; Minnis, Patrick; Lin, Bing; Sun-Mack, Sunny

2010-01-01

Introduction to the overlapped cloud properties derived from polar-orbiting (MODIS) and geostationary (GOES-12, -13, Meteosat-8, -9, etc.) meteorological satellites, which are produced at the NASA Langley Research Center (LaRC) cloud research & development team (NASA lead scientist: Dr. Patrick Minnis). Comparison of the LaRC CERES MODIS Edition-3 overlapped cloud properties to the CALIPSO and the CloudSat active sensing data. High clouds and overlapped clouds occur frequently as deduced by CALIPSO (44 & 25%), CloudSat (25 & 4%), and MODIS (37 & 6%). Large fractions of optically-thin cirrus and overlapped clouds are deduced from CALIPSO, but much smaller fractions are from CloudSat and MODIS. For overlapped clouds, the averaged upper-layer CTHs are about 12.8 (CALIPSO), 10.9 (CloudSat) and 10 km (MODIS), and the averaged lower-layer CTHs are about 3.6 (CALIPSO), 3.2 (CloudSat) and 3.9 km (MODIS). Based on comparisons of upper and lower-layer cloud properties as deduced from the MODIS, CALIPSO and CloudSat data, more enhanced passive satellite methods for retrieving thin cirrus and overlapped cloud properties are needed and are under development.

The Vasa homolog RDE-12 engages target mRNA and multiple Argonaute proteins to promote RNAi in C. elegans

PubMed Central

Shirayama, Masaki; Stanney, William; Gu, Weifeng; Seth, Meetu; Mello, Craig C.

2014-01-01

Summary Argonaute proteins (AGOs) are key nuclease effectors of RNA interference (RNAi) [1]. Although purified AGOs can mediate a single round of target-RNA cleavage in vitro, accessory factors are required for short-interfering (si)RNAs loading and to achieve multiple-target turnover [2, 3]. To identify AGO co-factors we immunoprecipitated the C. elegans AGO WAGO-1, which engages amplified small RNAs during RNAi [4]. These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12. rde-12 mutants are deficient in RNAi including viral suppression, and fail to produce amplified secondary siRNAs and certain endogenous siRNAs (endo-siRNAs). RDE-12 co-localizes with WAGO-1 in germline P-granules and in cytoplasmic and peri-nuclear foci in somatic cells. These findings and our genetic studies suggest that RDE-12 is first recruited to target mRNA by upstream AGOs (RDE-1 and ERGO-1) where it promotes small-RNA amplification and/or WAGO-1 loading. Downstream of these events, RDE-12 forms an RNase-resistant (target mRNA-independent) complex with WAGO-1 and may thus have additional functions in target mRNA surveillance and silencing. PMID:24684931

Overlapping meta-analyses on the same topic: survey of published studies.

PubMed

Siontis, Konstantinos C; Hernandez-Boussard, Tina; Ioannidis, John P A

2013-07-19

To assess how common it is to have multiple overlapping meta-analyses of randomized trials published on the same topic. Survey of published meta-analyses. PubMed. Meta-analyses published in 2010 were identified, and 5% of them were randomly selected. We further selected those that included randomized trials and examined effectiveness of any medical intervention. For eligible meta-analyses, we searched for other meta-analyses on the same topic (covering the same comparisons, indications/settings, and outcomes or overlapping subsets of them) published until February 2013. Of 73 eligible meta-analyses published in 2010, 49 (67%) had at least one other overlapping meta-analysis (median two meta-analyses per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author was involved in at least two of the overlapping meta-analyses. No characteristics of the index meta-analyses were associated with the potential for overlapping meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected topics, 13 of the more recent meta-analyses did not include any additional outcomes. In three of the four topics with eight or more published meta-analyses, many meta-analyses examined only a subset of the eligible interventions or indications/settings covered by the index meta-analysis. Conversely, for statins in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses were published with similar eligibility criteria for interventions and setting: there was still variability on which studies were included, but the results were always similar or even identical across meta-analyses. While some independent replication of meta-analyses by different teams is possibly useful, the overall picture suggests that there is a waste of efforts with many topics covered by multiple overlapping meta-analyses.

Genome-wide localization of exosome components to active promoters and chromatin insulators in Drosophila

PubMed Central

Lim, Su Jun; Boyle, Patrick J.; Chinen, Madoka; Dale, Ryan K.; Lei, Elissa P.

2013-01-01

Chromatin insulators are functionally conserved DNA–protein complexes situated throughout the genome that organize independent transcriptional domains. Previous work implicated RNA as an important cofactor in chromatin insulator activity, although the precise mechanisms are not yet understood. Here we identify the exosome, the highly conserved major cellular 3′ to 5′ RNA degradation machinery, as a physical interactor of CP190-dependent chromatin insulator complexes in Drosophila. Genome-wide profiling of exosome by ChIP-seq in two different embryonic cell lines reveals extensive and specific overlap with the CP190, BEAF-32 and CTCF insulator proteins. Colocalization occurs mainly at promoters but also boundary elements such as Mcp, Fab-8, scs and scs′, which overlaps with a promoter. Surprisingly, exosome associates primarily with promoters but not gene bodies of active genes, arguing against simple cotranscriptional recruitment to RNA substrates. Similar to insulator proteins, exosome is also significantly enriched at divergently transcribed promoters. Directed ChIP of exosome in cell lines depleted of insulator proteins shows that CTCF is required specifically for exosome association at Mcp and Fab-8 but not other sites, suggesting that alternate mechanisms must also contribute to exosome chromatin recruitment. Taken together, our results reveal a novel positive relationship between exosome and chromatin insulators throughout the genome. PMID:23358822

Target assembly

DOEpatents

Lewis, Richard A.

1980-01-01

A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis.

PubMed

Ren, Jiafa; Li, Jianzhong; Feng, Ye; Shu, Bingyan; Gui, Yuan; Wei, Wei; He, Weichun; Yang, Junwei; Dai, Chunsun

2017-08-01

Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury. In bone marrow-derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase Cα inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin-4-stimulated or transforming growth factor (TGF)-β1-stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF-β1-stimulated upregulation of multiple profibrotic cytokines, including platelet-derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF-β1-pretreated Rictor -/- macrophages stimulated fibroblast activation less efficiently than that from TGF-β1-pretreated Rictor +/+ macrophages. These results demonstrate that Rictor/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[The automatic iris map overlap technology in computer-aided iridiagnosis].

PubMed

He, Jia-feng; Ye, Hu-nian; Ye, Miao-yuan

2002-11-01

In the paper, iridology and computer-aided iridiagnosis technologies are briefly introduced and the extraction method of the collarette contour is then investigated. The iris map can be overlapped on the original iris image based on collarette contour extraction. The research on collarette contour extraction and iris map overlap is of great importance to computer-aided iridiagnosis technologies.

Influence of gate overlap engineering on ambipolar and high frequency characteristics of tunnel-CNTFET

NASA Astrophysics Data System (ADS)

Shaker, Ahmed; Ossaimee, Mahmoud; Zekry, A.; Abouelatta, Mohamed

2015-10-01

In this paper, we have investigated the effect of gate overlapping-on-drain on the ambipolar behavior and high frequency performance of tunnel CNTFET (T-CNTFET). It is found that gate overlapping-on-drain suppresses the ambipolar behavior and improves OFF-state current. The simulation results show that there is an optimum choice for the overlapped length. On the other hand, this overlap deteriorates the high frequency performance. The high frequency figure of merit is analyzed in terms of the unit-gain cutoff frequency (fT). Further, we propose two different approaches to improve the high frequency performance of the overlapped T-CNTFET. The first one is based on inserting a high-dielectric constant material below the overlapped part of the gate and the second is based on depositing a different work function gate metal for the overlapped region. The two solutions show very good improvement in the high frequency performance with maintaining the suppression of the ambipolar characteristics.

A 5' UTR-Overlapping LncRNA Activates the Male-Determining Gene doublesex1 in the Crustacean Daphnia magna.

PubMed

Kato, Yasuhiko; Perez, Christelle Alexa G; Mohamad Ishak, Nur Syafiqah; Nong, Quang D; Sudo, Yuumi; Matsuura, Tomoaki; Wada, Tadashi; Watanabe, Hajime

2018-06-04

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the eukaryotic genome [1] and are important for the control of master regulatory genes that are involved in cell differentiation and development [2, 3]. Here, we show that a 5' UTR-overlapping lncRNA regulates the male-specific expression of the DM-domain gene doublesex1 (dsx1) in the crustacean Daphnia magna, which produces males in response to environmental stimuli. This lncRNA, named doublesex1 alpha promoter-associated long RNA (DAPALR), is transcribed upstream the transcription start site (TSS) in a sense orientation and subjected to 5' end capping and 3' end processing at a stem-loop structure before the dsx1 coding exon. Similar to dsx1, its expression is only activated in males by the juvenile hormone (JH) and basic-leucine zipper (bZIP) transcription factor Vrille (Vri) and is maintained during embryogenesis. Knockdown of DAPALR in males silenced dsx1 and led to feminization, including egg production, whereas ectopic expression of DAPALR in dsx1-silenced females resulted in the de-repression of dsx1. We further demonstrate that the DAPALR transcript overlaps the dsx1 5'-UTR, and this overlapping region is required for dsx1 activation. Our results suggest that DAPALR can transactivate and possibly maintain dsx1 expression. This might be important for converting transient environmental signals into stable male development, controlled by the continuous expression of dsx1. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing the likely effectiveness of multispecies management for imperiled desert fishes with niche overlap analysis

USGS Publications Warehouse

Laub, P; Budy, Phaedra

2015-01-01

A critical decision in species conservation is whether to target individual species or a complex of ecologically similar species. Management of multispecies complexes is likely to be most effective when species share similar distributions, threats, and response to threats. We used niche overlap analysis to assess ecological similarity of 3 sensitive desert fish species currently managed as an ecological complex. We measured the amount of shared distribution of multiple habitat and life history parameters between each pair of species. Habitat use and multiple life history parameters, including maximum body length, spawning temperature, and longevity, differed significantly among the 3 species. The differences in habitat use and life history parameters among the species suggest they are likely to respond differently to similar threats and that most management actions will not benefit all 3 species equally. Habitat restoration, frequency of stream dewatering, non-native species control, and management efforts in tributaries versus main stem rivers are all likely to impact each of the species differently. Our results demonstrate that niche overlap analysis provides a powerful tool for assessing the likely effectiveness of multispecies versus single-species conservation plans.

a Non-Overlapping Discretization Method for Partial Differential Equations

NASA Astrophysics Data System (ADS)

Rosas-Medina, A.; Herrera, I.

2013-05-01

Mathematical models of many systems of interest, including very important continuous systems of Engineering and Science, lead to a great variety of partial differential equations whose solution methods are based on the computational processing of large-scale algebraic systems. Furthermore, the incredible expansion experienced by the existing computational hardware and software has made amenable to effective treatment problems of an ever increasing diversity and complexity, posed by engineering and scientific applications. The emergence of parallel computing prompted on the part of the computational-modeling community a continued and systematic effort with the purpose of harnessing it for the endeavor of solving boundary-value problems (BVPs) of partial differential equations. Very early after such an effort began, it was recognized that domain decomposition methods (DDM) were the most effective technique for applying parallel computing to the solution of partial differential equations, since such an approach drastically simplifies the coordination of the many processors that carry out the different tasks and also reduces very much the requirements of information-transmission between them. Ideally, DDMs intend producing algorithms that fulfill the DDM-paradigm; i.e., such that "the global solution is obtained by solving local problems defined separately in each subdomain of the coarse-mesh -or domain-decomposition-". Stated in a simplistic manner, the basic idea is that, when the DDM-paradigm is satisfied, full parallelization can be achieved by assigning each subdomain to a different processor. When intensive DDM research began much attention was given to overlapping DDMs, but soon after attention shifted to non-overlapping DDMs. This evolution seems natural when the DDM-paradigm is taken into account: it is easier to uncouple the local problems when the subdomains are separated. However, an important limitation of non-overlapping domain decompositions, as that

Clarifying Relations Between Dispositional Aggression and Brain Potential Response: Overlapping and Distinct Contributions of Impulsivity and Stress Reactivity

PubMed Central

Venables, Noah C.; Patrick, Christopher J.; Hall, Jason R.; Bernat, Edward M.

2011-01-01

Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. PMID:21262318

Solving radiative transfer with line overlaps using Gauss-Seidel algorithms

NASA Astrophysics Data System (ADS)

Daniel, F.; Cernicharo, J.

2008-09-01

Context: The improvement in observational facilities requires refining the modelling of the geometrical structures of astrophysical objects. Nevertheless, for complex problems such as line overlap in molecules showing hyperfine structure, a detailed analysis still requires a large amount of computing time and thus, misinterpretation cannot be dismissed due to an undersampling of the whole space of parameters. Aims: We extend the discussion of the implementation of the Gauss-Seidel algorithm in spherical geometry and include the case of hyperfine line overlap. Methods: We first review the basics of the short characteristics method that is used to solve the radiative transfer equations. Details are given on the determination of the Lambda operator in spherical geometry. The Gauss-Seidel algorithm is then described and, by analogy to the plan-parallel case, we see how to introduce it in spherical geometry. Doing so requires some approximations in order to keep the algorithm competitive. Finally, line overlap effects are included. Results: The convergence speed of the algorithm is compared to the usual Jacobi iterative schemes. The gain in the number of iterations is typically factors of 2 and 4 for the two implementations made of the Gauss-Seidel algorithm. This is obtained despite the introduction of approximations in the algorithm. A comparison of results obtained with and without line overlaps for N2H^+, HCN, and HNC shows that the J=3-2 line intensities are significantly underestimated in models where line overlap is neglected.

Improving de novo sequence assembly using machine learning and comparative genomics for overlap correction.

PubMed

Palmer, Lance E; Dejori, Mathaeus; Bolanos, Randall; Fasulo, Daniel

2010-01-15

With the rapid expansion of DNA sequencing databases, it is now feasible to identify relevant information from prior sequencing projects and completed genomes and apply it to de novo sequencing of new organisms. As an example, this paper demonstrates how such extra information can be used to improve de novo assemblies by augmenting the overlapping step. Finding all pairs of overlapping reads is a key task in many genome assemblers, and to this end, highly efficient algorithms have been developed to find alignments in large collections of sequences. It is well known that due to repeated sequences, many aligned pairs of reads nevertheless do not overlap. But no overlapping algorithm to date takes a rigorous approach to separating aligned but non-overlapping read pairs from true overlaps. We present an approach that extends the Minimus assembler by a data driven step to classify overlaps as true or false prior to contig construction. We trained several different classification models within the Weka framework using various statistics derived from overlaps of reads available from prior sequencing projects. These statistics included percent mismatch and k-mer frequencies within the overlaps as well as a comparative genomics score derived from mapping reads to multiple reference genomes. We show that in real whole-genome sequencing data from the E. coli and S. aureus genomes, by providing a curated set of overlaps to the contigging phase of the assembler, we nearly doubled the median contig length (N50) without sacrificing coverage of the genome or increasing the number of mis-assemblies. Machine learning methods that use comparative and non-comparative features to classify overlaps as true or false can be used to improve the quality of a sequence assembly.

Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination

PubMed Central

Han, Li; Masani, Shahnaz; Yu, Kefei

2011-01-01

Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-mediated cassette exchange, we established a cell line-based CSR assay that allows manipulation of switch sequences at the endogenous locus. We show that AGCT is only one of a family of four WGCW motifs in the switch region that can facilitate CSR. We go on to show that it is the overlap of AID hotspots at WGCW sites on the top and bottom strands that is critical. This finding leads to a much clearer model for the difference between CSR and somatic hypermutation. PMID:21709240

Mechanisms of signal transduction by ethylene: overlapping and non-overlapping signalling roles in a receptor family

PubMed Central

Shakeel, Samina N.; Wang, Xiaomin; Binder, Brad M.; Schaller, G. Eric

2013-01-01

The plant hormone ethylene regulates growth and development as well as responses to biotic and abiotic stresses. Over the last few decades, key elements involved in ethylene signal transduction have been identified through genetic approaches, these elements defining a pathway that extends from initial ethylene perception at the endoplasmic reticulum to changes in transcriptional regulation within the nucleus. Here, we present our current understanding of ethylene signal transduction, focusing on recent developments that support a model with overlapping and non-overlapping roles for members of the ethylene receptor family. We consider the evidence supporting this model for sub-functionalization within the receptor family, and then discuss mechanisms by which such a sub-functionalization may occur. To this end, we consider the importance of receptor interactions in modulating their signal output and how such interactions vary in the receptor family. In addition, we consider evidence indicating that ethylene signal output by the receptors involves both phosphorylation-dependent and phosphorylation-independent mechanisms. We conclude with a current model for signalling by the ethylene receptors placed within the overall context of ethylene signal transduction. PMID:23543258

A novel method for overlapping community detection using Multi-objective optimization

NASA Astrophysics Data System (ADS)

Ebrahimi, Morteza; Shahmoradi, Mohammad Reza; Heshmati, Zainabolhoda; Salehi, Mostafa

2018-09-01

The problem of community detection as one of the most important applications of network science can be addressed effectively by multi-objective optimization. In this paper, we aim to present a novel efficient method based on this approach. Also, in this study the idea of using all Pareto fronts to detect overlapping communities is introduced. The proposed method has two main advantages compared to other multi-objective optimization based approaches. The first advantage is scalability, and the second is the ability to find overlapping communities. Despite most of the works, the proposed method is able to find overlapping communities effectively. The new algorithm works by extracting appropriate communities from all the Pareto optimal solutions, instead of choosing the one optimal solution. Empirical experiments on different features of separated and overlapping communities, on both synthetic and real networks show that the proposed method performs better in comparison with other methods.

On the Global Character of Overlap Between Low and High Clouds

NASA Technical Reports Server (NTRS)

Yuan, Tianle; Oreopoulos, Lazaros

2013-01-01

The global character of overlap between low and high clouds is examined using active satellite sensors. Low-cloud fraction has a strong land-ocean contrast with oceanic values double those over land. Major low-cloud regimes include not only the eastern ocean boundary stratocumulus and shallow cumulus but also those associated with cold air outbreaks downwind of wintertime continents and land stratus over particular geographic areas. Globally, about 30% of low clouds are overlapped by high clouds. The overlap rate exhibits strong spatial variability ranging from higher than 90% in the tropics to less than 5% in subsidence areas and is anticorrelated with subsidence rate and low-cloud fraction. The zonal mean of vertical separation between cloud layers is never smaller than 5 km and its zonal variation closely follows that of tropopause height, implying a tight connection with tropopause dynamics. Possible impacts of cloud overlap on low clouds are discussed.

Effects of Application of Social Marketing Theory and the Health Belief Model in Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province, Thailand.

PubMed

Wichachai, Suparp; Songserm, Nopparat; Akakul, Theerawut; Kuasiri, Chanapong

2016-01-01

Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 3060 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample ttest and independent ttest were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in the control group (x=3.82; S.D. =0.20) with statistical significance (p<0.001). This research demonstrated an appropriate communication process in behavioral modification to prevent cervical cancer. It can be recommended that this program featuring social marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

Rapid response team calls that overlap in time: incidence, consequences and patient outcomes.

PubMed

Flabouris, Arthas; Mesecke, Michelle

2017-09-01

To investigate overlap rapid response team (RRT) calls, factors associated with overlap calls, and their impact on RRT call times and patient outcomes. Review of prospectively collected, linked clinical and administrative datasets, at a public adult tertiary hospital during July 2013 to May 2016. There were 11 669 RRT calls to 7223 patients, of which 10 868 calls (93.1%) were to inpatients. The median number of daily calls was 12 (interquartile range [IQR], 9-15 calls; range, 2-29 calls). The median number of daily calls per 1000 hospital admissions was 56.3 (IQR, 41.3- 78.9 calls/1000 admissions; range, 8.3-231.5 calls/1000 admissions), and the median proportion of the day spent at RRT calls was 22.8% (IQR, 16.9%-30.5%). In total, 4575 (39.2%) calls overlapped. Overlap calls, compared with non-overlap calls, had similar patient characteristics, but a longer response time (4 min v 3 min; P < 0.001) and scene time (20 min v 34 min; P < 0.001). The daily number of calls correlated with the number of overnight-stay hospital admissions (r = 0.104; P = 0.001), but not with the total number of hospital admissions (r = -0.035; P = 0.258). The number of overlap calls correlated with the number of RRT calls (r = 0.786; P < 0.001), and also correlated with the proportion of the day spent at RRT calls (r = 0.762; P < 0.001). Overlap calls, compared with non-overlap calls, were more likely to result in an ICU admission (484 calls [11.2%] v 571 calls [8.7%]; P < 0.001). In contrast, efferent limb failure (815 calls [17.8%] v 1195 calls [16.8%]; P = 0.389) and hospital mortality (496 calls [19.3%] v 781 calls [19.6%]; P = 0.823) was similar for overlap and nonoverlap calls, respectively. Overlap RRT calls are common and influenced by overall RRT and hospital activity. They are more likely to be associated with longer response and scene times and unanticipated ICU admissions.

Overexpression of microRNA-125b inhibits human acute myeloid leukemia cells invasion, proliferation and promotes cells apoptosis by targeting NF-κB signaling pathway

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

Wang, Yan; Tang, Ping; Chen, Yanli

microRNA-125b has been reported to play an novel biological function in the progression and development of several kinds of leukemia. However, the detail role of miR-125b in acute myeloid leukemia (AML) is remains largely unknown. The present study aimed to investigate the biological role of miR-125b in AML and the potential molecular mechanism involved in this process. Our results showed that overexpression of miR-125b suppressed AML cells proliferation, invasion and promotes cells apoptosis in a dose-dependent manner, while the miR-NC did not show the same effect. In addition, miR-125b induced AML cells G2/M cell cycle arrest in vitro. Overexpression of miR-125bmore » resulted in a significant decrease of the expression of p-IκB-α and inhibition of IκB-α degradation, and the nuclear translocation of NF-κB subunit p65 was abrogated by miR-125b simutaneously. To further verify that miR-125b targeted NF-κB signaling pathway, the NF-κB-regulated downstream genes that were associated with cell cycle arrest and apoptosis was also determined. The results showed that, miR-125b also affect NF-κB-regulated genes expression involved in cell cycle arrest and apoptosis. In conclusion, the present work certificates that miR-125b can significantly inhibit human AML cells invasion, proliferation and promotes cells apoptosis by targeting the NF-κB signaling pathway, and thus it can be viewed as an promising therapeutic target for AML. - Highlights: • Overexpression of miR-125b suppressed AML cells proliferation, invasion and promotes cells apoptosis. • miR-125b induced AML cells G2/M cell cycle arrest in vitro. • miR-125b suppressed AML cells tumorigenicity and promoted cells apoptosis by targeting NF-κB pathway.« less

Note: Eddy current displacement sensors independent of target conductivity.

PubMed

Wang, Hongbo; Li, Wei; Feng, Zhihua

2015-01-01

Eddy current sensors (ECSs) are widely used for non-contact displacement measurement. In this note, the quantitative error of an ECS caused by target conductivity was analyzed using a complex image method. The response curves (L-x) of the ECS with different targets were similar and could be overlapped by shifting the curves on x direction with √2δ/2. Both finite element analysis and experiments match well with the theoretical analysis, which indicates that the measured error of high precision ECSs caused by target conductivity can be completely eliminated, and the ECSs can measure different materials precisely without calibration.

A Heuristic Parameterization for the Integrated Vertical Overlap of Cumulus and Stratus

NASA Astrophysics Data System (ADS)

Park, Sungsu

2017-10-01

The author developed a heuristic parameterization to handle the contrasting vertical overlap structures of cumulus and stratus in an integrated way. The parameterization assumes that cumulus is maximum-randomly overlapped with adjacent cumulus; stratus is maximum-randomly overlapped with adjacent stratus; and radiation and precipitation areas at each model interface are grouped into four categories, that is, convective, stratiform, mixed, and clear areas. For simplicity, thermodynamic scalars within individual portions of cloud, radiation, and precipitation areas are assumed to be internally homogeneous. The parameterization was implemented into the Seoul National University Atmosphere Model version 0 (SAM0) in an offline mode and tested over the globe. The offline control simulation reasonably reproduces the online surface precipitation flux and longwave cloud radiative forcing (LWCF). Although the cumulus fraction is much smaller than the stratus fraction, cumulus dominantly contributes to precipitation production in the tropics. For radiation, however, stratus is dominant. Compared with the maximum overlap, the random overlap of stratus produces stronger LWCF and, surprisingly, more precipitation flux due to less evaporation of convective precipitation. Compared with the maximum overlap, the random overlap of cumulus simulates stronger LWCF and weaker precipitation flux. Compared with the control simulation with separate cumulus and stratus, the simulation with a single-merged cloud substantially enhances the LWCF in the tropical deep convection and midlatitude storm track regions. The process-splitting treatment of convective and stratiform precipitation with an independent precipitation approximation (IPA) simulates weaker surface precipitation flux than the control simulation in the tropical region.

Overlap between functional abdominal pain disorders and organic diseases in children.

PubMed

Langshaw, A H; Rosen, J M; Pensabene, L; Borrelli, O; Salvatore, S; Thapar, N; Concolino, D; Saps, M

2018-04-02

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59.

PubMed

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C M; Pieterse, Corné M J

2013-02-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCF(COI1), which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCF(COI1)-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59.

Uncovering the overlapping community structure of complex networks by maximal cliques

NASA Astrophysics Data System (ADS)

Li, Junqiu; Wang, Xingyuan; Cui, Yaozu

2014-12-01

In this paper, a unique algorithm is proposed to detect overlapping communities in the un-weighted and weighted networks with considerable accuracy. The maximal cliques, overlapping vertex, bridge vertex and isolated vertex are introduced. First, all the maximal cliques are extracted by the algorithm based on the deep and bread searching. Then two maximal cliques can be merged into a larger sub-graph by some given rules. In addition, the proposed algorithm successfully finds overlapping vertices and bridge vertices between communities. Experimental results using some real-world networks data show that the performance of the proposed algorithm is satisfactory.

Biodiversity Areas under Threat: Overlap of Climate Change and Population Pressures on the World’s Biodiversity Priorities

PubMed Central

Pricope, Narcisa G.; Husak, Gregory J.; Lopez-Carr, David

2017-01-01

Humans and the ecosystem services they depend on are threatened by climate change. Places with high or growing human population as well as increasing climate variability, have a reduced ability to provide ecosystem services just as the need for these services is most critical. A spiral of vulnerability and ecosystem degradation often ensues in such places. We apply different global conservation schemes as proxies to examine the spatial relation between wet season precipitation, population change over three decades, and natural resource conservation. We pose two research questions: 1) Where are biodiversity and ecosystem services vulnerable to the combined effects of climate change and population growth? 2) Where are human populations vulnerable to degraded ecosystem services? Results suggest that globally only about 20% of the area between 50 degrees latitude North and South has experienced significant change–largely wetting–in wet season precipitation. Approximately 40% of rangelands and 30% of rainfed agriculture lands have experienced significant precipitation changes, with important implications for food security. Over recent decades a number of critical conservation areas experienced high population growth concurrent with significant wetting or drying (e.g. the Horn of Africa, Himalaya, Western Ghats, and Sri Lanka), posing challenges not only for human adaptation but also to the protection and sustenance of biodiversity and ecosystem services. Identifying areas of climate and population risk and their overlap with conservation priorities can help to target activities and resources that promote biodiversity and ecosystem services while improving human well-being. PMID:28125659

A vicious loop of fatty acid-binding protein 4 and DNA methyltransferase 1 promotes acute myeloid leukemia and acts as a therapeutic target

PubMed Central

Yan, F; Shen, N; Pang, JX; Zhao, N; Zhang, YW; Bode, AM; Al-Kali, A; Litzow, MR; Li, B; Liu, SJ

2017-01-01

Aberrant DNA methylation mediated by deregulation of DNA methyltransferases (DNMT) is a key hallmark of acute myeloid leukemia (AML), yet efforts to target DNMT deregulation for drug development have lagged. We previously demonstrated that upregulation of fatty acid-binding protein 4 (FABP4) promotes AML aggressiveness through enhanced DNMT1-dependent DNA methylation. Here we demonstrate that FABP4 upregulation in AML cells occurs through vascular endothelial growth factor (VEGF) signaling, thus elucidating a crucial FABP4-DNMT1 regulatory feedback loop in AML biology. We show that FABP4 dysfunction by its selective inhibitor BMS309403 leads to downregulation of DNMT1, decrease of global DNA methylation and re-expression of p15INK4B tumor suppressor gene by promoter DNA hypomethylation in vitro, ex vivo and in vivo. Functionally, BMS309403 suppresses cell colony formation, induces cell differentiation, and, importantly, impairs leukemic disease progression in mouse models of leukemia. Our findings highlight AML-promoting properties of the FABP4-DNMT1 vicious loop, and identify an attractive class of therapeutic agents with a high potential for clinical use in AML patients. The results will also assist in establishing the FABP4-DNMT1 loop as a target for therapeutic discovery to enhance the index of current epigenetic therapies. PMID:28993705

ROS1 fusions rarely overlap with other oncogenic drivers in non-small cell lung cancer

PubMed Central

Lin, Jessica J.; Ritterhouse, Lauren L.; Ali, Siraj M.; Bailey, Mark; Schrock, Alexa B.; Gainor, Justin F.; Ferris, Lorin A.; Mino-Kenudson, Mari; Miller, Vincent A.; Iafrate, Anthony J.; Lennerz, Jochen K.; Shaw, Alice T.

2017-01-01

Introduction Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). Methods We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK). Clinicopathologic features and genetic testing results were reviewed. We also examined a separate database of ROS1-rearranged NSCLCs identified through a commercial FoundationOne assay. Results Among 62 patients with ROS1-rearranged NSCLC evaluated at our institution, none harbored concurrent ALK fusions (0%) or EGFR activating mutations (0%). KRAS mutations were detected in two cases (3.2%), one of which harbored a concurrent non-canonical KRAS I24N mutation of unknown biological significance. In a separate ROS1 FISH-positive case, targeted sequencing failed to confirm a ROS1 fusion, but instead identified a KRAS G13D mutation. No concurrent mutations in BRAF, ERBB2, PIK3CA, AKT1, or MAP2K1 were detected. Analysis of an independent dataset of 166 ROS1-rearranged NSCLCs identified by FoundationOne demonstrated rare cases with co-occurring driver mutations in EGFR (1/166) and KRAS (3/166), and no cases with co-occurring ROS1 and ALK rearrangements. Conclusions ROS1 rearrangements rarely overlap with alterations in EGFR, KRAS, ALK, or other targetable oncogenes in NSCLC. PMID:28088512

Architecture and dynamics of overlapped RNA regulatory networks.

PubMed

Lapointe, Christopher P; Preston, Melanie A; Wilinski, Daniel; Saunders, Harriet A J; Campbell, Zachary T; Wickens, Marvin

2017-11-01

A single protein can bind and regulate many mRNAs. Multiple proteins with similar specificities often bind and control overlapping sets of mRNAs. Yet little is known about the architecture or dynamics of overlapped networks. We focused on three proteins with similar structures and related RNA-binding specificities-Puf3p, Puf4p, and Puf5p of S. cerevisiae Using RNA Tagging, we identified a "super-network" comprised of four subnetworks: Puf3p, Puf4p, and Puf5p subnetworks, and one controlled by both Puf4p and Puf5p. The architecture of individual subnetworks, and thus the super-network, is determined by competition among particular PUF proteins to bind mRNAs, their affinities for binding elements, and the abundances of the proteins. The super-network responds dramatically: The remaining network can either expand or contract. These strikingly opposite outcomes are determined by an interplay between the relative abundance of the RNAs and proteins, and their affinities for one another. The diverse interplay between overlapping RNA-protein networks provides versatile opportunities for regulation and evolution. © 2017 Lapointe et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Chemometric Data Analysis for Deconvolution of Overlapped Ion Mobility Profiles

NASA Astrophysics Data System (ADS)

Zekavat, Behrooz; Solouki, Touradj

2012-11-01

We present the details of a data analysis approach for deconvolution of the ion mobility (IM) overlapped or unresolved species. This approach takes advantage of the ion fragmentation variations as a function of the IM arrival time. The data analysis involves the use of an in-house developed data preprocessing platform for the conversion of the original post-IM/collision-induced dissociation mass spectrometry (post-IM/CID MS) data to a Matlab compatible format for chemometric analysis. We show that principle component analysis (PCA) can be used to examine the post-IM/CID MS profiles for the presence of mobility-overlapped species. Subsequently, using an interactive self-modeling mixture analysis technique, we show how to calculate the total IM spectrum (TIMS) and CID mass spectrum for each component of the IM overlapped mixtures. Moreover, we show that PCA and IM deconvolution techniques provide complementary results to evaluate the validity of the calculated TIMS profiles. We use two binary mixtures with overlapping IM profiles, including (1) a mixture of two non-isobaric peptides (neurotensin (RRPYIL) and a hexapeptide (WHWLQL)), and (2) an isobaric sugar isomer mixture of raffinose and maltotriose, to demonstrate the applicability of the IM deconvolution.

An improved game-theoretic approach to uncover overlapping communities

NASA Astrophysics Data System (ADS)

Sun, Hong-Liang; Ch'Ng, Eugene; Yong, Xi; Garibaldi, Jonathan M.; See, Simon; Chen, Duan-Bing

How can we uncover overlapping communities from complex networks to understand the inherent structures and functions? Chen et al. firstly proposed a community game (Game) to study this problem, and the overlapping communities have been discovered when the game is convergent. It is based on the assumption that each vertex of the underlying network is a rational game player to maximize its utility. In this paper, we investigate how similar vertices affect the formation of community game. The Adamic-Adar Index (AA Index) has been employed to define the new utility function. This novel method has been evaluated on both synthetic and real-world networks. Experimental study shows that it has significant improvement of accuracy (from 4.8% to 37.6%) compared with the Game on 10 real networks. It is more efficient on Facebook networks (FN) and Amazon co-purchasing networks than on other networks. This result implicates that “friend circles of friends” of Facebook are valuable to understand the overlapping community division.

Quantum state and mode profile tomography by the overlap

NASA Astrophysics Data System (ADS)

Tiedau, J.; Shchesnovich, V. S.; Mogilevtsev, D.; Ansari, V.; Harder, G.; Bartley, T. J.; Korolkova, N.; Silberhorn, Ch

2018-03-01

Any measurement scheme involving interference of quantum states of the electromagnetic field necessarily mixes information about the spatiotemporal structure of these fields and quantum states in the recorded data. We show that in this case, a trade-off is possible between extracting information about the quantum states and the structure of the underlying fields, with the modal overlap being either a goal or a convenient tool of the reconstruction. We show that varying quantum states in a controlled way allows one to infer temporal profiles of modes. Vice versa, for the known quantum state of the probe and controlled variable overlap, one can infer the quantum state of the signal. We demonstrate this trade-off by performing an experiment using the simplest on-off detection in an unbalanced weak homodyning scheme. For the single-mode case, we demonstrate experimentally inference of the overlap and a few-photon signal state. Moreover, we show theoretically that the same single-detector scheme is sufficient even for arbitrary multi-mode fields.

STITCHER 2.0: primer design for overlapping PCR applications.

PubMed

O'Halloran, Damien M; Uriagereka-Herburger, Isabel; Bode, Katrin

2017-03-30

Overlapping polymerase chain reaction (PCR) is a common technique used by researchers in very diverse fields that enables the user to 'stitch' individual pieces of DNA together. Previously, we have reported a web based tool called STITCHER that provides a platform for researchers to automate the design of primers for overlapping PCR applications. Here we present STITCHER 2.0, which represents a substantial update to STITCHER. STITCHER 2.0 is a newly designed web tool that automates the design of primers for overlapping PCR. Unlike STITCHER, STITCHER 2.0 considers diverse algorithmic parameters, and returns multiple result files that include a facility for the user to draw their own primers as well as comprehensive visual guides to the user's input, output, and designed primers. These result files provide greater control and insight during experimental design and troubleshooting. STITCHER 2.0 is freely available to all users without signup or login requirements and can be accessed at the following webpage: www.ohalloranlab.net/STITCHER2.html.

MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2.

PubMed

He, Yu; Ge, Yugang; Jiang, Mingkun; Zhou, Jundong; Luo, Dakui; Fan, Hao; Shi, Liang; Lin, Linling; Yang, Li

2018-06-21

Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial-mesenchymal transition (EMT) were detected with western blot. The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC. © 2018 The Author(s). Published by S. Karger AG, Basel.

Successful COG8 and PDF overlap is mediated by alterations in splicing and polyadenylation signals.

PubMed

Pereira-Castro, Isabel; Quental, Rita; da Costa, Luís T; Amorim, António; Azevedo, Luisa

2012-02-01

Although gene-free areas compose the great majority of eukaryotic genomes, a significant fraction of genes overlaps, i.e., unique nucleotide sequences are part of more than one transcription unit. In this work, the evolutionary history and origin of a same-strand gene overlap is dissected through the analysis of COG8 (component of oligomeric Golgi complex 8) and PDF (peptide deformylase). Comparative genomic surveys reveal that the relative locations of these two genes have been changing over the last 445 million years from distinct chromosomal locations in fish to overlapping in rodents and primates, indicating that the overlap between these genes precedes their divergence. The overlap between the two genes was initiated by the gain of a novel splice donor site between the COG8 stop codon and PDF initiation codon. Splicing is accomplished by the use of the PDF acceptor, leading COG8 to share the 3'end with PDF. In primates, loss of the ancestral polyadenylation signal for COG8 makes the overlap between COG8 and PDF mandatory, while in mouse and rat concurrent overlapping and non-overlapping Cog8 transcripts exist. Altogether, we demonstrate that the origin, evolution and preservation of the COG8/PDF same-strand overlap follow similar mechanistic steps as those documented for antisense overlaps where gain and/or loss of splice sites and polyadenylation signals seems to drive the process.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

PubMed

Liu, Chuanxia; Feng, Xiaoxia; Wang, Baixiang; Wang, Xinhua; Wang, Chaowei; Yu, Mengfei; Cao, Guifen; Wang, Huiming

2018-03-01

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

[Symptom overlaps between functional heartburn, functional dyspepsia, and irritable bowel syndrome].

PubMed

2014-05-01

To determine symptom overlaps between functional heartburn (FH), functional dyspepsia (FD), and irritable bowel syndrome (IBS). One hundred and ten patients with frequent heartburn but no mucosa breakage under endoscopy were enrolled consecutively. They were required to fill out a questionnaire. The overlapped symptoms of FD and IBS symptoms were screened using Rome ill criteria. The participants were also examined using Hamilton anxiety scale/Hamilton depression scale. All of the participants were followed with 24 h esophageal multichannel intra-luminal impedance monitoring with pH sensor (MII-pH) monitoring and proton pump inhibitor (PPI) trials. The participants were divided into non-erosive reflux disease (NERD) and FH groups. The prevalence of symptom overlaps FD and IBS, between NERD and FH groups was analyzed. Women were more likely to present with FH than with NERD (P < 0.05). The participants with FH had higher prevalence of anxiety and depression than those with NERD (92% vs. 75%, 88% vs. 65% respectively, P < 0.05). Fifty-two (47.3%) patients with heartburn symptom had FD symptoms; 31 (28.2%) had IBS symptoms, and 10 (9.09%) had both FD and IBS symptoms. Patients with FH were more likely to have symptom overlaps of FD and IBS than those with NERD (62% vs. 35%, 48% vs. 11.7%, respectively; P < 0.01). Epigastric pain syndrome (EPS), a subtype of FD, was slightly more likely to have overlapped NERD and FH symptoms than postprandial discomfort symdrome (PDS). But the difference was not significant (29. 1% vs. 18.2%, P > 0.05). IBS-diarrhea was also slightly more likely to have overlapped NERD and FH symptoms than IBS-constipation. Again, the difference was not significant (16.4% vs. 11.8%, P > 0.05). Female, higher prevalence of anxiety and depression, overlapped FD and IBS symptoms are more likely to appear in FH patients than in NERD patients.

miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4

PubMed Central

Zhang, Chen-Peng; Xiao, Qian; Lin, Xiao-Lin

2017-01-01

Aim Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. Methods miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. Results We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. Conclusions Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. PMID:29065177

On the radiative properties of soot aggregates part 1: Necking and overlapping

NASA Astrophysics Data System (ADS)

Yon, J.; Bescond, A.; Liu, F.

2015-09-01

There is a strong interest in accurately modelling the radiative properties of soot aggregates (also known as black carbon particles) emitted from combustion systems and fires to gain improved understanding of the role of black carbon to global warming. This study conducted a systematic investigation of the effects of overlapping and necking between neighbouring primary particles on the radiative properties of soot aggregates using the discrete dipole approximation. The degrees of overlapping and necking are quantified by the overlapping and necking parameters. Realistic soot aggregates were generated numerically by constructing overlapping and necking to fractal aggregates formed by point-touch primary particles simulated using a diffusion-limited cluster aggregation algorithm. Radiative properties (differential scattering, absorption, total scattering, specific extinction, asymmetry factor and single scattering albedo) were calculated using the experimentally measured soot refractive index over the spectral range of 266-1064 nm for 9 combinations of the overlapping and necking parameters. Overlapping and necking affect significantly the absorption and scattering properties of soot aggregates, especially in the near UV spectrum due to the enhanced multiple scattering effects within an aggregate. By using correctly modified aggregate properties (fractal dimension, prefactor, primary particle radius, and the number of primary particle) and by accounting for the effects of multiple scattering, the simple Rayleigh-Debye-Gans theory for fractal aggregates can reproduce reasonably accurate radiative properties of realistic soot aggregates.

Universal Multifunctional Nanoplatform Based on Target-Induced in Situ Promoting Au Seeds Growth to Quench Fluorescence of Upconversion Nanoparticles.

PubMed

Wu, Qiongqiong; Chen, Hongyu; Fang, Aijin; Wu, Xinyang; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

2017-12-22

Construction of a new multifunctional chemo/biosensing platform for small biomolecules and tumor markers is of great importance in analytical chemistry. Herein, a novel universal multifunctional nanoplatform for biomolecules and enzyme activity detection was proposed based on fluorescence resonance energy transfer (FRET) between upconversion nanoparticles (UCNPs) and target-inducing enlarged gold nanoparticles (AuNPs). The reductive molecule such as H 2 O 2 can act as the reductant to reduce HAuCl 4 , which will make the Au seeds grow. The enlarged AuNPs can effectively quench the fluorescence of UCNPs owing to the good spectral overlap between the absorption band of the AuNPs and the emission band of the UCNPs. Utilizing the FRET between the UCNPs and enlarged AuNPs, good linear relationship between the fluorescence of UCNPs and the concentration of H 2 O 2 can be found. Based on this strategy, H 2 O 2 related molecules such as l-lactate, glucose, and uric acid can also be quantified. On the basis of UCNPs and PVP/HAuCl 4 , a general strategy for other reductants such as ascorbic acid (AA), dopamine (DA), or enzyme activity can be established. Therefore, the universal multifunctional nanoplatform based on UCNPs and the target-inducing in situ enlarged Au NPs will show its potential as a simple method for the detection of some life related reductive molecules, enzyme substrates, as well as enzyme activity.

Interleukin-22 promotes aerobic glycolysis associated with tumor progression via targeting hexokinase-2 in human colon cancer cells.

PubMed

Liu, Yulin; Xiang, Fan; Huang, Yongming; Shi, Liang; Hu, Chaojie; Yang, Yiming; Wang, Di; He, Nan; Tao, Kaixiong; Wu, Ke; Wang, Guobin

2017-04-11

Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.

Investigation of Overlap Correction Techniques for Application in the Micro-Pulse Lidar Network (MPLNET)

NASA Technical Reports Server (NTRS)

Berkoff, Timothy A.; Welton, Ellsworth J.; Campbell, James R.; Scott, Vibart S.; Spinhirne, James D.

2003-01-01

The Micro-Pulse Lidar NETwork (MPLNET) is comprised of micro-pulse lidars (MPL) stationed around the globe to provide measurements of aerosol and cloud vertical distribution on a continuous basis. MPLNET sites are co-located with sunphotometers in the AErosol Robotic NETwork (AERONET) to provide joint measurements of aerosol optical depth, size, and other inherent optical properties. The IPCC 2001 report discusses . the importance of obtaining routine measurements of aerosol vertical structure, especially for absorbing aerosols. MPLNET provides exactly this sort of measurement, including calculation of aerosol extinction profiles, in a near real-time basis for all sites in the network. In order to obtain aerosol profiles, near range signal returns (0-6 km) must be accurately measured by the MPL. This measurement is complicated by the instrument s overlap range: Le., the minimum distance at which returning signals are completely in the instrument s field-of-view (FOV). Typical MPL overlap distances are large, between 5 - 6 km, due to the narrow FOV of the MPL receiver. A function describing the MPL overlap must be determined and used to correct signals in this range. Currently, overlap functions for MPLNET are determined using horizontal MPL measurements along a path with 10-1 5 km clear line-of-sight and a homogenous atmosphere. These conditions limit the location and ease in which successful overlaps can be obtained. Furthermore, the current MPLNET process of correcting for overlap increases the uncertainty and bias error for the near range signals and the resulting aerosol extinction profiles. To address these issues, an alternative overlap correction method using a small-diameter, wide FOV receiver is being considered for potential use in MPLNET. The wide FOV receiver has a much shorter overlap distance and will be used to calculate the overlap function of the MPL receiver. This approach has a significant benefit in that overlap corrections could be obtained

miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis

PubMed Central

Sun, Xiaojuan; Charbonneau, Cherie; Wei, Lei; Chen, Qian; Terek, Richard M.

2015-01-01

Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis, however its role in chondrosarcoma is undetermined. MicroRNA-181a is overexpressed in high grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine if miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis, however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the anti-angiogenic and anti-metastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. PMID:26013170

Efficient and Flexible Computation of Many-Electron Wave Function Overlaps.

PubMed

Plasser, Felix; Ruckenbauer, Matthias; Mai, Sebastian; Oppel, Markus; Marquetand, Philipp; González, Leticia

2016-03-08

A new algorithm for the computation of the overlap between many-electron wave functions is described. This algorithm allows for the extensive use of recurring intermediates and thus provides high computational efficiency. Because of the general formalism employed, overlaps can be computed for varying wave function types, molecular orbitals, basis sets, and molecular geometries. This paves the way for efficiently computing nonadiabatic interaction terms for dynamics simulations. In addition, other application areas can be envisaged, such as the comparison of wave functions constructed at different levels of theory. Aside from explaining the algorithm and evaluating the performance, a detailed analysis of the numerical stability of wave function overlaps is carried out, and strategies for overcoming potential severe pitfalls due to displaced atoms and truncated wave functions are presented.

Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection.

PubMed

Li, Wenna; Ke, Yuehua; Wang, Yufei; Yang, Mingjuan; Gao, Junguang; Zhan, Shaoxia; Xinying, Du; Huang, Liuyu; Li, Wenfeng; Chen, Zeliang; Li, Juan

2016-08-26

Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-κB activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified. Here, we confirmed the effect of TcpB on B.melitensis virulence in mice and found that TcpB selectively targets MAL. By using siRNA against MAL, we found that TcpB from B.melitensis is involved in intracellular survival and that MAL affects intracellular replication of B.melitensis. Our results confirm that TcpB specifically targets MAL/TIRAP to disrupt downstream signaling pathways and promote intra-host survival of Brucella spp. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

The influence of dimensional overlap on location-related priming in the Simon task.

PubMed

Lehle, Carola; Stürmer, Birgit; Sommer, Werner

2013-01-01

Choice reaction times are shorter when stimulus and response locations are compatible than when they are incompatible as in the Simon effect. Recent studies revealed that Simon effects are strongly attenuated when there is temporal overlap with a different high-priority task, accompanied by a decrease of early location-related response priming as reflected in the lateralized readiness potential (LRP). The latter result was obtained in a study excluding overlap of stimulus location with any other dimension in the tasks. Independent evidence suggests that location-related priming might be present in conditions with dimensional overlap. Here we tested this prediction in a dual-task experiment supplemented with recording LRPs. The secondary task was either a standard Simon task where irrelevant stimulus location overlapped with dimensions of the primary task or a Stroop-like Simon task including additional overlap of irrelevant and relevant stimulus attributes. At high temporal overlap, there was no Simon effect nor was there stimulus-related response priming in either condition. Therefore stimulus-triggered response priming seems to be abolished in conditions of limited capacity even if the likelihood of an S-R compatibility effect is maximized.

Extracting attosecond delays from spectrally overlapping interferograms

NASA Astrophysics Data System (ADS)

Jordan, Inga; Wörner, Hans Jakob

2018-02-01

Attosecond interferometry is becoming an increasingly popular technique for measuring the dynamics of photoionization in real time. Whereas early measurements focused on atomic systems with very simple photoelectron spectra, the technique is now being applied to more complex systems including isolated molecules and solids. The increase in complexity translates into an augmented spectral congestion, unavoidably resulting in spectral overlap in attosecond interferograms. Here, we discuss currently used methods for phase retrieval and introduce two new approaches for determining attosecond photoemission delays from spectrally overlapping photoelectron spectra. We show that the previously used technique, consisting in the spectral integration of the areas of interest, does in general not provide reliable results. Our methods resolve this problem, thereby opening the technique of attosecond interferometry to complex systems and fully exploiting its specific advantages in terms of spectral resolution compared to attosecond streaking.

[The Discursive Analysis of Mental Health Promotion Efforts Targeting Community-Dwelling Young Adults at High Risk of Mental Illness].

PubMed

Hsiung, Der-Yun; Yang, Tzu-Ching; Ma, Wei-Fen

2015-08-01

The mental health of adolescents and young adults is an issue of concern worldwide due to the increase in violent incidents that have been perpetrated by members of this age group. Young people at high-risk of mental disability are easily ignored. Therefore, social tensions in society have increased due to safety issues arising from the problems that are associated with mental disabilities in this population. This paper discusses the importance of early identification and early prevention of mental disabilities in high-risk young people, defines high-risk mental illness, and identifies the various subcategories of mental diseases. Based on our review of the literature, the present paper suggests targeting young people in high-risk categories with health promotion that addresses the following six health-promotion lifestyle habits: engaging in regular exercise, eating a balanced diet, managing stress, engaging in social relationships, taking responsibility for personal health, and fulfilling self-actualization. This discursive analysis discusses these strategies as safe and sustained interventions for adolescents and young adults that may improve self-awareness and thus maintain health and enhance opportunities to promote an ideal health status.

Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe.

PubMed

Hickey, Anthony; Esnault, Caroline; Majumdar, Anasuya; Chatterjee, Atreyi Ghatak; Iben, James R; McQueen, Philip G; Yang, Andrew X; Mizuguchi, Takeshi; Grewal, Shiv I S; Levin, Henry L

2015-11-01

Transposable elements (TEs) constitute a substantial fraction of the eukaryotic genome and, as a result, have a complex relationship with their host that is both adversarial and dependent. To minimize damage to cellular genes, TEs possess mechanisms that target integration to sequences of low importance. However, the retrotransposon Tf1 of Schizosaccharomyces pombe integrates with a surprising bias for promoter sequences of stress-response genes. The clustering of integration in specific promoters suggests that Tf1 possesses a targeting mechanism that is important for evolutionary adaptation to changes in environment. We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration. A mutation in Sap1 resulted in a 10-fold drop in Tf1 transposition, and measures of transposon intermediates support the argument that the defect occurred in the process of integration. Published ChIP-Seq data on Sap1 binding combined with high-density maps of Tf1 integration that measure independent insertions at single-nucleotide positions show that 73.4% of all integration occurs at genomic sequences bound by Sap1. This represents high selectivity because Sap1 binds just 6.8% of the genome. A genome-wide analysis of promoter sequences revealed that Sap1 binding and amounts of integration correlate strongly. More important, an alignment of the DNA-binding motif of Sap1 revealed integration clustered on both sides of the motif and showed high levels specifically at positions +19 and -9. These data indicate that Sap1 contributes to the efficiency and position of Tf1 integration. Copyright © 2015 by the Genetics Society of America.

Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe

PubMed Central

Hickey, Anthony; Esnault, Caroline; Majumdar, Anasuya; Chatterjee, Atreyi Ghatak; Iben, James R.; McQueen, Philip G.; Yang, Andrew X.; Mizuguchi, Takeshi; Grewal, Shiv I. S.; Levin, Henry L.

2015-01-01

Transposable elements (TEs) constitute a substantial fraction of the eukaryotic genome and, as a result, have a complex relationship with their host that is both adversarial and dependent. To minimize damage to cellular genes, TEs possess mechanisms that target integration to sequences of low importance. However, the retrotransposon Tf1 of Schizosaccharomyces pombe integrates with a surprising bias for promoter sequences of stress-response genes. The clustering of integration in specific promoters suggests that Tf1 possesses a targeting mechanism that is important for evolutionary adaptation to changes in environment. We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration. A mutation in Sap1 resulted in a 10-fold drop in Tf1 transposition, and measures of transposon intermediates support the argument that the defect occurred in the process of integration. Published ChIP-Seq data on Sap1 binding combined with high-density maps of Tf1 integration that measure independent insertions at single-nucleotide positions show that 73.4% of all integration occurs at genomic sequences bound by Sap1. This represents high selectivity because Sap1 binds just 6.8% of the genome. A genome-wide analysis of promoter sequences revealed that Sap1 binding and amounts of integration correlate strongly. More important, an alignment of the DNA-binding motif of Sap1 revealed integration clustered on both sides of the motif and showed high levels specifically at positions +19 and −9. These data indicate that Sap1 contributes to the efficiency and position of Tf1 integration. PMID:26358720

Can a model of overlapping gestures account for scanning speech patterns?

PubMed

Tjaden, K

1999-06-01

A simple acoustic model of overlapping, sliding gestures was used to evaluate whether coproduction was reduced for neurologic speakers with scanning speech patterns. F2 onset frequency was used as an acoustic measure of coproduction or gesture overlap. The effects of speaking rate (habitual versus fast) and utterance position (initial versus medial) on F2 frequency, and presumably gesture overlap, were examined. Regression analyses also were used to evaluate the extent to which across-repetition temporal variability in F2 trajectories could be explained as variation in coproduction for consonants and vowels. The lower F2 onset frequencies for disordered speakers suggested that gesture overlap was reduced for neurologic individuals with scanning speech. Speaking rate change did not influence F2 onset frequencies, and presumably gesture overlap, for healthy or disordered speakers. F2 onset frequency differences for utterance-initial and -medial repetitions were interpreted to suggest reduced coproduction for the utterance-initial position. The utterance-position effects on F2 onset frequency, however, likely were complicated by position-related differences in articulatory scaling. The results of the regression analysis indicated that gesture sliding accounts, in part, for temporal variability in F2 trajectories. Taken together, the results of this study provide support for the idea that speech production theory for healthy talkers helps to account for disordered speech production.

The Influence of Sex and Season on Conspecific Spatial Overlap in a Large, Actively-Foraging Colubrid Snake

PubMed Central

Bauder, Javan M.; Breininger, David R.; Bolt, M. Rebecca; Legare, Michael L.; Jenkins, Christopher L.; Rothermel, Betsie B.; McGarigal, Kevin

2016-01-01

Understanding the factors influencing the degree of spatial overlap among conspecifics is important for understanding multiple ecological processes. Compared to terrestrial carnivores, relatively little is known about the factors influencing conspecific spatial overlap in snakes, although across snake taxa there appears to be substantial variation in conspecific spatial overlap. In this study, we described conspecific spatial overlap of eastern indigo snakes (Drymarchon couperi) in peninsular Florida and examined how conspecific spatial overlap varied by sex and season (breeding season vs. non-breeding season). We calculated multiple indices of spatial overlap using 6- and 3-month utilization distributions (UD) of dyads of simultaneously adjacent telemetered snakes. We also measured conspecific UD density values at each telemetry fix and modeled the distribution of those values as a function of overlap type, sex, and season using generalized Pareto distributions. Home range overlap between males and females was significantly greater than overlap between individuals of the same sex and male home ranges often completely contained female home ranges. Male home ranges overlapped little during both seasons, whereas females had higher levels of overlap during the non-breeding season. The spatial patterns observed in our study are consistent with those seen in many mammalian carnivores, in which low male-male overlap and high inter-sexual overlap provides males with greater access to females. We encourage additional research on the influence of prey availability on conspecific spatial overlap in snakes as well as the behavioral mechanisms responsible for maintaining the low levels of overlap we observed. PMID:27490346

[Novel bidirectional promoter from human genome].

PubMed

Orekhova, A S; Sverdlova, P S; Spirin, P V; Leonova, O G; Popenko, V I; Prasolov, V S; Rubtsov, P M

2011-01-01

In human and other mammalian genomes a number of closely linked gene pairs transcribed in opposite directions are found. According to bioinformatic analysis up to 10% of human genes are arranged in this way. In present work the fragment of human genome was cloned that separates genes localized at 2p13.1 and oriented "head-to-head", coding for hypothetical proteins with unknown functions--CCDC (Coiled Coil Domain Containing) 142 and TTC (TetraTricopeptide repeat Containing) 31. Intergenic CCDC142-TTC31 region overlaps with CpG-island and contains a number of potential binding sites for transcription factors. This fragment functions as bidirectional promoter in the system ofluciferase reporter gene expression upon transfection of human embryonic kidney (HEK293) cells. The vectors containing genes of two fluorescent proteins--green (EGFP) and red (DsRed2) in opposite orientations separated by the fragment of CCDC142-TTC31 intergenic region were constructed. In HEK293 cells transfected with these vectors simultaneous expression of two fluorescent proteins is observed. Truncated versions of intergenic region were obtained and their promoter activity measured. Minimal promoter fragment contains elements Inr, BRE, DPE characteristic for TATA-less promoters. Thus, from the human genome the novel bidirectional promoter was cloned that can be used for simultaneous constitutive expression of two genes in human cells.

Local–global overlap in diversity informs mechanisms of bacterial biogeography

PubMed Central

Livermore, Joshua A; Jones, Stuart E

2015-01-01

Spatial variation in environmental conditions and barriers to organism movement are thought to be important factors for generating endemic species, thus enhancing global diversity. Recent microbial ecology research suggested that the entire diversity of bacteria in the global oceans could be recovered at a single site, thus inferring a lack of bacterial endemism. We argue this is not the case in the global ocean, but might be in other bacterial ecosystems with higher dispersal rates and lower global diversity, like the human gut. We quantified the degree to which local and global bacterial diversity overlap in a diverse set of ecosystems. Upon comparison of observed local–global diversity overlap with predictions from a neutral biogeography model, human-associated microbiomes (gut, skin, mouth) behaved much closer to neutral expectations whereas soil, lake and marine communities deviated strongly from the neutral expectations. This is likely a result of differences in dispersal rate among ‘patches', global diversity of these systems, and local densities of bacterial cells. It appears that overlap of local and global bacterial diversity is surprisingly large (but likely not one-hundred percent), and most importantly this overlap appears to be predictable based upon traditional biogeographic parameters like community size, global diversity, inter-patch environmental heterogeneity and patch connectivity. PMID:25848869

Unsupervised Learning of Overlapping Image Components Using Divisive Input Modulation

PubMed Central

Spratling, M. W.; De Meyer, K.; Kompass, R.

2009-01-01

This paper demonstrates that nonnegative matrix factorisation is mathematically related to a class of neural networks that employ negative feedback as a mechanism of competition. This observation inspires a novel learning algorithm which we call Divisive Input Modulation (DIM). The proposed algorithm provides a mathematically simple and computationally efficient method for the unsupervised learning of image components, even in conditions where these elementary features overlap considerably. To test the proposed algorithm, a novel artificial task is introduced which is similar to the frequently-used bars problem but employs squares rather than bars to increase the degree of overlap between components. Using this task, we investigate how the proposed method performs on the parsing of artificial images composed of overlapping features, given the correct representation of the individual components; and secondly, we investigate how well it can learn the elementary components from artificial training images. We compare the performance of the proposed algorithm with its predecessors including variations on these algorithms that have produced state-of-the-art performance on the bars problem. The proposed algorithm is more successful than its predecessors in dealing with overlap and occlusion in the artificial task that has been used to assess performance. PMID:19424442

Overlapping Modularity at the Critical Point of k-Clique Percolation

NASA Astrophysics Data System (ADS)

Tóth, Bálint; Vicsek, Tamás; Palla, Gergely

2013-05-01

One of the most remarkable social phenomena is the formation of communities in social networks corresponding to families, friendship circles, work teams, etc. Since people usually belong to several different communities at the same time, the induced overlaps result in an extremely complicated web of the communities themselves. Thus, uncovering the intricate community structure of social networks is a non-trivial task with great potential for practical applications, gaining a notable interest in the recent years. The Clique Percolation Method (CPM) is one of the earliest overlapping community finding methods, which was already used in the analysis of several different social networks. In this approach the communities correspond to k-clique percolation clusters, and the general heuristic for setting the parameters of the method is to tune the system just below the critical point of k-clique percolation. However, this rule is based on simple physical principles and its validity was never subject to quantitative analysis. Here we examine the quality of the partitioning in the vicinity of the critical point using recently introduced overlapping modularity measures. According to our results on real social and other networks, the overlapping modularities show a maximum close to the critical point, justifying the original criteria for the optimal parameter settings.

Stitching interferometry of a full cylinder without using overlap areas

NASA Astrophysics Data System (ADS)

Peng, Junzheng; Chen, Dingfu; Yu, Yingjie

2017-08-01

Traditional stitching interferometry requires finding out the overlap correspondence and computing the discrepancies in the overlap regions, which makes it complex and time-consuming to obtain the 360° form map of a cylinder. In this paper, we develop a cylinder stitching model based on a new set of orthogonal polynomials, termed Legendre Fourier (LF) polynomials. With these polynomials, individual subaperture data can be expanded as a composition of the inherent form of a partial cylinder surface and additional misalignment parameters. Then the 360° form map can be acquired by simultaneously fitting all subaperture data with the LF polynomials. A metal shaft was measured to experimentally verify the proposed method. In contrast to traditional stitching interferometry, our technique does not require overlapping of adjacent subapertures, thus significantly reducing the measurement time and making the stitching algorithm simple.

Living as an LGBTQ Adolescent and a Parent's Child: Overlapping or Separate Experiences.

PubMed

Mehus, Christopher J; Watson, Ryan J; Eisenberg, Marla E; Corliss, Heather L; Porta, Carolyn M

2017-05-01

It is well known that parental and community-based support are each related to healthy development in lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) youth, but little research has explored the ways these contexts interact and overlap. Through go-along interviews (a method in which participants guide the interviewer around the community) with 66 youth in British Columbia, Massachusetts, and Minnesota, adolescents (aged 14-19 years) reported varying extent of overlap between their LGBTQ experiences and their parent-youth experiences; parents and youth each contributed to the extent of overlap. Youth who reported high overlap reported little need for resources outside their families but found resources easy to access if wanted. Youth who reported little overlap found it difficult to access resources. Findings suggest that in both research and practice, considering the extent to which youth feel they can express their authentic identity in multiple contexts may be more useful than simply evaluating parental acceptance or access to resources.

miR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

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

Wang, Baocan; Li, Wenxi; Guo, Kun

2012-04-27

Highlights: Black-Right-Pointing-Pointer miR-181a and miR-181b, especially, miR-181b could be induced by transforming growth factor-beta 1 (TGF-{beta}1) in hepatic stellate cells. Black-Right-Pointing-Pointer miR-181b could promote HSC-T6 cell proliferation by directly targeting the negative cell regulator-p27 in HSC-T6 cell. Black-Right-Pointing-Pointer miR-181b was identified as potential serum diagnostic marker for liver cirrhosis patients. -- Abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because ofmore » the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-{beta}1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-{beta}1 pathway by a currently unknown mechanism.« less

Parenting for the promotion of adolescent mental health: a scoping review of programmes targeting ethnoculturally diverse families.

PubMed

Ruiz-Casares, Mónica; Drummond, Jennifer D; Beeman, Irene; Lach, Lucyna M

2017-03-01

A scoping review of the literature on parenting programmes that target the promotion of adolescent mental health was conducted to examine the quality of the studies and unique content of programmes for parents from ethnoculturally diverse communities. PsycINFO and Web of Science were searched in April, 2011 (for all publications prior to that date) and again in August, 2015 (for publications from April, 2011 to August, 2015) using specific keywords and inclusion criteria. A hand search was also conducted. Overall, 107 studies met inclusion criteria for final data extraction and included evaluations of interventions targeted at substance use, early/risky sexual activity and behavioural problems. Eighteen of the 107 studies described programmes targeting parents of adolescents from diverse ethnocultural communities; the quality of these 18 studies was assessed using a marginally modified version of the Downs and Black Checklist (Downs & Black 1998). Their average quality assessment score was 16 out of 28. In addition, two key themes reflected in successful interventions emerged: strengthening parent-adolescent relationship through communication, and importance of community engagement in designing and implementing the intervention. Findings indicate gaps in service delivery to parents of adolescents from ethnoculturally diverse communities; there are a limited number of studies on programmes targeting ethnoculturally diverse parents of adolescents, and the quality of studies that do exist is overall low. Given increasing diversity, more emphasis should be placed on developing and modifying programmes to meet the needs of ethnoculturally diverse communities. More rigorous, standardised efforts should be made to evaluate programmes that do exist. © 2016 John Wiley & Sons Ltd.

A Partitioning Algorithm for Block-Diagonal Matrices With Overlap

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

Guy Antoine Atenekeng Kahou; Laura Grigori; Masha Sosonkina

2008-02-02

We present a graph partitioning algorithm that aims at partitioning a sparse matrix into a block-diagonal form, such that any two consecutive blocks overlap. We denote this form of the matrix as the overlapped block-diagonal matrix. The partitioned matrix is suitable for applying the explicit formulation of Multiplicative Schwarz preconditioner (EFMS) described in [3]. The graph partitioning algorithm partitions the graph of the input matrix into K partitions, such that every partition {Omega}{sub i} has at most two neighbors {Omega}{sub i-1} and {Omega}{sub i+1}. First, an ordering algorithm, such as the reverse Cuthill-McKee algorithm, that reduces the matrix profile ismore » performed. An initial overlapped block-diagonal partition is obtained from the profile of the matrix. An iterative strategy is then used to further refine the partitioning by allowing nodes to be transferred between neighboring partitions. Experiments are performed on matrices arising from real-world applications to show the feasibility and usefulness of this approach.« less

STITCHER 2.0: primer design for overlapping PCR applications

PubMed Central

O’Halloran, Damien M.; Uriagereka-Herburger, Isabel; Bode, Katrin

2017-01-01

Overlapping polymerase chain reaction (PCR) is a common technique used by researchers in very diverse fields that enables the user to ‘stitch’ individual pieces of DNA together. Previously, we have reported a web based tool called STITCHER that provides a platform for researchers to automate the design of primers for overlapping PCR applications. Here we present STITCHER 2.0, which represents a substantial update to STITCHER. STITCHER 2.0 is a newly designed web tool that automates the design of primers for overlapping PCR. Unlike STITCHER, STITCHER 2.0 considers diverse algorithmic parameters, and returns multiple result files that include a facility for the user to draw their own primers as well as comprehensive visual guides to the user’s input, output, and designed primers. These result files provide greater control and insight during experimental design and troubleshooting. STITCHER 2.0 is freely available to all users without signup or login requirements and can be accessed at the following webpage: www.ohalloranlab.net/STITCHER2.html. PMID:28358011

Securely Measuring the Overlap between Private Datasets with Cryptosets

PubMed Central

Swamidass, S. Joshua; Matlock, Matthew; Rozenblit, Leon

2015-01-01

Many scientific questions are best approached by sharing data—collected by different groups or across large collaborative networks—into a combined analysis. Unfortunately, some of the most interesting and powerful datasets—like health records, genetic data, and drug discovery data—cannot be freely shared because they contain sensitive information. In many situations, knowing if private datasets overlap determines if it is worthwhile to navigate the institutional, ethical, and legal barriers that govern access to sensitive, private data. We report the first method of publicly measuring the overlap between private datasets that is secure under a malicious model without relying on private protocols or message passing. This method uses a publicly shareable summary of a dataset’s contents, its cryptoset, to estimate its overlap with other datasets. Cryptosets approach “information-theoretic” security, the strongest type of security possible in cryptography, which is not even crackable with infinite computing power. We empirically and theoretically assess both the accuracy of these estimates and the security of the approach, demonstrating that cryptosets are informative, with a stable accuracy, and secure. PMID:25714898

Evidence for the recent origin of a bacterial protein-coding, overlapping orphan gene by evolutionary overprinting.

PubMed

Fellner, Lea; Simon, Svenja; Scherling, Christian; Witting, Michael; Schober, Steffen; Polte, Christine; Schmitt-Kopplin, Philippe; Keim, Daniel A; Scherer, Siegfried; Neuhaus, Klaus

2015-12-18

Gene duplication is believed to be the classical way to form novel genes, but overprinting may be an important alternative. Overprinting allows entirely novel proteins to evolve de novo, i.e., formerly non-coding open reading frames within functional genes become expressed. Only three cases have been described for Escherichia coli. Here, a fourth example is presented. RNA sequencing revealed an open reading frame weakly transcribed in cow dung, coding for 101 residues and embedded completely in the -2 reading frame of citC in enterohemorrhagic E. coli. This gene is designated novel overlapping gene, nog1. The promoter region fused to gfp exhibits specific activities and 5' rapid amplification of cDNA ends indicated the transcriptional start 40-bp upstream of the start codon. nog1 was strand-specifically arrested in translation by a nonsense mutation silent in citC. This Nog1-mutant showed a phenotype in competitive growth against wild type in the presence of MgCl2. Small differences in metabolite concentrations were also found. Bioinformatic analyses propose Nog1 to be inner membrane-bound and to possess at least one membrane-spanning domain. A phylogenetic analysis suggests that the orphan gene nog1 arose by overprinting after Escherichia/Shigella separated from the other γ-proteobacteria. Since nog1 is of recent origin, non-essential, short, weakly expressed and only marginally involved in E. coli's central metabolism, we propose that this gene is in an initial stage of evolution. While we present specific experimental evidence for the existence of a fourth overlapping gene in enterohemorrhagic E. coli, we believe that this may be an initial finding only and overlapping genes in bacteria may be more common than is currently assumed by microbiologists.

Long noncoding RNA LINC00460 targets miR-539/MMP-9 to promote meningioma progression and metastasis.

PubMed

Xing, Hongshun; Wang, Shilei; Li, Quancai; Ma, Yongqian; Sun, Peng

2018-06-12

Emerging evidence reveal that long noncoding RNAs (lncRNAs) participates in the epigenetic regulation of pathophysiological process. However, the deepgoing role of lncRNAs on meningioma is still unclear. In present study, we investigate the roles of lncRNA LINC00460 in meningeoma tissue and uncover its molecular mechanism. Results revealed that LINC00460 expression level was significantly up-regulated in meningeoma tissues and malignant meningeoma cell lines (IOMM-Lee, CH157-MN). Mechanically, loss-of-function assays showed that LINC00460 knockdown significantly suppressed the proliferation ability, increased the apoptosis and decreased the proteins (MMP-2, MMP-9, ZEB1) expression. Bioinformatics tools predicted that miR-539 both targeted with the 3'-UTR of LINC00460 and MMP-9 mRNA, which was confirmed by luciferase reporter assay and western blot analysis. In summary, our study reveals that LINC00460 promotes MMP-9 expression through targeting miR-539, acting as an oncogenic RNA in the meningeoma malignancy and accelerating the proliferation and metastasis of meningeoma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway

PubMed Central

Wang, Yong; Yang, Tao; Liu, Yadong; Zhao, Wei; Zhang, Zhen; Lu, Ming; Zhang, Weiguo

2017-01-01

Slow growth and rapid loss of chondrogenic phenotypes are the major problems affecting chronic cartilage lesions. The role of microRNA-195 (miR-195) and its detailed working mechanism in the fore-mentioned process remains unknown. Fibroblastic growth factor 18 (FGF-18) plays a key role in cartilage homeostasis; whether miR-195 could regulate FGF-18 and its downstream signal pathway in chondrocyte proliferation and maintenance of chondrogenic phenotypes still remains unclear. The present research shows elevated miR-195 but depressed FGF-18 expressed in joint fluid specimens of 20 patients with chronic cartilage lesions and in CH1M and CH3M chondrocytes when compared with that in joint fluid specimens without cartilage lesions and in CH1W and CH2W chondrocytes, respectively. The following loss of function test revealed that downregulation of miR-195 by transfection of miR-195 inhibitors promoted chondrocyte proliferation and expression of a type II collagen α I chain (Col2a1)/aggrecan. Through the online informatics analysis we theoretically predicted that miR-195 could bind to a FGF-18 3′ untranslated region (3′UTR), also, we verified that a miR-195 could regulate the FGF-18 and its downstream pathway. The constructed dual luciferase assay further confirmed that FGF-18 was a direct target of miR-195. The executed anti-sense experiment displayed that miR-195 could regulate chondrocyte proliferation and Col2a1/aggrecan expression via the FGF-18 pathway. Finally, through an in vivo anterior cruciate ligament transection (ACLT) model, downregulation of miR-195 presented a significantly protective effect on chronic cartilage lesions. Evaluating all of the outcomes of the current research revealed that a decrease of miR-195 protected chronic cartilage lesions by promoting chondrocyte proliferation and maintenance of chondrogenic phenotypes via the targeting of the FGF-18 pathway and that the miR-195/FGF-18 axis could be a potential target in the treatment of

Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway.

PubMed

Wang, Yong; Yang, Tao; Liu, Yadong; Zhao, Wei; Zhang, Zhen; Lu, Ming; Zhang, Weiguo

2017-05-04

Slow growth and rapid loss of chondrogenic phenotypes are the major problems affecting chronic cartilage lesions. The role of microRNA-195 (miR-195) and its detailed working mechanism in the fore-mentioned process remains unknown. Fibroblastic growth factor 18 (FGF-18) plays a key role in cartilage homeostasis; whether miR-195 could regulate FGF-18 and its downstream signal pathway in chondrocyte proliferation and maintenance of chondrogenic phenotypes still remains unclear. The present research shows elevated miR-195 but depressed FGF-18 expressed in joint fluid specimens of 20 patients with chronic cartilage lesions and in CH1M and CH3M chondrocytes when compared with that in joint fluid specimens without cartilage lesions and in CH1W and CH2W chondrocytes, respectively. The following loss of function test revealed that downregulation of miR-195 by transfection of miR-195 inhibitors promoted chondrocyte proliferation and expression of a type II collagen α I chain (Col2a1)/aggrecan. Through the online informatics analysis we theoretically predicted that miR-195 could bind to a FGF-18 3' untranslated region (3'UTR), also, we verified that a miR-195 could regulate the FGF-18 and its downstream pathway. The constructed dual luciferase assay further confirmed that FGF-18 was a direct target of miR-195. The executed anti-sense experiment displayed that miR-195 could regulate chondrocyte proliferation and Col2a1/aggrecan expression via the FGF-18 pathway. Finally, through an in vivo anterior cruciate ligament transection (ACLT) model, downregulation of miR-195 presented a significantly protective effect on chronic cartilage lesions. Evaluating all of the outcomes of the current research revealed that a decrease of miR-195 protected chronic cartilage lesions by promoting chondrocyte proliferation and maintenance of chondrogenic phenotypes via the targeting of the FGF-18 pathway and that the miR-195/FGF-18 axis could be a potential target in the treatment of cartilage

Binding Sites Analyser (BiSA): Software for Genomic Binding Sites Archiving and Overlap Analysis

PubMed Central

Khushi, Matloob; Liddle, Christopher; Clarke, Christine L.; Graham, J. Dinny

2014-01-01

Genome-wide mapping of transcription factor binding and histone modification reveals complex patterns of interactions. Identifying overlaps in binding patterns by different factors is a major objective of genomic studies, but existing methods to archive large numbers of datasets in a personalised database lack sophistication and utility. Therefore we have developed transcription factor DNA binding site analyser software (BiSA), for archiving of binding regions and easy identification of overlap with or proximity to other regions of interest. Analysis results can be restricted by chromosome or base pair overlap between regions or maximum distance between binding peaks. BiSA is capable of reporting overlapping regions that share common base pairs; regions that are nearby; regions that are not overlapping; and average region sizes. BiSA can identify genes located near binding regions of interest, genomic features near a gene or locus of interest and statistical significance of overlapping regions can also be reported. Overlapping results can be visualized as Venn diagrams. A major strength of BiSA is that it is supported by a comprehensive database of publicly available transcription factor binding sites and histone modifications, which can be directly compared to user data. The documentation and source code are available on http://bisa.sourceforge.net PMID:24533055

A decision theoretical approach for diffusion promotion

NASA Astrophysics Data System (ADS)

Ding, Fei; Liu, Yun

2009-09-01

In order to maximize cost efficiency from scarce marketing resources, marketers are facing the problem of which group of consumers to target for promotions. We propose to use a decision theoretical approach to model this strategic situation. According to one promotion model that we develop, marketers balance between probabilities of successful persuasion and the expected profits on a diffusion scale, before making their decisions. In the other promotion model, the cost for identifying influence information is considered, and marketers are allowed to ignore individual heterogeneity. We apply the proposed approach to two threshold influence models, evaluate the utility of each promotion action, and provide discussions about the best strategy. Our results show that efforts for targeting influentials or easily influenced people might be redundant under some conditions.

MicroRNA-134-5p promotes high glucose-induced podocyte apoptosis by targeting bcl-2

PubMed Central

Qian, Xiaoxiao; Tan, Juan; Liu, Ling; Chen, Sheng; You, Na; Yong, Huijuan; Pan, Minglin; You, Qiang; Ding, Dafa; Lu, Yibing

2018-01-01

Podocyte apoptosis is a typical early feature of diabetic nephropathy (DN), with loss of nephrin integrity contributing to increased proteinuria in patients with DN. Emerging evidence shows that microRNAs (miRNAs) play vital roles in the pathogenesis of DN. Thus, we aimed to further elucidate the role of miRNAs in podocyte apoptosis in DN. We used db/db and db/m mice maintained under a continuous feeding regime for 12 weeks. Using microarray analysis, we found several miRNAs potentially related to podocyte apoptosis. In addition, we cultured a conditionally immortalized human podocyte cell line in 30 mM D-glucose and found that miR-134-5p was upregulated in both db/db mice and high-glucose (HG)-treated podocytes. Upregulation of miR-134-5p was accompanied by podocyte apoptosis and downregulation of nephrin. Inhibition of miR-134-5p produced the opposite effect. Dual-luciferase reporter assays showed that miR-134-5p directly targeted the 3’-untranslated region of the B-cell lymphoma-2 gene (BCL2), and further study confirmed an increase in bcl-2 protein level in HG-treated podocytes transfected with anti-miR-134-5p. Knockdown of BCL2 impeded the antiapoptotic effect of anti-miR-134-5p. Finally, we found that miR-134-5p might regulate apoptosis in db/db mice and podocytes by targeting BCL2. Taken together, our findings suggest that miR-134-5p promotes podocyte apoptosis under HG conditions by targeting BCL2. Our study provides a meaningful approach to interpret the mechanisms of action of miRNAs involved in DN. PMID:29636888

MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.

PubMed

Huang, Dabing; Bian, Geng; Pan, Yueyin; Han, Xinghua; Sun, Yubei; Wang, Yong; Shen, Guodong; Cheng, Min; Fang, Xiang; Hu, Shilian

2017-01-01

MicroRNAs (miRNAs) was reported to be involved in cancer radio-resistance, which remains a major obstacle for effective cancer therapy. The differently expressed miRNAs were detected by RNA-seq experiment in nasopharyngeal cancer (NPC) cells. MiR-20a-5p was selected as our target, which was subject to finding its target gene Rab27B via bioinformatics analysis. The qRT-PCR, western blot and the luciferase reporter assays were performed to confirm Rab27B as the target of miR-20a-5p. In addition, the roles of miR-20a-5p in NPC radio-resistance were detected by transfection of either miR-20a-5p-mimic or miR-20a-5p-antagomiR. The involvement of Rab27B with NPC radio-resistance was also detected by the experiments with siRNA-mediated repression of Rab27B or over-expression of GFP-Rab27B. Wound healing and invasion assays were performed to detect the roles of both miR-20a-5p and Rab27B. MiR-20a-5p promotes NPC radio-resistance. We identified that its target gene Rab27B negatively correlates with miR-20a-5p-mediated NPC radio-resistance by systematic studies of a radio-sensitive (CNE-2) and resistant (CNE-1) NPC cell lines. Repression of Rab27B by siRNA suppresses cell apoptosis and passivates CNE-2 cells, whereas over-expression of Rab27B triggered cell apoptosis and sensitizes CNE-1 cells. MiR-20a-5p and its target gene Rab27B might be involved in the NPC radio-resistance. Thus the key players and regulators involved in this pathway might be the potential targets for developing effective therapeutic strategies against NPC.

The predominant WT1 isoform (+KTS) encodes a DNA binding protein targeting the planar cell polarity gene Scribble in renal podocytes

PubMed Central

Wells, Julie; Rivera, Miguel N.; Kim, Woo Jae; Starbuck, Kristen; Haber, Daniel A.

2010-01-01

WT1 encodes a tumor suppressor, first identified by its inactivation in Wilms Tumor. While one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three amino acid (KTS) insertion. Using cells which conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning (ChIP-cloning) analysis to identify candidate WT1(+KTS) regulated promoters. We identified the planar cell polarity (PCP) gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33 nucleotide region within the Scribble promoter in both mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway. PMID:20571064

The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in renal podocytes.

PubMed

Wells, Julie; Rivera, Miguel N; Kim, Woo Jae; Starbuck, Kristen; Haber, Daniel A

2010-07-01

WT1 encodes a tumor suppressor first identified by its inactivation in Wilms' Tumor. Although one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three-amino acid (KTS) insertion. Using cells that conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning analysis to identify candidate WT1(+KTS)-regulated promoters. We identified the planar cell polarity gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33-nucleotide region within the Scribble promoter in mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway.

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

Federally Funded Programs Related to Building Energy Use: Overlaps, Challenges, and Opportunities for Collaboration

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

Cort, Katherine A.; Butner, Ryan S.; Hostick, Donna J.

2010-10-01

As energy efficiency in buildings continues to move from discreet technology development to an integrated systems approach, the need to understand and integrate complementary goals and targets becomes more pronounced. Whether within Department of Energy’s (DOE) Building Technologies Program (BTP), across the Office of Energy Efficiency and Renewable Energy (EERE), or throughout DOE and the Federal government, mutual gains and collaboration synergies exist that are not easily achieved because of organizational and time constraints. There also cases where federal agencies may be addressing similar issues, but with different (and sometimes conflicting) outcomes in mind. This report conducts a comprehensive inventorymore » across all EERE and other relevant Federal agencies of potential activities with synergistic benefits. A taxonomy of activities with potential interdependencies is presented. The report identifies a number of federal program objectives, products, and plans related to building energy efficiency and characterizes the current structure and interactions related to these plans and programs. Areas where overlap occurs are identified as are the challenges of addressing issues related to overlapping goals and programs. Based on the input gathered from various sources, including 20 separate interviews with federal agency staff and contractor staff supporting buildings programs, this study identifies a number of synergistic opportunities and makes recommends a number of areas where further collaboration could be beneficial.« less

Safety of Running Two Rooms: A Systematic Review and Meta-Analysis of Overlapping Neurosurgical Procedures.

PubMed

Self, D Mitchell; Ilyas, Adeel; Stetler, William R

2018-04-27

Overlapping surgery, a long-standing practice within academic neurosurgery centers nationwide, has recently come under scrutiny from the government and media as potentially harmful to patients. Therefore, the objective of this systematic review and meta-analysis is to determine the safety of overlapping neurosurgical procedures. The authors performed a systematic review and meta-analysis in accordance with PRISMA guidelines. A review of PubMed and Medline databases was undertaken with the search phrase "overlapping surgery AND neurosurgery AND outcomes." Data regarding patient demographics, type of neurosurgical procedure, and outcomes and complications were extracted from each study. The principle summary measure was odds ratio (OR) of the association of overlapping versus non-overlapping surgery with outcomes. The literature search yielded a total of 36 studies, of which 5 studies met inclusion criteria and were included in this study. These studies included a total of 25,764 patients undergoing neurosurgical procedures. Overlapping surgery was associated with an increased likelihood of being discharged home (OR = 1.32; 95% CI 1.20 to 1.44; P < 0.001) and a reduced 30-day unexpected return to the operating room (OR = 0.79; 95% CI 0.72 to 0.87; P < 0.001). Overlapping surgery did not significantly affect OR of length of surgery, 30-day mortality, or 30-day readmission. Overlapping neurosurgical procedures were not associated with worse patient outcomes. Additional, prospective studies are needed to further assess the safety overlapping procedures. Copyright © 2018. Published by Elsevier Inc.

Clarifying relations between dispositional aggression and brain potential response: overlapping and distinct contributions of impulsivity and stress reactivity.

PubMed

Venables, Noah C; Patrick, Christopher J; Hall, Jason R; Bernat, Edward M

2011-03-01

Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

Overlapping community detection in weighted networks via a Bayesian approach

NASA Astrophysics Data System (ADS)

Chen, Yi; Wang, Xiaolong; Xiang, Xin; Tang, Buzhou; Chen, Qingcai; Fan, Shixi; Bu, Junzhao

2017-02-01

Complex networks as a powerful way to represent complex systems have been widely studied during the past several years. One of the most important tasks of complex network analysis is to detect communities embedded in networks. In the real world, weighted networks are very common and may contain overlapping communities where a node is allowed to belong to multiple communities. In this paper, we propose a novel Bayesian approach, called the Bayesian mixture network (BMN) model, to detect overlapping communities in weighted networks. The advantages of our method are (i) providing soft-partition solutions in weighted networks; (ii) providing soft memberships, which quantify 'how strongly' a node belongs to a community. Experiments on a large number of real and synthetic networks show that our model has the ability in detecting overlapping communities in weighted networks and is competitive with other state-of-the-art models at shedding light on community partition.

miR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 and promoting SOD2 expression

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

Zhang, Yanwei; Xu, Jing, E-mail: xujingdoc@163.com

miR-140-5p is down-regulated in patients with pulmonary arterial hypertension (PAH) and experimental models of PAH, and inhibits hypoxia-mediated pulmonary artery smooth muscle cell (PASMC) proliferation in vitro. Delivery of synthetic miR-140-5p prevents and treats established, experimental PAH. DNA methyltransferase 1 (Dnmt1) is up-regulated in PAH associated human PASMCs (HPASMCs), which promotes the development of PAH by hypermethylation of CpG islands within the promoter for superoxide dismutase 2 (SOD2) and down-regulating SOD2 expression. We searched for miR-140-5p targets using TargetScan, PicTar and MiRanda tools, and found that Dnmt1 is a potential target of miR-140-5p. Based on these findings, we speculated that miR-140-5pmore » might target Dnmt1 and regulate SOD2 expression to regulate hypoxia-mediated HPASMC proliferation, apoptosis and differentiation. We detected the expression of miR-140-5p, Dnmt1 and SOD2 by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays, respectively, and found down-regulation of miR-140-5p and SOD2 and up-regulation of Dnmt1 exist in PAH tissues and hypoxia-mediated HPASMCs. Cell proliferation, apoptosis and differentiation detection showed that miR-140-5p inhibits proliferation and promotes apoptosis and differentiation of HPASMCs in hypoxia, while the effect of Dnmt1 on hypoxia-mediated HPASMCs is reversed. Luciferase assay confirmed that miR-140-5p targets Dnmt1 directly. An inverse correlation is also found between miR-140-5p and Dnmt1 in HPASMCs. In addition, we further investigated whether miR-140-5p and Dnmt1 regulate HPASMC proliferation, apoptosis and differentiation by regulating SOD2 expression, and the results confirmed our speculation. Taken together, these results indicated that miR-140-5p at least partly targets Dnmt1 and regulates SOD2 expression to inhibit proliferation and promote apoptosis and differentiation of HPASMCs in hypoxia. - Highlights: • miR-140-5p and SOD2

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

PubMed

Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W K; Hsieh, Chia-Ling

2016-01-01

Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

Effect of Overlapping Operations on Outcomes in Microvascular Reconstructions of the Head and Neck.

PubMed

Sweeny, Larissa; Rosenthal, Eben L; Light, Tyler; Grayson, Jessica; Petrisor, Daniel; Troob, Scott H; Greene, Benjamin J; Carroll, William R; Wax, Mark K

2017-04-01

Objective To compare outcomes after microvascular reconstructions of head and neck defects between overlapping and nonoverlapping operations. Study Design Retrospective cohort study. Setting Tertiary care center. Subjects and Methods Patients undergoing microvascular free tissue transfer operations between January 2010 and February 2015 at 2 tertiary care institutions were included (n = 1315). Patients were divided into 2 cohorts by whether the senior authors performed a single or consecutive microvascular reconstruction (nonoverlapping; n = 773, 59%) vs performing overlapping microvascular reconstructions (overlapping; n = 542, 41%). Variables reviewed were as follows: defect location, indication, T classification, surgical details, duration of the operation and hospitalization, and complications (major, minor, medical). Results Microvascular free tissue transfers performed included radial forearm (49%, n = 639), osteocutaneous radial forearm (14%, n = 182), anterior lateral thigh (12%, n = 153), fibula (10%, n = 135), rectus abdominis (7%, n = 92), latissimus dorsi (6%, n = 78), and scapula (<1%, n = 4). The mean duration of the overlapping operations was 21 minutes longer than nonoverlapping operations ( P = .003). Mean duration of hospitalization was similar for nonoverlapping (9.5 days) and overlapping (9.1 days) cohorts ( P = .39). There was no difference in complication rates when stratified by overlapping (45%, n = 241) and nonoverlapping (45%, n = 344) ( P = .99). Subset analysis yielded similar results when minor, major, and medical complications between groups were assessed. The overall survival rate of free tissue transfers was 96%, and this was same for overlapping (96%) and nonoverlapping (96%) operations ( P = .71). Conclusions Patients had similar complication rates and durations of hospitalization for overlapping and nonoverlapping operations.

More inclusive bipolar mixed depression definition by permitting overlapping and non-overlapping mood elevation symptoms.

PubMed

Kim, H; Kim, W; Citrome, L; Akiskal, H S; Goffin, K C; Miller, S; Holtzman, J N; Hooshmand, F; Wang, P W; Hill, S J; Ketter, T A

2016-09-01

The objective of this study was to assess the strengths and limitations of a mixed bipolar depression definition made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by counting not only 'non-overlapping' mood elevation symptoms (NOMES) as in DSM-5, but also 'overlapping' mood elevation symptoms (OMES, psychomotor agitation, distractibility, and irritability). Among bipolar disorder (BD) out-patients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using more inclusive (≥3 NOMES/OMES) and less inclusive DSM-5 (≥3 NOMES) definitions. Among 153 depressed BD, counting not only NOMES but also OMES yielded a three-fold higher mixed depression rate (22.9% vs. 7.2%) and important statistically significant clinical correlates for mixed compared to pure depression (more lifetime anxiety disorder comorbidity, more current irritability, and less current antidepressant use), which were not significant using the DSM-5 threshold. To conclude, further studies with larger numbers of patients with DSM-5 bipolar mixed depression assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including efforts to ascertain whether or not OMES should count toward mixed depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recovery of Spectrally Overlapping QPSK Signals Using a Nonlinear Optoelectronic Filter

DTIC Science & Technology

2017-03-19

Spectrally Overlapping QPSK Signals Using a Nonlinear Optoelectronic Filter William Loh, Siva Yegnanarayanan, Kenneth E. Kolodziej, and Paul...recovery of a weak QPSK signal buried 35-dB beneath an interfering QPSK signal having an overlapping spectrum. This nonlinear optoelectronic filter ...from increased detection sensitivity. Here, we demonstrate an optoelectronic filter that enables the detection of a desired signal hidden beneath a

Visual and cross-modal cues increase the identification of overlapping visual stimuli in Balint's syndrome.

PubMed

D'Imperio, Daniela; Scandola, Michele; Gobbetto, Valeria; Bulgarelli, Cristina; Salgarello, Matteo; Avesani, Renato; Moro, Valentina

2017-10-01

Cross-modal interactions improve the processing of external stimuli, particularly when an isolated sensory modality is impaired. When information from different modalities is integrated, object recognition is facilitated probably as a result of bottom-up and top-down processes. The aim of this study was to investigate the potential effects of cross-modal stimulation in a case of simultanagnosia. We report a detailed analysis of clinical symptoms and an 18 F-fluorodeoxyglucose (FDG) brain positron emission tomography/computed tomography (PET/CT) study of a patient affected by Balint's syndrome, a rare and invasive visual-spatial disorder following bilateral parieto-occipital lesions. An experiment was conducted to investigate the effects of visual and nonvisual cues on performance in tasks involving the recognition of overlapping pictures. Four modalities of sensory cues were used: visual, tactile, olfactory, and auditory. Data from neuropsychological tests showed the presence of ocular apraxia, optic ataxia, and simultanagnosia. The results of the experiment indicate a positive effect of the cues on the recognition of overlapping pictures, not only in the identification of the congruent valid-cued stimulus (target) but also in the identification of the other, noncued stimuli. All the sensory modalities analyzed (except the auditory stimulus) were efficacious in terms of increasing visual recognition. Cross-modal integration improved the patient's ability to recognize overlapping figures. However, while in the visual unimodal modality both bottom-up (priming, familiarity effect, disengagement of attention) and top-down processes (mental representation and short-term memory, the endogenous orientation of attention) are involved, in the cross-modal integration it is semantic representations that mainly activate visual recognition processes. These results are potentially useful for the design of rehabilitation training for attentional and visual-perceptual deficits.

ADHD and autism: differential diagnosis or overlapping traits? A selective review.

PubMed

Taurines, Regina; Schwenck, Christina; Westerwald, Eva; Sachse, Michael; Siniatchkin, Michael; Freitag, Christine

2012-09-01

According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD). However, despite the different conceptualization, population-based twin studies reported symptom overlap, and a recent epidemiologically based study reported a high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic disorder and ADHD will not be mutually exclusive any longer. This provides the basis of more differentiated studies on overlap and distinction between both disorders. This review presents data on comorbidity rates and symptom overlap and discusses common and disorder-specific risk factors, including recent proteomic studies. Neuropsychological findings in the areas of attention, reward processing, and social cognition are then compared between both disorders, as these cognitive abilities show overlapping as well as specific impairment for one of both disorders. In addition, selective brain imaging findings are reported. Therapeutic options are summarized, and new approaches are discussed. The review concludes with a prospectus on open questions for research and clinical practice.

Long noncoding RNA PVT1 promotes EMT via mediating microRNA-186 targeting of Twist1 in prostate cancer.

PubMed

Chang, Zhongwen; Cui, Jun; Song, Yongsheng

2018-05-15

The pathogenesis and the underlying mechanism of endothelial-mesenchymal transition in prostate cancer remain unclear. Plasmacytoma variant translocation 1 (PVT1), a novel long non-coding RNA maps to 8q24.21, and in many tumor studies the up-regulation of PVT1 has already been reported. PVT1 is closely related to tumor cell proliferation, invasion, and metastasis. In this study, we employed a combination of techniques to study the role of PVT1 in prostate cancer, which included bioinformatic analysis, Western blotting and cell migration assays of prostate cancer cell lines. We report that PVT1 promotes prostate cancer invasion and metastasis by modulating EMT. Furthermore, PVT1 can promote EMT by up-regulation of Twist1, a transcription factor associated with EMT. We then confirmed that PVT1 acts as a sponge for miRNA-186-5p and positively regulates Twist1 by a sponge effect. Therefore, this study has revealed a novel MECHANISM for the promotion of EMT in prostate cancer by PVT1. Our findings suggest that the PVT1/miR-186/Twist1 regulatory axis may be a new therapeutic target for prostate cancer. Copyright © 2018. Published by Elsevier B.V.

STAT3 or USF2 Contributes to HIF Target Gene Specificity

PubMed Central

Pawlus, Matthew R.; Wang, Liyi; Murakami, Aya; Dai, Guanhai; Hu, Cheng-Jun

2013-01-01

The HIF1- and HIF2-mediated transcriptional responses play critical roles in solid tumor progression. Despite significant similarities, including their binding to promoters of both HIF1 and HIF2 target genes, HIF1 and HIF2 proteins activate unique subsets of target genes under hypoxia. The mechanism for HIF target gene specificity has remained unclear. Using siRNA or inhibitor, we previously reported that STAT3 or USF2 is specifically required for activation of endogenous HIF1 or HIF2 target genes. In this study, using reporter gene assays and chromatin immuno-precipitation, we find that STAT3 or USF2 exhibits specific binding to the promoters of HIF1 or HIF2 target genes respectively even when over-expressed. Functionally, HIF1α interacts with STAT3 to activate HIF1 target gene promoters in a HIF1α HLH/PAS and N-TAD dependent manner while HIF2α interacts with USF2 to activate HIF2 target gene promoters in a HIF2α N-TAD dependent manner. Physically, HIF1α HLH and PAS domains are required for its interaction with STAT3 while both N- and C-TADs of HIF2α are involved in physical interaction with USF2. Importantly, addition of functional USF2 binding sites into a HIF1 target gene promoter increases the basal activity of the promoter as well as its response to HIF2+USF2 activation while replacing HIF binding site with HBS from a HIF2 target gene does not change the specificity of the reporter gene. Importantly, RNA Pol II on HIF1 or HIF2 target genes is primarily associated with HIF1α or HIF2α in a STAT3 or USF2 dependent manner. Thus, we demonstrate here for the first time that HIF target gene specificity is achieved by HIF transcription partners that are required for HIF target gene activation, exhibit specific binding to the promoters of HIF1 or HIF2 target genes and selectively interact with HIF1α or HIF2α protein. PMID:23991099

Targeting hardwoods

Treesearch

Douglass F. Jacobs

2011-01-01

Increasing demand for hardwood seedlings has prompted research to identify target seedling characteristics that promote hardwood plantation establishment. Operational establishment of hardwood plantations has typically emphasized seed collection from non-improved genetic sources, bareroot nursery seedling production, and spring planting using machine planters. The...

Temporal overlap estimation based on interference spectrum in CARS microscopy

NASA Astrophysics Data System (ADS)

Zhang, Yongning; Jiang, Junfeng; Liu, Kun; Huang, Can; Wang, Shuang; Zhang, Xuezhi; Liu, Tiegen

2018-01-01

Coherent Anti-Stokes Raman Scattering (CARS) microscopy has attracted lots of attention because of the advantages, such as noninvasive, label-free, chemical specificity, intrinsic three-dimension spatial resolution and so on. However, the temporal overlap of pump and Stokes has not been solved owing to the ultrafast optical pulse used in CARS microscopy. We combine interference spectrum of residual pump in Stokes path and nonlinear Schrodinger equation (NLSE) to realize the temporal overlap of pump pulse and Stokes pulse. At first, based on the interference spectrum of pump pulse and residual pump in Stokes path, the optical delay is defined when optical path difference between pump path and Stokes path is zero. Then the relative optical delay between Stokes pulse and residual pump in PCF can be calculated by NLSE. According to the spectrum interference and NLSE, temporal overlap of pump pulse and Stokes pulse will be realized easily and the imaging speed will be improved in CARS microscopy.

Short superstrings and the structure of overlapping strings.

PubMed

Armen, C; Stein, C

1995-01-01

Given a collection of strings S = [s1,...,sn] over an alphabet sigma, a superstring alpha of S is a string containing each si as a substring, that is, for each i, 1 < or = i < or = n, alpha contains a block of magnitude of si consecutive characters that match si exactly. The shortest superstring problem is the problem of finding a superstring alpha of minimum length. The shortest superstring problem has applications in both computational biology and data compression. The shortest superstring problem is NP-hard (Gallant et al., 1980); in fact, it was recently shown to be MAX SNP-hard (Blum et al., 1994). Given the importance of the applications, several heuristics and approximation algorithms have been proposed. Constant factor approximation algorithms have been given in Blum et al. (1994) (factor of 3), Teng and Yao (1993) (factor of 2 8/9), Czumaj et al. (1994) (factor of 2 5/6), and Kosaraju et al. (1994) (factor of 2 50/63). Informally, the key to any algorithm for the shortest superstring problem is to identify sets of strings with large amounts of similarity, or overlap. Although the previous algorithms and their analyses have grown increasingly sophisticated, they reveal remarkably little about the structure of strings with large amounts of overlap. In this sense, they are solving a more general problem than the one at hand. In this paper, we study the structure of strings with large amounts of overlap and use our understanding to give an algorithm that finds a superstring whose length is no more than 2 3/4 times that of the optimal superstring. Our algorithm runs in O(magnitude of S + n3) time, which matches that of previous algorithms. We prove several interesting properties about short periodic strings, allowing us to answer questions of the following form: Given a string with some periodic structure, characterize all the possible periodic strings that can have a large amount of overlap with the first string.

Enhanced angular overlap model for nonmetallic f -electron systems

NASA Astrophysics Data System (ADS)

Gajek, Z.

2005-07-01

An efficient method of interpretation of the crystal field effect in nonmetallic f -electron systems, the enhanced angular overlap model (EAOM), is presented. The method is established on the ground of perturbation expansion of the effective Hamiltonian for localized electrons and first-principles calculations related to available experimental data. The series of actinide compounds AO2 , oxychalcogenides AOX , and dichalcogenides UX2 where X=S ,Se,Te and A=U ,Np serve as probes of the effectiveness of the proposed method. An idea is to enhance the usual angular overlap model with ab initio calculations of those contributions to the crystal field potential, which cannot be represented by the usual angular overlap model (AOM). The enhancement leads to an improved fitting and makes the approach intrinsically coherent. In addition, the ab initio calculations of the main, AOM-consistent part of the crystal field potential allows one to fix the material-specific relations for the EAOM parameters in the effective Hamiltonian. Consequently, the electronic structure interpretation based on EAOM can be extended to systems of the lowest point symmetries or/and deficient experimental data. Several examples illustrating the promising capabilities of EAOM are given.

Diffusion amid random overlapping obstacles: Similarities, invariants, approximations

PubMed Central

Novak, Igor L.; Gao, Fei; Kraikivski, Pavel; Slepchenko, Boris M.

2011-01-01

Efficient and accurate numerical techniques are used to examine similarities of effective diffusion in a void between random overlapping obstacles: essential invariance of effective diffusion coefficients (Deff) with respect to obstacle shapes and applicability of a two-parameter power law over nearly entire range of excluded volume fractions (ϕ), except for a small vicinity of a percolation threshold. It is shown that while neither of the properties is exact, deviations from them are remarkably small. This allows for quick estimation of void percolation thresholds and approximate reconstruction of Deff (ϕ) for obstacles of any given shape. In 3D, the similarities of effective diffusion yield a simple multiplication “rule” that provides a fast means of estimating Deff for a mixture of overlapping obstacles of different shapes with comparable sizes. PMID:21513372

Severe Cutaneous Drug Reactions: Do Overlapping Forms Exist?

PubMed

Horcajada-Reales, C; Pulido-Pérez, A; Suárez-Fernández, R

2016-01-01

Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Strong Unitary and Overlap Uncertainty Relations: Theory and Experiment

NASA Astrophysics Data System (ADS)

Bong, Kok-Wei; Tischler, Nora; Patel, Raj B.; Wollmann, Sabine; Pryde, Geoff J.; Hall, Michael J. W.

2018-06-01

We derive and experimentally investigate a strong uncertainty relation valid for any n unitary operators, which implies the standard uncertainty relation and others as special cases, and which can be written in terms of geometric phases. It is saturated by every pure state of any n -dimensional quantum system, generates a tight overlap uncertainty relation for the transition probabilities of any n +1 pure states, and gives an upper bound for the out-of-time-order correlation function. We test these uncertainty relations experimentally for photonic polarization qubits, including the minimum uncertainty states of the overlap uncertainty relation, via interferometric measurements of generalized geometric phases.

Mitigating effect on turbulent scintillation using non-coherent multi-beam overlapped illumination

NASA Astrophysics Data System (ADS)

Zhou, Lu; Tian, Yuzhen; Wang, Rui; Wang, Tingfeng; Sun, Tao; Wang, Canjin; Yang, Xiaotian

2017-12-01

In order to find an effective method to mitigate the turbulent scintillation for applications involved laser propagation through atmosphere, we demonstrated one model using non-coherent multi-beam overlapped illumination. Based on lognormal distribution and the statistical moments of overlapped field, the reduction effect on turbulent scintillation of this method was discussed and tested against numerical wave optics simulation and laboratory experiments with phase plates. Our analysis showed that the best mitigating effect, the scintillation index of overlapped field reduced to 1/N of that when using single beam illuminating, could be obtained using this method when the intensity of N emitting beams equaled to each other.

Overlaps with arbitrary two-site states in the XXZ spin chain

NASA Astrophysics Data System (ADS)

Pozsgay, B.

2018-05-01

We present a conjectured exact formula for overlaps between the Bethe states of the spin-1/2 XXZ chain and generic two-site states. The result takes the same form as in the previously known cases: it involves the same ratio of two Gaudin-like determinants, and a product of single-particle overlap functions, which can be fixed using a combination of the quench action and quantum transfer matrix methods. Our conjecture is confirmed by numerical data from exact diagonalization. For one-site states, the formula is found to be correct even in chains with odd length. It is also pointed out that the ratio of the Gaudin-like determinants plays a crucial role in the overlap sum rule: it guarantees that in the thermodynamic limit there remains no term in the quench action.

Overlapping Neural Endophenotypes in Addiction and Obesity

PubMed Central

Michaud, Andréanne; Vainik, Uku; Garcia-Garcia, Isabel; Dagher, Alain

2017-01-01

Impulsivity refers to a tendency to act rapidly without full consideration of consequences. The trait is thought to result from the interaction between high arousal responses to potential rewards and poor self-control. Studies have suggested that impulsivity confers vulnerability to both addiction and obesity. However, results in this area are unclear, perhaps due to the high phenotypic complexity of addictions and obesity. Focusing on impulsivity, the aim of this review is to tackle the putative overlaps between addiction and obesity in four domains: (1) personality research, (2) neurocognitive tasks, (3) brain imaging, and (4) clinical evidence. We suggest that three impulsivity-related domains are particularly relevant for our understanding of similarities between addiction and obesity: lower self-control (high Disinhibition/low Conscientiousness), reward sensitivity (high Extraversion/Positive Emotionality), and negative affect (high Neuroticism/Negative Emotionality). Neurocognitive studies have shown that obesity and addiction are both associated with increased impulsive decision-making and attention bias in response to drug or food cues, respectively. Mirroring this, obesity and different forms of addiction seem to exhibit similar alterations in functional MRI brain activity in response to reward processing and during self-control tasks. Overall, our review provides an integrative approach to understand those facets of obesity that present similarities to addictive behaviors. In addition, we suggest that therapeutic interventions targeting inhibitory control may represent a promising approach for the prevention and/or treatment of obesity. PMID:28659866

Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

PubMed

Hunt, E; Bornovalova, M A; Patrick, C J

2015-05-01

Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma

PubMed Central

Yao, Bowen; Xu, Meng; Ding, Linglong; Wang, Yufeng; Jia, Yuli; Li, Qing; Zhang, Hongyong; Tu, Kangsheng; Song, Tao; Liu, Qingguang

2016-01-01

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Accumulating studies have demonstrated that aberrant expression of several lncRNAs was found to be involved in the hepatocarcinogenesis. In this study, a lncRNA Ftx was chosen to investigate its effects on HCC cells, and clarify the possible mechanism. We demonstrated that the lncRNA Ftx and Ftx-derived miR-545 were up-regulated in both HCC tissues and cells. MiR-545 was positively correlated with lncRNA Ftx expression. Notably, clinical association analysis revealed that the high expression of lncRNA Ftx and miR-545 was associated with poor prognostic features, and conferred a reduced 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. We found that miR-545 was a pivotal mediator in Ftx-induced promotion of HCC cell growth. Subsequently, we identified RIG-I as a direct target of miR-545. The expression of RIG-I was downregulated in HCC tissues and was inversely correlated with miR-545 expression. Our data revealed that ectopic expression of RIG-I abrogated the effects of lncRNA Ftx or miR-545 on HCC cells. LncRNA Ftx/miR-545-mediated downregulation of RIG-I led to increased Akt phosphorylation in vitro and in vivo. Inhibition of Akt phosphorylation abolished the effects of lncRNA Ftx/miR-545 on HCC cells. In conclusion, our study demonstrates that the novel pathway lncRNA Ftx/miR-545/RIG-I promotes HCC development by activating PI3K/Akt signaling, and it may serve as a novel prognostic biomarker and therapeutic target for HCC. PMID:26992218

Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma.

PubMed

Liu, Zhikui; Dou, Changwei; Yao, Bowen; Xu, Meng; Ding, Linglong; Wang, Yufeng; Jia, Yuli; Li, Qing; Zhang, Hongyong; Tu, Kangsheng; Song, Tao; Liu, Qingguang

2016-05-03

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Accumulating studies have demonstrated that aberrant expression of several lncRNAs was found to be involved in the hepatocarcinogenesis. In this study, a lncRNA Ftx was chosen to investigate its effects on HCC cells, and clarify the possible mechanism. We demonstrated that the lncRNA Ftx and Ftx-derived miR-545 were up-regulated in both HCC tissues and cells. MiR-545 was positively correlated with lncRNA Ftx expression. Notably, clinical association analysis revealed that the high expression of lncRNA Ftx and miR-545 was associated with poor prognostic features, and conferred a reduced 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. We found that miR-545 was a pivotal mediator in Ftx-induced promotion of HCC cell growth. Subsequently, we identified RIG-I as a direct target of miR-545. The expression of RIG-I was downregulated in HCC tissues and was inversely correlated with miR-545 expression. Our data revealed that ectopic expression of RIG-I abrogated the effects of lncRNA Ftx or miR-545 on HCC cells. LncRNA Ftx/miR-545-mediated downregulation of RIG-I led to increased Akt phosphorylation in vitro and in vivo. Inhibition of Akt phosphorylation abolished the effects of lncRNA Ftx/miR-545 on HCC cells. In conclusion, our study demonstrates that the novel pathway lncRNA Ftx/miR-545/RIG-I promotes HCC development by activating PI3K/Akt signaling, and it may serve as a novel prognostic biomarker and therapeutic target for HCC.

Separation of high-resolution samples of overlapping latent fingerprints using relaxation labeling

NASA Astrophysics Data System (ADS)

Qian, Kun; Schott, Maik; Schöne, Werner; Hildebrandt, Mario

2012-06-01

The analysis of latent fingerprint patterns generally requires clearly recognizable friction ridge patterns. Currently, overlapping latent fingerprints pose a major problem for traditional crime scene investigation. This is due to the fact that these fingerprints usually have very similar optical properties. Consequently, the distinction of two or more overlapping fingerprints from each other is not trivially possible. While it is possible to employ chemical imaging to separate overlapping fingerprints, the corresponding methods require sophisticated fingerprint acquisition methods and are not compatible with conventional forensic fingerprint data. A separation technique that is purely based on the local orientation of the ridge patterns of overlapping fingerprints is proposed by Chen et al. and quantitatively evaluated using off-the-shelf fingerprint matching software with mostly artificially composed overlapping fingerprint samples, which is motivated by the scarce availability of authentic test samples. The work described in this paper adapts the approach presented by Chen et al. for its application on authentic high resolution fingerprint samples acquired by a contactless measurement device based on a Chromatic White Light (CWL) sensor. An evaluation of the work is also given, with the analysis of all adapted parameters. Additionally, the separability requirement proposed by Chen et al. is also evaluated for practical feasibility. Our results show promising tendencies for the application of this approach on high-resolution data, yet the separability requirement still poses a further challenge.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

PubMed

Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

2008-01-01

To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo.

PubMed

Zeng, Yuanyuan; Zhu, Jianjie; Shen, Dan; Qin, Hualong; Lei, Zhe; Li, Wei; Liu, Zeyi; Huang, Jian-An

2017-05-09

Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor; therefore, improved understanding of the disease mechanism and novel treatment strategies are needed. Downregulation of SMAD4 and dysregulated expression of miR-205 have been reported. However, the relationship between them remains unclear. We investigated the effect of microRNA (miR)-205 on the expression of SMAD4 in NSCLC. Knockdown and overexpression of SMAD4 promoted or suppressed cellular viability and proliferation, and accelerated or inhibited the cell cycle in NSCLC cells, respectively. The 3'-untranslated region (3'-UTR) of SMAD4 was predicted as a target of miR-205. Luciferase assays validated that miR-205 binds directly to the SMAD4 3'-UTR. Protein and mRNA expression analyses confirmed that miR-205 overexpression in NSCLC cells inhibited the expression of SMAD4 mRNA and protein. In human NSCLC tissues, increased miR-205 expression was observed frequently and was inversely correlated with decreased SMAD4 expression. Ectopic expression of miR-205 in NSCLC cells suppressed cellular viability and proliferation, accelerated the cell cycle, and promoted tumor growth of lung carcinoma xenografts in nude mice. Our study showed that miR-205 decreased SMAD4 expression, thus promoting NSCLC cell growth. Our findings highlighted the therapeutic potential of targeting miR-205 in NSCLC treatment.

MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo

PubMed Central

Qin, Hualong; Lei, Zhe; Li, Wei; Liu, Zeyi; Huang, Jian-an

2017-01-01

Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor; therefore, improved understanding of the disease mechanism and novel treatment strategies are needed. Downregulation of SMAD4 and dysregulated expression of miR-205 have been reported. However, the relationship between them remains unclear. We investigated the effect of microRNA (miR)-205 on the expression of SMAD4 in NSCLC. Knockdown and overexpression of SMAD4 promoted or suppressed cellular viability and proliferation, and accelerated or inhibited the cell cycle in NSCLC cells, respectively. The 3′-untranslated region (3′-UTR) of SMAD4 was predicted as a target of miR-205. Luciferase assays validated that miR-205 binds directly to the SMAD4 3′-UTR. Protein and mRNA expression analyses confirmed that miR-205 overexpression in NSCLC cells inhibited the expression of SMAD4 mRNA and protein. In human NSCLC tissues, increased miR-205 expression was observed frequently and was inversely correlated with decreased SMAD4 expression. Ectopic expression of miR-205 in NSCLC cells suppressed cellular viability and proliferation, accelerated the cell cycle, and promoted tumor growth of lung carcinoma xenografts in nude mice. Our study showed that miR-205 decreased SMAD4 expression, thus promoting NSCLC cell growth. Our findings highlighted the therapeutic potential of targeting miR-205 in NSCLC treatment. PMID:28199217

Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among Veterans dually enrolled in VA and Medicare Part D

PubMed Central

Gellad, Walid F.; Zhao, Xinhua; Thorpe, Carolyn T.; Thorpe, Joshua M.; Sileanu, Florentina E.; Cashy, John P.; Mor, Maria; Hale, Jennifer A.; Radomski, Thomas; Hausmann, Leslie R. M.; Fine, Michael J.; Good, Chester B.

2016-01-01

Background Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among Veterans dually enrolled in VA and Medicare Part D. Methods We constructed a cohort of all Veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a non-buprenorphine opioid or benzodiazepine, focusing on Veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). Results We identified 1,790 dually enrolled Veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1,091 (61%) from Part D (61 Veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Conclusions Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their

ARNetMiT R Package: association rules based gene co-expression networks of miRNA targets.

PubMed

Özgür Cingiz, M; Biricik, G; Diri, B

2017-03-31

miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.

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

NASA Astrophysics Data System (ADS)

Pham, C. C.

2009-12-01

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

Termination of String Rewriting Rules that have One Pair of Overlaps

NASA Technical Reports Server (NTRS)

Geser, Alfons; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

This paper presents a partial solution to the long standing open problem of termination of one-rule string rewriting. Overlaps between the two sides of the rule play a central role in existing termination criteria. We characterize termination of all one-rule string rewriting systems that have one such overlap at either end. This both completes a result of Kurth and generalizes a result of Shikishima-Tsuji et al.

Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps

PubMed Central

2016-01-01

Abstract Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor‐preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface‐based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory‐motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory‐motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M‐I. Hum Brain Mapp 37:2784–2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061771

Song matching, overlapping, and switching in the banded wren: the sender’s perspective

PubMed Central

Vehrencamp, Sandra L.; Hall, Michelle L.; Bohman, Erin R.; Depeine, Catherine D.; Dalziell, Anastasia H.

2008-01-01

Interpreting receiver responses to on-territory playback of aggressive signals is problematic. One solution is to combine such receiver-perspective experiments with a sender-perspective experiment that allows subjects to demonstrate how their choice of singing strategies is associated with their approach behavior. Here we report the results of a sender-perspective study on the banded wren (Thryothorus pleurostictus), and combine information on context and results of previous receiver-perspective experiments to clarify function. Territorial males were presented with a 5-min playback consisting of song types present in their repertoire. We assessed the degree to which the subjects’ song matching rate, overlapping rate, and song-type versatility were correlated with their approach latency, closeness of approach, latency to first retreat, and time spent close to the speaker. Male age, breeding stage, and features of the playback stimuli were also considered. Song matching was associated with rapid and close approach, consistent with the receiver-perspective interpretation of type matching as a conventional signal of aggressive motivation. Overlapping was associated with earlier retreat, and together with the aversive receiver response to our previous overlapping playback experiment suggests that overlapping is a defensive withdrawal signal. High versatility was associated with slower first retreat from the speaker and high levels of reciprocal matching between subject and playback. Males with fledglings sang with particularly low versatility and approached the speaker aggressively, whereas males with nestlings overlapped more and retreated quickly. Finally, older males matched more but overlapped less. PMID:18392112

Composite operators in cubic field theories and link-overlap fluctuations in spin-glass models

NASA Astrophysics Data System (ADS)

Altieri, Ada; Parisi, Giorgio; Rizzo, Tommaso

2016-01-01

We present a complete characterization of the fluctuations and correlations of the squared overlap in the Edwards-Anderson spin-glass model in zero field. The analysis reveals that the energy-energy correlation (and thus the specific heat) has a different critical behavior than the fluctuations of the link overlap in spite of the fact that the average energy and average link overlap have the same critical properties. More precisely the link-overlap fluctuations are larger than the specific heat according to a computation at first order in the 6 -ɛ expansion. An unexpected outcome is that the link-overlap fluctuations have a subdominant power-law contribution characterized by an anomalous logarithmic prefactor which is absent in the specific heat. In order to compute the ɛ expansion we consider the problem of the renormalization of quadratic composite operators in a generic multicomponent cubic field theory: the results obtained have a range of applicability beyond spin-glass theory.

Hybridized Kibble-Zurek scaling in the driven critical dynamics across an overlapping critical region

NASA Astrophysics Data System (ADS)

Zhai, Liang-Jun; Wang, Huai-Yu; Yin, Shuai

2018-04-01

The conventional Kibble-Zurek scaling describes the scaling behavior in the driven dynamics across a single critical region. In this paper, we study the driven dynamics across an overlapping critical region, in which a critical region (Region A) is overlaid by another critical region (Region B). We develop a hybridized Kibble-Zurek scaling (HKZS) to characterize the scaling behavior in the driven process. According to the HKZS, the driven dynamics in the overlapping region can be described by the critical theories for both Region A and Region B simultaneously. This results in a constraint on the scaling function in the overlapping critical region. We take the quantum Ising chain in an imaginary longitudinal field as an example. In this model, the critical region of the Yang-Lee edge singularity and the critical region of the ferromagnetic-paramagnetic phase transition overlap with each other. We numerically confirm the HKZS by simulating the driven dynamics in this overlapping critical region. The HKZSs in other models are also discussed.

Living as an LGBTQ adolescent and a parent’s child: Overlapping or separate experiences

PubMed Central

Watson, Ryan J.; Eisenberg, Marla E.; Corliss, Heather L.; Porta, Carolyn M.

2017-01-01

It is well known that parental and community-based support are each related to healthy development in LGBTQ youth, but little research has explored the ways these contexts interact and overlap. Through go-along interviews (a method in which participants guide the interviewer around the community) with 66 youth in British Columbia, Massachusetts, and Minnesota, adolescents (aged 14–19 years) reported varying extent of overlap between their LGBTQ experiences and their parent-youth experiences; parents and youth each contributed to the extent of overlap. Youth who reported high overlap reported little need for resources outside their families but found resources easy to access if wanted. Youth who reported little overlap found it difficult to access resources. Findings suggest that in both research and practice, considering the extent to which youth feel they can express their authentic identity in multiple contexts may be more useful than simply evaluating parental acceptance or access to resources. PMID:28795897

Habitat use and diel vertical migration of bigeye thresher shark: Overlap with pelagic longline fishing gear.

PubMed

Coelho, Rui; Fernandez-Carvalho, Joana; Santos, Miguel N

2015-12-01

Pelagic longliners targeting swordfish and tunas in oceanic waters regularly capture sharks as bycatch, including currently protected species as the bigeye thresher, Alopias superciliosus. Fifteen bigeye threshers were tagged with pop-up satellite archival tags (PSATs) in 2012-2014 in the tropical northeast Atlantic, with successful transmissions received from 12 tags for a total of 907 tracking days. Marked diel vertical movements were recorded on all specimens, with most of the daytime spent in deeper colder water (mean depth = 353 m, SD = 73; mean temperature = 10.7 °C, SD = 1.8) and nighttime spent in warmer water closer to the surface (mean depth = 72 m, SD = 54; mean temperature = 21.9 °C, SD = 3.7). The operating depth of the pelagic longline gear was measured with Minilog Temperature and Depth Recorders (TDRs), and the overlap with habitat utilization was calculated. Overlap is taking place mainly during the night and is higher for juveniles. The results presented herein can be used as inputs for Ecological Risk Assessments for bigeye threshers captured in oceanic tuna fisheries, and serve as a basis for efficient management and conservation of this vulnerable shark species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Introducing Overlapping Grain Boundaries in Chemical Vapor Deposited Hexagonal Boron Nitride Monolayer Films

PubMed Central

2017-01-01

We demonstrate the growth of overlapping grain boundaries in continuous, polycrystalline hexagonal boron nitride (h-BN) monolayer films via scalable catalytic chemical vapor deposition. Unlike the commonly reported atomically stitched grain boundaries, these overlapping grain boundaries do not consist of defect lines within the monolayer films but are composed of self-sealing bilayer regions of limited width. We characterize this overlapping h-BN grain boundary structure in detail by complementary (scanning) transmission electron microscopy techniques and propose a catalytic growth mechanism linked to the subsurface/bulk of the process catalyst and its boron and nitrogen solubilities. Our data suggest that the overlapping grain boundaries are comparatively resilient against deleterious pinhole formation associated with grain boundary defect lines and thus may reduce detrimental breakdown effects when polycrystalline h-BN monolayer films are used as ultrathin dielectrics, barrier layers, or separation membranes. PMID:28410557

Targeting Obesity through Health Promotion Programs for School Staff

ERIC Educational Resources Information Center

Herbert, Patrick C.; Lohrmann, David K.; Hall, Cougar

2017-01-01

Health promotion programs for school staff are an overlooked and under-utilized resource that can lead to reductions in overweight and obesity among teachers and other staff members if implemented properly. In addition to increasing the overall staff wellness, boosting morale, increasing productivity, improving academic achievement, providing…

Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment

PubMed Central

Le Hellard, Stéphanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco; Hugdahl, Kenneth; Espeseth, Thomas; Steen, Vidar M.; Melle, Ingrid; Desikan, Rahul; Schork, Andrew J.; Thompson, Wesley K.; Dale, Anders M.; Djurovic, Srdjan

2017-01-01

Abstract There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a “proxy phenotype” for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion (“College,” n = 95 427), and years of education (“EduYears,” n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ. PMID:27338279

Scalable Multicast Protocols for Overlapped Groups in Broker-Based Sensor Networks

NASA Astrophysics Data System (ADS)

Kim, Chayoung; Ahn, Jinho

In sensor networks, there are lots of overlapped multicast groups because of many subscribers, associated with their potentially varying specific interests, querying every event to sensors/publishers. And gossip based communication protocols are promising as one of potential solutions providing scalability in P(Publish)/ S(Subscribe) paradigm in sensor networks. Moreover, despite the importance of both guaranteeing message delivery order and supporting overlapped multicast groups in sensor or P2P networks, there exist little research works on development of gossip-based protocols to satisfy all these requirements. In this paper, we present two versions of causally ordered delivery guaranteeing protocols for overlapped multicast groups. The one is based on sensor-broker as delegates and the other is based on local views and delegates representing subscriber subgroups. In the sensor-broker based protocol, sensor-broker might lead to make overlapped multicast networks organized by subscriber's interests. The message delivery order has been guaranteed consistently and all multicast messages are delivered to overlapped subscribers using gossip based protocols by sensor-broker. Therefore, these features of the sensor-broker based protocol might be significantly scalable rather than those of the protocols by hierarchical membership list of dedicated groups like traditional committee protocols. And the subscriber-delegate based protocol is much stronger rather than fully decentralized protocols guaranteeing causally ordered delivery based on only local views because the message delivery order has been guaranteed consistently by all corresponding members of the groups including delegates. Therefore, this feature of the subscriber-delegate protocol is a hybrid approach improving the inherent scalability of multicast nature by gossip-based technique in all communications.

MicroRNA-128b suppresses tumor growth and promotes apoptosis by targeting A2bR in gastric cancer

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

Wang, Ping; Guo, Xueyan; Zong, Wei

2015-11-27

MicroRNAs (miRNAs) play crucial roles in the development and progression of human cancers, including gastric cancer (GC). The discovery of miRNAs may provide a new and powerful tool for studying the mechanism, diagnosis, and treatment of GC. In this study, we aimed to investigate the role and mechanism of miR-128b in the development and progression of GC. Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-128b in GC tissues and cell lines. We found that miR-128b was significantly down-regulated in GC tissues and cell lines. In addition, over-expression of miR-128b inhibited GC cell proliferation, migration andmore » invasion of GC cells in vitro. Gain-of-function in vitro experiments further showed that the miR-128b mimic significantly promoted GC cell apoptosis. Subsequent dual-luciferase reporter assay identified one of the proto-oncogene A2bR as direct target of miR-128b. Therefore, our results indicate that miR-128b is a proto-oncogene miRNA that can suppresses GC proliferation and migration through down-regulation of the oncogene gene A2bR. Taken together, our results indicate that miR-128b could serve as a potential diagnostic biomarker and therapeutic option for human GC in the near future. - Highlights: • The expression of MiR-128b is significantly down-regulated in GC tissues and cell lines. • Ectopic expression of miR-128b directly affects cell proliferation, migration and invasion in vitro. • Overexpression of miR-128b increases apoptosis in GC cells. • A2bR is a candidate target gene of miR-128b. • MiR-128b represses cell proliferation, migration and invasion and promotes apoptosis by targeting A2bR in GC.« less

Strong Genetic Overlap Between Executive Functions and Intelligence

PubMed Central

Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

2016-01-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7-15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically-mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. PMID:27359131

Strong genetic overlap between executive functions and intelligence.

PubMed

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Individual Foraging Strategies Reveal Niche Overlap between Endangered Galapagos Pinnipeds

PubMed Central

Villegas-Amtmann, Stella; Jeglinski, Jana W. E.; Costa, Daniel P.; Robinson, Patrick W.; Trillmich, Fritz

2013-01-01

Most competition studies between species are conducted from a population-level approach. Few studies have examined inter-specific competition in conjunction with intra-specific competition, with an individual-based approach. To our knowledge, none has been conducted on marine top predators. Sympatric Galapagos fur seals (Arctocephalus galapagoensis) and sea lions (Zalophus wollebaeki) share similar geographic habitats and potentially compete. We studied their foraging niche overlap at Cabo Douglas, Fernandina Island from simultaneously collected dive and movement data to examine spatial and temporal inter- and intra-specific competition. Sea lions exhibited 3 foraging strategies (shallow, intermediate and deep) indicating intra-specific competition. Fur seals exhibited one foraging strategy, diving predominantly at night, between 0–80 m depth and mostly at 19–22 h. Most sea lion dives also occurred at night (63%), between 0–40 m, within fur seals' diving depth range. 34% of sea lions night dives occurred at 19–22 h, when fur seals dived the most, but most of them occurred at dawn and dusk, when fur seals exhibited the least amount of dives. Fur seals and sea lions foraging behavior overlapped at 19 and 21 h between 0–30 m depths. Sea lions from the deep diving strategy exhibited the greatest foraging overlap with fur seals, in time (19 h), depth during overlapping time (21–24 m), and foraging range (37.7%). Fur seals foraging range was larger. Cabo Douglas northwest coastal area, region of highest diving density, is a foraging “hot spot” for both species. Fur seals and sea lions foraging niche overlap occurred, but segregation also occurred; fur seals primarily dived at night, while sea lions exhibited night and day diving. Both species exploited depths and areas exclusive to their species. Niche breadth generally increases with environmental uncertainty and decreased productivity. Potential competition between these species could be greater during

miR-188 promotes senescence of lineage-negative bone marrow cells by targeting MAP3K3 expression.

PubMed

Zheng, Yue; Liu, Hua; Kong, Ye

2017-08-01

Lineage-negative bone marrow cells (lin-BMCs) have reparative potential for overcoming endothelial dysfunction and reducing cardiovascular risk. Here, we found that miR-188 is upregulated and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is downregulated in aged lin-BMCs, whereas their expression is reversed in young lin-BMCs. We identified and confirmed MAP3K3 as a direct target of miR-188. MiR-188 overexpression or MAP3K3 silencing in young lin-BMCs increases p16 and p21 expression, enhances cell senescence, and decreases the ability for cell proliferation, migration, and tube formation. Conversely, miR-188 suppression in aged lin-BMCs yields the opposite results. We further found that MAP3K3 is involved in miR-188-induced promotion of lin-BMC senescence. All data reveal that miR-188 induces lin-BMC senescence by targeting MAP3K3 expression, thus, providing new theoretical basis for the prevention and treatment of cardiovascular diseases. © 2017 Federation of European Biochemical Societies.

Auditing complex concepts in overlapping subsets of SNOMED.

PubMed

Wang, Yue; Wei, Duo; Xu, Junchuan; Elhanan, Gai; Perl, Yehoshua; Halper, Michael; Chen, Yan; Spackman, Kent A; Hripcsak, George

2008-11-06

Limited resources and the sheer volume of concepts make auditing a large terminology, such as SNOMED CT, a daunting task. It is essential to devise techniques that can aid an auditor by automatically identifying concepts that deserve attention. A methodology for this purpose based on a previously introduced abstraction network (called the p-area taxonomy) for a SNOMED CT hierarchy is presented. The methodology algorithmically gathers concepts appearing in certain overlapping subsets, defined exclusively with respect to the p-area taxonomy, for review. The results of applying the methodology to SNOMED's Specimen hierarchy are presented. These results are compared against a control sample composed of concepts residing in subsets without the overlaps. With the use of the double bootstrap, the concept group produced by our methodology is shown to yield a statistically significant higher proportion of error discoveries.

Auditing Complex Concepts in Overlapping Subsets of SNOMED

PubMed Central

Wang, Yue; Wei, Duo; Xu, Junchuan; Elhanan, Gai; Perl, Yehoshua; Halper, Michael; Chen, Yan; Spackman, Kent A.; Hripcsak, George

2008-01-01

Limited resources and the sheer volume of concepts make auditing a large terminology, such as SNOMED CT, a daunting task. It is essential to devise techniques that can aid an auditor by automatically identifying concepts that deserve attention. A methodology for this purpose based on a previously introduced abstraction network (called the p-area taxonomy) for a SNOMED CT hierarchy is presented. The methodology algorithmically gathers concepts appearing in certain overlapping subsets, defined exclusively with respect to the p-area taxonomy, for review. The results of applying the methodology to SNOMED’s Specimen hierarchy are presented. These results are compared against a control sample composed of concepts residing in subsets without the overlaps. With the use of the double bootstrap, the concept group produced by our methodology is shown to yield a statistically significant higher proportion of error discoveries. PMID:18998838

Importance of mesh overlap on hernia recurrence after open umbilical hernia repair with bilayer prosthesis.

PubMed

Porrero, Jose L; Cano-Valderrama, Oscar; Castillo, María J; Marcos, Alberto; Tejerina, Gabriel; Cendrero, Manuel; Porrero, Belén; Alonso, María T; Torres, Antonio J

2018-02-02

importance of mesh overlap on recurrence after open umbilical hernia repair has been poorly studied. a retrospective cohort study was performed with patients who underwent open umbilical hernia repair with bilayer prosthesis between 2004 and 2015. 1538 patients were included. Fifty patients (3.3%) had a mesh overlap lower than 1 cm. After a mean follow-up of 4.1 years 53 patients (3.5%) developed a recurrence. Recurrence was associated with a mesh overlap smaller than 1 cm (10.2% vs. 3.3%, p = 0.010, OR = 3.3). In the logistic regression model an overlap smaller than 1 cm was not statistically associated with recurrence (OR = 2.5, p = 0.123). Female gender, postoperative complications and prosthesis size were associated with hernia recurrence. mesh overlap seems to be an important factor for hernia recurrence. A mesh overlap of at least 1 cm should be used until more studies are performed about this issue. Copyright © 2018 Elsevier Inc. All rights reserved.

Examining the overlap in internet harassment and school bullying: implications for school intervention.

PubMed

Ybarra, Michele L; Diener-West, Marie; Leaf, Philip J

2007-12-01

As more and more youth utilize the Internet, concern about Internet harassment and its consequences for adolescents is growing. This paper examines the potential overlap in online and school harassment, as well as the concurrence of Internet harassment and school behavior problems. The Growing Up with Media survey is a national cross-sectional online survey of 1588 youth between the ages of 10 and 15 years old. Our main measures were Internet harassment (i.e., rude or nasty comments, spreading of rumors, threatening or aggressive comments) and school functioning (i.e., academic performance; skipping school; detentions and suspensions; and carrying a weapon to school in the last 30 days). Although some overlap existed, 64% of youth who were harassed online did not report also being bullied at school. Nonetheless, youth harassed online were significantly more likely to also report two or more detentions or suspensions, and skipping school in the previous year. Especially concerning, youth who reported being targeted by Internet harassment were eight times more likely than all other youth to concurrently report carrying a weapon to school in the past 30 days (odds ratio = 8.0, p = .002). Although the data do not support the assumption that many youth who are harassed online are bullied by the same (or even different) peers at school, findings support the need for professionals working with children and adolescents, especially those working in the schools, to be aware of the possible linkages between school behavior and online harassment for some youth.

Ultrafast Synthetic Transmit Aperture Imaging Using Hadamard-Encoded Virtual Sources With Overlapping Sub-Apertures.

PubMed

Ping Gong; Pengfei Song; Shigao Chen

2017-06-01

The development of ultrafast ultrasound imaging offers great opportunities to improve imaging technologies, such as shear wave elastography and ultrafast Doppler imaging. In ultrafast imaging, there are tradeoffs among image signal-to-noise ratio (SNR), resolution, and post-compounded frame rate. Various approaches have been proposed to solve this tradeoff, such as multiplane wave imaging or the attempts of implementing synthetic transmit aperture imaging. In this paper, we propose an ultrafast synthetic transmit aperture (USTA) imaging technique using Hadamard-encoded virtual sources with overlapping sub-apertures to enhance both image SNR and resolution without sacrificing frame rate. This method includes three steps: 1) create virtual sources using sub-apertures; 2) encode virtual sources using Hadamard matrix; and 3) add short time intervals (a few microseconds) between transmissions of different virtual sources to allow overlapping sub-apertures. The USTA was tested experimentally with a point target, a B-mode phantom, and in vivo human kidney micro-vessel imaging. Compared with standard coherent diverging wave compounding with the same frame rate, improvements on image SNR, lateral resolution (+33%, with B-mode phantom imaging), and contrast ratio (+3.8 dB, with in vivo human kidney micro-vessel imaging) have been achieved. The f-number of virtual sources, the number of virtual sources used, and the number of elements used in each sub-aperture can be flexibly adjusted to enhance resolution and SNR. This allows very flexible optimization of USTA for different applications.

Cenozoic Motion of Greenland - Overlaps and Seaways

NASA Astrophysics Data System (ADS)

Lawver, L. A.; Norton, I. O.; Gahagan, L.

2014-12-01

Using the seafloor magnetic anomalies found in the Labrador Sea, North Atlantic and Eurasian basin to constrain the Cenozoic motion of Greenland, we have produced a new model for the tectonic evolution of the region. The aeromagnetic data collected by the Naval Research Lab [Brozena et al., 2003] in the Eurasian Basin and Canadian data from the Labrador Sea have been re-evaluated using new gridding algorithms and profile modeling using ModMag (Mendel et al., 2005). As a consequence, we have changed the published correlations, mostly prior to Chron C6 [19.05 Ma]. Presently published seafloor magnetic anomalies from the Labrador Sea assume that seafloor spreading ceased at C13 [33.06 Ma] but such an assumption produces an unacceptable overlap of Kronprins Christian Land of northeast Greenland with Svalbard, up to 140 km of overlap in some models. Our new model does not need any "unacceptable" overlap but does produce a slight amount of Eocene compression on Svalbard as is found on land there. Our model allows for an Early Eocene seaway between Ellesmere Island and northwest Greenland that may have connected the Labrador Sea through Baffin Bay and ultimately to the nascent Eurasian Basin, although its depth or even its essential existence is unknowable. During the Miocene, there is no room for a deepwater seaway in Fram Strait until at least the very end of the Early Miocene and perhaps not until Middle Miocene. Brozena, J. and six others, 2003. New aerogeophysical study of the Eurasia Basin and Lomonosov Ridge: Implications for basin development. Geology 31, 825-828. Mendel, V., M. Munschy and D.Sauter, 2005, MODMAG, a MATLAB program to model marine magnetic anomalies, Comp. Geosci., 31, .589-597

Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium.

PubMed

Wang, Jun; Wang, Youliang; Wang, Yu; Ma, Ying; Lan, Yu; Yang, Xiao

2013-04-12

The TGF-β pathway plays an important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18- to 25-nucleotide, small, noncoding RNAs that function by regulating gene expression. A number of miRNAs have been found to be regulated by the TGF-β pathway. However, the role of endothelial miRNAs in the TGF-β-mediated control of angiogenesis is still largely unknown. Here we investigated the regulation of endothelial microRNA-29a (miR-29a) by TGF-β signaling and the potential role of miR-29a in angiogenesis. MiR-29a was directly up-regulated by TGF-β/Smad4 signaling in human and mice endothelial cells. In a chick chorioallantoic membrane assay, miR-29a overexpression promoted the formation of new blood vessels, and miR-29a suppression completely blocked TGF-β1-stimulated angiogenesis. Consistently, miR-29a overexpression increased tube formation and migration in endothelial cultures. Mechanistically, miR-29a directly targeted the phosphatase and tensin homolog (PTEN) in endothelial cells, leading to activation of the AKT pathway. PTEN knockdown recapitulated the role of miR-29a in endothelial migration, whereas AKT inhibition completely attenuated the stimulating role of miR-29a in angiogenesis. Taken together, these results reveal a crucial role of a TGF-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity.

Autism and ADHD: Overlapping and Discriminating Symptoms

ERIC Educational Resources Information Center

Mayes, Susan Dickerson; Calhoun, Susan L.; Mayes, Rebecca D.; Molitoris, Sarah

2012-01-01

Children with ADHD and autism have some similar features, complicating a differential diagnosis. The purpose of our study was to determine the degree to which core ADHD and autistic symptoms overlap in and discriminate between children 2-16 years of age with autism and ADHD. Our study demonstrated that 847 children with autism were easily…

An Integrated Centroid Finding and Particle Overlap Decomposition Algorithm for Stereo Imaging Velocimetry

NASA Technical Reports Server (NTRS)

McDowell, Mark

2004-01-01

An integrated algorithm for decomposing overlapping particle images (multi-particle objects) along with determining each object s constituent particle centroid(s) has been developed using image analysis techniques. The centroid finding algorithm uses a modified eight-direction search method for finding the perimeter of any enclosed object. The centroid is calculated using the intensity-weighted center of mass of the object. The overlap decomposition algorithm further analyzes the object data and breaks it down into its constituent particle centroid(s). This is accomplished with an artificial neural network, feature based technique and provides an efficient way of decomposing overlapping particles. Combining the centroid finding and overlap decomposition routines into a single algorithm allows us to accurately predict the error associated with finding the centroid(s) of particles in our experiments. This algorithm has been tested using real, simulated, and synthetic data and the results are presented and discussed.

Heterojunction fully depleted SOI-TFET with oxide/source overlap

NASA Astrophysics Data System (ADS)

Chander, Sweta; Bhowmick, B.; Baishya, S.

2015-10-01

In this work, a hetero-junction fully depleted (FD) Silicon-on-Insulator (SOI) Tunnel Field Effect Transistor (TFET) nanostructure with oxide overlap on the Germanium-source region is proposed. Investigations using Synopsys Technology Computer Aided Design (TCAD) simulation tools reveal that the simple oxide overlap on the Germanium-source region increases the tunneling area as well as the tunneling current without degrading the band-to-band tunneling (BTBT) and improves the device performance. More importantly, the improvement is independent of gate overlap. Simulation study shows improvement in ON current, subthreshold swing (SS), OFF current, ION/IOFF ration, threshold voltage and transconductance. The proposed device with hafnium oxide (HfO2)/Aluminium Nitride (AlN) stack dielectric material offers an average subthreshold swing of 22 mV/decade and high ION/IOFF ratio (∼1010) at VDS = 0.4 V. Compared to conventional TFET, the Miller capacitance of the device shows the enhanced performance. The impact of the drain voltage variation on different parameters such as threshold voltage, subthreshold swing, transconductance, and ION/IOFF ration are also found to be satisfactory. From fabrication point of view also it is easy to utilize the existing CMOS process flows to fabricate the proposed device.

Statistically validated network of portfolio overlaps and systemic risk.

PubMed

Gualdi, Stanislao; Cimini, Giulio; Primicerio, Kevin; Di Clemente, Riccardo; Challet, Damien

2016-12-21

Common asset holding by financial institutions (portfolio overlap) is nowadays regarded as an important channel for financial contagion with the potential to trigger fire sales and severe losses at the systemic level. We propose a method to assess the statistical significance of the overlap between heterogeneously diversified portfolios, which we use to build a validated network of financial institutions where links indicate potential contagion channels. The method is implemented on a historical database of institutional holdings ranging from 1999 to the end of 2013, but can be applied to any bipartite network. We find that the proportion of validated links (i.e. of significant overlaps) increased steadily before the 2007-2008 financial crisis and reached a maximum when the crisis occurred. We argue that the nature of this measure implies that systemic risk from fire sales liquidation was maximal at that time. After a sharp drop in 2008, systemic risk resumed its growth in 2009, with a notable acceleration in 2013. We finally show that market trends tend to be amplified in the portfolios identified by the algorithm, such that it is possible to have an informative signal about institutions that are about to suffer (enjoy) the most significant losses (gains).

Statistically validated network of portfolio overlaps and systemic risk

PubMed Central

Gualdi, Stanislao; Cimini, Giulio; Primicerio, Kevin; Di Clemente, Riccardo; Challet, Damien

2016-01-01

Common asset holding by financial institutions (portfolio overlap) is nowadays regarded as an important channel for financial contagion with the potential to trigger fire sales and severe losses at the systemic level. We propose a method to assess the statistical significance of the overlap between heterogeneously diversified portfolios, which we use to build a validated network of financial institutions where links indicate potential contagion channels. The method is implemented on a historical database of institutional holdings ranging from 1999 to the end of 2013, but can be applied to any bipartite network. We find that the proportion of validated links (i.e. of significant overlaps) increased steadily before the 2007–2008 financial crisis and reached a maximum when the crisis occurred. We argue that the nature of this measure implies that systemic risk from fire sales liquidation was maximal at that time. After a sharp drop in 2008, systemic risk resumed its growth in 2009, with a notable acceleration in 2013. We finally show that market trends tend to be amplified in the portfolios identified by the algorithm, such that it is possible to have an informative signal about institutions that are about to suffer (enjoy) the most significant losses (gains). PMID:28000764

Specificity and overlap of attention and memory biases in depression.

PubMed

Marchetti, Igor; Everaert, Jonas; Dainer-Best, Justin; Loeys, Tom; Beevers, Christopher G; Koster, Ernst H W

2018-01-01

Attentional and memory biases are viewed as crucial cognitive processes underlying symptoms of depression. However, it is still unclear whether these two biases are uniquely related to depression or whether they show substantial overlap. We investigated the degree of specificity and overlap of attentional and memory biases for depressotypic stimuli in relation to depression and anxiety by means of meta-analytic commonality analysis. By including four published studies, we considered a pool of 463 healthy and subclinically depressed individuals, different experimental paradigms, and different psychological measures. Memory bias is reliably and strongly related to depression and, specifically, to symptoms of negative mood, worthlessness, feelings of failure, and pessimism. Memory bias for negative information was minimally related to anxiety. Moreover, neither attentional bias nor the overlap between attentional and memory biases were significantly related to depression. Limitations include cross-sectional nature of the study. Our study showed that, across different paradigms and psychological measures, memory bias (and not attentional bias) represents a primary mechanism in depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Network neighborhood analysis with the multi-node topological overlap measure.

PubMed

Li, Ai; Horvath, Steve

2007-01-15

The goal of neighborhood analysis is to find a set of genes (the neighborhood) that is similar to an initial 'seed' set of genes. Neighborhood analysis methods for network data are important in systems biology. If individual network connections are susceptible to noise, it can be advantageous to define neighborhoods on the basis of a robust interconnectedness measure, e.g. the topological overlap measure. Since the use of multiple nodes in the seed set may lead to more informative neighborhoods, it can be advantageous to define multi-node similarity measures. The pairwise topological overlap measure is generalized to multiple network nodes and subsequently used in a recursive neighborhood construction method. A local permutation scheme is used to determine the neighborhood size. Using four network applications and a simulated example, we provide empirical evidence that the resulting neighborhoods are biologically meaningful, e.g. we use neighborhood analysis to identify brain cancer related genes. An executable Windows program and tutorial for multi-node topological overlap measure (MTOM) based analysis can be downloaded from the webpage (http://www.genetics.ucla.edu/labs/horvath/MTOM/).

Overlapping community detection based on link graph using distance dynamics

NASA Astrophysics Data System (ADS)

Chen, Lei; Zhang, Jing; Cai, Li-Jun

2018-01-01

The distance dynamics model was recently proposed to detect the disjoint community of a complex network. To identify the overlapping structure of a network using the distance dynamics model, an overlapping community detection algorithm, called L-Attractor, is proposed in this paper. The process of L-Attractor mainly consists of three phases. In the first phase, L-Attractor transforms the original graph to a link graph (a new edge graph) to assure that one node has multiple distances. In the second phase, using the improved distance dynamics model, a dynamic interaction process is introduced to simulate the distance dynamics (shrink or stretch). Through the dynamic interaction process, all distances converge, and the disjoint community structure of the link graph naturally manifests itself. In the third phase, a recovery method is designed to convert the disjoint community structure of the link graph to the overlapping community structure of the original graph. Extensive experiments are conducted on the LFR benchmark networks as well as real-world networks. Based on the results, our algorithm demonstrates higher accuracy and quality than other state-of-the-art algorithms.

Impossible spaces: maximizing natural walking in virtual environments with self-overlapping architecture.

PubMed

Suma, Evan A; Lipps, Zachary; Finkelstein, Samantha; Krum, David M; Bolas, Mark

2012-04-01

Walking is only possible within immersive virtual environments that fit inside the boundaries of the user's physical workspace. To reduce the severity of the restrictions imposed by limited physical area, we introduce "impossible spaces," a new design mechanic for virtual environments that wish to maximize the size of the virtual environment that can be explored with natural locomotion. Such environments make use of self-overlapping architectural layouts, effectively compressing comparatively large interior environments into smaller physical areas. We conducted two formal user studies to explore the perception and experience of impossible spaces. In the first experiment, we showed that reasonably small virtual rooms may overlap by as much as 56% before users begin to detect that they are in an impossible space, and that the larger virtual rooms that expanded to maximally fill our available 9.14 m x 9.14 m workspace may overlap by up to 31%. Our results also demonstrate that users perceive distances to objects in adjacent overlapping rooms as if the overall space was uncompressed, even at overlap levels that were overtly noticeable. In our second experiment, we combined several well-known redirection techniques to string together a chain of impossible spaces in an expansive outdoor scene. We then conducted an exploratory analysis of users' verbal feedback during exploration, which indicated that impossible spaces provide an even more powerful illusion when users are naive to the manipulation.

Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps.

PubMed

Sood, Mariam R; Sereno, Martin I

2016-08-01

Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor-preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface-based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory-motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory-motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M-I. Hum Brain Mapp 37:2784-2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The class I protein AtTCP15 modulates plant development through a pathway that overlaps with the one affected by CIN-like TCP proteins.

PubMed

Uberti-Manassero, Nora G; Lucero, Leandro E; Viola, Ivana L; Vegetti, Abelardo C; Gonzalez, Daniel H

2012-01-01

The function of the class I TCP transcription factor TCP15 from Arabidopsis thaliana has been studied through the analysis of plants that express a fusion of this protein to the EAR repressor domain. Constitutive expression of TCP15-EAR produces growth arrest at the seedling stage, before leaf emergence. Expression of the repressor fusion from the AtTCP15 promoter produces small plants with leaves whose margins progressively curve upwards, starting from the basal part of the lamina. Leaves contain smaller and less differentiated cells, both on the adaxial and abaxial sides. The abaxial domain is relatively enlarged, with disorganized cells separated by empty spaces. TCP15-EAR also affects the growth of leaf petioles, flower pedicels, and anther filaments. Flowers show reduced elongation of the three outer whorls and altered gynoecia with irregular carpel surfaces and enlarged repla. Ectopic stigma-like structures develop from medial and basal parts of the replum. TCP15-EAR produces an increase in expression of the boundary-specific genes LOB, CUC1, and CUC2. Changes in CUC1 and CUC2 expression can be explained by the existence of lower levels of miR164 in leaves and the repression of IAA3/SHY2 and the SAUR-like gene At1g29460 in leaves and flowers. TCP15 binds to the promoter regions of IAA3/SHY2 and At1g29460, suggesting that these genes may be direct targets of the transcription factor. The results indicate that TCP15 regulates the expression of boundary-specific genes through a pathway that affects auxin homeostasis and partially overlaps with the one modulated by class II CIN-like TCP proteins.

Multiple mobile promoter regions for the rare carbapenem resistance gene of Bacteroides fragilis.

PubMed

Podglajen, I; Breuil, J; Rohaut, A; Monsempes, C; Collatz, E

2001-06-01

Two novel insertion sequences (IS), IS1187 and IS1188, are described upstream from the carbapenem resistance gene cfiA in strains of Bacteroides fragilis. Mapping, with the RACE procedure, of transcription start sites of cfiA in these and two other previously reported IS showed that transcription of this rarely encountered gene is initiated close to a variety of B. fragilis consensus promoter sequences, as recently defined (D. P. Bayley, E. R. Rocha, and C. J. Smith, FEMS Microbiol. Lett. 193:149-154, 2000). In the cases of IS1186 and IS1188, these sequences overlap with putative Esigma(70) promoter sequences, while in IS942 and IS1187 such sequences can be observed either upstream or downstream of the B. fragilis promoters.

Tobacco related bar promotions: insights from tobacco industry documents.

PubMed

Katz, S K; Lavack, A M

2002-03-01

To examine the tobacco industry's use of bar promotions, including their target groups, objectives, strategies, techniques, and results. Over 2000 tobacco industry documents available as a result of the Master Settlement Agreement were reviewed on the internet at several key web sites using keyword searches that included "bar", "night", "pub", "party", and "club". The majority of the documents deal with the US market, with a minor emphasis on Canadian and overseas markets. The documents indicate that bar promotions are important for creating and maintaining brand image, and are generally targeted at a young adult audience. Several measures of the success of these promotions are used, including number of individuals exposed to the promotion, number of promotional items given away, and increased sales of a particular brand during and after the promotion. Bar promotions position cigarettes as being part of a glamorous lifestyle that includes attendance at nightclubs and bars, and appear to be highly successful in increasing sales of particular brands.

Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis

PubMed Central

Chen, Zhen; Lai, Tsung-Ching; Jan, Yi-Hua; Lin, Feng-Mao; Wang, Wei-Chi; Xiao, Han; Wang, Yun-Ting; Sun, Wei; Cui, Xiaopei; Li, Ying-Shiuan; Fang, Tzan; Zhao, Hongwei; Padmanabhan, Chellappan; Sun, Ruobai; Wang, Danny Ling; Jin, Hailing; Chau, Gar-Yang; Huang, Hsien-Da; Hsiao, Michael; Shyy, John Y-J.

2013-01-01

Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3′ untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These findings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies. PMID:23426184

Combined node and link partitions method for finding overlapping communities in complex networks

PubMed Central

Jin, Di; Gabrys, Bogdan; Dang, Jianwu

2015-01-01

Community detection in complex networks is a fundamental data analysis task in various domains, and how to effectively find overlapping communities in real applications is still a challenge. In this work, we propose a new unified model and method for finding the best overlapping communities on the basis of the associated node and link partitions derived from the same framework. Specifically, we first describe a unified model that accommodates node and link communities (partitions) together, and then present a nonnegative matrix factorization method to learn the parameters of the model. Thereafter, we infer the overlapping communities based on the derived node and link communities, i.e., determine each overlapped community between the corresponding node and link community with a greedy optimization of a local community function conductance. Finally, we introduce a model selection method based on consensus clustering to determine the number of communities. We have evaluated our method on both synthetic and real-world networks with ground-truths, and compared it with seven state-of-the-art methods. The experimental results demonstrate the superior performance of our method over the competing ones in detecting overlapping communities for all analysed data sets. Improved performance is particularly pronounced in cases of more complicated networked community structures. PMID:25715829

Ripple artifact reduction using slice overlap in slice encoding for metal artifact correction.

PubMed

den Harder, J Chiel; van Yperen, Gert H; Blume, Ulrike A; Bos, Clemens

2015-01-01

Multispectral imaging (MSI) significantly reduces metal artifacts. Yet, especially in techniques that use gradient selection, such as slice encoding for metal artifact correction (SEMAC), a residual ripple artifact may be prominent. Here, an analysis is presented of the ripple artifact and of slice overlap as an approach to reduce the artifact. The ripple artifact was analyzed theoretically to clarify its cause. Slice overlap, conceptually similar to spectral bin overlap in multi-acquisition with variable resonances image combination (MAVRIC), was achieved by reducing the selection gradient and, thus, increasing the slice profile width. Time domain simulations and phantom experiments were performed to validate the analyses and proposed solution. Discontinuities between slices are aggravated by signal displacement in the frequency encoding direction in areas with deviating B0. Specifically, it was demonstrated that ripple artifacts appear only where B0 varies both in-plane and through-plane. Simulations and phantom studies of metal implants confirmed the efficacy of slice overlap to reduce the artifact. The ripple artifact is an important limitation of gradient selection based MSI techniques, and can be understood using the presented simulations. At a scan-time penalty, slice overlap effectively addressed the artifact, thereby improving image quality near metal implants. © 2014 Wiley Periodicals, Inc.

Contingent capture in cueing: the role of color search templates and cue-target color relations.

PubMed

Ansorge, Ulrich; Becker, Stefanie I

2014-03-01

Visual search studies have shown that attention can be top-down biased to a specific target color, so that only items with this color or a similar color can capture attention. According to some theories of attention, colors from different categories (i.e., red, green, blue, yellow) are represented independently. However, other accounts have proposed that these are related--either because color is filtered through broad overlapping channels (4-channel view), or because colors are represented in one continuous feature space (e.g., CIE space) and search is governed by specific principles (e.g., linear separability between colors, or top-down tuning to relative colors). The present study tested these different views using a cueing experiment in which observers had to select one target color (e.g., red) and ignore two or four differently colored distractors that were presented prior to the target (cues). The results showed clear evidence for top-down contingent capture by colors, as a target-colored cue captured attention more strongly than differently colored cues. However, the results failed to support any of the proposed views that different color categories are related to one another by overlapping channels, linear separability, or relational guidance (N = 96).

On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies

NASA Astrophysics Data System (ADS)

Degiacomi, Matteo T.

2018-05-01

Ion mobility mass spectrometry (IM/MS) can provide structural information on intact protein complexes. Such data, including connectivity and collision cross sections (CCS) of assemblies' subunits, can in turn be used as a guide to produce representative super coarse-grained models. These models are constituted by ensembles of overlapping spheres, each representing a protein subunit. A model is considered plausible if the CCS and sphere-overlap levels of its subunits fall within predetermined confidence intervals. While the first is determined by experimental error, the latter is based on a statistical analysis on a range of protein dimers. Here, we first propose a new expression to describe the overlap between two spheres. Then we analyze the effect of specific overlap cutoff choices on the precision and accuracy of super coarse-grained models. Finally, we propose a method to determine overlap cutoff levels on a per-case scenario, based on collected CCS data, and show that it can be applied to the characterization of the assembly topology of symmetrical homo-multimers. [Figure not available: see fulltext.

Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment.

PubMed

Le Hellard, Stéphanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco; Hugdahl, Kenneth; Espeseth, Thomas; Steen, Vidar M; Melle, Ingrid; Desikan, Rahul; Schork, Andrew J; Thompson, Wesley K; Dale, Anders M; Djurovic, Srdjan; Andreassen, Ole A

2017-05-01

There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a "proxy phenotype" for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion ("College," n = 95 427), and years of education ("EduYears," n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Overlapping illusions by transformation optics without any negative refraction material.

PubMed

Sun, Fei; He, Sailing

2016-01-11

A novel method to achieve an overlapping illusion without any negative refraction index material is introduced with the help of the optic-null medium (ONM) designed by an extremely stretching spatial transformation. Unlike the previous methods to achieve such an optical illusion by transformation optics (TO), our method can achieve a power combination and reshape the radiation pattern at the same time. Unlike the overlapping illusion with some negative refraction index material, our method is not sensitive to the loss of the materials. Other advantages over existing methods are discussed. Numerical simulations are given to verify the performance of the proposed devices.

Overlapping double etch technique for evaluation of metallic alloys to stress corrosion cracking

DOEpatents

Steeves, Arthur F.; Stewart, James C.

1981-01-01

A double overlapping etch zone technique for evaluation of the resistance of metallic alloys to stress corrosion cracking. The technique involves evaluating the metallic alloy along the line of demarcation between an overlapping double etch zone and single etch zone formed on the metallic alloy surface.

Identifying Overlapping Language Communities: The Case of Chiriquí and Panamanian Signed Languages

ERIC Educational Resources Information Center

Parks, Elizabeth S.

2016-01-01

In this paper, I use a holographic metaphor to explain the identification of overlapping sign language communities in Panama. By visualizing Panama's complex signing communities as emitting community "hotspots" through social drama on multiple stages, I employ ethnographic methods to explore overlapping contours of Panama's sign language…

Complex overlapping concepts: An effective auditing methodology for families of similarly structured BioPortal ontologies.

PubMed

Zheng, Ling; Chen, Yan; Elhanan, Gai; Perl, Yehoshua; Geller, James; Ochs, Christopher

2018-05-28

In previous research, we have demonstrated for a number of ontologies that structurally complex concepts (for different definitions of "complex") in an ontology are more likely to exhibit errors than other concepts. Thus, such complex concepts often become fertile ground for quality assurance (QA) in ontologies. They should be audited first. One example of complex concepts is given by "overlapping concepts" (to be defined below.) Historically, a different auditing methodology had to be developed for every single ontology. For better scalability and efficiency, it is desirable to identify family-wide QA methodologies. Each such methodology would be applicable to a whole family of similar ontologies. In past research, we had divided the 685 ontologies of BioPortal into families of structurally similar ontologies. We showed for four ontologies of the same large family in BioPortal that "overlapping concepts" are indeed statistically significantly more likely to exhibit errors. In order to make an authoritative statement concerning the success of "overlapping concepts" as a methodology for a whole family of similar ontologies (or of large subhierarchies of ontologies), it is necessary to show that "overlapping concepts" have a higher likelihood of errors for six out of six ontologies of the family. In this paper, we are demonstrating for two more ontologies that "overlapping concepts" can successfully predict groups of concepts with a higher error rate than concepts from a control group. The fifth ontology is the Neoplasm subhierarchy of the National Cancer Institute thesaurus (NCIt). The sixth ontology is the Infectious Disease subhierarchy of SNOMED CT. We demonstrate quality assurance results for both of them. Furthermore, in this paper we observe two novel, important, and useful phenomena during quality assurance of "overlapping concepts." First, an erroneous "overlapping concept" can help with discovering other erroneous "non-overlapping concepts" in its vicinity

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

Salicylic Acid Suppresses Jasmonic Acid Signaling Downstream of SCFCOI1-JAZ by Targeting GCC Promoter Motifs via Transcription Factor ORA59[C][W][OA

PubMed Central

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C.; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P.; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C.M.; Pieterse, Corné M.J.

2013-01-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCFCOI1, which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCFCOI1-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59. PMID:23435661

Bar and Club Tobacco Promotions in the Alternative Press: Targeting Young Adults.

ERIC Educational Resources Information Center

Sepe, Edward; Glantz, Stanton A.

2002-01-01

Investigated changes in tobacco promotions in two alternative newspapers in San Francisco and Philadelphia from 1994-99. Results indicated that the numbers of tobacco advertisements increased dramatically during those years. The tobacco industry increased its use of bars and clubs as promotional venues and used the alternative press to reach young…

Measuring droplet size distributions from overlapping interferometric particle images.

PubMed

Bocanegra Evans, Humberto; Dam, Nico; van der Voort, Dennis; Bertens, Guus; van de Water, Willem

2015-02-01

Interferometric particle imaging provides a simple way to measure the probability density function (PDF) of droplet sizes from out-focus images. The optical setup is straightforward, but the interpretation of the data is a problem when particle images overlap. We propose a new way to analyze the images. The emphasis is not on a precise identification of droplets, but on obtaining a good estimate of the PDF of droplet sizes in the case of overlapping particle images. The algorithm is tested using synthetic and experimental data. We next use these methods to measure the PDF of droplet sizes produced by spinning disk aerosol generators. The mean primary droplet diameter agrees with predictions from the literature, but we find a broad distribution of satellite droplet sizes.

Overlapped Partitioning for Ensemble Classifiers of P300-Based Brain-Computer Interfaces

PubMed Central

Onishi, Akinari; Natsume, Kiyohisa

2014-01-01

A P300-based brain-computer interface (BCI) enables a wide range of people to control devices that improve their quality of life. Ensemble classifiers with naive partitioning were recently applied to the P300-based BCI and these classification performances were assessed. However, they were usually trained on a large amount of training data (e.g., 15300). In this study, we evaluated ensemble linear discriminant analysis (LDA) classifiers with a newly proposed overlapped partitioning method using 900 training data. In addition, the classification performances of the ensemble classifier with naive partitioning and a single LDA classifier were compared. One of three conditions for dimension reduction was applied: the stepwise method, principal component analysis (PCA), or none. The results show that an ensemble stepwise LDA (SWLDA) classifier with overlapped partitioning achieved a better performance than the commonly used single SWLDA classifier and an ensemble SWLDA classifier with naive partitioning. This result implies that the performance of the SWLDA is improved by overlapped partitioning and the ensemble classifier with overlapped partitioning requires less training data than that with naive partitioning. This study contributes towards reducing the required amount of training data and achieving better classification performance. PMID:24695550

Overlapped partitioning for ensemble classifiers of P300-based brain-computer interfaces.

PubMed

Onishi, Akinari; Natsume, Kiyohisa

2014-01-01

A P300-based brain-computer interface (BCI) enables a wide range of people to control devices that improve their quality of life. Ensemble classifiers with naive partitioning were recently applied to the P300-based BCI and these classification performances were assessed. However, they were usually trained on a large amount of training data (e.g., 15300). In this study, we evaluated ensemble linear discriminant analysis (LDA) classifiers with a newly proposed overlapped partitioning method using 900 training data. In addition, the classification performances of the ensemble classifier with naive partitioning and a single LDA classifier were compared. One of three conditions for dimension reduction was applied: the stepwise method, principal component analysis (PCA), or none. The results show that an ensemble stepwise LDA (SWLDA) classifier with overlapped partitioning achieved a better performance than the commonly used single SWLDA classifier and an ensemble SWLDA classifier with naive partitioning. This result implies that the performance of the SWLDA is improved by overlapped partitioning and the ensemble classifier with overlapped partitioning requires less training data than that with naive partitioning. This study contributes towards reducing the required amount of training data and achieving better classification performance.

Simultaneous Drug Targeting of the Promoter MYC G-Quadruplex and BCL2 i-Motif in Diffuse Large B-Cell Lymphoma Delays Tumor Growth.

PubMed

Kendrick, Samantha; Muranyi, Andrea; Gokhale, Vijay; Hurley, Laurence H; Rimsza, Lisa M

2017-08-10

Secondary DNA structures are uniquely poised as therapeutic targets due to their molecular switch function in turning gene expression on or off and scaffold-like properties for protein and small molecule interaction. Strategies to alter gene transcription through these structures thus far involve targeting single DNA conformations. Here we investigate the feasibility of simultaneously targeting different secondary DNA structures to modulate two key oncogenes, cellular-myelocytomatosis (MYC) and B-cell lymphoma gene-2 (BCL2), in diffuse large B-cell lymphoma (DLBCL). Cotreatment with previously identified ellipticine and pregnanol derivatives that recognize the MYC G-quadruplex and BCL2 i-motif promoter DNA structures lowered mRNA levels and subsequently enhanced sensitivity to a standard chemotherapy drug, cyclophosphamide, in DLBCL cell lines. In vivo repression of MYC and BCL2 in combination with cyclophosphamide also significantly slowed tumor growth in DLBCL xenograft mice. Our findings demonstrate concurrent targeting of different DNA secondary structures offers an effective, precise, medicine-based approach to directly impede transcription and overcome aberrant pathways in aggressive malignancies.

Overlapping double etch technique for evaluation of metallic alloys to stress corrosion cracking

DOEpatents

Not Available

1980-05-28

A double overlapping etch zone technique for evaluation of the resistance of metallic alloys to stress corrosion cracking is described. The technique involves evaluating the metallic alloy along the line of demarcation between an overlapping double etch zone and single etch zone formed on the metallic alloy surface.

Decoding Overlapping Memories in the Medial Temporal Lobes Using High-Resolution fMRI

ERIC Educational Resources Information Center

Chadwick, Martin J.; Hassabis, Demis; Maguire, Eleanor A.

2011-01-01

The hippocampus is proposed to process overlapping episodes as discrete memory traces, although direct evidence for this in human episodic memory is scarce. Using green-screen technology we created four highly overlapping movies of everyday events. Participants were scanned using high-resolution fMRI while recalling the movies. Multivariate…

Pleiotrophin, a target of miR-384, promotes proliferation, metastasis and lipogenesis in HBV-related hepatocellular carcinoma.

PubMed

Bai, Pei-Song; Xia, Nan; Sun, Hong; Kong, Ying

2017-11-01

Hepatitis B virus (HBV) infection plays a crucial role and is a major cause of hepatocellular carcinoma (HCC) in China. microRNAs (miRNAs) have emerged as key players in hepatic steatosis and carcinogenesis. We found that down-regulation of miR-384 expression was a common event in HCC, especially HBV-related HCC. However, the possible function of miR-384 in HBV-related HCC remains unclear. The oncogene pleiotrophin (PTN) was a target of miR-384. HBx inhibited miR-384, increasing PTN expression. The PTN receptor N-syndecan was highly expressed in HCC. PTN induced by HBx acted as a growth factor via N-syndecan on hepatocytes and further promoted cell proliferation, metastasis and lipogenesis. PTN up-regulated sterol regulatory element-binding protein 1c (SREBP-1c) through the N-syndecan/PI3K/Akt/mTORC1 pathway and the expression of lipogenic genes, including fatty acid synthesis (FAS). PTN-mediated de novo lipid synthesis played an important role in HCC proliferation and metastasis. PI3K/AKT and an mTORC1 inhibitor diminished PTN-induced proliferation, metastasis and lipogenesis. Taken together, these data strongly suggest that the dysregulation of miR-384 could play a crucial role in HBV related to HCC, and the target gene of miR-384, PTN, represents a new potential therapeutic target for the prevention of hepatic steatosis and further progression to HCC after chronic HBV infection. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Mammalian target of rapamycin inhibitors, temsirolimus and torin 1, attenuate stemness-associated properties and expression of mesenchymal markers promoted by phorbol-myristate-acetate and oncostatin-M in glioblastoma cells.

PubMed

Chandrika, Goparaju; Natesh, Kumar; Ranade, Deepak; Chugh, Ashish; Shastry, Padma

2017-03-01

The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway is crucial for tumor survival, proliferation, and progression, making it an attractive target for therapeutic intervention. In glioblastoma, activated mammalian target of rapamycin promotes invasive phenotype and correlates with poor patient survival. A wide range of mammalian target of rapamycin inhibitors are currently being evaluated for cytotoxicity and anti-proliferative activity in various tumor types but are not explored sufficiently for controlling tumor invasion and recurrence. We recently reported that mammalian target of rapamycin inhibitors-rapamycin, temsirolimus, torin 1, and PP242-suppressed invasion and migration promoted by tumor necrosis factor-alpha and phorbol-myristate-acetate in glioblastoma cells. As aggressive invasion and migration of tumors are associated with mesenchymal and stem-like cell properties, this study aimed to examine the effect of mammalian target of rapamycin inhibitors on these features in glioblastoma cells. We demonstrate that temsirolimus and torin 1 effectively reduced the constitutive as well as phorbol-myristate-acetate/oncostatin-M-induced expression of mesenchymal markers (fibronectin, vimentin, and YKL40) and neural stem cell markers (Sox2, Oct4, nestin, and mushashi1). The inhibitors significantly abrogated the neurosphere-forming capacity induced by phorbol-myristate-acetate and oncostatin-M. Furthermore, we demonstrate that the drugs dephosphorylated signal transducer and activator transcription factor 3, a major regulator of mesenchymal and neural stem cell markers implicating the role of signal transducer and activator transcription factor 3 in the inhibitory action of these drugs. The findings demonstrate the potential of mammalian target of rapamycin inhibitors as "stemness-inhibiting drugs" and a promising therapeutic approach to target glioma stem cells.

A separable surface-enhanced Raman scattering substrate modified with MIL-101 for detection of overlapping and invisible compounds after thin-layer chromatography development.

PubMed

Zhang, Bin Bin; Shi, Yi; Chen, Hui; Zhu, Qing Xia; Lu, Feng; Li, Ying Wei

2018-01-02

By coupling surface-enhanced Raman spectroscopy (SERS) with thin-layer chromatography (TLC), a powerful method for detecting complex samples was successfully developed. However, in the TLC-SERS method, metal nanoparticles serving as the SERS-active substrate are likely to disturb the detection of target compounds, particularly in overlapping compounds after TLC development. In addition, the SERS detection of compounds that are invisible under both visible light and UV 254/365 after TLC development is still a significant challenge. In this study, we demonstrated a facile strategy to fabricate a TLC plate with metal-organic framework-modified gold nanoparticles as a separable SERS substrate, on which all separated components, including overlapping and invisible compounds, could be detected by a point-by-point SERS scan along the developing direction. Rhodamine 6G (R6G) was used as a probe to evaluate the performance of the substrate. The results indicated that the substrate provided good sensitivity and reproducibility, and optimal SERS signals could be collected in 5 s. Furthermore, this new substrate exhibited a long shelf life. Thus, our method has great potential for the sensitive and rapid detection of overlapping and invisible compounds in complex samples after TLC development. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

c-Myb Binds to a Sequence in the Proximal Region of the RAG-2 Promoter and Is Essential for Promoter Activity in T-Lineage Cells

PubMed Central

Wang, Qian-Fei; Lauring, Josh; Schlissel, Mark S.

2000-01-01

The RAG-2 gene encodes a component of the V(D)J recombinase which is essential for the assembly of antigen receptor genes in B and T lymphocytes. Previously, we reported that the transcription factor BSAP (PAX-5) regulates the murine RAG-2 promoter in B-cell lines. A partially overlapping but distinct region of the proximal RAG-2 promoter was also identified as an important element for promoter activity in T cells; however, the responsible factor was unknown. In this report, we present data demonstrating that c-Myb binds to a Myb consensus site within the proximal promoter and is critical for its activity in T-lineage cells. We show that c-Myb can transactivate a RAG-2 promoter-reporter construct in cotransfection assays and that this transactivation depends on the proximal promoter Myb consensus site. By using a chromatin immunoprecipitation (ChIP) strategy, fractionation of chromatin with anti-c-Myb antibody specifically enriched endogenous RAG-2 promoter DNA sequences. DNase I genomic footprinting revealed that the c-Myb site is occupied in a tissue-specific fashion in vivo. Furthermore, an integrated RAG-2 promoter construct with mutations at the c-Myb site was not enriched in the ChIP assay, while a wild-type integrated promoter construct was enriched. Finally, this lack of binding of c-Myb to a chromosomally integrated mutant RAG-2 promoter construct in vivo was associated with a striking decrease in promoter activity. We conclude that c-Myb regulates the RAG-2 promoter in T cells by binding to this consensus c-Myb binding site. PMID:11094072

Measuring content overlap during handoff communication using distributional semantics: An exploratory study.

PubMed

Abraham, Joanna; Kannampallil, Thomas G; Srinivasan, Vignesh; Galanter, William L; Tagney, Gail; Cohen, Trevor

2017-01-01

We develop and evaluate a methodological approach to measure the degree and nature of overlap in handoff communication content within and across clinical professions. This extensible, exploratory approach relies on combining techniques from conversational analysis and distributional semantics. We audio-recorded handoff communication of residents and nurses on the General Medicine floor of a large academic hospital (n=120 resident and n=120 nurse handoffs). We measured semantic similarity, a proxy for content overlap, between resident-resident and nurse-nurse communication using multiple steps: a qualitative conversational content analysis; an automated semantic similarity analysis using Reflective Random Indexing (RRI); and comparing semantic similarity generated by RRI analysis with human ratings of semantic similarity. There was significant association between the semantic similarity as computed by the RRI method and human rating (ρ=0.88). Based on the semantic similarity scores, content overlap was relatively higher for content related to patient active problems, assessment of active problems, patient-identifying information, past medical history, and medications/treatments. In contrast, content overlap was limited on content related to allergies, family-related information, code status, and anticipatory guidance. Our approach using RRI analysis provides new opportunities for characterizing the nature and degree of overlap in handoff communication. Although exploratory, this method provides a basis for identifying content that can be used for determining shared understanding across clinical professions. Additionally, this approach can inform the development of flexibly standardized handoff tools that reflect clinical content that are most appropriate for fostering shared understanding during transitions of care. Copyright © 2016 Elsevier Inc. All rights reserved.

Finite Element Analysis of Composite Joint Configurations with Gaps and Overlaps

NASA Technical Reports Server (NTRS)

Krueger, Ronald

2014-01-01

The goal of the current study is to identify scenarios for which thermal and moisture effects become significant in the loading of a composite structure. In the current work, a simple configuration was defined, and material properties were selected. A Fortran routine was created to automate the mesh generation process. The routine was used to create the models for the initial mesh refinement study. A combination of element length and width suitable for further studies was identified. Also, the effect of the overlap length and gap length on computed shear and through-thickness stresses along the bondline of the joints was studied for the mechanical load case. Further, the influence of neighboring gaps and overlaps on these joint stresses was studied and was found to be negligible. The results suggest that for an initial study it is sufficient to focus on one configuration with fixed overlap and gap lengths to study the effects of mechanical, thermal and moisture loading and combinations thereof on computed joint stresses

A game theoretic algorithm to detect overlapping community structure in networks

NASA Astrophysics Data System (ADS)

Zhou, Xu; Zhao, Xiaohui; Liu, Yanheng; Sun, Geng

2018-04-01

Community detection can be used as an important technique for product and personalized service recommendation. A game theory based approach to detect overlapping community structure is introduced in this paper. The process of the community formation is converted into a game, when all agents (nodes) cannot improve their own utility, the game process will be terminated. The utility function is composed of a gain and a loss function and we present a new gain function in this paper. In addition, different from choosing action randomly among join, quit and switch for each agent to get new label, two new strategies for each agent to update its label are designed during the game, and the strategies are also evaluated and compared for each agent in order to find its best result. The overlapping community structure is naturally presented when the stop criterion is satisfied. The experimental results demonstrate that the proposed algorithm outperforms other similar algorithms for detecting overlapping communities in networks.

Targeted exome sequencing of suspected mitochondrial disorders

PubMed Central

Lieber, Daniel S.; Calvo, Sarah E.; Shanahan, Kristy; Slate, Nancy G.; Liu, Shangtao; Hershman, Steven G.; Gold, Nina B.; Chapman, Brad A.; Thorburn, David R.; Berry, Gerard T.; Schmahmann, Jeremy D.; Borowsky, Mark L.; Mueller, David M.; Sims, Katherine B.

2013-01-01

Objective: To evaluate the utility of targeted exome sequencing for the molecular diagnosis of mitochondrial disorders, which exhibit marked phenotypic and genetic heterogeneity. Methods: We considered a diverse set of 102 patients with suspected mitochondrial disorders based on clinical, biochemical, and/or molecular findings, and whose disease ranged from mild to severe, with varying age at onset. We sequenced the mitochondrial genome (mtDNA) and the exons of 1,598 nuclear-encoded genes implicated in mitochondrial biology, mitochondrial disease, or monogenic disorders with phenotypic overlap. We prioritized variants likely to underlie disease and established molecular diagnoses in accordance with current clinical genetic guidelines. Results: Targeted exome sequencing yielded molecular diagnoses in established disease loci in 22% of cases, including 17 of 18 (94%) with prior molecular diagnoses and 5 of 84 (6%) without. The 5 new diagnoses implicated 2 genes associated with canonical mitochondrial disorders (NDUFV1, POLG2), and 3 genes known to underlie other neurologic disorders (DPYD, KARS, WFS1), underscoring the phenotypic and biochemical overlap with other inborn errors. We prioritized variants in an additional 26 patients, including recessive, X-linked, and mtDNA variants that were enriched 2-fold over background and await further support of pathogenicity. In one case, we modeled patient mutations in yeast to provide evidence that recessive mutations in ATP5A1 can underlie combined respiratory chain deficiency. Conclusion: The results demonstrate that targeted exome sequencing is an effective alternative to the sequential testing of mtDNA and individual nuclear genes as part of the investigation of mitochondrial disease. Our study underscores the ongoing challenge of variant interpretation in the clinical setting. PMID:23596069

O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

PubMed Central

Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

2014-01-01

Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448