Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.

PubMed

Harrison, Christine J; Schwab, Claire

2016-03-01

In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer. Copyright © 2016. Published by Elsevier Masson SAS.

77 FR 59878 - Additional Requirements for Charitable Hospitals; Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... public hearing is being held in the IRS Auditorium, Internal Revenue Service Building, 1111 Constitution... Constitution Avenue entrance. In addition, all visitors must present photo identification to enter the building... Constitution Avenue NW., Washington, DC or sent electronically via the Federal eRulemaking Portal at www...

Latitudinal Gradients in Induced and Constitutive Resistance against Herbivores.

PubMed

Anstett, Daniel N; Chen, Wen; Johnson, Marc T J

2016-08-01

Plants are hypothesized to evolve increased defense against herbivores at lower latitudes, but an increasing number of studies report evidence that contradicts this hypothesis. Few studies have examined the evolution of constitutive and induced resistance along latitudinal gradients. When induction is not considered, underlying patterns of latitudinal clines in resistance can be obscured because plant resistance represents a combination of induced and constitutive resistance, which may show contrasting patterns with latitude. Here, we asked if there are latitudinal gradients in constitutive versus induced resistance by using genotypes of Oenothera biennis (Onagraceae) sampled along an 18° latitudinal gradient. We conducted two bioassay experiments to compare the resistance of plant genotypes against one generalist (Spodoptera exigua) and one specialist (Acanthoscelidius acephalus) herbivore. These insects were assayed on: i) undamaged control plants, ii) plants that had been induced with jasmonic acid, and iii) plants induced with herbivore damage. Additionally, we examined latitudinal gradients of constitutive and induced chemical resistance by measuring the concentrations of total phenolics, the concentration of oxidized phenolics, and the percentage of phenolics that were oxidized. Spodoptera exigua showed lower performance on plants from lower latitudes, whereas A. acephalus showed no latitudinal pattern. Constitutive total phenolics were greater in plants from lower latitudes, but induced plants showed higher total phenolics at higher latitudes. Oxidative activity was greatest at higher latitudes regardless of induction. Overall, both latitude and induction have an impact on different metrics of plant resistance to herbivory. Further studies should consider the effect of induction and herbivore specialization more explicitly, which may help to resolve the controversy in latitudinal gradients in herbivory and defense.

Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores.

PubMed

Moreira, X; Zas, R; Sampedro, L

2013-05-01

The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future.

Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility.

PubMed

Crépin, Michel; Dieu, Marie-Claire; Lejeune, Sophie; Escande, Fabienne; Boidin, Denis; Porchet, Nicole; Morin, Gilles; Manouvrier, Sylvie; Mathieu, Michèle; Buisine, Marie-Pierre

2012-01-01

Constitutional epimutations of DNA mismatch repair (MMR) genes have been recently reported as a possible cause of Lynch syndrome. However, little is known about their prevalence, the risk of transmission through the germline and the risk for carriers to develop cancers. In this study, we evaluated the contribution of constitutional epimutations of MMR genes in Lynch syndrome. A cohort of 134 unrelated Lynch syndrome-suspected patients without MMR germline mutation was screened for constitutional epimutations of MLH1 and MSH2 by quantitative bisulfite pyrosequencing. Patients were also screened for the presence of EPCAM deletions, a possible cause of MSH2 methylation. Tumors from patients with constitutional epimutations were extensively analyzed. We identified a constitutional MLH1 epimutation in two proband patients. For one of them, we report for the first time evidence of transmission to two children who also developed early colonic tumors, indicating that constitutional MLH1 epimutations are associated to a real risk of transgenerational inheritance of cancer susceptibility. Moreover, a somatic BRAF mutation was detected in one affected child, indicating that tumors from patients carrying constitutional MLH1 epimutation can mimic MSI-high sporadic tumors. These findings may have important implications for future diagnostic strategies and genetic counseling. © 2011 Wiley Periodicals, Inc.

Sputnik, a virophage infecting the viral domain of life.

PubMed

Desnues, Christelle; Boyer, Mickaël; Raoult, Didier

2012-01-01

This chapter discusses the astonishing discovery of the Sputnik virophage, a new virus infecting giant viruses of the genera Mimivirus and Mamavirus. While other virophages have also since been described, this chapter focuses mainly on Sputnik, which is the best described. We detail the general properties of the virophage life cycle, as well as its hosts, genomic characteristics, ecology, and origin. In addition to genetic, phylogenetic, and structural evidence, the existence of virophages has deeply altered our view of the tripartite division of life to include the addition of a fourth domain constituted of the nucleocytoplasmic large DNA viruses, an important point that is discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessing the influence of biogeographical region and phylogenetic history on chemical defences and herbivory in Quercus species.

PubMed

Moreira, Xoaquín; Abdala-Roberts, Luis; Galmán, Andrea; Francisco, Marta; Fuente, María de la; Butrón, Ana; Rasmann, Sergio

2018-06-07

Biogeographical factors and phylogenetic history are key determinants of inter-specific variation in plant defences. However, few studies have conducted broad-scale geographical comparisons of plant defences while controlling for phylogenetic relationships, and, in doing so, none have separated constitutive from induced defences. This gap has limited our understanding of how historical or large-scale processes mediate biogeographical patterns in plant defences since these may be contingent upon shared evolutionary history and phylogenetic constraints. We conducted a phylogenetically-controlled experiment testing for differences in constitutive leaf chemical defences and their inducibility between Palearctic and Nearctic oak species (Quercus, total 18 species). We induced defences in one-year old plants by inflicting damage by gypsy moth larvae (Lymantria dispar), estimated the amount of leaf area consumed, and quantified various groups of phenolic compounds. There was no detectable phylogenetic signal for constitutive or induced levels of most defensive traits except for constitutive condensed tannins, as well as no phylogenetic signal in leaf herbivory. We did, however, find marked differences in defence levels between oak species from each region: Palearctic species had higher levels of constitutive condensed tannins, but less constitutive lignins and less constitutive and induced hydrolysable tannins compared with Nearctic species. Additionally, Palearctic species had lower levels of leaf damage compared with Nearctic species. These differences in leaf damage, lignins and hydrolysable (but not condensed) tannins were lost after accounting for phylogeny, suggesting that geographical structuring of phylogenetic relationships mediated biogeographical differences in defences and herbivore resistance. Together, these findings suggest that historical processes and large-scale drivers have shaped differences in allocation to constitutive defences (and in turn resistance) between Palearctic and Nearctic oaks. Moreover, although evidence of phylogenetic conservatism in the studied traits is rather weak, shared evolutionary history appears to mediate some of these biogeographical patterns in allocation to chemical defences. Copyright © 2018 Elsevier Ltd. All rights reserved.

The use of phenobarbital and other anti-seizure drugs in newborns.

PubMed

El-Dib, Mohamed; Soul, Janet S

2017-10-01

Neonatal seizures constitute the most frequent presenting neurologic sign encountered in the neonatal intensive care unit. Despite limited efficacy and safety data, phenobarbital continues to be used near-universally as the first-line anti-seizure drug (ASD) in neonates. The choice of second-line ASDs varies by provider and institution, and is still not supported by sufficient scientific evidence. In this review, we discuss the available evidence supporting the efficacy, mechanism of action, potential adverse effects, key pharmacokinetic characteristics such as interaction with therapeutic hypothermia, logistical issues, and rationale for use of neonatal ASDs. We describe the widely used neonatal ASDs, namely phenobarbital, phenytoin, midazolam, and levetiracetam, in addition to potential ASDs, including lidocaine, topiramate, and bumetanide. Copyright © 2017. Published by Elsevier Ltd.

What Would Constitute Evidence for Life on Icy Moons?

NASA Technical Reports Server (NTRS)

Pohorille, A.; Hoehler, T. M.

2017-01-01

For the first time since Viking, NASA is considering missions that would include life detection as a primary objective, making it critical to develop and evaluate a diverse set of strategies for seeking evidence of life. The central question is: what should be the target of our search that, if found, would constitute a near-certain evidence for life? Since life on icy moons might be quite different from terrestrial life, we should concentrate on features of biological systems that are considered universal and are unlikely to emerge through abiotic means.

77 FR 63309 - Constitution Pipeline Company, LLC; Notice of Public Scoping Meeting and Extension of Scoping...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PF12-9-000] Constitution... Constitution Pipeline Project On October 24, 2012, the Federal Energy Regulatory Commission (FERC or Commission) will hold an additional public scoping meeting for Constitution Pipeline Company's (Constitution...

The first evidence for vertical transmission of Babesia canis in a litter of Central Asian Shepherd dogs.

PubMed

Mierzejewska, Ewa J; Welc-Falęciak, Renata; Bednarska, Małgorzata; Rodo, Anna; Bajer, Anna

2014-01-01

Tick-borne infections constitute an increasing health problem in dogs and may lead to death, especially in young or elderly individuals. Canine babesiosis constitutes a serious health problem in dogs worldwide. The aim of the study was to verify the probability of vertical transmission of Babesia canis between the bitch and the pups. In Autumn 2011, cases of babesiosis were diagnosed in a litter of 6-week-old puppies of a Central Asian Shepherd dog. Immediately following the first case of infection, blood samples were collected from all the pups in the litter (n=10) and from the female. Detection of Babesia infection was performed by molecular and microscopical techniques. The presence of B. canis DNA was detected using PCR in three pups, presenting at the time or 24-48 hours later with babesiosis symptoms, and in their asymptomatic mother. The isolates derived from the pups and the female - 520 bp 18S rRNA gene fragment - were compared and analyzed. All isolates from the pups and their mother were identical and showed 100% homology with B. canis group B (EU622793), supporting the same source of infection. Additionally, the USG of the peritoneal cavity was performed in the female, presenting evidence for splenomegaly. On the basis of (1) the same timing of three pup cases; (2) the identical B. canis sequences derived from all positive dogs; (3) evident splenomegaly in the asymptomatic female, this provides the first evidence of the vertical transmission of this piroplasm in dogs.

State Constitutional Commitment to Health and Health Care and Population Health Outcomes: Evidence From Historical US Data

PubMed Central

2015-01-01

Objectives. I investigated whether the introduction of health and health care provisions in US state constitutions can make health systems more equitable and improve health outcomes by urging state policymakers and administrative agencies to uphold their human rights obligations at state level. Methods. I constructed a panel of infant mortality rates from 50 US states over the period 1929 through 2000 to examine their association with the timing and details of introducing a constitutional right to health and health care provisions. Results. The introduction of a stronger constitutional commitment that obligates state legislature to provide health care was associated with a subsequent reduction in the infant mortality rate of approximately 7.8%. The introduction of provisions explicitly targeting the poor was also associated with a reduction in the infant mortality rate of 6.5%. These health benefits are primarily evident in non-White populations. Conclusions. This empirical result supports Elizabeth Leonard’s view that although state constitutional rights have been poorly enforced through the judiciary, a constitutional expression of health care duties has fueled the political and social process, ultimately allowing states to identify the best way to address citizens’ health inequality concerns. PMID:25905857

State constitutional commitment to health and health care and population health outcomes: evidence from historical US data.

PubMed

Matsuura, Hiroaki

2015-07-01

I investigated whether the introduction of health and health care provisions in US state constitutions can make health systems more equitable and improve health outcomes by urging state policymakers and administrative agencies to uphold their human rights obligations at state level. I constructed a panel of infant mortality rates from 50 US states over the period 1929 through 2000 to examine their association with the timing and details of introducing a constitutional right to health and health care provisions. The introduction of a stronger constitutional commitment that obligates state legislature to provide health care was associated with a subsequent reduction in the infant mortality rate of approximately 7.8%. The introduction of provisions explicitly targeting the poor was also associated with a reduction in the infant mortality rate of 6.5%. These health benefits are primarily evident in non-White populations. This empirical result supports Elizabeth Leonard's view that although state constitutional rights have been poorly enforced through the judiciary, a constitutional expression of health care duties has fueled the political and social process, ultimately allowing states to identify the best way to address citizens' health inequality concerns.

77 FR 62216 - Proposed Foreign-Trade Zone-Eloy, AZ Comment Period on New Evidence

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

.... Department of Commerce, 1401 Constitution Avenue NW., Washington, DC 20230-0002. Rebuttal comments in.... Department of Commerce, 1401 Constitution Avenue NW., Washington, DC 20230-0002, and in the ``Reading Room...

Tight junctions and the modulation of barrier function in disease

PubMed Central

2008-01-01

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease. PMID:18415116

Transcription factor NF-kappaB regulates inducible CD83 gene expression in activated T lymphocytes.

PubMed

McKinsey, T A; Chu, Z; Tedder, T F; Ballard, D W

2000-01-01

The immunoglobulin superfamily member CD83 is expressed on the surface of mature dendritic cells that present processed antigens to T lymphocytes. In addition, T cells acquire CD83 expression following mitogenic stimulation in vitro. Here we report two lines of evidence demonstrating that this inducible lymphocyte response is genetically programmed by transcription factor NF-kappaB and contingent upon proteolytic breakdown of its cytoplasmic inhibitor IkappaBalpha. First, signal-dependent induction of CD83 mRNA expression is blocked in both transformed and primary T cells harboring a degradation-resistant mutant of IkappaBalpha that constitutively represses NF-kappaB. Second, as revealed in gel retardation assays, the IkappaBalpha constitutive repressor prevents the inducible interaction of NF-kappaB with consensus recognition sites identified in the CD83 promoter. Given that IkappaBalpha is functionally coupled to the T-cell antigen receptor, these findings suggest that the downstream transcription unit for CD83 is triggered by NF-kappaB during an adaptive immune response.

Observational constraint on dynamical evolution of dark energy

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

Gong, Yungui; Cai, Rong-Gen; Chen, Yun

2010-01-01

We use the Constitution supernova, the baryon acoustic oscillation, the cosmic microwave background, and the Hubble parameter data to analyze the evolution property of dark energy. We obtain different results when we fit different baryon acoustic oscillation data combined with the Constitution supernova data to the Chevallier-Polarski-Linder model. We find that the difference stems from the different values of Ω{sub m0}. We also fit the observational data to the model independent piecewise constant parametrization. Four redshift bins with boundaries at z = 0.22, 0.53, 0.85 and 1.8 were chosen for the piecewise constant parametrization of the equation of state parametermore » w(z) of dark energy. We find no significant evidence for evolving w(z). With the addition of the Hubble parameter, the constraint on the equation of state parameter at high redshift is improved by 70%. The marginalization of the nuisance parameter connected to the supernova distance modulus is discussed.« less

Atrial cardiopathy: a mechanism of cryptogenic stroke.

PubMed

Yaghi, Shadi; Kamel, Hooman; Elkind, Mitchell S V

2017-08-01

Cryptogenic stroke accounts for approximately 30% of all ischemic strokes. Recently, atrial cardiopathy diagnosed by the presence of one of its serum, imaging, or electrocardiogram biomarkers has been shown to be associated with ischemic stroke, particularly of embolic subtypes. Areas covered: This paper aims to summarize data on occult atrial fibrillation and stroke, provide an overview on mechanisms, such as inflammation and fibrosis, of stroke in atrial cardiopathy, critically review data on biomarkers of atrial cardiopathy and their association with stroke, and suggest therapeutic implications, including directions for future research. Expert commentary: Atrial cardiopathy may constitute one of the mechanisms in cryptogenic stroke, and patients with evidence of atrial cardiopathy constitute a group of patients in whom clinical trials are warranted to test anticoagulation versus antiplatelet therapy to reduce stroke recurrence risk. In addition, more studies are needed to determine the degree of overlap between these atrial cardiopathy biomarkers and which one is more useful in predicting the risk of stroke and response to anticoagulation therapy.

Overexpression of ShCYP51B and ShatrD in Sclerotinia homoeocarpa Isolates Exhibiting Practical Field Resistance to a Demethylation Inhibitor Fungicide

PubMed Central

Hulvey, Jon; Popko, James T.; Sang, Hyunkyu; Berg, Andrew

2012-01-01

We investigated genetic factors that govern the reduced propiconazole sensitivity of Sclerotinia homoeocarpa field isolates collected during a 2-year field efficacy study on dollar spot disease of turf in five New England sites. These isolates displayed a >50-fold range of in vitro sensitivity to a sterol demethylation inhibitor (DMI) fungicide, propiconazole, making them ideal for investigations of genetic mechanisms of reduced DMI sensitivity. The CYP51 gene homolog in S. homoeocarpa (ShCYP51B), encoding the enzyme target of DMIs, is likely a minor genetic factor for reduced propiconazole sensitivity, since there were no differences in constitutive relative expression (RE) values and only 2-fold-higher induced RE values for insensitive than for sensitive isolate groups. Next, we mined RNA-Seq transcriptome data for additional genetic factors and found evidence for the overexpression of a homolog of Botrytis cinerea atrD (BcatrD), ShatrD, a known efflux transporter of DMI fungicides. The ShatrD gene showed much higher constitutive and induced RE values for insensitive isolates. Several polymorphisms were found upstream of ShatrD but were not definitively linked to overexpression. The screening of constitutive RE values of ShCYP51B and ShatrD in isolates from two golf courses that exhibited practical field resistance to propiconazole uncovered evidence for significant population-specific overexpression of both genes. However, linear regression demonstrated that the RE of ShatrD displays a more significant relationship with propiconazole sensitivity than that of ShCYP51B. In summary, our results suggest that efflux is a major determinant of the reduced DMI sensitivity of S. homoeocarpa genotypes in New England, which may have implications for the emergence of practical field resistance in this important turfgrass pathogen. PMID:22798361

The Two Stage Model of Preeclampsia: Variations on the Theme

PubMed Central

Roberts, James M; Hubel, Carl A.

2009-01-01

The Two Stage Model of preeclampsia proposes that a poorly perfused placenta (Stage 1) produces factor(s) leading to the clinical manifestations of preeclampsia (Stage2). Stage 1 is not sufficient to cause the maternal syndrome but interacts with maternal constitutional factors (genetic, behavioral or environmental) to result in Stage 2. Recent information indicates the necessity for modifications of this model. It is apparent that changes relevant to preeclampsia and other implantation disorders can be detected in the first trimester, long before the failed vascular remodeling necessary to reduce placental perfusion. In addition, although the factor(s) released from the placenta has usually been considered a toxin, we suggest that what is released may also be an appropriate signal from the fetal/placental unit to overcome reduced nutrient availability that cannot by tolerated by some women who develop preeclampsia. Further, it is evident that linkage is not likely to be by one factor but several, different for different women. Also although the initial model limited the role of maternal constitutional factors to the genesis of Stage 2, this does not appear to be the case. It is evident that the factors increasing risk for preeclampsia are also associated with abnormal implantation. These several modifications have important implications. An earlier origin for Stage 1, which appears to be recognizable by altered concentrations of placental products, could allow earlier intervention. The possibility of a fetal placental factor increasing nutrient availability could provide novel therapeutic options. Different linkages and preeclampsia subtypes could direct specific preventive treatments for different women while the role of maternal constitutional factors to affect placentation provides targets for prepregnancy therapy. The modified Two Stage Model provides a useful guide towards investigating pathophysiology and guiding therapy. PMID:19070896

Multiple Pathways Linking Racism to Health Outcomes

PubMed Central

Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

2012-01-01

This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils.

PubMed

Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

2016-01-01

Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance.

12 CFR 1209.51 - Evidence.

Code of Federal Regulations, 2014 CFR

2014-01-01

... prepared by FHFA or by another Federal or State financial institution's regulatory agency, is admissible... evidence or to any ruling constitutes a waiver of the objection. (e) Stipulations. The parties may...

12 CFR 1209.51 - Evidence.

Code of Federal Regulations, 2012 CFR

2012-01-01

... prepared by FHFA or by another Federal or State financial institution's regulatory agency, is admissible... evidence or to any ruling constitutes a waiver of the objection. (e) Stipulations. The parties may...

12 CFR 1209.51 - Evidence.

Code of Federal Regulations, 2013 CFR

2013-01-01

... prepared by FHFA or by another Federal or State financial institution's regulatory agency, is admissible... evidence or to any ruling constitutes a waiver of the objection. (e) Stipulations. The parties may...

A critical look at descriptive epidemiology of sexual dysfunction in Asia compared to the rest of the world - a call for evidence-based data

PubMed Central

2013-01-01

Recently evidence-based medicine has been applied to comparative epidemiological papers regarding sexual dysfunction that have appeared in the literature. This review is intended to focus the readers on a validated and standardized methodological evidence-based process for preparing such articles. It reviews four key articles that have been published in the English language that have obtained a high evidence-based score for reliability that have included descriptive epidemiology of sexual dysfunctions in men and women in Asia compared to the rest of the world. These four papers are analyzed in detail in order to provide stress of what constitutes evidence-based studies in descriptive epidemiology for sexual function. As can be seen there has not yet been a perfect article that compares the prevalence of sexual function in Asia compared to the rest of the world since there are key methodological problems in the collection of the data. In addition, there is a paucity of incidence studies for sexual dysfunction in Asian populations. The readers are encouraged to use this data in preparation of future descriptive epidemiological studies that involve Asian countries. PMID:26816724

A critical look at descriptive epidemiology of sexual dysfunction in Asia compared to the rest of the world - a call for evidence-based data.

PubMed

Lewis, Ronald W

2013-03-01

Recently evidence-based medicine has been applied to comparative epidemiological papers regarding sexual dysfunction that have appeared in the literature. This review is intended to focus the readers on a validated and standardized methodological evidence-based process for preparing such articles. It reviews four key articles that have been published in the English language that have obtained a high evidence-based score for reliability that have included descriptive epidemiology of sexual dysfunctions in men and women in Asia compared to the rest of the world. These four papers are analyzed in detail in order to provide stress of what constitutes evidence-based studies in descriptive epidemiology for sexual function. As can be seen there has not yet been a perfect article that compares the prevalence of sexual function in Asia compared to the rest of the world since there are key methodological problems in the collection of the data. In addition, there is a paucity of incidence studies for sexual dysfunction in Asian populations. The readers are encouraged to use this data in preparation of future descriptive epidemiological studies that involve Asian countries.

The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype.

PubMed

Kwok, Chau-To; Vogelaar, Ingrid P; van Zelst-Stams, Wendy A; Mensenkamp, Arjen R; Ligtenberg, Marjolijn J; Rapkins, Robert W; Ward, Robyn L; Chun, Nicolette; Ford, James M; Ladabaum, Uri; McKinnon, Wendy C; Greenblatt, Marc S; Hitchins, Megan P

2014-05-01

Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6-≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.

Comment: What Constitutes Evidence in Science Education Research?

ERIC Educational Resources Information Center

Roth, Wolff-Michael

2011-01-01

In the wake of an increasing political commitment to evidence-based decision making and evidence-based educational reform that emerged with the No Child Left Behind effort, the question of what counts as evidence has become increasingly important in the field of science education. In current public discussions, academics, politicians, and other…

77 FR 15003 - Passive Activity Losses and Credits Limited; Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-14

... Service Building, 1111 Constitution Avenue NW., Washington, DC 20224. Due to building security procedures, visitors must enter at the Constitution Avenue entrance. In addition, all visitors must present photo..., Internal Revenue Service, 1111 Constitution Avenue NW., Washington, DC or sent electronically via the...

Hydrodynamics in a Degenerate, Strongly Attractive Fermi Gas

NASA Technical Reports Server (NTRS)

Thomas, John E.; Kinast, Joseph; Hemmer, Staci; Turlapov, Andrey; O'Hara, Ken; Gehm, Mike; Granade, Stephen

2004-01-01

In summary, we use all-optical methods with evaporative cooling near a Feshbach resonance to produce a strongly interacting degenerate Fermi gas. We observe hydrodynamic behavior in the expansion dynamics. At low temperatures, collisions may not explain the expansion dynamics. We observe hydrodynamics in the trapped gas. Our observations include collisionally-damped excitation spectra at high temperature which were not discussed above. In addition, we observe weakly damped breathing modes at low temperature. The observed temperature dependence of the damping time and hydrodynamic frequency are not consistent with collisional dynamics nor with collisionless mean field interactions. These observations constitute the first evidence for superfluid hydrodynamics in a Fermi gas.

Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

PubMed Central

Lazennec, Gwendal

2006-01-01

Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

Randomized Clinical Trials of Constitutional Acupuncture: A Systematic Review

PubMed Central

Lee, Myeong Soo; Shin, Byung-Cheul; Choi, Sun-Mi; Kim, Jong Yeol

2009-01-01

The aim of this systematic review is to compile and critically evaluate the evidence from randomized clinical trials (RCTs) for the effectiveness of acupuncture using constitutional medicine compared to standard acupuncture. Ten databases were searched through to December 2008 without language restrictions. We also hand-searched nine Korean journals of oriental medicine. We included prospective RCTs of any form of acupuncture with or without electrical stimulation. The included trials had to investigate constitutional medicine. There were no restrictions on population characteristics. Forty-one relevant studies were identified, and three RCTs were included. The methodological quality of the trials was variable. One RCT found Sasang constitutional acupuncture to be superior to standard acupuncture in terms of the Unified PD Rating Scale and freezing gate in Parkinson's disease (PD). Another two RCTs reported favorable effects of eight constitutional acupuncture on pain reduction in patients with herniated nucleus pulposi and knee osteoarthritis. Meta-analysis demonstrated positive results for eight constitutional acupuncture compared to standard acupuncture on pain reduction (weighted mean difference: 10 cm VAS, 1.69, 95% CI 0.85–2.54, P < 0.0001; heterogeneity: τ2 = 0.00, χ2 = 0.00, P = 0.96, I2 = 0%). Our results provide suggestive evidence for the effectiveness of constitutional acupuncture in treating pain conditions compared to standard acupuncture. However, the total number of RCTs and the total sample size included in our analysis were too small to draw definite conclusions. Future RCTs should assess larger patient samples with longer treatment periods and appropriate controls. PMID:19745012

Providing Children and Adolescents Opportunities for Social Interaction as a Standard of Care in Pediatric Oncology.

PubMed

Christiansen, Heather L; Bingen, Kristin; Hoag, Jennifer A; Karst, Jeffrey S; Velázquez-Martin, Blanca; Barakat, Lamia P

2015-12-01

Experiences with peers constitute an important aspect of socialization, and children and adolescents with cancer may experience reduced social interaction due to treatment. A literature review was conducted to investigate the evidence to support a standard of care evaluating these experiences. Sixty-four articles were reviewed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Moderate quality of evidence suggest that social interaction can be beneficial to increase knowledge, decrease isolation, and improve adjustment and constitute an important, unmet need. The evidence supports a strong recommendation for youth with cancer to be provided opportunities for social interaction following a careful assessment of their unique characteristics and preferences. © 2015 Wiley Periodicals, Inc.

Constitutive Expression of Short Hairpin RNA in Vivo Triggers Buildup of Mature Hairpin Molecules

PubMed Central

Ahn, M.; Witting, S.R.; Ruiz, R.; Saxena, R.

2011-01-01

Abstract RNA interference (RNAi) has become the cornerstone technology for studying gene function in mammalian cells. In addition, it is a promising therapeutic treatment for multiple human diseases. Virus-mediated constitutive expression of short hairpin RNA (shRNA) has the potential to provide a permanent source of silencing molecules to tissues, and it is being devised as a strategy for the treatment of liver conditions such as hepatitis B and hepatitis C virus infection. Unintended interaction between silencing molecules and cellular components, leading to toxic effects, has been described in vitro. Despite the enormous interest in using the RNAi technology for in vivo applications, little is known about the safety of constitutively expressing shRNA for multiple weeks. Here we report the effects of in vivo shRNA expression, using helper-dependent adenoviral vectors. We show that gene-specific knockdown is maintained for at least 6 weeks after injection of 1 × 1011 viral particles. Nonetheless, accumulation of mature shRNA molecules was observed up to weeks 3 and 4, and then declined gradually, suggesting the buildup of mature shRNA molecules induced cell death with concomitant loss of viral DNA and shRNA expression. No evidence of well-characterized innate immunity activation (such as interferon production) or saturation of the exportin-5 pathway was observed. Overall, our data suggest constitutive expression of shRNA results in accumulation of mature shRNA molecules, inducing cellular toxicity at late time points, despite the presence of gene silencing. PMID:21780944

Optimizing Mexico’s Water Distribution Services

DTIC Science & Technology

2011-10-28

government pursued a decentralization policy in the water distribution infrastructure sector.5 This is evident in Article 115 of the Mexican Constitution ...infrastructure, monitoring water 5 Ibid, 47. 6 Mexican Constitution . http://www.oas.org/juridico...54 Apogee Research International, Ltd., Innovative Financing of Water and Wastewater Infrastructure in the NAFTA Partners: A Focus on

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils

PubMed Central

Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

2017-01-01

Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance. PMID:28123386

Cascadedness in Chinese written word production

PubMed Central

Qu, Qingqing; Damian, Markus F.

2015-01-01

In written word production, is activation transmitted from lexical-semantic selection to orthographic encoding in a serial or cascaded fashion? Very few previous studies have addressed this issue, and the existing evidence comes from languages with alphabetic orthographic systems. We report a study in which Chinese participants were presented with colored line drawings of objects and were instructed to write the name of the color while attempting to ignore the object. Significant priming was found when on a trial, the written response shared an orthographic radical with the written name of the object. This finding constitutes clear evidence that task-irrelevant lexical codes activate their corresponding orthographic representation, and hence suggests that activation flows in a cascaded fashion within the written production system. Additionally, the results speak to how the time interval between processing of target and distractor dimensions affects and modulates the emergence of orthographic facilitation effects. PMID:26379595

Entomologic and serologic evidence of zoonotic transmission of Babesia microti, eastern Switzerland.

PubMed

Foppa, Ivo M; Krause, Peter J; Spielman, Andrew; Goethert, Heidi; Gern, Lise; Brand, Brigit; Telford, Sam R

2002-07-01

We evaluated human risk for infection with Babesia microti at a site in eastern Switzerland where several B. microti-infected nymphal Ixodes ricinus ticks had been found. DNA from pooled nymphal ticks amplified by polymerase chain reaction was highly homologous to published B. microti sequences. More ticks carried babesial infection in the lower portion of the rectangular 0.7-ha grid than in the upper (11% vs. 0.8%). In addition, we measured seroprevalence of immunoglobulin (Ig) G antibodies against B. microti antigen in nearby residents. Serum from 1.5% of the 396 human residents of the region reacted to B. microti antigen (>1:64), as determined by indirect immunofluorescence assay (IgG). These observations constitute the first report demonstrating B. microti in a human-biting vector, associated with evidence of human exposure to this agent in a European site.

76 FR 52561 - Timely Mailing Treated as Timely Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... to the only ways to establish prima facie evidence of delivery of documents that have a filing... (PDS) designated under criteria established by the IRS, will constitute prima facie evidence of... taxpayers to be able to establish the postmark date and prima facie evidence of delivery when using...

Survey questions evidence of US female hiring bias

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2013-09-01

An analysis by the American Institute of Physics (AIP) suggests that the complete absence of female faculty in more than a third of US university physics departments does not necessarily constitute evidence that they discriminate against women.

78 FR 16446 - Awards for Information Relating To Detecting Underpayments of Tax or Violations of the Internal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

... Building, 1111 Constitution Avenue NW., Washington, DC 20224. Due to building security procedures, visitors must enter at the Constitution Avenue entrance. In addition, all visitors must present photo..., 1111 Constitution Avenue NW., Washington, DC 20224 or sent electronically via the Federal eRulemaking...

Angiotensinogen gene polymorphism predicts hypertension, and iridological constitutional classification enhances the risk for hypertension in Koreans.

PubMed

Cho, Joo-Jang; Hwang, Woo-Jun; Hong, Seung-Heon; Jeong, Hyun-Ja; Lee, Hye-Jung; Kim, Hyung-Min; Um, Jae-Young

2008-05-01

This study investigated the relationship between iridological constitution and angiotensinogen (AGN) gene polymorphism in hypertensives. In addition to angiotensin converting enzyme gene, AGN genotype is also one of the most well studied genetic markers of hypertension. Furthermore, iridology, one of complementary and alternative medicine, is the diagnosis of the medical conditions through noting irregularities of the pigmentation in the iris. Iridological constitution has a strong familial aggregation and is implicated in heredity. Therefore, the study classified 87 hypertensive patients with familial history of cerebral infarction and controls (n = 88) according to Iris constitution, and determined AGN genotype. As a result, the AGN/TT genotype was associated with hypertension (chi2 = 13.413, p < .05). The frequency of T allele was 0.92 in patients and 0.76 in controls (chi2 = 13.159, p < .05). In addition, iridological constitutional classification increased the relative risk for hypertension in the subjects with AGN/T allele. These results suggest that AGN polymorphism predicts hypertension, and iridological constitutional classification enhances the risk for hypertension associated with AGN/T in a Korean population.

The Owl and other strigiform nebulae: multipolar cavities within a filled shell

NASA Astrophysics Data System (ADS)

García-Díaz, Ma T.; Steffen, W.; Henney, W. J.; López, J. A.; García-López, F.; González-Buitrago, D.; Áviles, A.

2018-06-01

We present the results of long-slit echelle spectroscopy and deep narrow-band imaging of the Owl Nebula (NGC 3587), obtained at the Observatorio Astronómico Nacional, San Pedro Mártir. These data allow us to construct an iso-velocity data cube and develop a 3-D morpho-kinematic model. We find that, instead of the previously assumed bipolar dumbbell shape, the inner cavity consists of multi-polar fingers within an overall tripolar structure. We identify three additional planetary nebulae that show very similar morphologies and kinematics to the Owl, and propose that these constitute a new class of strigiform (owl-like) nebulae. Common characteristics of the strigiform nebulae include a double-shell (thin outside thick) structure, low-luminosity and high-gravity central stars, the absence of a present-day stellar wind, and asymmetric inner cavities, visible in both optical and mid-infrared emission lines, that show no evidence for surrounding bright rims. The origin of the cavities is unclear, but they may constitute relics of an earlier stage of evolution when the stellar wind was active.

29 CFR 1607.15 - Documentation of impact and validity evidence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... national origin group (see section 4 above) constituting more than two percent (2%) of the labor force in... origin (see § 4 above) if one race or national origin group in the relevant labor area constitutes more... selection process for that job has an adverse impact on any of the groups for which records are called for...

Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries.

PubMed

Badia, J M; Casey, A L; Petrosillo, N; Hudson, P M; Mitchell, S A; Crosby, C

2017-05-01

Surgical site infections (SSIs) are associated with increased morbidity and mortality. Furthermore, SSIs constitute a financial burden and negatively impact on patient quality of life (QoL). To assess, and evaluate the evidence for, the cost and health-related QoL (HRQoL) burden of SSIs across various surgical specialties in six European countries. Electronic databases and conference proceedings were systematically searched to identify studies reporting the cost and HRQoL burden of SSIs. Studies published post 2005 in France, Germany, the Netherlands, Italy, Spain, and the UK were eligible for data extraction. Studies were categorized by surgical specialty, and the primary outcomes were the cost of infection, economic evaluations, and HRQoL. Twenty-six studies met the eligibility criteria and were included for analysis. There was a paucity of evidence in the countries of interest; however, SSIs were consistently associated with elevated costs, relative to uninfected patients. Several studies reported that SSI patients required prolonged hospitalization, reoperation, readmission, and that SSIs increased mortality rates. Only one study reported QoL evidence, the results of which demonstrated that SSIs reduced HRQoL scores (EQ-5D). Hospitalization reportedly constituted a substantial cost burden, with additional costs arising from medical staff, investigation, and treatment costs. Disparate reporting of SSIs makes direct cost comparisons difficult, but this review indicated that SSIs are extremely costly. Thus, rigorous procedures must be implemented to minimize SSIs. More economic and QoL studies are required to make accurate cost estimates and to understand the true burden of SSIs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Practice of Using Evidence in Kindergarten: The Role of Purposeful Observation

ERIC Educational Resources Information Center

Monteira, Sabela F.; Jiménez-Aleixandre, María Pilar

2016-01-01

This article examines kindergarten children's (5-6 years old) engagement in scientific practices, with a focus on generating and using evidence to support claims, during a 5-month project about snails. The research questions are as follows: (1) what meanings do kindergarteners construct for what constitutes evidence? How are those meanings…

Evidence that the recA441 (tif-1) mutant of Escherichia coli K-12 contains a thermosensitive intragenic suppressor of RecA constitutive protease activity.

PubMed Central

Wang, W B; Tessman, E S

1985-01-01

The recA441 mutant of Escherichia coli, which has been thought to have thermoinducible constitutive RecA protease activity, is known to have two mutations within recA. We show here that the mutation that alters codon 38 actually confers temperature-independent constitutive protease activity; the second mutation in recA441, which is at codon 298, appears to be acting as a temperature-sensitive suppressor of the protease activity. Images PMID:3891740

Evidence that the recA441 (tif-1) mutant of Escherichia coli K-12 contains a thermosensitive intragenic suppressor of RecA constitutive protease activity.

PubMed

Wang, W B; Tessman, E S

1985-07-01

The recA441 mutant of Escherichia coli, which has been thought to have thermoinducible constitutive RecA protease activity, is known to have two mutations within recA. We show here that the mutation that alters codon 38 actually confers temperature-independent constitutive protease activity; the second mutation in recA441, which is at codon 298, appears to be acting as a temperature-sensitive suppressor of the protease activity.

The Physics of Earthquakes: In the Quest for a Unified Theory (or Model) That Quantitatively Describes the Entire Process of an Earthquake Rupture, From its Nucleation to the Dynamic Regime and to its Arrest

NASA Astrophysics Data System (ADS)

Ohnaka, M.

2004-12-01

For the past four decades, great progress has been made in understanding earthquake source processes. In particular, recent progress in the field of the physics of earthquakes has contributed substantially to unraveling the earthquake generation process in quantitative terms. Yet, a fundamental problem remains unresolved in this field. The constitutive law that governs the behavior of earthquake ruptures is the basis of earthquake physics, and the governing law plays a fundamental role in accounting for the entire process of an earthquake rupture, from its nucleation to the dynamic propagation to its arrest, quantitatively in a unified and consistent manner. Therefore, without establishing the rational constitutive law, the physics of earthquakes cannot be a quantitative science in a true sense, and hence it is urgent to establish the rational constitutive law. However, it has been controversial over the past two decades, and it is still controversial, what the constitutive law for earthquake ruptures ought to be, and how it should be formulated. To resolve the controversy is a necessary step towards a more complete, unified theory of earthquake physics, and now the time is ripe to do so. Because of its fundamental importance, we have to discuss thoroughly and rigorously what the constitutive law ought to be from the standpoint of the physics of rock friction and fracture on the basis of solid evidence. There are prerequisites for the constitutive formulation. The brittle, seismogenic layer and individual faults therein are characterized by inhomogeneity, and fault inhomogeneity has profound implications for earthquake ruptures. In addition, rupture phenomena including earthquakes are inherently scale dependent; indeed, some of the physical quantities inherent in rupture exhibit scale dependence. To treat scale-dependent physical quantities inherent in the rupture over a broad scale range quantitatively in a unified and consistent manner, it is critical to formulate the governing law properly so as to incorporate the scaling property. Thus, the properties of fault inhomogeneity and physical scaling are indispensable prerequisites to be incorporated into the constitutive formulation. Thorough discussion in this context necessarily leads to the consistent conclusion that the constitutive law must be formulated in such a manner that the shear traction is a primary function of the slip displacement, with the secondary effect of slip rate or stationary contact time. This constitutive formulation makes it possible to account for the entire process of an earthquake rupture over a broad scale range quantitatively in a unified and consistent manner.

Root-expressed maize lipoxygenase 3 negatively regulates induced systemic resistance to Colletotrichum graminicola in shoots

PubMed Central

Constantino, Nasie N.; Mastouri, Fatemeh; Damarwinasis, Ramadhika; Borrego, Eli J.; Moran-Diez, Maria E.; Kenerley, Charley M.; Gao, Xiquan; Kolomiets, Michael V.

2013-01-01

We have previously reported that disruption of a maize root-expressed 9-lipoxygenase (9-LOX) gene, ZmLOX3, results in dramatic increase in resistance to diverse leaf and stalk pathogens. Despite evident economic significance of these findings, the mechanism behind this increased resistance remained elusive. In this study, we found that increased resistance of the lox3-4 mutants is due to constitutive activation of induced systemic resistance (ISR) signaling. We showed that ZmLOX3 lacked expression in leaves in response to anthracnose leaf blight pathogen Colletotrichum graminicola, but was expressed constitutively in the roots, thus, prompting our hypothesis: the roots of lox3-4 mutants are the source of increased resistance in leaves. Supporting this hypothesis, treatment of wild-type plants (WT) with xylem sap of lox3-4 mutant induced resistance to C. graminicola to the levels comparable to those observed in lox3-4 mutant. Moreover, treating mutants with the sap collected from WT plants partially restored the susceptibility to C. graminicola. lox3-4 mutants showed primed defense responses upon infection, which included earlier and greater induction of defense-related PAL and GST genes compared to WT. In addition to the greater expression of the octadecanoid pathway genes, lox3-4 mutant responded earlier and with a greater accumulation of H2O2 in response to C. graminicola infection or treatment with alamethicin. These findings suggest that lox3-4 mutants display constitutive ISR-like signaling. In support of this idea, root colonization by Trichoderma virens strain GV29-8 induced the same level of disease resistance in WT as the treatment with the mutant sap, but had no additional resistance effect in lox3-4 mutant. While treatment with T. virens GV29 strongly and rapidly suppressed ZmLOX3 expression in hydroponically grown WT roots, T. virens Δsml mutant, which is deficient in ISR induction, was unable to suppress expression of ZmLOX3, thus, providing genetic evidence that SM1 function in ISR, at least in part, by suppressing host ZmLOX3 gene. This study and the genetic tools generated herein will allow the identification of the signals regulating the induction of resistance to aboveground attackers by beneficial soil microorganisms in the future. PMID:24391653

Genetic bases of the nutritional approach to migraine.

PubMed

De Marchis, Maria Laura; Guadagni, Fiorella; Silvestris, Erica; Lovero, Domenica; Della-Morte, David; Ferroni, Patrizia; Barbanti, Piero; Palmirotta, Raffaele

2018-03-08

Migraine is a common multifactorial and polygenic neurological disabling disorder characterized by a genetic background and associated to environmental, hormonal and food stimulations. A large series of evidence suggest a strong correlation between nutrition and migraine and indicates several commonly foods, food additives and beverages that may be involved in the mechanisms triggering the headache attack in migraine-susceptible persons. There are foods and drinks, or ingredients of the same, that can trigger the migraine crisis as well as some foods play a protective function depending on the specific genetic sensitivity of the subject. The recent biotechnological advances have enhanced the identification of some genetic factors involved in onset diseases and the identification of sequence variants of genes responsible for the individual sensitivity to migraine trigger-foods. Therefore many studies are aimed at the analysis of polymorphisms of genes coding for the enzymes involved in the metabolism of food factors in order to clarify the different ways in which people respond to foods based on their genetic constitution. This review discusses the latest knowledge and scientific evidence of the role of gene variants and nutrients, food additives and nutraceuticals interactions in migraine.

New York and the Union: Contributions to the American Constitutional Experience.

ERIC Educational Resources Information Center

Schechter, Stephen L., Ed.; Bernstein, Richard B., Ed.

This book provides a detailed account of the role of the state of New York in the history and development of the United States Constitution. The document consists of some 68 essays, in addition to a foreword, editors' introduction, and chronology of bicentennial dates. Part 1, "Origins of Constitutionalism in New York," addresses such…

Leaching of plastic additives to marine organisms.

PubMed

Koelmans, Albert A; Besseling, Ellen; Foekema, Edwin M

2014-04-01

It is often assumed that ingestion of microplastics by aquatic species leads to increased exposure to plastic additives. However, experimental data or model based evidence is lacking. Here we assess the potential of leaching of nonylphenol (NP) and bisphenol A (BPA) in the intestinal tracts of Arenicola marina (lugworm) and Gadus morhua (North Sea cod). We use a biodynamic model that allows calculations of the relative contribution of plastic ingestion to total exposure of aquatic species to chemicals residing in the ingested plastic. Uncertainty in the most crucial parameters is accounted for by probabilistic modeling. Our conservative analysis shows that plastic ingestion by the lugworm yields NP and BPA concentrations that stay below the lower ends of global NP and BPA concentration ranges, and therefore are not likely to constitute a relevant exposure pathway. For cod, plastic ingestion appears to be a negligible pathway for exposure to NP and BPA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Compressive Properties of PTFE/Al/Ni Composite Under Uniaxial Loading

NASA Astrophysics Data System (ADS)

Wang, Huai-xi; Li, Yu-chun; Feng, Bin; Huang, Jun-yi; Zhang, Sheng; Fang, Xiang

2017-05-01

To investigate the mechanical properties of pressed and sintered PTFE/Al/Ni (polytetrafluoroethylene/aluminum/nickel) composite, uniaxial quasi-static and dynamic compression experiments were conducted at strain rates from 10-2 to 3 × 103/s. The prepared samples were tested by an electrohydraulic press with 300 kN loading capacity and a split Hopkinson pressure bar (SHPB) device at room temperature. Experimental results show that PTFE/Al/Ni composite exhibits evident strain hardening and strain rate hardening. Additionally, a bilinear relationship between stress and {{log(}}\\dot{ɛ} ) is observed. The experimental data were fit to Johnson-Cook constitutive model, and the results are in well agreement with measured data.

Comparing Attentional Networks in fetal alcohol spectrum disorder and the inattentive and combined subtypes of attention deficit hyperactivity disorder.

PubMed

Kooistra, Libbe; Crawford, Susan; Gibbard, Ben; Kaplan, Bonnie J; Fan, Jin

2011-01-01

The Attention Network Test (ANT) was used to examine alerting, orienting, and executive control in fetal alcohol spectrum disorder (FASD) versus attention deficit hyperactivity disorder (ADHD). Participants were 113 children aged 7 to 10 years (31 ADHD-Combined, 16 ADHD-Primarily Inattentive, 28 FASD, 38 controls). Incongruent flanker trials triggered slower responses in both the ADHD-Combined and the FASD groups. Abnormal conflict scores in these same two groups provided additional evidence for the presence of executive function deficits. The ADHD-Primarily Inattentive group was indistinguishable from the controls on all three ANT indices, which highlights the possibility that this group constitutes a pathologically distinct entity.

Delivering sustainable crop protection systems via the seed: exploiting natural constitutive and inducible defence pathways

PubMed Central

Pickett, John A.; Aradottír, Gudbjorg I.; Birkett, Michael A.; Bruce, Toby J. A.; Hooper, Antony M.; Midega, Charles A. O.; Jones, Huw D.; Matthes, Michaela C.; Napier, Johnathan A.; Pittchar, Jimmy O.; Smart, Lesley E.; Woodcock, Christine M.; Khan, Zeyaur R.

2014-01-01

To reduce the need for seasonal inputs, crop protection will have to be delivered via the seed and other planting material. Plant secondary metabolism can be harnessed for this purpose by new breeding technologies, genetic modification and companion cropping, the latter already on-farm in sub-Saharan Africa. Secondary metabolites offer the prospect of pest management as robust as that provided by current pesticides, for which many lead compounds were, or are currently deployed as, natural products. Evidence of success and promise is given for pest management in industrial and developing agriculture. Additionally, opportunities for solving wider problems of sustainable crop protection, and also production, are discussed. PMID:24535389

TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.

PubMed

da Silveira Cruz-Machado, Sanseray; Carvalho-Sousa, Claudia Emanuele; Tamura, Eduardo Koji; Pinato, Luciana; Cecon, Erika; Fernandes, Pedro Augusto Carlos Magno; de Avellar, Maria Christina Werneck; Ferreira, Zulma Silva; Markus, Regina Pekelmann

2010-09-01

Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.

Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan

PubMed Central

Sigismund, Sara; Confalonieri, Stefano; Ciliberto, Andrea; Polo, Simona; Scita, Giorgio; Di Fiore, Pier Paolo

2017-01-01

Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A possible framework, to rationalize all this new knowledge, requires us to “upgrade” our vision of endocytosis. By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan. PMID:22298658

Endocytosis and signaling: cell logistics shape the eukaryotic cell plan.

PubMed

Sigismund, Sara; Confalonieri, Stefano; Ciliberto, Andrea; Polo, Simona; Scita, Giorgio; Di Fiore, Pier Paolo

2012-01-01

Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A possible framework, to rationalize all this new knowledge, requires us to "upgrade" our vision of endocytosis. By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan.

Distinguishing pathological from constitutional small for gestational age births in population-based studies.

PubMed

Ananth, Cande V; Vintzileos, Anthony M

2009-10-01

Small for gestational age (SGA) can occur following a pathological process or may represent constitutionally small fetuses. However, distinguishing these processes is often difficult, especially in large studies, where the term SGA is often used as a proxy for restricted fetal growth. Since biologic variation in fetal size is largely a third trimester phenomenon, we hypothesized that the definition of SGA at term may include a sizeable proportion of constitutionally small fetuses. In contrast, since biologic variation in fetal size is not fully expressed in (early) preterm gestations, it is plausible that SGA in early preterm gestations would comprise a large proportion of growth restricted fetuses. We compared mortality and morbidity rates between SGA and appropriate for gestational age (AGA) babies. A population-based study of over 19million non-malformed, singleton births (1995-04) in the United States was performed. Gestational age (24-44weeks) was based on a clinical estimate. SGA and AGA were defined as sex-specific birthweight <10th and 25-74th centiles, respectively, for gestational age. All analyses were adjusted for a variety of confounding factors. Excess mortality risk in SGA and AGA babies. On an additive scale, stillbirth and neonatal mortality rates were higher at every preterm gestation among SGA than AGA births, and similar at term gestations. An inverse relationship between gestational age and excess deaths between SGA and AGA babies delivered at <37weeks was evident. In early preterm gestations, the definition of SGA may well be justified as a proxy for IUGR. In contrast, SGA babies that are delivered at term are likely to be constitutionally small.

Peyronie’s Disease: AUA Guideline

PubMed Central

Nehra, Ajay; Alterowitz, Ralph; Culkin, Daniel J.; Faraday, Martha M.; Hakim, Lawrence S.; Heidelbaugh, Joel J.; Khera, Mohit; Kirkby, Erin; McVary, Kevin T.; Miner, Martin M.; Nelson, Christian J.; Sadeghi-Nejad, Hossein; Seftel, Allen D.; Shindel, Alan W.; Burnett, Arthur L.

2016-01-01

Purpose The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of Peyronie’s disease. Materials and Methods A systematic review of the literature using the PubMed®, EMBASE® and Cochrane databases (search dates 1/1/1965 to 1/26/15) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of PD. The review yielded an evidence base of 303 articles after application of inclusion/exclusion criteria. Results The systematic review was used to create guideline statements regarding treatment of PD. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high quality evidence; high certainty), B (moderate quality evidence; moderate certainty), or C (low quality evidence; low certainty). Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional consensus statements related to the diagnosis of PD are provided as Clinical Principles and Expert Opinions due to insufficient published evidence. Conclusions There is a continually expanding literature on PD; the Panel notes that this document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient’s history, values, and goals for treatment. As the science relevant to PD evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care. PMID:26066402

Folate and carcinogenesis-mechanisms

USDA-ARS?s Scientific Manuscript database

A large and growing body of both pre-clinical and clinical studies pertaining to colorectal neoplasms constitutes the most compelling evidence for the protective effect of folate against the development of cancer, although evidence is also accruing in this regard for cancers of the breast, lung, pan...

Allergic constitution theory of Chinese medicine and its assessment criterion and related studies.

PubMed

Wang, Ji; Wang, Ting; Li, Ying-shuai; Li, Ling-ru; Zheng, Yan-fei; Wang, Qi

2015-09-01

Constitution factor plays an important role in the occurrence, development, and transformation of diseases. The occurrence of allergic diseases is mainly caused by the disorganized physiological function and suitability regulation of patients, except for their exposure to outside allergens. Moreover, it represents susceptibility and hypersensitivity to allergens. The current study expresses the concept of allergic constitution from the perspective of Chinese medicine (CM) and presents the criterion of allergic constitution. In addition, the distribution of allergic constitution in population, its factors, and its relation to health-related quality of life (HRQOL) were investigated. The HRQOL scores of allergic constitution were found to be lower than those of the Pinghe constitution. After making a study on the gene expression profile of allergic constitution, the characteristics of up-regulated or down-regulated genes were found. Finally, CM drug was researched and developed to improve allergic constitution. Based on clinical trials and animal experiments, CM is found to have good regulatory effects on allergic constitution.

Closing in on the constitution of consciousness

PubMed Central

Miller, Steven M.

2014-01-01

The science of consciousness is a nascent and thriving field of research that is founded on identifying the minimally sufficient neural correlates of consciousness. However, I have argued that it is the neural constitution of consciousness that science seeks to understand and that there are no evident strategies for distinguishing the correlates and constitution of (phenomenal) consciousness. Here I review this correlation/constitution distinction problem and challenge the existing foundations of consciousness science. I present the main analyses from a longer paper in press on this issue, focusing on recording, inhibition, stimulation, and combined inhibition/stimulation strategies, including proposal of the Jenga analogy to illustrate why identifying the minimally sufficient neural correlates of consciousness should not be considered the ultimate target of consciousness science. Thereafter I suggest that while combined inhibition and stimulation strategies might identify some constitutive neural activities—indeed minimally sufficient constitutive neural activities—such strategies fail to identify the whole neural constitution of consciousness and thus the correlation/constitution distinction problem is not fully solved. Various clarifications, potential objections and related scientific and philosophical issues are also discussed and I conclude by proposing new foundational claims for consciousness science. PMID:25452738

The Role of Rumination and Stressful Life Events in the Relationship between the Qi Stagnation Constitution and Depression in Women: A Moderated Mediation Model.

PubMed

Liu, Mingfan; Jiang, Ying; Wang, Xiumei; Liu, Qiaosheng; Wu, Hou

2017-01-01

The qi stagnation constitution is associated with depression in traditional Chinese medicine. It is unclear how rumination and stressful life events affect the relationship between the qi stagnation constitution and depression. The Qi Stagnation Constitution Scale, Ruminative Response Scale, Center for Epidemiologic Studies Depression Scale, and Adolescent Self-Rating Life Events Checklist were used to assess this association in 1200 female college students. The results revealed that the qi stagnation constitution was positively associated with depression. Furthermore, rumination was a partial mediator of the relationship between the qi stagnation constitution and depression. In addition, stressful life events moderated the direct effect and mediating effect of the qi stagnation constitution on depression. These findings indicate that rumination and stressful life events may affect the relationship between the qi stagnation constitution and depression in women.

The Role of Rumination and Stressful Life Events in the Relationship between the Qi Stagnation Constitution and Depression in Women: A Moderated Mediation Model

PubMed Central

Liu, Qiaosheng

2017-01-01

The qi stagnation constitution is associated with depression in traditional Chinese medicine. It is unclear how rumination and stressful life events affect the relationship between the qi stagnation constitution and depression. The Qi Stagnation Constitution Scale, Ruminative Response Scale, Center for Epidemiologic Studies Depression Scale, and Adolescent Self-Rating Life Events Checklist were used to assess this association in 1200 female college students. The results revealed that the qi stagnation constitution was positively associated with depression. Furthermore, rumination was a partial mediator of the relationship between the qi stagnation constitution and depression. In addition, stressful life events moderated the direct effect and mediating effect of the qi stagnation constitution on depression. These findings indicate that rumination and stressful life events may affect the relationship between the qi stagnation constitution and depression in women. PMID:28757889

Paraprofessional Implementation of Evidence-Based Practices for Special Education Students

ERIC Educational Resources Information Center

Bubb-McKinnie, Esther

2017-01-01

Paraprofessionals often constitute the primary support system for special education students and are core members of special education instructional teams. Therefore, the Individuals With Disabilities Education Act requires that paraprofessionals receive adequate training, including training in evidence-based practices (EBP). However,…

The Use of Returned Martian Samples to Evaluate the Possibility of Extant Life on Mars

NASA Astrophysics Data System (ADS)

iMOST Team; ten Kate, I. L.; Mackelprang, R.; Rettberg, P.; Smith, C. L.; Altieri, F.; Amelin, Y.; Ammannito, E.; Anand, M.; Beaty, D. W.; Benning, L. G.; Bishop, J. L.; Borg, L. E.; Boucher, D.; Brucato, J. R.; Busemann, H.; Campbell, K. A.; Carrier, B. L.; Czaja, A. D.; Debaille, V.; Des Marais, D. J.; Dixon, M.; Ehlmann, B. L.; Farmer, J. D.; Fernandez-Remolar, D. C.; Fogarty, J.; Glavin, D. P.; Goreva, Y. S.; Grady, M. M.; Hallis, L. J.; Harrington, A. D.; Hausrath, E. M.; Herd, C. D. K.; Horgan, B.; Humayun, M.; Kleine, T.; Kleinhenz, J.; Mangold, N.; Mayhew, L. E.; McCoy, J. T.; McCubbin, F. M.; McLennan, S. M.; McSween, H. Y.; Moser, D. E.; Moynier, F.; Mustard, J. F.; Niles, P. B.; Ori, G. G.; Raulin, F.; Rucker, M. A.; Schmitz, N.; Sefton-Nash, E.; Sephton, M. A.; Shaheen, R.; Shuster, D. L.; Siljestrom, S.; Spry, J. A.; Steele, A.; Swindle, T. D.; Tosca, N. J.; Usui, T.; Van Kranendonk, M. J.; Wadhwa, M.; Weiss, B. P.; Werner, S. C.; Westall, F.; Wheeler, R. M.; Zipfel, J.; Zorzano, M. P.

2018-04-01

The astrobiological community is highly interested in interrogating returned martian samples for evidence of extant life. A single observation with one method will not constitute evidence of extant life — it will require a suite of investigations.

How the Alchemy Makes Inquiry, Evidence, and Exclusion.

ERIC Educational Resources Information Center

Popkewitz, Thomas S.

2002-01-01

Modern teaching and teacher education "magically" transform sciences, social sciences, and humanities. The alchemy of school subjects provides a way to think about frames of reference organizing inquiry and constitutes evidence in teacher education, also obscuring the normalizing and dividing practices of teaching (including…

Integrating Brain Science and Law: Neuroscientific Evidence and Legal Perspectives on Protecting Individual Liberties

PubMed Central

Kraft, Calvin J.; Giordano, James

2017-01-01

Advances in neuroscientific techniques have found increasingly broader applications, including in legal neuroscience (or “neurolaw”), where experts in the brain sciences are called to testify in the courtroom. But does the incursion of neuroscience into the legal sphere constitute a threat to individual liberties? And what legal protections are there against such threats? In this paper, we outline individual rights as they interact with neuroscientific methods. We then proceed to examine the current uses of neuroscientific evidence, and ultimately determine whether the rights of the individual are endangered by such approaches. Based on our analysis, we conclude that while federal evidence rules constitute a substantial hurdle for the use of neuroscientific evidence, more ethical safeguards are needed to protect against future violations of fundamental rights. Finally, we assert that it will be increasingly imperative for the legal and neuroscientific communities to work together to better define the limits, capabilities, and intended direction of neuroscientific methods applicable for use in law. PMID:29167633

Outcomes of Fat-Augmented Latissimus Dorsi (FALD) Flap Versus Implant-Based Latissimus Dorsi Flap for Delayed Post-radiation Breast Reconstruction.

PubMed

Demiri, Efterpi C; Dionyssiou, Dimitrios D; Tsimponis, Antonios; Goula, Christina-Olga; Pavlidis, Leonidas C; Spyropoulou, Georgia-Alexandra

2018-06-01

Although free abdominal flaps constitute the gold standard in post-radiation delayed breast reconstruction, latissimus dorsi-based methods offer alternative reconstructive options. This retrospective study aims to compare outcomes of delayed breast reconstruction using the fat-augmented latissimus dorsi (FALD) autologous reconstruction and the latissimus dorsi-plus-implant reconstruction in irradiated women. We reviewed the files of 47 post-mastectomy irradiated patients (aged 29-73 years), who underwent delayed latissimus dorsi-based breast reconstruction between 2010 and 2016. Twenty-three patients (Group A) had an extended FALD flap and twenty-four patients (Group B) an implant-based latissimus dorsi reconstruction. Patients' age, BMI, pregnancies, volume of injected fat, implant size, postoperative complications, and secondary surgical procedures were recorded and analyzed. Age, BMI, pregnancies, and donor-site complications were similar in both groups (p > 0.05). Mean fat volume injected initially was 254 cc (ranged 130-380 cc/session); mean implant volume was 323 cc (ranged 225-420 cc). Breast complications were significantly fewer in Group A (one wound dehiscence, two oily cysts) compared to Group B (three cases with wound dehiscence, two extrusions, thirteen severe capsular contractions). Non-statistically significant difference was documented for secondary procedures between groups; although the mean number of additional surgeries/patient was higher in Group A, they referred to secondary lipofilling, whereas in Group B they were revision surgeries for complications. The FALD flap constitutes an alternative method for delayed autologous reconstruction after post-mastectomy irradiation, avoiding implant-related complications. Although additional fat graft sessions might be required, it provides an ideal autogenous reconstructive option for thin nulliparous women, with a small opposite breast and adequate fat donor sites. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Researcher's Agenda for Evidence

ERIC Educational Resources Information Center

Oakley, Ann

2004-01-01

Policy makers and researchers may have different agendas as to what constitutes "evidence". This paper reviews some of the issues currently debated in the UK and elsewhere about researchers' understandings of how social research can usefully inform the policy-making process, and their techniques for making it available. Using examples…

OA01.25.The first direct experimental evidence correlating ayurveda based tridosha prakriti, with western constitutional psychology somatotypes

PubMed Central

Metri, Kashinath G; Bhargav, Hemant; Ramarao, Nagendra Hongasandra; Rizzo-Sierra; Basavakatti, Ramakrishna R

2012-01-01

Purpose: Ayurveda is one of the most ancient systems of medical health care. The basic principles, diagnosis of the diseases and their treatment are based on individual prakriti (constitutional type). Ayurveda further classifies the prakriti of an individual on the basis of a set of psychosomatic attributes of personality, depending on whether this individual belongs to Vata, Pitta, or Kapha prakriti, or any combination of them (Patwardhan et al., 2005). The appropriate prakriti assessment is done by several means including questionnaires (Rastogi, 2012; Shilpa and Venkatesha-Murthy, 2011). We aimed to obtain experimental evidence correlating Ayurveda based tridosha-prakriti with western constitutional psychology somatotypes (Rizzo-Sierra, 2011). Method: We employed our Tridosha-prakriti questionnaire (Ramakrishna and Nagendra, 2012), and compared its results with a set of body composition parameters: Height, body weight, body mass index (BMI), muscle mass, fat mass, and fat percentage in normal healthy volunteers (25 males and 25 females, mean age was 26 (± 4) and 25 (± 6) years respectively). Moreover, two-tailed Pearson's correlations were investigated to match the extreme prakriti types with the western constitutional psychology somatotypes, through the mentioned body composition measures. Result: Significant negative correlations were observed between the percentage of Vata attributes as per the questionnaire in the individuals and their BMI, body weight and fat mass respectively (p<0.05). Similarly, there was a significant positive correlation between the percentage of Pitta attributes with the height, body weight, and muscle mass respectively. Also, a significant positive correlation was observed between the percentage of Kapha attributes with fat mass and fat percentage, along with a negative correlation with height. Conclusion: We provide evidence-linking Ayurveda to modern constitutional psychology. In this way, a concept such as prakriti is suggested to lie behind the body mass composition of an individual, and deserves attention within the scientific community.

Interaction with a kinesin-2 tail propels choline acetyltransferase flow towards synapse

PubMed Central

Sadananda, Aparna; Hamid, Runa; Doodhi, Harinath; Ghosal, Debnath; Girotra, Mukul; Jana, Swadhin Chandra; Ray, Krishanu

2012-01-01

Bulk flow constitutes a substantial part of the slow transport of soluble proteins in axons. Though the underlying mechanism is unclear, evidences indicate that intermittent, kinesin based movement of large protein-aggregates aids this process. Choline acetyl-transferase (ChAT), a soluble enzyme catalyzing acetylcholine synthesis, propagates towards synapse at an intermediate, slow rate. The presynaptic enrichment of ChAT requires heterotrimeric kinesin-2, comprising KLP64D, KLP68D and DmKAP, in Drosophila. Here, we show that the bulk flow of a recombinant Green Fluorescent Protein-tagged ChAT (GFP::ChAT), in Drosophila axons, lacks particulate features. It occurs for a brief period during the larval stages. In addition, both the endogenous ChAT and GFP::ChAT directly bind to the KLP64D tail, which is essential for the GFP::ChAT entry and anterograde flow in axon. These evidences suggest that a direct interaction with motor proteins could regulate the bulk flow of soluble proteins, and thus establish their asymmetric distribution. PMID:22486887

Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

PubMed

Elsenbruch, Sigrid

2011-03-01

Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain modulation in IBS is reflected by functional and possibly structural brain changes involving prefrontal as well as cingulate regions. At the same time, there is growing evidence linking peripheral and mucosal immune changes and abdominal pain in IBS, supporting disturbed peripheral pain signalling. Findings in post-infectious IBS emphasize the interaction between centrally-mediated psychosocial risk factors and local inflammation in predicting long-term IBS symptoms. Investigating afferent immune-to-brain communication in visceral hyperalgesia as a component of the sickness response constitutes a promising future research goal. Copyright © 2010 Elsevier Inc. All rights reserved.

Control of gravitropic orientation. II. Dual receptor model for gravitropism

NASA Technical Reports Server (NTRS)

LaMotte, Clifford E.; Pickard, Barbara G.

2004-01-01

Gravitropism of vascular plants has been assumed to require a single gravity receptor mechanism. However, based on the evidence in Part I of this study, we propose that maize roots require two. The first mechanism is without a directional effect and, by itself, cannot give rise to tropism. Its role is quantitative facilitation of the second mechanism, which is directional like the gravitational force itself and provides the impetus for tropic curvature. How closely coupled the two mechanisms may be is, as yet, unclear. The evidence for dual receptors supports a general model for roots. When readiness for gravifacilitation, or gravifacilitation itself, is constitutive, orthogravitropic curvature can go to completion. If not constitutively enabled, gravifacilitation can be weak in the absence of light and water deficit or strong in the presence of light and water deficit. In either case, it can decay and permit roots to assume reproducible non-vertical orientations (plagiogravitropic or plagiotropic orientations) without using non-vertical setpoints. In this way roots are deployed in a large volume of soil. Gravitropic behaviours in shoots are more diverse than in roots, utilising oblique and horizontal as well as vertical setpoints. As a guide to future experiments, we assess how constitutive v. non-constitutive modes of gravifacilitation might contribute to behaviours based on each kind of setpoint.

What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing

ERIC Educational Resources Information Center

Chang, Mark

2017-01-01

We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical…

32 CFR 644.63 - Contracting for title evidence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... title). (2) In those States where the furnishing of title evidence is held to constitute the practice of law and the State canons of legal ethics prohibit attorneys from engaging in competitive bidding for..., negotiations shall be conducted with attorneys or law firms duly authorized to practice law in the jurisdiction...

Accommodating Ontologies to Biological Reality—Top-Level Categories of Cumulative-Constitutively Organized Material Entities

PubMed Central

Vogt, Lars; Grobe, Peter; Quast, Björn; Bartolomaeus, Thomas

2012-01-01

Background The Basic Formal Ontology (BFO) is a top-level formal foundational ontology for the biomedical domain. It has been developed with the purpose to serve as an ontologically consistent template for top-level categories of application oriented and domain reference ontologies within the Open Biological and Biomedical Ontologies Foundry (OBO). BFO is important for enabling OBO ontologies to facilitate in reliably communicating and managing data and metadata within and across biomedical databases. Following its intended single inheritance policy, BFO's three top-level categories of material entity (i.e. ‘object’, ‘fiat object part’, ‘object aggregate’) must be exhaustive and mutually disjoint. We have shown elsewhere that for accommodating all types of constitutively organized material entities, BFO must be extended by additional categories of material entity. Methodology/Principal Findings Unfortunately, most biomedical material entities are cumulative-constitutively organized. We show that even the extended BFO does not exhaustively cover cumulative-constitutively organized material entities. We provide examples from biology and everyday life that demonstrate the necessity for ‘portion of matter’ as another material building block. This implies the necessity for further extending BFO by ‘portion of matter’ as well as three additional categories that possess portions of matter as aggregate components. These extensions are necessary if the basic assumption that all parts that share the same granularity level exhaustively sum to the whole should also apply to cumulative-constitutively organized material entities. By suggesting a notion of granular representation we provide a way to maintain the single inheritance principle when dealing with cumulative-constitutively organized material entities. Conclusions/Significance We suggest to extend BFO to incorporate additional categories of material entity and to rearrange its top-level material entity taxonomy. With these additions and the notion of granular representation, BFO would exhaustively cover all top-level types of material entities that application oriented ontologies may use as templates, while still maintaining the single inheritance principle. PMID:22253856

Definition of drug-resistant epilepsy: is it evidence based?

PubMed

Wiebe, Samuel

2013-05-01

Clinical case definitions are the cornerstone of clinical communication and of clinical and epidemiologic research. The ramifications of establishing a case definition are extensive, including potentially large changes in epidemiologic estimates of frequency, and decisions for clinical management. Yet, defining a condition entails numerous challenges such as defining the scope and purpose, incorporating the strongest evidence base with clinical expertise, accounting for patients' values, and considering impact on care. The clinical case definition of drug-resistant epilepsy, in addition, must address what constitutes an adequate intervention for an individual drug, what are the outcomes of relevance, what period of observation is sufficient to determine success or failure, how many medications should be tried, whether seizure frequency should play a role, and what is the role of side effects and tolerability. On the other hand, the principles of evidence-based medicine (EBM) aim at providing a systematic approach to incorporating the best available evidence into the process of clinical decision for individual patients. The case definition of drug-resistant epilepsy proposed by the the International League Against Epilepsy (ILAE) in 2009 is evaluated in terms of the principles of EBM as well as the stated goals of the authors of the definition. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Spontaneous supersymmetry breaking in two dimensional lattice super QCD

DOE PAGES

Catterall, Simon; Veernala, Aarti

2015-10-02

We report on a non-perturbative study of two dimensional N=(2,2) super QCD. Our lattice formulation retains a single exact supersymmetry at non-zero lattice spacing, and contains N f fermions in the fundamental representation of a U(N c) gauge group. The lattice action we employ contains an additional Fayet-Iliopoulos term which is also invariant under the exact lattice supersymmetry. This work constitutes the first numerical study of this theory which serves as a toy model for understanding some of the issues that are expected to arise in four dimensional super QCD. As a result, we present evidence that the exact supersymmetrymore » breaks spontaneously when N f < N c in agreement with theoretical expectations.« less

Coexistence of translocation(1,19) and the Philadelphia chromosome in a child's first presentation of chronic myeloid leukemia in blast crisis treated with dasatinib.

PubMed

Eckardt, Mark A; Chang, Vivian Y; Rao, Nagesh P; Federman, Noah

2011-11-01

Chronic myelogenous leukemia (CML) constitutes less than 5% of childhood leukemias. The authors describe a rare case of a 14-year-old boy who presented with CML in blast crisis. Unique to this patient was the evidence of both breakpoint cluster region-c-abl oncogene 1 (BCR-ABL1) fusions as well as an additional unbalanced t(1;19) translocation. This combination has not previously been reported in the same patient. Initial treatment with dasatinib achieved a complete cytogenetic response within 2 months of therapy. This case highlights the heterogeneous presentation of CML in children and rationale for use of dasatinib as a first-line agent for patients with blast crisis.

First description of a fossil chamaeleonid from Greece and its relevance for the European biogeographic history of the group

NASA Astrophysics Data System (ADS)

Georgalis, Georgios L.; Villa, Andrea; Delfino, Massimo

2016-02-01

The fossil record of Chamaeleonidae is very scarce and any new specimen is therefore considered important for our understanding of the evolutionary and biogeographic history of the group. New specimens from the early Miocene of Aliveri (Evia Island), Greece constitute the only fossils of these lizards from southeastern Europe. Skull roofing material is tentatively attributed to the Czech species Chamaeleo cf. andrusovi, revealing a range extension for this taxon, whereas tooth-bearing elements are described as indeterminate chamaeleonids. The Aliveri fossils rank well among the oldest known reptiles from Greece, provide evidence for the dispersal routes of chameleons out of Africa towards the European continent and, additionally, imply strong affinities with coeval chamaeleonids from Central Europe.

School-Based Programs Aimed at the Prevention and Treatment of Obesity: Evidence-Based Interventions for Youth in Latin America

ERIC Educational Resources Information Center

Lobelo, Felipe; Garcia de Quevedo, Isabel; Holub, Christina K.; Nagle, Brian J.; Arredondo, Elva M.; Barquera, Simon; Elder, John P.

2013-01-01

Background: Rapidly rising childhood obesity rates constitute a public health priority in Latin America which makes it imperative to develop evidence-based strategies. Schools are a promising setting but to date it is unclear how many school-based obesity interventions have been documented in Latin America and what level of evidence can be…

On Multi-Objective Based Constitutive Modelling Methodology and Numerical Validation in Small-Hole Drilling of Al6063/SiCp Composites

PubMed Central

Xiang, Junfeng; Xie, Lijing; Gao, Feinong; Zhang, Yu; Yi, Jie; Wang, Tao; Pang, Siqin; Wang, Xibin

2018-01-01

Discrepancies in capturing material behavior of some materials, such as Particulate Reinforced Metal Matrix Composites, by using conventional ad hoc strategy make the applicability of Johnson-Cook constitutive model challenged. Despites applicable efforts, its extended formalism with more fitting parameters would increase the difficulty in identifying constitutive parameters. A weighted multi-objective strategy for identifying any constitutive formalism is developed to predict mechanical behavior in static and dynamic loading conditions equally well. These varying weighting is based on the Gaussian-distributed noise evaluation of experimentally obtained stress-strain data in quasi-static or dynamic mode. This universal method can be used to determine fast and directly whether the constitutive formalism is suitable to describe the material constitutive behavior by measuring goodness-of-fit. A quantitative comparison of different fitting strategies on identifying Al6063/SiCp’s material parameters is made in terms of performance evaluation including noise elimination, correlation, and reliability. Eventually, a three-dimensional (3D) FE model in small-hole drilling of Al6063/SiCp composites, using multi-objective identified constitutive formalism, is developed. Comparison with the experimental observations in thrust force, torque, and chip morphology provides valid evidence on the applicability of the developed multi-objective identification strategy in identifying constitutive parameters. PMID:29324688

The impact of institutional discrimination on psychiatric disorders in lesbian, gay, and bisexual populations: a prospective study.

PubMed

Hatzenbuehler, Mark L; McLaughlin, Katie A; Keyes, Katherine M; Hasin, Deborah S

2010-03-01

We examined the relation between living in states that instituted bans on same-sex marriage during the 2004 and 2005 elections and the prevalence of psychiatric morbidity among lesbian, gay, and bisexual (LGB) populations. We used data from wave 1 (2001-2002) and wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653), a longitudinal, nationally representative study of noninstitutionalized US adults. Psychiatric disorders defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, increased significantly between waves 1 and 2 among LGB respondents living in states that banned gay marriage for the following outcomes: any mood disorder (36.6% increase), generalized anxiety disorder (248.2% increase), any alcohol use disorder (41.9% increase), and psychiatric comorbidity (36.3% increase). These psychiatric disorders did not increase significantly among LGB respondents living in states without constitutional amendments. Additionally, we found no evidence for increases of the same magnitude among heterosexuals living in states with constitutional amendments. Living in states with discriminatory policies may have pernicious consequences for the mental health of LGB populations. These findings lend scientific support to recent efforts to overturn these policies.

Quantification of mutation-derived bias for alternate mating functionalities of the Saccharomyces cerevisiae Ste2p pheromone receptor.

PubMed

Choudhary, Pooja; Loewen, Michele C

2016-01-01

Although well documented for mammalian G-protein-coupled receptors, alternate functionalities and associated alternate signalling remain to be unequivocally established for the Saccharomyces cerevisiae pheromone Ste2p receptor. Here, evidence supporting alternate functionalities for Ste2p is re-evaluated, extended and quantified. In particular, strong mating and constitutive signalling mutations, focusing on residues S254, P258 and S259 in TM6 of Ste2p, are stacked and investigated in terms of their effects on classical G-protein-mediated signal transduction associated with cell cycle arrest, and alternatively, their impact on downstream mating projection and zygote formation events. In relative dose response experiments, accounting for systemic and observational bias, mutational-derived functional differences were observed, validating the S254L-derived bias for downstream mating responses and highlighting complex relationships between TM6-mutation derived constitutive signalling and ligand-induced functionalities. Mechanistically, localization studies suggest that alterations to receptor trafficking may contribute to mutational bias, in addition to expected receptor conformational stabilization effects. Overall, these results extend previous observations and quantify the contributions of Ste2p variants to mediating cell cycle arrest versus downstream mating functionalities. © Crown copyright 2015.

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

PubMed Central

Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

2012-01-01

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

Genetic variation in plant volatile emission does not result in differential attraction of natural enemies in the field.

PubMed

Wason, Elizabeth L; Hunter, Mark D

2014-02-01

Volatile organic chemical (VOC) emission by plants may serve as an adaptive plant defense by attracting the natural enemies of herbivores. For plant VOC emission to evolve as an adaptive defense, plants must show genetic variability for the trait. To date, such variability has been investigated primarily in agricultural systems, yet relatively little is known about genetic variation in VOCs emitted by natural populations of native plants. Here, we investigate intraspecific variation in constitutive and herbivore-induced plant VOC emission using the native common milkweed plant (Asclepias syriaca) and its monarch caterpillar herbivore (Danaus plexippus) in complementary field and common garden greenhouse experiments. In addition, we used a common garden field experiment to gauge natural enemy attraction to milkweed VOCs induced by monarch damage. We found evidence of genetic variation in the total constitutive and induced concentrations of VOCs and the composition of VOC blends emitted by milkweed plants. However, all milkweed genotypes responded similarly to induction by monarchs in terms of their relative change in VOC concentration and blend. Natural enemies attacked decoy caterpillars more frequently on damaged than on undamaged milkweed, and natural enemy visitation was associated with higher total VOC concentrations and with VOC blend. Thus, we present evidence that induced VOCs emitted by milkweed may function as a defense against herbivores. However, plant genotypes were equally attractive to natural enemies. Although milkweed genotypes diverge phenotypically in their VOC concentrations and blends, they converge into similar phenotypes with regard to magnitude of induction and enemy attraction.

Genomic Biomarkers for Breast Cancer Risk

PubMed Central

Walsh, Michael F.; Nathanson, Katherine L.; Couch, Fergus J.

2016-01-01

Clinical risk assessment for cancer predisposition includes a three-generation pedigree and physical examination to identify inherited syndromes. Additionally genetic and genomic biomarkers may identify individuals with a constitutional basis for their disease that may not be evident clinically. Genomic biomarker testing may detect molecular variations in single genes, panels of genes, or entire genomes. The strength of evidence for the association of a genomic biomarker with disease risk may be weak or strong. The factors contributing to clinical validity and utility of genomic biomarkers include functional laboratory analyses and genetic epidemiologic evidence. Genomic biomarkers may be further classified as low, moderate or highly penetrant based on the likelihood of disease. Genomic biomarkers for breast cancer are comprised of rare highly penetrant mutations of genes such as BRCA1 or BRCA2, moderately penetrant mutations of genes such as CHEK2, as well as more common genomic variants, including single nucleotide polymorphisms, associated with modest effect sizes. When applied in the context of appropriate counseling and interpretation, identification of genomic biomarkers of inherited risk for breast cancer may decrease morbidity and mortality, allow for definitive prevention through assisted reproduction, and serve as a guide to targeted therapy. PMID:26987529

Patch testing with rubber series in Europe: a critical review and recommendation.

PubMed

Warburton, Katharine L; Uter, Wolfgang; Geier, Johannes; Spiewak, Radoslaw; Mahler, Vera; Crépy, Marie-Noëlle; Schuttelaar, Marie Louise; Bauer, Andrea; Wilkinson, Mark

2017-04-01

Rubber additives constitute an important group of contact allergens, particularly in certain occupations. To collect information regarding the current practice of using a 'rubber series' in Europe, and discuss this against the background of evidence concerning the prevalence of allergy in order to derive a recommendation for a 'European rubber series'. The following were performed: (i) a survey targeting all members of the COST action 'StanDerm' consortium, (ii) analysis of rubber contact allergy data in the database of the European Surveillance System on Contact Allergies, and (iii) a literature review. Information from 13 countries was available, from one or several departments of dermatology, and occasionally occupational health. Apart from some substances tested only in single departments, a broad overlap regarding important allergens was evident, but considerable variation existed between departments. An up-to-date 'European rubber series' is recommended, with the exclusion of substances only of historical concern. A 'supplementary rubber series' containing allergens of less proven importance, requiring further analysis, is recommended for departments specializing in occupational contact allergy. These should be continually updated as new evidence emerges. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interpretation and use of evidence in state policymaking: a qualitative analysis

PubMed Central

Apollonio, Dorie E; Bero, Lisa A

2017-01-01

Introduction Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Methods Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Results Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Conclusions Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and researchers can apply to encourage evidence-informed policymaking. PMID:28219958

Challenging the Knowledge-Transfer Orthodoxy: Knowledge Co-construction in Technology-Enhanced Learning for Children with Autism

ERIC Educational Resources Information Center

Guldberg, Karen; Parsons, Sarah; Porayska-Pomsta, Kaska; Keay-Bright, Wendy

2017-01-01

Experimental intervention studies constitute the current dominant research designs in the autism education field. Such designs are based on a "knowledge-transfer" model of evidence-based practice in which research is conducted by researchers, and is then "transferred" to practitioners to enable them to implement evidence-based…

47 CFR 51.305 - Interconnection.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., interconnection with the incumbent LEC's network: (1) For the transmission and routing of telephone exchange... interface or protocol standards shall constitute evidence of the substantial similarity of network...

47 CFR 51.305 - Interconnection.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., interconnection with the incumbent LEC's network: (1) For the transmission and routing of telephone exchange... interface or protocol standards shall constitute evidence of the substantial similarity of network...

47 CFR 51.305 - Interconnection.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., interconnection with the incumbent LEC's network: (1) For the transmission and routing of telephone exchange... interface or protocol standards shall constitute evidence of the substantial similarity of network...

47 CFR 51.305 - Interconnection.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., interconnection with the incumbent LEC's network: (1) For the transmission and routing of telephone exchange... interface or protocol standards shall constitute evidence of the substantial similarity of network...

Searching for Life on Early Mars: Lessons from the Pilbara

NASA Technical Reports Server (NTRS)

Clarke, J. D. A.; Stoker, C. R.

2016-01-01

Stromatolites in the Pilbara region of Western Australia constitute the earliest outcrop-scale evidence of life on Earth (Figure 1). The stromatolites in the 3.4 Ga Strelley Pool Formation (SPF) provide an important analog for searching for fossil evidence of early life on Mars, as Noachian aged sediments on Mars were formed under similar environmental conditions. Stromatolites represent possibly the best evidence that could be collected by a rover because they form recognizable macroscopic structures and are often associated with chemical and microscopic evidence.

Parameter Estimation for Viscoplastic Material Modeling

NASA Technical Reports Server (NTRS)

Saleeb, Atef F.; Gendy, Atef S.; Wilt, Thomas E.

1997-01-01

A key ingredient in the design of engineering components and structures under general thermomechanical loading is the use of mathematical constitutive models (e.g. in finite element analysis) capable of accurate representation of short and long term stress/deformation responses. In addition to the ever-increasing complexity of recent viscoplastic models of this type, they often also require a large number of material constants to describe a host of (anticipated) physical phenomena and complicated deformation mechanisms. In turn, the experimental characterization of these material parameters constitutes the major factor in the successful and effective utilization of any given constitutive model; i.e., the problem of constitutive parameter estimation from experimental measurements.

Counterpoint: A Constitutional Right to Party?

ERIC Educational Resources Information Center

Hunsicker, J. Freedley, Jr.

1992-01-01

Takes issues with Gregory Hauser's previous article positing a constitutional right of social fraternities to formal recognition at public institutions of higher education. Reanalyzes each of the associational cases cited by Hauser, cites additional cases, adds a waiver argument, and wraps up with a public policy comparison of higher education…

77 FR 63287 - Additional Requirements for Charitable Hospitals; Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... Auditorium, Internal Revenue Service Building, 1111 Constitution Avenue NW., Washington, DC 20224. Due to... organizations, would be held on Monday, October 29, 2012, beginning at 10 a.m. in the auditorium of the Internal.... in the auditorium of the Internal Revenue Service at 1111 Constitution Avenue NW., Washington, DC...

Need of The Ministry of Health in Federal Democratic Republic of Nepal.

PubMed

Regmi, K; Upadhyay, M; Tarin, E; Chand, P B; Uprety, S R; Lekhak, S C

2017-01-01

The constitution of Nepal provides appointing a council of ministers both at federal and provincial levels without defining portfolios. There is a political agreement that MOH will be retained at the federal level. This article draws evidences around the world to meet health needs of Nepalese, the role of provincial ministry of health and coordinating structure at district/local level. The constitution emphasises on health and pronounced in 46 articles which provides guidance for the creation of federalized governance levels at federal, provincial and local levels. Retaining ministry of health at federal level without creating devolved structure at province and local levels in health sector will create difficulty in translating the spirit of the constitution and may not be effective in addressing health issues nationally and meeting global achievements like SDGs. It is suggested to establish an elaborate health system accordingly in Nepal to ensure constitutional mandate of health as a basic human right.

Mapping a Mirage: Documenting the Scholarship of Teaching and Learning

ERIC Educational Resources Information Center

Simmons, Nicola

2008-01-01

The purpose of the conference session upon which this paper is based was to challenge the notion that evidence of scholarship must be limited to publication in a peer-reviewed journal, and to open the doors for creative thinking about what might constitute evidence of scholarship of teaching and learning. Existing theory around defining…

Learning Analytics and Educational Data Mining in Practice: A Systematic Literature Review of Empirical Evidence

ERIC Educational Resources Information Center

Papamitsiou, Zacharoula; Economides, Anastasios A.

2014-01-01

This paper aims to provide the reader with a comprehensive background for understanding current knowledge on Learning Analytics (LA) and Educational Data Mining (EDM) and its impact on adaptive learning. It constitutes an overview of empirical evidence behind key objectives of the potential adoption of LA/EDM in generic educational strategic…

Educational Research and Evidence-Based Policy: The Mixed-Method Approach of the EPPE Project

ERIC Educational Resources Information Center

Siraj-Blatchford, I.

2006-01-01

In a review of the challenges to progress in providing social research evidence that might usefully inform policy, Oakley (2004) argues strongly that the "paradigm divide" between qualitative and quantitative research communities continues to constitute a major problem. Oakley refers to a number of recent critiques of what is seen as "misplaced…

10 CFR 820.33 - Default order.

Code of Federal Regulations, 2010 CFR

2010-01-01

... respondent unless the Director presents sufficient evidence to the Presiding Officer to establish a prima facie case against the respondent. Default by respondent constitutes, for purposes of the pending action...

Genetic constraints predict evolutionary divergence in Dalechampia blossoms.

PubMed

Bolstad, Geir H; Hansen, Thomas F; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W Scott

2014-08-19

If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance.

Cellular solidification of transparent monotectics

NASA Technical Reports Server (NTRS)

Kaulker, W. F.

1986-01-01

Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

Structural and functional adaptations of the mammalian nuclear envelope to meet the meiotic requirements.

PubMed

Link, Jana; Jahn, Daniel; Alsheimer, Manfred

2015-01-01

Numerous studies in the past years provided definite evidence that the nuclear envelope is much more than just a simple barrier. It rather constitutes a multifunctional platform combining structural and dynamic features to fulfill many fundamental functions such as chromatin organization, regulation of transcription, signaling, but also structural duties like maintaining general nuclear architecture and shape. One additional and, without doubt, highly impressive aspect is the recently identified key function of selected nuclear envelope components in driving meiotic chromosome dynamics, which in turn is essential for accurate recombination and segregation of the homologous chromosomes. Here, we summarize the recent work identifying new key players in meiotic telomere attachment and movement and discuss the latest advances in our understanding of the actual function of the meiotic nuclear envelope.

49 CFR 209.5 - Service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... official United States Postal Service receipt from the registered or certified mailing constitutes prima facie evidence of service. (d) Service of requests for admission and motions may be made by first-class...

Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling

PubMed Central

Ochsner, Scott A.; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian

2016-01-01

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities. PMID:27409825

Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling.

PubMed

Ochsner, Scott A; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian; McKenna, Neil J

2016-08-01

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities.

Constitutive Lck Activity Drives Sensitivity Differences between CD8+ Memory T Cell Subsets.

PubMed

Moogk, Duane; Zhong, Shi; Yu, Zhiya; Liadi, Ivan; Rittase, William; Fang, Victoria; Dougherty, Janna; Perez-Garcia, Arianne; Osman, Iman; Zhu, Cheng; Varadarajan, Navin; Restifo, Nicholas P; Frey, Alan B; Krogsgaard, Michelle

2016-07-15

CD8(+) T cells develop increased sensitivity following Ag experience, and differences in sensitivity exist between T cell memory subsets. How differential TCR signaling between memory subsets contributes to sensitivity differences is unclear. We show in mouse effector memory T cells (TEM) that >50% of lymphocyte-specific protein tyrosine kinase (Lck) exists in a constitutively active conformation, compared with <20% in central memory T cells (TCM). Immediately proximal to Lck signaling, we observed enhanced Zap-70 phosphorylation in TEM following TCR ligation compared with TCM Furthermore, we observed superior cytotoxic effector function in TEM compared with TCM, and we provide evidence that this results from a lower probability of TCM reaching threshold signaling owing to the decreased magnitude of TCR-proximal signaling. We provide evidence that the differences in Lck constitutive activity between CD8(+) TCM and TEM are due to differential regulation by SH2 domain-containing phosphatase-1 (Shp-1) and C-terminal Src kinase, and we use modeling of early TCR signaling to reveal the significance of these differences. We show that inhibition of Shp-1 results in increased constitutive Lck activity in TCM to levels similar to TEM, as well as increased cytotoxic effector function in TCM Collectively, this work demonstrates a role for constitutive Lck activity in controlling Ag sensitivity, and it suggests that differential activities of TCR-proximal signaling components may contribute to establishing the divergent effector properties of TCM and TEM. This work also identifies Shp-1 as a potential target to improve the cytotoxic effector functions of TCM for adoptive cell therapy applications. Copyright © 2016 by The American Association of Immunologists, Inc.

Systematic review of the association between physical activity and burnout.

PubMed

Naczenski, Lea M; Vries, Juriena D de; Hooff, Madelon L M van; Kompier, Michiel A J

2017-11-25

Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical activity and burnout by conducting a systematic review of longitudinal and intervention studies. A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). In longitudinal studies, we found moderately strong evidence (SIC (4) = -1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC (6) = -0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout.

Trade-offs between constitutive and induced defences drive geographical and climatic clines in pine chemical defences.

PubMed

Moreira, Xoaquín; Mooney, Kailen A; Rasmann, Sergio; Petry, William K; Carrillo-Gavilán, Amparo; Zas, Rafael; Sampedro, Luis

2014-05-01

There is increasing evidence that geographic and climatic clines drive the patterns of plant defence allocation and defensive strategies. We quantified early growth rate and both constitutive and inducible chemical defences of 18 Pinaceae species in a common greenhouse environment and assessed their defensive allocation with respect to each species' range across climatic gradients spanning 31° latitude and 2300 m elevation. Constitutive defences traded-off with induced defences, and these defensive strategies were associated with growth rate such that slow-growing species invested more in constitutive defence, whereas fast-growing species invested more in inducible defence. The position of each pine species along this trade-off axis was in turn associated with geography; moving poleward and to higher elevations, growth rate and inducible defences decreased, while constitutive defence increased. These geographic patterns in plant defence were most strongly associated with variation in temperature. Climatic and geographical clines thus act as drivers of defence profiles by mediating the constraints imposed by trade-offs, and this dynamic underlays global patterns of defence allocation.

Multiple Deficits in ADHD: Executive Dysfunction, Delay Aversion, Reaction Time Variability, and Emotional Deficits

ERIC Educational Resources Information Center

Sjowall, Douglas; Roth, Linda; Lindqvist, Sofia; Thorell, Lisa B.

2013-01-01

Background: The notion that ADHD constitutes a heterogeneous disorder is well accepted. However, this study contributes with new important knowledge by examining independent effects of a large range of neuropsychological deficits. In addition, the study investigated whether deficits in emotional functioning constitute a dissociable component of…

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.

PubMed

Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

2005-06-06

In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

PubMed Central

Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

2005-01-01

In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma. PMID:15928660

The Self-Liking Brain: A VBM Study on the Structural Substrate of Self-Esteem

PubMed Central

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource. PMID:24489727

The self-liking brain: a VBM study on the structural substrate of self-esteem.

PubMed

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource.

A Generalization of the Einstein-Maxwell Equations

NASA Astrophysics Data System (ADS)

Cotton, Fredrick

2016-03-01

The proposed modifications of the Einstein-Maxwell equations include: (1) the addition of a scalar term to the electromagnetic side of the equation rather than to the gravitational side, (2) the introduction of a 4-dimensional, nonlinear electromagnetic constitutive tensor and (3) the addition of curvature terms arising from the non-metric components of a general symmetric connection. The scalar term is defined by the condition that a spherically symmetric particle be force-free and mathematically well-behaved everywhere. The constitutive tensor introduces two auxiliary fields which describe the particle structure. The additional curvature terms couple both to particle solutions and to electromagnetic and gravitational wave solutions. http://sites.google.com/site/fwcotton/em-30.pdf

Cigarette smoking and lung cancer: a continuing controversy.

PubMed

Burch, P R

1982-09-01

During the late 1950s Sir Ronald Fisher questioned the already popular, but in his view precipitate, causal interpretation of the association between smoking and lung cancer. His pungently expressed views began a controversy that has smouldered and sometimes flared ever since. The most recent attack on Fisher's constitutional hypothesis was launched by Reif and in this paper I consider the validity of his criticisms. A range of evidence shows that it is not yet possible to distinguish between constitutional and causal-plus-constitutional interpretations although recent studies indicate that a pure causal hypothesis is incapable of explaining the full association as observed in Western populations. Unfortunately, errors of diagnosis and death certification still impede the rigorous testing of adequately formulated hypotheses.

The Impact of Institutional Discrimination on Psychiatric Disorders in Lesbian, Gay, and Bisexual Populations: A Prospective Study

PubMed Central

McLaughlin, Katie A.; Keyes, Katherine M.; Hasin, Deborah S.

2010-01-01

Objectives. We examined the relation between living in states that instituted bans on same-sex marriage during the 2004 and 2005 elections and the prevalence of psychiatric morbidity among lesbian, gay, and bisexual (LGB) populations. Methods. We used data from wave 1 (2001–2002) and wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (N = 34 653), a longitudinal, nationally representative study of noninstitutionalized US adults. Results. Psychiatric disorders defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, increased significantly between waves 1 and 2 among LGB respondents living in states that banned gay marriage for the following outcomes: any mood disorder (36.6% increase), generalized anxiety disorder (248.2% increase), any alcohol use disorder (41.9% increase), and psychiatric comorbidity (36.3% increase). These psychiatric disorders did not increase significantly among LGB respondents living in states without constitutional amendments. Additionally, we found no evidence for increases of the same magnitude among heterosexuals living in states with constitutional amendments. Conclusions. Living in states with discriminatory policies may have pernicious consequences for the mental health of LGB populations. These findings lend scientific support to recent efforts to overturn these policies. PMID:20075314

Reduction of ferric iron by acidophilic heterotrophic bacteria: evidence for constitutive and inducible enzyme systems in Acidiphilium spp.

PubMed

Johnson, D B; Bridge, T A M

2002-01-01

To compare the abilities of two obligately acidophilic heterotrophic bacteria, Acidiphilium acidophilum and Acidiphilium SJH, to reduce ferric iron to ferrous when grown under different culture conditions. Bacteria were grown in batch culture, under different aeration status, and in the presence of either ferrous or ferric iron. The specific rates of ferric iron reduction by fermenter-grown Acidiphilium SJH were unaffected by dissolved oxygen (DO) concentrations, while iron reduction by A. acidophilum was highly dependent on DO concentrations in the growth media. The ionic form of iron present (ferrous or ferric) had a minimal effect on the abilities of harvested cells to reduce ferric iron. Whole cell protein profiles of Acidiphilium SJH were very similar, regardless of the DO status of the growth medium, while additional proteins were present in A. acidophilum grown microaerobically compared with aerobically-grown cells. The dissimilatory reduction of ferric iron is constitutive in Acidiphilium SJH while it is inducible in A. acidophilum. Ferric iron reduction by Acidiphilium spp. may occur in oxygen-containing as well as anoxic acidic environments. This will detract from the effectiveness of bioremediation systems where removal of iron from polluted waters is mediated via oxidation and precipitation of the metal.

Evidence for Knowledge of the Syntax of Large Numbers in Preschoolers

ERIC Educational Resources Information Center

Barrouillet, Pierre; Thevenot, Catherine; Fayol, Michel

2010-01-01

The aim of this study was to provide evidence for knowledge of the syntax governing the verbal form of large numbers in preschoolers long before they are able to count up to these numbers. We reasoned that if such knowledge exists, it should facilitate the maintenance in short-term memory of lists of lexical primitives that constitute a number…

Evidence-Based Fitness Promotion in an Afterschool Setting: Implementation Fidelity and Its Policy Implications

ERIC Educational Resources Information Center

Thaw, Jean M.; Villa, Manuela; Reitman, David; DeLucia, Christian; Gonzalez, Vanessa; Hanson, K. Lori

2014-01-01

Little is known about how the adoption of evidence-based physical activity (PA) curricula by out-of-school time (OST) programs affects children's physical fitness, and there are no clear guidelines of what constitutes reasonable gains given the types of PA instruction currently offered in these programs. Using a three-wave,…

An exploratory study identifying where local government public health decision makers source their evidence for policy.

PubMed

Stoneham, Melissa; Dodds, James

2014-08-01

The Western Australian (WA) Public Health Bill will replace the antiquated Health Act 1911. One of the proposed clauses of the Bill requires all WA local governments to develop a Public Health Plan. The Bill states that Public Health Plans should be based on evidence from all levels, including national and statewide priorities, community needs, local statistical evidence, and stakeholder data. This exploratory study, which targeted 533 WA local government officers, aimed to identify the sources of evidence used to generate the list of public health risks to be included in local government Public Health Plans. The top four sources identified for informing local policy were: observation of the consequences of the risks in the local community (24.5%), statewide evidence (17.6%), local evidence (17.6%) and coverage in local media (16.2%). This study confirms that both hard and soft data are used to inform policy decisions at the local level. Therefore, the challenge that this study has highlighted is in the definition or constitution of evidence. SO WHAT? Evidence is critical to the process of sound policy development. This study highlights issues associated with what actually constitutes evidence in the policy development process at the local government level. With the exception of those who work in an extremely narrow field, it is difficult for local government officers, whose role includes policymaking, to read the vast amount of information that has been published in their area of expertise. For those who are committed to the notion of evidence-based policymaking, as advocated within the WA Public Health Bill, this presents a considerable challenge.

Association between iris constitution and apolipoprotein e gene polymorphism in hypertensives.

PubMed

Um, Jae-Young; Hwang, Chung-Yeon; Hwang, Woo-Jun; Kang, Sung-Do; Do, Keum-Rok; Cho, Ju-Jang; Cho, Jae-Woon; Kim, Sung-Hoon; Shin, Tae-Yong; Kim, Yun-Kyung; Kim, Hyung-Min; Hong, Seung-Heon

2004-12-01

Iridology is a complementary and alternative medicine (CAM) that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong familial aggregation and heredity is implicated. Apolipoprotein E (apoE) gene polymorphism is one of the most well-studied genetic markers for vascular diseases, including hypertension. In this study, we investigated the relationship between iris constitution and apoE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the apoE genotype of each individual. A significantly higher percentage of individuals with neurogenic constitutions was found in the hypertensive group when compared with the control group (chi(2) = 40.244, p < 0.001). In addition, a neurogenic constitution increased the relative risk for hypertension for subjects with an apo epsilon2 or an epsilon4 allele (chi(2) = 4.086, p = 0.049, odds ratio = 2.633, confidence interval = 1.004-6.905). Our results imply that a neurogenic iris constitution enhances the relative risk for hypertension in subjects with the apo epsilon2 or epsilon4 allele. Furthermore, we attempted to evaluate the efficacy of iris constitutional medicine and to find an association with hypertension.

What is an evidence map? A systematic review of published evidence maps and their definitions, methods, and products.

PubMed

Miake-Lye, Isomi M; Hempel, Susanne; Shanman, Roberta; Shekelle, Paul G

2016-02-10

The need for systematic methods for reviewing evidence is continuously increasing. Evidence mapping is one emerging method. There are no authoritative recommendations for what constitutes an evidence map or what methods should be used, and anecdotal evidence suggests heterogeneity in both. Our objectives are to identify published evidence maps and to compare and contrast the presented definitions of evidence mapping, the domains used to classify data in evidence maps, and the form the evidence map takes. We conducted a systematic review of publications that presented results with a process termed "evidence mapping" or included a figure called an "evidence map." We identified publications from searches of ten databases through 8/21/2015, reference mining, and consulting topic experts. We abstracted the research question, the unit of analysis, the search methods and search period covered, and the country of origin. Data were narratively synthesized. Thirty-nine publications met inclusion criteria. Published evidence maps varied in their definition and the form of the evidence map. Of the 31 definitions provided, 67 % described the purpose as identification of gaps and 58 % referenced a stakeholder engagement process or user-friendly product. All evidence maps explicitly used a systematic approach to evidence synthesis. Twenty-six publications referred to a figure or table explicitly called an "evidence map," eight referred to an online database as the evidence map, and five stated they used a mapping methodology but did not present a visual depiction of the evidence. The principal conclusion of our evaluation of studies that call themselves "evidence maps" is that the implied definition of what constitutes an evidence map is a systematic search of a broad field to identify gaps in knowledge and/or future research needs that presents results in a user-friendly format, often a visual figure or graph, or a searchable database. Foundational work is needed to better standardize the methods and products of an evidence map so that researchers and policymakers will know what to expect of this new type of evidence review. Although an a priori protocol was developed, no registration was completed; this review did not fit the PROSPERO format.

Water addition regulates the metabolic activity of ammonia oxidizers responding to environmental perturbations in dry subhumid ecosystems.

PubMed

Hu, Hang-Wei; Macdonald, Catriona A; Trivedi, Pankaj; Holmes, Bronwyn; Bodrossy, Levente; He, Ji-Zheng; Singh, Brajesh K

2015-02-01

Terrestrial arid and semi-arid ecosystems (drylands) constitute about 41% of the Earth's land surface and are predicted to experience increasing fluctuations in water and nitrogen availability. Mounting evidence has confirmed the significant importance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in nitrification, plant nitrogen availability and atmospheric N2 O emissions, but their responses to environmental perturbations in drylands remain largely unknown. Here we evaluate how the factorial combinations of irrigation and fertilization in forests and land-use change from grassland to forest affects the dynamics of AOA and AOB following a 6-year dryland field study. Potential nitrification rates and AOA and AOB abundances were significantly higher in the irrigated plots, accompanied by considerable changes in community compositions, but their responses to fertilization alone were not significant. DNA-stable isotope probing results showed increased (13) CO2 incorporation into the amoA gene of AOA, but not of AOB, in plots receiving water addition, coupled with significantly higher net mineralization and nitrification rates. High-throughput microarray analysis revealed that active AOA assemblages belonging to Nitrosopumilus and Nitrosotalea were increasingly labelled by (13) CO2 following irrigation. However, no obvious effects of land-use changes on nitrification rates or metabolic activity of AOA and AOB could be observed under dry conditions. We provide evidence that water addition had more important roles than nitrogen fertilization in influencing the autotrophic nitrification in dryland ecosystems, and AOA are increasingly involved in ammonia oxidation when dry soils become wetted. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

The receptor protein tyrosine phosphatase (RPTP){beta}/{zeta} is expressed in different subtypes of human breast cancer

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

Perez-Pinera, Pablo; Garcia-Suarez, Olivia; Instituto Universitario de Oncologia del Principado de Asturias, Oviedo

2007-10-12

Increasing evidence suggests mutations in human breast cancer cells that induce inappropriate expression of the 18-kDa cytokine pleiotrophin (PTN, Ptn) initiate progression of breast cancers to a more malignant phenotype. Pleiotrophin signals through inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP){beta}/{zeta}, leading to increased tyrosine phosphorylation of different substrate proteins of RPTP{beta}/{zeta}, including {beta}-catenin, {beta}-adducin, Fyn, GIT1/Cat-1, and P190RhoGAP. PTN signaling thus has wide impact on different important cellular systems. Recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTP{beta}/{zeta} signaling pathway; this discovery potentially is very important, since constitutive ALK activity of nucleophosmin (NPM)-ALK fusionmore » protein is causative of anaplastic large cell lymphomas, and, activated ALK is found in other malignant cancers. Recently ALK was identified in each of 63 human breast cancers from 22 subjects. We now demonstrate that RPTP{beta}/{zeta} is expressed in each of these same 63 human breast cancers that previously were found to express ALK and in 10 additional samples of human breast cancer. RPTP{beta}/{zeta} furthermore was localized not only in its normal association with the cell membrane but also scattered in cytoplasm and in nuclei in different breast cancer cells and, in the case of infiltrating ductal carcinomas, the distribution of RPTP{beta}/{zeta} changes as the breast cancer become more malignant. The data suggest that the PTN/RPTP{beta}/{zeta} signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer.« less

Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB.

PubMed

McKinsey, T A; Brockman, J A; Scherer, D C; Al-Murrani, S W; Green, P L; Ballard, D W

1996-05-01

In resting T lymphocytes, the transcription factor NF-kappaB is sequestered in the cytoplasm via interactions with members of the I kappa B family of inhibitors, including IkappaBalpha and IkappaBbeta. During normal T-cell activation, IkappaBalpha is rapidly phosphorylated, ubiquitinated, and degraded by the 26S proteasome, thus permitting the release of functional NF-kappaB. In contrast to its transient pattern of nuclear induction during an immune response, NF-kappaB is constitutively activated in cells expressing the Tax transforming protein of human T-cell leukemia virus type I (HTLV-1). Recent studies indicate that HTLV-1 Tax targets IkappaBalpha to the ubiquitin-proteasome pathway. However, it remains unclear how this viral protein induces a persistent rather than transient NF-kappaB response. In this report, we provide evidence that in addition to acting on IkappaBalpha, Tax stimulates the turnover Of IkappaBbeta via a related targeting mechanism. Like IkappaBalpha, Tax-mediated breakdown of IkappaBbeta in transfected T lymphocytes is blocked either by cell-permeable proteasome inhibitors or by mutation Of IkappaBbeta at two serine residues present within its N-terminal region. Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level, Tax selectively stimulates NF-kappaB-directed transcription of the IkappaBalpha gene. Consequently, IkappaBbeta protein expression is chronically downregulated in HTLV-1-infected T lymphocytes. These findings with IkappaBbeta provide a potential mechanism for the constitutive activation of NF-kappaB in Tax-expressing cells.

Evidence for metabolic activity of airborne bacteria

NASA Technical Reports Server (NTRS)

Chatigny, M. A.; Wolochow, H.

1974-01-01

Aerosols of the bacterium Serratia marcescens, and of uniformly labeled C-14 glucose were produced simultaneously and mixed in tubing leading to an aerosol chamber. During a subsequent period of about 5 hrs, carbon dioxide was produced metabolically within the chamber, and labeled material incorporated within the suspended particles first increased then decreased. This constitutes the first direct evidence of microbial metabolism of bacteria suspended in the air.

Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation.

PubMed

Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui; Vedeld, Hege Marie; Yohannes, Zeremariam; Peixoto, Ana; Santos, Catarina; Pinto, Pedro; Lopes, Paula; Lothe, Ragnhild; Lind, Guro Elisabeth; Henrique, Rui; Teixeira, Manuel R

2018-02-01

Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Genetic constraints predict evolutionary divergence in Dalechampia blossoms

PubMed Central

Bolstad, Geir H.; Hansen, Thomas F.; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W. Scott

2014-01-01

If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance. PMID:25002700

How infants and toddlers react to antisocial others

PubMed Central

Hamlin, J. Kiley; Wynn, Karen; Bloom, Paul; Mahajan, Neha

2011-01-01

Although adults generally prefer helpful behaviors and those who perform them, there are situations (in particular, when the target of an action is disliked) in which overt antisocial acts are seen as appropriate, and those who perform them are viewed positively. The current studies explore the developmental origins of this capacity for selective social evaluation. We find that although 5-mo-old infants uniformly prefer individuals who act positively toward others regardless of the status of the target, 8-mo-old infants selectively prefer characters who act positively toward prosocial individuals and characters who act negatively toward antisocial individuals. Additionally, young toddlers direct positive behaviors toward prosocial others and negative behaviors toward antisocial others. These findings constitute evidence that the nuanced social judgments and actions readily observable in human adults have their foundations in early developing cognitive mechanisms. PMID:22123953

The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens.

PubMed

Ellis, C; Turner, J G

2001-05-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway.

The Arabidopsis Mutant cev1 Has Constitutively Active Jasmonate and Ethylene Signal Pathways and Enhanced Resistance to Pathogens

PubMed Central

Ellis, Christine; Turner, John G.

2001-01-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway. PMID:11340179

The Receptor-Binding Site of the Measles Virus Hemagglutinin Protein Itself Constitutes a Conserved Neutralizing Epitope

PubMed Central

Ohno, Shinji; Sakai, Kouji; Ito, Yuri; Fukuhara, Hideo; Komase, Katsuhiro; Brindley, Melinda A.; Rota, Paul A.; Plemper, Richard K.; Maenaka, Katsumi; Takeda, Makoto

2013-01-01

Here, we provide direct evidence that the receptor-binding site of measles virus (MV) hemagglutinin protein itself forms an effective conserved neutralizing epitope (CNE). Several receptor-interacting residues constitute the CNE. Thus, viral escape from neutralization has to be associated with loss of receptor-binding activity. Since interactions with both the signaling lymphocyte activation molecule (SLAM) and nectin4 are critical for MV pathogenesis, its escape, which results from loss of receptor-binding activity, should not occur in nature. PMID:23283964

Smoking and pregnancy.

PubMed

Abel, E L

1984-01-01

Smoking during pregnancy is associated with many adverse outcomes, including fetal and neonatal death. These consequences are tragic in many ways, but perhaps the greatest tragedy is that they are preventable if the smoker ceases to smoke during pregnancy. Although in some instances the so-called constitutional hypothesis is difficult to disprove, the available evidence seems more than convincing that it is smoking itself, and not the smoker's unique constitution, that is responsible. Cessation from smoking is clearly advisable at any time, but more so during pregnancy when every cigarette affects both the smoker and her unborn child.

PROGRESS ON THE STUDY OF THE URANIUM-ALUMINUM-IRON CONSTITUTION DIAGRAM FOR THE PERIOD SEPTEMBER 1-DECEMBER 31, 1963

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

Russell, R.B.

The U--Al--Fe constitution diagram up to about 1000 ppm each of aluminum and iron is sthdied. The techniques used for this study include optical, electron, and x-ray metallography; microprobe analysis, electric conductivity, and hardness measurements. A combination of techniques are giving evidence of the amount of solid solubility of aluminum and iron in alpha, beta, and gamma uranium at selected higher temperatures. The U-Al and U-Fe phase diagrams are also being determined. (N.W.R.)

Modeling flow stress constitutive behavior of SA508-3 steel for nuclear reactor pressure vessels

NASA Astrophysics Data System (ADS)

Sun, Mingyue; Hao, Luhan; Li, Shijian; Li, Dianzhong; Li, Yiyi

2011-11-01

Based on the measured stress-strain curves under different temperatures and strain rates, a series of flow stress constitutive equations for SA508-3 steel were firstly established through the classical theories on work hardening and softening. The comparison between the experimental and modeling results has confirmed that the established constitutive equations can correctly describe the mechanical responses and microstructural evolutions of the steel under various hot deformation conditions. We further represented a successful industrial application of this model to simulate a forging process for a large conical shell used in a nuclear steam generator, which evidences its practical and promising perspective of our model with an aim of widely promoting the hot plasticity processing for heavy nuclear components of fission reactors.

Interpretation and use of evidence in state policymaking: a qualitative analysis.

PubMed

Apollonio, Dorie E; Bero, Lisa A

2017-02-20

Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and researchers can apply to encourage evidence-informed policymaking. 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/.

Evidence-based dentistry: a clinician's perspective.

PubMed

Bauer, Janet; Spackman, Sue; Chiappelli, Francesco; Prolo, Paolo; Stevenson, Richard

2006-07-01

Evidence-based dentistry is a discipline that provides best, explicit-based evidence to dentists and their patients in shared decision-making. Currently, dentists are being trained and directed to adopt the role of translational researchers in developing evidence-based dental practices. Practically, evidence-based dentistry is not usable in its current mode for the provision of labor-intensive services that characterize current dental practice. The purpose of this article is to introduce a model of evidence-based dental practice. This model conceptualizes a team approach in explaining problems and solutions to change current dental practice. These changes constitute an evidence-based dental practice that involves the electronic chart, centralized database, knowledge management software, and personnel in optimizing effective oral health care to dental patients.

Structure/property (constitutive and dynamic strength/damage) characterization of additively manufactured 316L SS

NASA Astrophysics Data System (ADS)

Gray, G. T., III; Livescu, V.; Rigg, P. A.; Trujillo, C. P.; Cady, C. M.; Chen, S. R.; Carpenter, J. S.; Lienert, T. J.; Fensin, S.

2015-09-01

For additive manufacturing (AM), the certification and qualification paradigm needs to evolve as there exists no "ASTM-type" additive manufacturing certified process or AM-material produced specifications. Accordingly, utilization of AM materials to meet engineering applications requires quantification of the constitutive properties of these evolving materials in comparison to conventionally-manufactured metals and alloys. Cylinders of 316L SS were produced using a LENS MR-7 laser additive manufacturing system from Optomec (Albuquerque, NM) equipped with a 1kW Yb-fiber laser. The microstructure of the AM-316L SS is detailed in both the as-built condition and following heat-treatments designed to obtain full recrystallization. The constitutive behavior as a function of strain rate and temperature is presented and compared to that of nominal annealed wrought 316L SS plate. The dynamic damage evolution and failure response of all three materials was probed using flyer-plate impact driven spallation experiments at a peak stress of 4.5 GPa to examine incipient spallation response. The spall strength of AM-produced 316L SS was found to be very similar for the peak shock stress studied to that of annealed wrought or AM-316L SS following recrystallization. The damage evolution as a function of microstructure was characterized using optical metallography.

Systematic review of the association between physical activity and burnout

PubMed Central

Naczenski, Lea M.; de Vries, Juriena D.; van Hooff, Madelon L. M.; Kompier, Michiel A. J.

2017-01-01

Objective: Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical activity and burnout by conducting a systematic review of longitudinal and intervention studies. Methods: A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). Results: In longitudinal studies, we found moderately strong evidence (SIC (4) = -1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC (6) = -0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. Conclusions: This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout. PMID:28993574

Knowledge and Power in the Technology Classroom: A Framework for Studying Teachers and Students in Action

ERIC Educational Resources Information Center

Danielsson, Anna T.; Berge, Maria; Lidar, Malena

2018-01-01

The purpose of this paper is to develop and illustrate an analytical framework for exploring how relations between knowledge and power are constituted in science and technology classrooms. In addition, the empirical purpose of this paper is to explore how disciplinary knowledge and knowledge-making are constituted in teacher-student interactions.…

26 CFR 1.954-6 - Foreign base company shipping income.

Code of Federal Regulations, 2011 CFR

2011-04-01

... by A from its management and operating services constitutes income derived in connection with the... accounts receivable and evidences of indebtedness described in § 1.955A-2(b)(2)(ii), (iv) Income derived...

26 CFR 1.954-6 - Foreign base company shipping income.

Code of Federal Regulations, 2012 CFR

2012-04-01

... by A from its management and operating services constitutes income derived in connection with the... accounts receivable and evidences of indebtedness described in § 1.955A-2(b)(2)(ii), (iv) Income derived...

26 CFR 1.954-6 - Foreign base company shipping income.

Code of Federal Regulations, 2013 CFR

2013-04-01

... by A from its management and operating services constitutes income derived in connection with the... accounts receivable and evidences of indebtedness described in § 1.955A-2(b)(2)(ii), (iv) Income derived...

26 CFR 1.954-6 - Foreign base company shipping income.

Code of Federal Regulations, 2010 CFR

2010-04-01

... by A from its management and operating services constitutes income derived in connection with the... accounts receivable and evidences of indebtedness described in § 1.955A-2(b)(2)(ii), (iv) Income derived...

Exploring Nurse Manager Support of Evidence-Based Practice: Clinical Nurse Perceptions.

PubMed

Caramanica, Laura; Spiva, LeeAnna

2018-05-01

The study identifies what constitutes nurse manager (NM) support and other resources that enable clinical nurses (CNs) to engage in evidence-based practice (EBP). Clinical nurses report that NM support enables them to use EBP but what constitutes NM support is still unclear. Nurse managers, CNs, and EBP mentors received specialized education and use a team approach for EBP. Data were collected preintervention, mid-intervention, and postintervention from observations, interviews, journaling, and surveys. Results demonstrate how NMs can perform their role responsibilities and still engage CNs to develop a spirit of inquiry, seek answers to their clinical questions using EBP, and advance their clinical performance to improve patient outcomes. Four NM supportive behaviors emerged: cultivating a shared EBP vision, ensuring use of EBP, communicating the value of EBP, and providing resources for EBP. Through education and support, NMs describe supportive behaviors necessary for the successful conduction of EBP by CNs.

Genome-Wide Identification of Medicago Peptides Involved in Macronutrient Responses and Nodulation1[OPEN

PubMed Central

Dai, Xinbin; Zhuang, Zhaohong; Torres-Jerez, Ivone; Nogales, Joaquina

2017-01-01

Growing evidence indicates that small, secreted peptides (SSPs) play critical roles in legume growth and development, yet the annotation of SSP-coding genes is far from complete. Systematic reannotation of the Medicago truncatula genome identified 1,970 homologs of established SSP gene families and an additional 2,455 genes that are potentially novel SSPs, previously unreported in the literature. The expression patterns of known and putative SSP genes based on 144 RNA sequencing data sets covering various stages of macronutrient deficiencies and symbiotic interactions with rhizobia and mycorrhiza were investigated. Focusing on those known or suspected to act via receptor-mediated signaling, 240 nutrient-responsive and 365 nodulation-responsive Signaling-SSPs were identified, greatly expanding the number of SSP gene families potentially involved in acclimation to nutrient deficiencies and nodulation. Synthetic peptide applications were shown to alter root growth and nodulation phenotypes, revealing additional regulators of legume nutrient acquisition. Our results constitute a powerful resource enabling further investigations of specific SSP functions via peptide treatment and reverse genetics. PMID:29030416

Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts.

PubMed

Jeffrey, A M; Blobstein, S H; Weinstein, I B; Beland, F A; Harvey, R G; Kasai, H; Nakanishi, K

1976-07-01

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established.

Deposits of Claiborne and Jackson age in Georgia

USGS Publications Warehouse

Cooke, Charles Wythe; Shearer, Harold Kurtz

1919-01-01

In 1911 the Geological Survey of Georgia published as Bulletin 26 a "Preliminary report on the geology of the Coastal Plain of Georgia," by Otto Veatch and Lloyd William Stephenson, prepared in cooperation with the United States Geological Survey under the supervision of T. Wayland Vaughan, a geologist in charge of Coastal Plain investigations, who contributed the determinations of the invertebrate fossils of the Tertiary and Quaternary formations. Although this report constituted a decided advance in our knowledge of the geology of the Coastal Plain of Georgia, it was admittedly of reconnaissance character, and corrections and additions to it were to be expected. During the last few years field work has been prosecuted vigorously in the Coastal Plain of Georgia, and the additional information thus accumulated throws light upon certain problems of stratigraphy left unsolved by Veatch and Stephenson and alters considerably some of their correlations. The object of the present paper is to present the new evidence regarding the age and correlation of the Eocene formations of Georgia and to revise in accordance with present knowledge the descriptions of the deposits of Claiborne and Jackson age.

Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation.

PubMed

Hitchins, Megan P

2016-07-01

Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma-wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. 'Primary' MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. 'Secondary' MLH1 epimutations have a genetic basis and have been linked to non-coding genetic alterations in the vicinity of MLH1. These demonstrate autosomal dominant inheritance. Despite convincing evidence of their role in causing Lynch-type cancers, routine screening for MLH1 epimutations has not been widely adopted. Complicating factors may include: the need to perform additional methylation-based testing beyond the standard genetic screening for a germline mutation; the lack of a consensus algorithm for the selection of patients warranting MLH1 epimutation testing; overlapping molecular pathology features of MLH1 methylation and loss of MLH1 expression with more prevalent sporadic MSI cancers; the rarity of MLH1 epimutation; the variable inter-generational inheritance patterns; and the cost-effectiveness of screening. Nevertheless, a positive molecular diagnosis of MLH1 epimutation is clinically important because carriers have a high personal risk of developing metachronous Lynch-type cancers, and their relatives may also be at risk of carriage. Extending existing universal and clinic-based screening algorithms for Lynch syndrome to include an additional arm of selection criteria for cases warranting MLH1 epimutation testing could provide a cost-effective means of diagnosing these cases.

Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology.

PubMed

Bidmon, H J; Emde, B; Kowalski, T; Schmitt, M; Mayer, B; Kato, K; Asayama, K; Witte, O W; Zilles, K

2001-09-01

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.

Properties of Streptococcus mutans Grown in a Synthetic Medium: Binding of Glucosyltransferase and In Vitro Adherence, and Binding of Dextran/Glucan and Glycoprotein and Agglutination

PubMed Central

Wu-Yuan, Christine D.; Tai, Stella; Slade, Hutton D.

1979-01-01

The influence of culture media on various properties of Streptococcus mutans was investigated. Strains of S. mutans (serotypes c, d, f, and g) were grown in a complex medium (Todd-Hewitt broth [THB]) or a synthetic medium (SYN). The SYN cells, in contrast to THB cells, did not bind extracellular glucosyltransferase and did not produce in vitro adherence. Both types of cells possessed constitutive levels of glucosyltransferase. B13 cells grown in SYN plus invertase-treated glucose possessed the same level of constitutive enzyme as THB cells. In contrast to THB cells, the SYN cells of seven serotype strains did not agglutinate upon the addition of high-molecular-weight dextran/glucan. Significant quantities of lower-molecular-weight (2 × 104 or 7 × 104) dextran and B13 glucan were bound by SYN cells. SYN cells agglutinated weakly in anti-glucan serum (titers, 0 to 16), whereas THB cells possessed titers of 32 to 256. Evidence for the existence of a second binding site in agglutination which does not possess a glucan-like polymer has been obtained. B13 cells grown in invertase-treated THB agglutinated to the same degree as normal THB cells. The nature of this site is unknown. SYN cells possess the type-specific polysaccharide antigen. B13 cells did not bind from THB a glycoprotein which reacts with antisera to the A, B, or T blood group antigens or which allows agglutination upon the addition of dextran. The results demonstrate that S. mutans grown in a chemically defined medium possesse markedly different biochemical and biological activities than cells grown in a complex organic medium. PMID:457252

Sasang Constitution as a Risk Factor for Diabetes Mellitus: A Cross-Sectional Study

PubMed Central

Lee, Tae-Gyu; Koh, Byunghee

2009-01-01

Sasang Constitutional Medicine, which is a branch of traditional Korean medicine, states that medications for diabetes should be individualized according to the patient's individual constitution. However, the effect of constitution on diabetes has not been evaluated to date. Therefore, this study was conducted to determine if constitution is an independent risk factor for diabetes by comparing the prevalence and odds ratios (ORs) of the disease according to constitution. The medical records of 1443 adults who had been examined and classified based on their constitution at Kyung Hee University Hospital in Seoul, Korea were reviewed. A chi-squared test and Fisher's exact test were used to compare the prevalence of diabetes according to constitution, and multiple logistic regression was used to calculate the ORs for diabetes. The prevalence of diabetes differed significantly according to constitution (χ2 = 36.20, df = 2, P < 0.001). Specifically, the prevalence of the disease was higher in Tae-eumin (11.4%) individuals than in Soyangin (5.0%) or Soeumin (1.7%) individuals. In addition, multiple logistic regression revealed that Tae-eumin individuals had a greater risk for diabetes than Soeumin individuals. When compared to Soeumin individuals, the adjusted ORs were 2.01 (95% CI 0.77–5.26) for Soyangin individuals and 3.96 (95% CI 1.48–10.60) for Tae-eumin individuals. These results show that constitution has a significant and independent association with diabetes, which suggests that constitution is an independent risk factor for diabetes that should be considered when attempting to detect and prevent the disease. PMID:19745018

Electromagnetic Energy Released in the Subduction (Benioff) Zone in Weeks Previous to Earthquake Occurrence in Central Peru and the Estimation of Earthquake Magnitudes.

NASA Astrophysics Data System (ADS)

Heraud, J. A.; Centa, V. A.; Bleier, T.

2017-12-01

During the past four years, magnetometers deployed in the Peruvian coast have been providing evidence that the ULF pulses received are indeed generated at the subduction or Benioff zone and are connected with the occurrence of earthquakes within a few kilometers of the source of such pulses. This evidence was presented at the AGU 2015 Fall meeting, showing the results of triangulation of pulses from two magnetometers located in the central area of Peru, using data collected during a two-year period. Additional work has been done and the method has now been expanded to provide the instantaneous energy released at the stress areas on the Benioff zone during the precursory stage, before an earthquake occurs. Collected data from several events and in other parts of the country will be shown in a sequential animated form that illustrates the way energy is released in the ULF part of the electromagnetic spectrum. The process has been extended in time and geographical places. Only pulses associated with the occurrence of earthquakes are taken into account in an area which is highly associated with subduction-zone seismic events and several pulse parameters have been used to estimate a function relating the magnitude of the earthquake with the value of a function generated with those parameters. The results shown, including the animated data video, constitute additional work towards the estimation of the magnitude of an earthquake about to occur, based on electromagnetic pulses that originated at the subduction zone. The method is providing clearer evidence that electromagnetic precursors in effect conveys physical and useful information prior to the advent of a seismic event

Handbook For Military Justice and Civil Law

DTIC Science & Technology

1996-02-01

cases, however, to an individual to identify himself is not an "interrogation," and production of the identification is not a "statement" within the...evidence obtained in violation of constitutional mandates will not be admissible in any later criminal prosecution. With this in mind, the most productive ...reasonable searches, and other command activities which, although permissible and productive of admissible evidence, are not actually true searches or

Laboratory Information Management Systems for Forensic Laboratories: A White Paper for Directors and Decision Makers

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

Anthony Hendrickson; Brian Mennecke; Kevin Scheibe

2005-10-01

Modern, forensics laboratories need Laboratory Information Management Systems (LIMS) implementations that allow the lab to track evidentiary items through their examination lifecycle and also serve all pertinent laboratory personnel. The research presented here presents LIMS core requirements as viewed by respondents serving in different forensic laboratory capacities as well as different forensic laboratory environments. A product-development methodology was employed to evaluate the relative value of the key features that constitute a LIMS, in order to develop a set of relative values for these features and the specifics of their implementation. In addition to the results of the product development analysis,more » this paper also provides an extensive review of LIMS and provides an overview of the preparation and planning process for the successful upgrade or implementation of a LIMS. Analysis of the data indicate that the relative value of LIMS components are viewed differently depending upon respondents' job roles (i.e., evidence technicians, scientists, and lab management), as well as by laboratory size. Specifically, the data show that: (1) Evidence technicians place the most value on chain of evidence capabilities and on chain of custody tracking; (2) Scientists generally place greatest value on report writing and generation, and on tracking daughter evidence that develops during their analyses; (3) Lab. Managers place the greatest value on chain of custody, daughter evidence, and not surprisingly, management reporting capabilities; and (4) Lab size affects LIMS preference in that, while all labs place daughter evidence tracking, chain of custody, and management and analyst report generation as their top three priorities, the order of this prioritization is size dependent.« less

Law and Politics, an Emerging Epidemic: A Call for Evidence-Based Public Health Law.

PubMed

Ulrich, Michael R

2016-05-01

As Jacobson v. Massachusetts recognized in 1905, the basis of public health law, and its ability to limit constitutional rights, is the use of scientific data and empirical evidence. Far too often, this important fact is lost. Fear, misinformation, and politics frequently take center stage and drive the implementation of public health law. In the recent Ebola scare, political leaders passed unnecessary and unconstitutional quarantine measures that defied scientific understanding of the disease and caused many to have their rights needlessly constrained. Looking at HIV criminalization and exemptions to childhood vaccine requirements, it becomes clear that the blame cannot be placed on the hysteria that accompanies emergencies. Indeed, these examples merely illustrate an unfortunate array of examples where empirical evidence is ignored in the hopes of quelling paranoia. These policy approaches are not only constitutionally questionable, they generate their own risk to public health. The ability of the law to jeopardize public health approaches to infectious disease control can, and should, be limited through a renewed emphasis on science as the foundation of public health, coordination through all levels and branches of government, and through a serious commitment by the judiciary to provide oversight. Infectious disease creates public anxiety, but this cannot justify unwarranted dogmatic approaches as a response. If we as a society hope to ensure efficient, constitutional control over the spread of disease, it is imperative that science take its rightful place at the forefront of governmental decision-making and judicial review. Otherwise, the law becomes its own public health threat.

A constitutive model for the mechanical characterization of the plantar fascia.

PubMed

Natali, Arturo N; Pavan, Piero G; Stecco, Carla

2010-10-01

A constitutive model is proposed to describe the mechanical behavior of the plantar fascia. The mechanical characterization of the plantar fascia regards the role in the foot biomechanics and it is involved in many alterations of its functional behavior, both of mechanical and nonmechanical origin. The structural conformation of the plantar fascia in its middle part is characterized by the presence of collagen fibers reinforcing the tissue along a preferential orientation, which is that supporting the major loading. According to this anatomical evidence, the tissue is described by developing an isotropic fiber-reinforced constitutive model and since the elastic response of the fascia is here considered, the constitutive model is based on the theory of hyperelasticity. The model is consistent with a kinematical description of large strains mechanical behavior, which is typical of soft tissues. A fitting procedure of the constitutive model is implemented making use of experimental curves taken from the literature and referring to specimens of human plantar fascia. A satisfactory fitting of the tensile behavior of the plantar fascia has been performed, showing that the model correctly interprets the mechanical behavior of the tissue in the light of comparison to experimental data at disposal. A critical analysis of the model with respect to the problem of the identification of the constitutive parameters is proposed as the basis for planning a future experimental investigation of mechanical behavior of the plantar fascia.

Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release.

PubMed

Spahl, Daniela U; Berendji-Grün, Denise; Suschek, Christoph V; Kolb-Bachofen, Victoria; Kröncke, Klaus-D

2003-11-25

Zn2+ is critical for the functional and structural integrity of cells and contributes to a number of important processes including gene expression. It has been shown that NO exogenously applied via NO donors resulting in nitrosative stress leads to cytoplasmic Zn2+ release from the zinc storing protein metallothionein (MT) and probably other proteins that complex Zn2+ via cysteine thiols. We show here that, in cytokine-activated murine aortic endothelial cells, NO derived from the inducible NO synthase (iNOS) induces a transient nuclear release of Zn2+. This nuclear Zn2+ release depends on the presence of MT as shown by the lack of this effect in activated endothelial cells from MT-deficient mice and temporally correlates with nuclear MT translocation. Data also show that NO is an essential but not sufficient signal for MT-mediated Zn2+ trafficking from the cytoplasm into the nucleus. In addition, we found that, endogenously via iNOS, synthesized NO increases the constitutive mRNA expression of both MT-1 and MT-2 genes and that nitrosative stress exogenously applied via an NO donor increases constitutive MT mRNA expression via intracellular Zn2+ release. In conclusion, we here provide evidence for a signaling mechanism based on iNOS-derived NO through the regulation of intracellular Zn2+ trafficking and homeostasis.

Regulation of zinc homeostasis by inducible NO synthase-derived NO: Nuclear metallothionein translocation and intranuclear Zn2+ release

PubMed Central

Spahl, Daniela U.; Berendji-Grün, Denise; Suschek, Christoph V.; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.

2003-01-01

Zn2+ is critical for the functional and structural integrity of cells and contributes to a number of important processes including gene expression. It has been shown that NO exogenously applied via NO donors resulting in nitrosative stress leads to cytoplasmic Zn2+ release from the zinc storing protein metallothionein (MT) and probably other proteins that complex Zn2+ via cysteine thiols. We show here that, in cytokine-activated murine aortic endothelial cells, NO derived from the inducible NO synthase (iNOS) induces a transient nuclear release of Zn2+. This nuclear Zn2+ release depends on the presence of MT as shown by the lack of this effect in activated endothelial cells from MT-deficient mice and temporally correlates with nuclear MT translocation. Data also show that NO is an essential but not sufficient signal for MT-mediated Zn2+ trafficking from the cytoplasm into the nucleus. In addition, we found that, endogenously via iNOS, synthesized NO increases the constitutive mRNA expression of both MT-1 and MT-2 genes and that nitrosative stress exogenously applied via an NO donor increases constitutive MT mRNA expression via intracellular Zn2+ release. In conclusion, we here provide evidence for a signaling mechanism based on iNOS-derived NO through the regulation of intracellular Zn2+ trafficking and homeostasis. PMID:14617770

Bim, a Proapoptotic Protein, Up-regulated via Transcription Factor E2F1-dependent Mechanism, Functions as a Prosurvival Molecule in Cancer*

PubMed Central

Gogada, Raghu; Yadav, Neelu; Liu, Junwei; Tang, Shaohua; Zhang, Dianmu; Schneider, Andrea; Seshadri, Athul; Sun, Leimin; Aldaz, C. Marcelo; Tang, Dean G.; Chandra, Dhyan

2013-01-01

Proapoptotic Bcl-2 homology 3-only protein Bim plays an important role in Bax/Bak-mediated cytochrome c release and apoptosis. Here, we provide evidence for a novel prosurvival function of Bim in cancer cells. Bim was constitutively overexpressed in multiple prostate and breast cancer cells as well as in primary tumor cells. Quantitative real time PCR analysis showed that Bim was transcriptionally up-regulated. We have identified eight endogenous E2F1-binding sites on the Bim promoter using in silico analysis. Luciferase assay demonstrated that Bim expression was E2F1-dependent as mutation of the E2F1-binding sites on the Bim promoter inhibited luciferase activities. In support, E2F1 silencing led to the loss of Bim expression in cancer cells. Bim primarily localized to mitochondrial and cytoskeleton-associated fractions. Bim silencing or microinjection of anti-Bim antibodies into the cell cytoplasm resulted in cell rounding, detachment, and subsequent apoptosis. We observed up-regulation of prosurvival proteins Bcl-xL and Mcl-1, which sequester Bim in cancer cells. In addition, a phosphorylated form of Bim was also elevated in cancer cells. These findings suggest that the constitutively overexpressed Bim may function as a prosurvival molecule in epithelial cancer cells, and phosphorylation and association with Bcl-xL/Mcl-1 block its proapoptotic functions. PMID:23152504

Multifaceted Intervention by the Hsp90 Inhibitor Ganetespib (STA-9090) in Cancer Cells with Activated JAK/STAT Signaling

PubMed Central

Proia, David A.; Foley, Kevin P.; Korbut, Tim; Sang, Jim; Smith, Don; Bates, Richard C.; Liu, Yuan; Rosenberg, Alex F.; Zhou, Dan; Koya, Keizo; Barsoum, James; Blackman, Ronald K.

2011-01-01

There is accumulating evidence that dysregulated JAK signaling occurs in a wide variety of cancer types. In particular, mutations in JAK2 can result in the constitutive activation of STAT transcription factors and lead to oncogenic growth. JAK kinases are established Hsp90 client proteins and here we show that the novel small molecule Hsp90 inhibitor ganetespib (formerly STA-9090) exhibits potent in vitro and in vivo activity in a range of solid and hematological tumor cells that are dependent on JAK2 activity for growth and survival. Of note, ganetespib treatment results in sustained depletion of JAK2, including the constitutively active JAK2V617F mutant, with subsequent loss of STAT activity and reduced STAT-target gene expression. In contrast, treatment with the pan-JAK inhibitor P6 results in only transient effects on these processes. Further differentiating these modes of intervention, RNA and protein expression studies show that ganetespib additionally modulates cell cycle regulatory proteins, while P6 does not. The concomitant impact of ganetespib on both cell growth and cell division signaling translates to potent antitumor efficacy in mouse models of xenografts and disseminated JAK/STAT-driven leukemia. Overall, our findings support Hsp90 inhibition as a novel therapeutic approach for combating diseases dependent on JAK/STAT signaling, with the multimodal action of ganetespib demonstrating advantages over JAK-specific inhibitors. PMID:21533169

Persistence of evolutionary memory: primordial six-transmembrane helical domain mu opiate receptors selectively linked to endogenous morphine signaling.

PubMed

Kream, Richard M; Sheehan, Melinda; Cadet, Patrick; Mantione, Kirk J; Zhu, Wei; Casares, Federico; Stefano, George B

2007-12-01

Biochemical, molecular and pharmacological evidence for two unique six-transmembrane helical (TMH) domain opiate receptors expressed from the micro opioid receptor (MOR) gene have been shown. Designated micro3 and micro4 receptors, both protein species are Class A rhodopsin-like members of the superfamily of G-protein coupled receptors but are selectively tailored to mediate the cellular regulatory effects of endogenous morphine and related morphinan alkaloids via stimulation of nitric oxide (NO) production and release. Both micro3 and micro4 receptors lack an amino acid sequence of approximately 90 amino acids that constitute the extracellular N-terminal and TMH1 domains and part of the first intracellular loop of the micro1 receptor, but retain the empirically defined ligand binding pocket distributed across conserved TMH2, TMH3, and TMH7 domains of the micro1 sequence. Additionally, the receptor proteins are terminated by unique intracellular C-terminal amino acid sequences that serve as putative coupling or docking domains required for constitutive NO synthase activation. Because the recognition profile of micro3 and micro4 receptors is restricted to rigid benzylisoquinoline alkaloids typified by morphine and its extended family of chemical congeners, it is hypothesized that conformational stabilization provided by interaction of extended extracellular N-terminal protein domains and the extracellular loops is required for binding of endogenous opioid peptides as well as synthetic flexible opiate alkaloids.

Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

PubMed

Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

2014-06-01

G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

Relationships between source, chemistry and health effects

EPA Science Inventory

Air pollution has long been associated with detrimental health risks in susceptible populations. Experimental evidence in rodents indicates that inhaled or instilled air pollutants such as diesel exhaust particles, residual oil fly ash or its constitutive metals, and ambient PM f...

Adaptive Practice: Next Generation Evidence-Based Practice in Digital Environments.

PubMed

Kennedy, Margaret Ann

2016-01-01

Evidence-based practice in nursing is considered foundational to safe, competent care. To date, rigid traditional perceptions of what constitutes 'evidence' have constrained the recognition and use of practice-based evidence and the exploitation of novel forms of evidence from data rich environments. Advancements such as the conceptualization of clinical intelligence, the prevalence of increasingly sophisticated digital health information systems, and the advancement of the Big Data phenomenon have converged to generate a new contemporary context. In today's dynamic data-rich environments, clinicians have new sources of valid evidence, and need a new paradigm supporting clinical practice that is adaptive to information generated by diverse electronic sources. This opinion paper presents adaptive practice as the next generation of evidence-based practice in contemporary evidence-rich environments and provides recommendations for the next phase of evolution.

Relationship between iris constitution analysis and TNF-alpha gene polymorphism in hypertensives.

PubMed

Yoo, Chun-Sang; Hwang, Woo-Jun; Hong, Seung-Heon; Lee, Hye-Jung; Jeong, Hyun-Ja; Kim, Su-Jin; Kim, Hyung-Min; Um, Jae-Young

2007-01-01

Iridology is a complementary and alternative medicine that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong hereditary component. Tumor necrosis factor-alpha (TNFalpha), a pleiotropic cytokine, has been implicated in many pathological processes including hypertension. In this paper, the relationship between iris constitution and TNFalpha gene polymorphism in those with hypertension is investigated. Eighty seven hypertensive individuals and 79 controls were classified according to iris constitution and the TNFalpha genotype of each individual determined. Compared to the controls, the frequency of the TNFalpha GA heterozygote was lower in the hypertensive group, although the statistical significance was marginal (p = 0.08). This result implies an association with resistance to the disease. In addition, the frequency of the cardio-renal connective tissue weakness type was significantly higher in the hypertensive group with the TNFalpha GG genotype, as compared to the controls (p = 0.001). An association is demonstrated among TNFalpha gene polymorphism, Koreans with hypertension, and iris constitution.

Recent Trends in Coverage of the Mexican-Born Population of the United States: Results From Applying Multiple Methods Across Time

PubMed Central

Van Hook, Jennifer; Bean, Frank D.; Bachmeier, James D.; Tucker, Catherine

2014-01-01

The accuracy of counts of U.S. racial/ethnic and immigrant groups depends on coverage of the foreign-born in official data. Because Mexicans constitute by far the largest single national-origin group among the foreign-born in the United States, we compile new evidence about the coverage of the Mexican-born population in the 2000 census and 2001–2010 American Community Survey (ACS) using three techniques: a death registration, a birth registration, and a net migration method. For the late 1990s and first half of the 2000–2010 decade, results indicate that coverage error was somewhat higher than currently assumed but substantially declined by the latter half of the 2000–2010 decade. Additionally, we find evidence that U.S. census and ACS data miss substantial numbers of children of Mexican immigrants, as well as people who are most likely to be unauthorized: namely, working-aged Mexican immigrants (ages 15–64), especially males. The findings highlight the heterogeneity of the Mexican foreign-born population and the ways in which migration dynamics may affect population coverage. PMID:24570373

Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning.

PubMed

McDougle, Samuel D; Bond, Krista M; Taylor, Jordan A

2015-07-01

A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. Copyright © 2015 the authors 0270-6474/15/359568-12$15.00/0.

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling

PubMed Central

Phillips, Cristy; Baktir, Mehmet Akif; Srivatsan, Malathi; Salehi, Ahmad

2014-01-01

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations. PMID:24999318

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

PubMed

Phillips, Cristy; Baktir, Mehmet Akif; Srivatsan, Malathi; Salehi, Ahmad

2014-01-01

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning

PubMed Central

Bond, Krista M.; Taylor, Jordan A.

2015-01-01

A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. PMID:26134640

The potential of legislation on organ donation to increase the supply of donor organs.

PubMed

Coppen, Remco; Friele, Roland D; van der Zee, Jouke; Gevers, Sjef K

2010-12-01

The aim of this paper is to assess the possibilities to adapt the 1998 Dutch Organ Donation Act, taking account of fundamental principles such as the right to physical integrity, equitable access to and equal availability of care, and the non-commerciality principle, with a view to increasing the organ supply. In 2008 the Dutch Taskforce on Organ Donation presented several proposals to amend the Act and to increase the supply of organs. This paper describes the proposals to amend the Act and evaluates them by assessing their intrinsic adherence to basic principles and the available evidence that these proposals will indeed increase the organ supply. Several proposals could constitute an infringement of fundamental principles of the Act. Moreover, evidence for their impact on the organ supply is lacking. Changing the consent system is possible, as this would not incur legal objections. There are diverging views regarding the impact of consent systems on the organ supply. The scope for changing the Act and its impact on organ procurement is at best limited. Relying on legislation alone will possibly not bring much relief, whereas additional policy measures may be more successful. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Epilepsy, Cognition, and Behavior: The clinical picture

PubMed Central

Berg, Anne T.

2010-01-01

Although epilepsy is defined by the occurrence of spontaneous epileptic seizures, a large body of evidence indicates that epilepsy is linked to a spectrum behavioral, psychiatric, and cognitive disorders as well as to sudden death. Explanations for these associations include: (1) The effects of structural lesions which may impair the functions subserved by the regions of the brain involved in the lesion. (2) The effects of seizure activity which may begin well before a clinical seizure occurs and may persist long after it is over raising questions about what truly constitutes “interictal.” In addition, encephalopathic effects of epilepsy in infancy during critical periods in development may be particularly severe and potentially irreversible. (3) Shared mechanisms underlying seizures as well as these other disorders in the absence of structural lesions or separate diseases of the CNS. Epidemiological and clinical studies demonstrate the elevated risk of cognitive, psychiatric, and behavioral disorders not just during but also prior to the onset of epilepsy (seizures) itself. These may outlast the active phase of epilepsy as well. The mounting evidence argues strongly for the recognition of epilepsy as part of a spectrum of disorders and against the notion that even uncomplicated epilepsy can a priori be considered benign. PMID:21214534

Tagging the neuronal entrainment to beat and meter.

PubMed

Nozaradan, Sylvie; Peretz, Isabelle; Missal, Marcus; Mouraux, André

2011-07-13

Feeling the beat and meter is fundamental to the experience of music. However, how these periodicities are represented in the brain remains largely unknown. Here, we test whether this function emerges from the entrainment of neurons resonating to the beat and meter. We recorded the electroencephalogram while participants listened to a musical beat and imagined a binary or a ternary meter on this beat (i.e., a march or a waltz). We found that the beat elicits a sustained periodic EEG response tuned to the beat frequency. Most importantly, we found that meter imagery elicits an additional frequency tuned to the corresponding metric interpretation of this beat. These results provide compelling evidence that neural entrainment to beat and meter can be captured directly in the electroencephalogram. More generally, our results suggest that music constitutes a unique context to explore entrainment phenomena in dynamic cognitive processing at the level of neural networks.

Colour variation in cichlid fish: Developmental mechanisms, selective pressures and evolutionary consequences☆

PubMed Central

Maan, Martine E.; Sefc, Kristina M.

2013-01-01

Cichlid fishes constitute one of the most species-rich families of vertebrates. In addition to complex social behaviour and morphological versatility, they are characterised by extensive diversity in colouration, both within and between species. Here, we review the cellular and molecular mechanisms underlying colour variation in this group and the selective pressures responsible for the observed variation. We specifically address the evidence for the hypothesis that divergence in colouration is associated with the evolution of reproductive isolation between lineages. While we conclude that cichlid colours are excellent models for understanding the role of animal communication in species divergence, we also identify taxonomic and methodological biases in the current research effort. We suggest that the integration of genomic approaches with ecological and behavioural studies, across the entire cichlid family and beyond it, will contribute to the utility of the cichlid model system for understanding the evolution of biological diversity. PMID:23665150

Getting More Out of Less – A Quantitative Serological Screening Tool for Simultaneous Detection of Multiple Influenza A Hemagglutinin-Types in Chickens

PubMed Central

Freidl, Gudrun S.; de Bruin, Erwin; van Beek, Janko; Reimerink, Johan; de Wit, Sjaak; Koch, Guus; Vervelde, Lonneke; van den Ham, Henk-Jan; Koopmans, Marion P. G.

2014-01-01

Current avian influenza surveillance in poultry primarily targets subtypes of interest for the veterinary sector (H5, H7). However, as virological and serological evidence suggest, surveillance of additional subtypes is important for public health as well as for the poultry industry. Therefore, we developed a protein microarray enabling simultaneous identification of antibodies directed against different HA-types of influenza A viruses in chickens. The assay successfully discriminated negative from experimentally and naturally infected, seropositive chickens. Sensitivity and specificity depended on the cut-off level used but ranged from 84.4% to 100% and 100%, respectively, for a cut off level of ≥1∶40, showing minimal cross reactivity. As this testing platform is also validated for the use in humans, it constitutes a surveillance tool that can be applied in human-animal interface studies. PMID:25248105

Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment

NASA Astrophysics Data System (ADS)

An, F. P.; Balantekin, A. B.; Band, H. R.; Bishai, M.; Blyth, S.; Cao, D.; Cao, G. F.; Cao, J.; Cen, W. R.; Chan, Y. L.; Chang, J. F.; Chang, L. C.; Chang, Y.; Chen, H. S.; Chen, Q. Y.; Chen, S. M.; Chen, Y. X.; Chen, Y.; Cheng, J.-H.; Cheng, J.; Cheng, Y. P.; Cheng, Z. K.; Cherwinka, J. J.; Chu, M. C.; Chukanov, A.; Cummings, J. P.; de Arcos, J.; Deng, Z. Y.; Ding, X. F.; Ding, Y. Y.; Diwan, M. V.; Dolgareva, M.; Dove, J.; Dwyer, D. A.; Edwards, W. R.; Gill, R.; Gonchar, M.; Gong, G. H.; Gong, H.; Grassi, M.; Gu, W. Q.; Guan, M. Y.; Guo, L.; Guo, R. P.; Guo, X. H.; Guo, Z.; Hackenburg, R. W.; Han, R.; Hans, S.; He, M.; Heeger, K. M.; Heng, Y. K.; Higuera, A.; Hor, Y. K.; Hsiung, Y. B.; Hu, B. Z.; Hu, T.; Hu, W.; Huang, E. C.; Huang, H. X.; Huang, X. T.; Huber, P.; Huo, W.; Hussain, G.; Jaffe, D. E.; Jaffke, P.; Jen, K. L.; Jetter, S.; Ji, X. P.; Ji, X. L.; Jiao, J. B.; Johnson, R. A.; Joshi, J.; Kang, L.; Kettell, S. H.; Kohn, S.; Kramer, M.; Kwan, K. K.; Kwok, M. W.; Kwok, T.; Langford, T. J.; Lau, K.; Lebanowski, L.; Lee, J.; Lee, J. H. C.; Lei, R. T.; Leitner, R.; Leung, J. K. C.; Li, C.; Li, D. J.; Li, F.; Li, G. S.; Li, Q. J.; Li, S.; Li, S. C.; Li, W. D.; Li, X. N.; Li, Y. F.; Li, Z. B.; Liang, H.; Lin, C. J.; Lin, G. L.; Lin, S.; Lin, S. K.; Lin, Y.-C.; Ling, J. J.; Link, J. M.; Littenberg, L.; Littlejohn, B. R.; Liu, D. W.; Liu, J. L.; Liu, J. C.; Loh, C. W.; Lu, C.; Lu, H. Q.; Lu, J. S.; Luk, K. B.; Lv, Z.; Ma, Q. M.; Ma, X. Y.; Ma, X. B.; Ma, Y. Q.; Malyshkin, Y.; Martinez Caicedo, D. A.; McDonald, K. T.; McKeown, R. D.; Mitchell, I.; Mooney, M.; Nakajima, Y.; Napolitano, J.; Naumov, D.; Naumova, E.; Ngai, H. Y.; Ning, Z.; Ochoa-Ricoux, J. P.; Olshevskiy, A.; Pan, H.-R.; Park, J.; Patton, S.; Pec, V.; Peng, J. C.; Pinsky, L.; Pun, C. S. J.; Qi, F. Z.; Qi, M.; Qian, X.; Raper, N.; Ren, J.; Rosero, R.; Roskovec, B.; Ruan, X. C.; Steiner, H.; Sun, G. X.; Sun, J. L.; Tang, W.; Taychenachev, D.; Treskov, K.; Tsang, K. V.; Tull, C. E.; Viaux, N.; Viren, B.; Vorobel, V.; Wang, C. H.; Wang, M.; Wang, N. Y.; Wang, R. G.; Wang, W.; Wang, X.; Wang, Y. F.; Wang, Z.; Wang, Z.; Wang, Z. M.; Wei, H. Y.; Wen, L. J.; Whisnant, K.; White, C. G.; Whitehead, L.; Wise, T.; Wong, H. L. H.; Wong, S. C. F.; Worcester, E.; Wu, C.-H.; Wu, Q.; Wu, W. J.; Xia, D. M.; Xia, J. K.; Xing, Z. Z.; Xu, J. Y.; Xu, J. L.; Xu, Y.; Xue, T.; Yang, C. G.; Yang, H.; Yang, L.; Yang, M. S.; Yang, M. T.; Ye, M.; Ye, Z.; Yeh, M.; Young, B. L.; Yu, Z. Y.; Zeng, S.; Zhan, L.; Zhang, C.; Zhang, H. H.; Zhang, J. W.; Zhang, Q. M.; Zhang, X. T.; Zhang, Y. M.; Zhang, Y. X.; Zhang, Y. M.; Zhang, Z. J.; Zhang, Z. Y.; Zhang, Z. P.; Zhao, J.; Zhao, Q. W.; Zhao, Y. B.; Zhong, W. L.; Zhou, L.; Zhou, N.; Zhuang, H. L.; Zou, J. H.; Daya Bay Collaboration

2016-10-01

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2 ×10-4≲|Δ m412|≲0.3 eV2 mass range. The resulting limits on sin22 θ14 are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δ m412|≲0.2 eV2 region.

Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts.

PubMed

Bosco, Joseph; Bookman, Jared; Slover, James; Edusei, Emmanuel; Levine, Brett

2016-01-01

Infection is a rare, serious complication after total joint arthroplasty and constitutes a considerable emotional and financial burden for patients, surgeons, and healthcare systems. Prevention of surgical site and periprosthetic joint infections is crucial. This requires knowledge of the microorganisms that commonly cause these infections, including Staphylococcus species. Selection of the appropriate antibiotic regimen to treat infection remains controversial, but cefazolin and cefuroxime are the most commonly recommended antibiotics for prophylaxis. Appropriate timing of administration before surgery, with redosing performed as needed, can help to ensure optimal antibiotic concentration during surgery. Given the increasing evidence that S aureus colonization is a risk factor for periprosthetic joint infection, an exploration of the potential benefits of preoperative S aureus carrier screening and decolonization protocols is warranted. The use of antibiotic-loaded bone cement in primary total joint arthroplasty and antibiotic powder at wound closure are other controversial topics that require additional research.

Boundary conditions for the Middle Miocene Climate Transition (MMCT v1.0)

NASA Astrophysics Data System (ADS)

Frigola, Amanda; Prange, Matthias; Schulz, Michael

2018-04-01

The Middle Miocene Climate Transition was characterized by major Antarctic ice sheet expansion and global cooling during the interval ˜ 15-13 Ma. Here we present two sets of boundary conditions for global general circulation models characterizing the periods before (Middle Miocene Climatic Optimum; MMCO) and after (Middle Miocene Glaciation; MMG) the transition. These boundary conditions include Middle Miocene global topography, bathymetry, and vegetation. Additionally, Antarctic ice volume and geometry, sea level, and atmospheric CO2 concentration estimates for the MMCO and the MMG are reviewed. The MMCO and MMG boundary conditions have been successfully applied to the Community Climate System Model version 3 (CCSM3) to provide evidence of their suitability for global climate modeling. The boundary-condition files are available for use as input in a wide variety of global climate models and constitute a valuable tool for modeling studies with a focus on the Middle Miocene.

Understanding Engineers' Responsibilities: A Prerequisite to Designing Engineering Education : Commentary on "Educating Engineers for the Public Good Through International Internships: Evidence from a Case Study at Universitat Politècnica de València".

PubMed

Murphy, Colleen; Gardoni, Paolo

2017-07-18

The development of the curriculum for engineering education (course requirements as well as extra-curricular activities like study abroad and internships) should be based on a comprehensive understanding of engineers' responsibilities. The responsibilities that are constitutive of being an engineer include striving to fulfill the standards of excellence set by technical codes; to improve the idealized models that engineers use to predict, for example, the behavior of alternative designs; and to achieve the internal goods such as safety and sustainability as they are reflected in the design codes. Globalization has implications for these responsibilities and, in turn, for engineering education, by, for example, modifying the collection of possible solutions recognized for existing problems. In addition, international internships can play an important role in fostering the requisite moral imagination of engineering students.

Development of BEM for ceramic composites

NASA Technical Reports Server (NTRS)

Henry, D. P.; Banerjee, P. K.; Dargush, G. F.

1991-01-01

It is evident that for proper micromechanical analysis of ceramic composites, one needs to use a numerical method that is capable of idealizing the individual fibers or individual bundles of fibers embedded within a three-dimensional ceramic matrix. The analysis must be able to account for high stress or temperature gradients from diffusion of stress or temperature from the fiber to the ceramic matrix and allow for interaction between the fibers through the ceramic matrix. The analysis must be sophisticated enough to deal with the failure of fibers described by a series of increasingly sophisticated constitutive models. Finally, the analysis must deal with micromechanical modeling of the composite under nonlinear thermal and dynamic loading. This report details progress made towards the development of a boundary element code designed for the micromechanical studies of an advanced ceramic composite. Additional effort has been made in generalizing the implementation to allow the program to be applicable to real problems in the aerospace industry.

Proposed in situ secondary ion mass spectrometry on Mars.

PubMed

Inglebert, R L; Klossa, B; Lorin, J C; Thomas, R

1995-01-01

Secondary ion mass spectrometry is a powerful analytical tool, which has the potentiality, through molecular ion emission, of detecting minor phases, as well as the unique capability of directly measuring isotope abundances in mineral or organic phases without any prior physical, chemical or thermal processing. Applied to the in situ analysis of the Martian regolith, it can provide evidence of the presence of carbonates and, by inference (if carbonates constitute significant deposits), of past liquid water--a necessary condition for the development of life. In addition, oxygen isotopic composition of carbonates preserves a record of the temperature at which this phase precipitated and may therefore help decipher the past climatology of Mars. Detection of a carbon isotopic composition shift between carbonates and organic matter (on Earth, the result of a kinetic fractionation effect during photosynthesis) would provide a definite clue regarding the existence of a past biochemical activity on Mars.

How Cryptococcus interacts with the blood-brain barrier.

PubMed

Tseng, Hsiang-Kuang; Huang, Tseng-Yu; Wu, Alice Ying-Jung; Chen, Hsin-Hong; Liu, Chang-Pan; Jong, Ambrose

2015-01-01

Cryptococcus demonstrates predilection for invasion of the brain, but the mechanism by which Cryptococcus crosses the blood-brain barrier (BBB) to cause brain invasion is largely unknown. In order for Cryptococcus to cross the BBB, there must be a way to either cross human brain microvascular endothelial cells, which are the main constitute of the BBB, or go in between tight junctions. Recent evidence of human brain microvascular endothelial cell responses to transcellular brain invasions includes membrane rearrangements, intracellular signaling pathways and cytoskeletal activations. Several Cryptococcal genes related to the traversal of BBB have been identified, including CPS1, ITR1a, ITR3c, PLB1, MPR1, FNX1 and RUB1. In addition, Cryptococcus neoformans-derived microvesicles may contribute to cryptococcal brain invasion. Paracellularly, Cryptococcus may traverse across BBB using either routes utilizing plasmin, ammonia or macrophages in a Trojan horse mechanism.

New insights on stromules: stroma filled tubules extended by independent plastids.

PubMed

Schattat, Martin H; Klösgen, Ralf Bernd; Mathur, Jaideep

2012-09-01

The recognition of stromules as sporadically extended stroma filled tubules from all kinds of plastids constitutes one of the major insights that resulted from the direct application of green fluorescent protein aided imaging of living plant cells. Observations of dynamic green fluorescent stromules strongly suggested that plastids frequently interact with each other while photo-bleaching of interconnected plastids indicated that proteins can move within the stroma filled tubules. These observations readily fit into the prevailing concept of the endosymbiogenic origins of plastids and provided stromules the status of conduits for inter-plastid communication and macromolecule transfer. However, experimental evidence obtained recently through the use of photoconvertible protein labeled stromules strongly supports plastid independence rather than their interconnectivity. Additional information on stress conditions inducing stromules and observations on their alignment with other organelles suggests that the major role of stromules is to increase the interactive surface of a plastid with the rest of the cytoplasm.

Estimation of True Change with Three-Wave Data.

ERIC Educational Resources Information Center

Gupta, J. K.; And Others

1988-01-01

A multiple regression model for estimating true change of an individual by using information in addition to pretest-posttest data is described. Longitudinal panel or multi-wave data taken between the pretest and the posttest constitute the additional information. (TJH)

26 CFR 1.274-5A - Substantiation requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Any activity which is of a type generally considered to constitute entertainment, amusement, or... the evidence indicated a taxpayer incurred deductible travel or entertainment expense but the exact... section, the term entertainment means entertainment, amusement, or recreation, and use of a facility...

26 CFR 1.274-5A - Substantiation requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Any activity which is of a type generally considered to constitute entertainment, amusement, or... the evidence indicated a taxpayer incurred deductible travel or entertainment expense but the exact... section, the term entertainment means entertainment, amusement, or recreation, and use of a facility...

26 CFR 1.274-5A - Substantiation requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Any activity which is of a type generally considered to constitute entertainment, amusement, or... the evidence indicated a taxpayer incurred deductible travel or entertainment expense but the exact... section, the term entertainment means entertainment, amusement, or recreation, and use of a facility...

31 CFR 515.543 - Proof of origin.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of goods of Cuban origin are generally not issued unless the applicant submits satisfactory... constitute satisfactory proof varies depending upon the facts of the particular case, it is not possible to... satisfactory proof of origin. Independent corroborating documentary evidence, such as insurance documents...

[Perspectives of an existential interdisciplinary body theory].

PubMed

Kühn, R

1990-01-01

The existence analytical inquiry has developed corporal models that admit in their integrative-anthropological form fertile comparisons with a phenomenological radical immanence-philosophy of the constitution. The "body as partner" (W. Blankenburg) and the not objectivitical measurable connection of the "figure- and functionbody" contain estimates, to understand the body as living "I can" (Maine de Biran; Husserl) that means as really final subjectivity, ipseity or "soul", like the french phenomenologist Michel Henry from the creature of the not secularized affectivity has analyzed. With that the remained rests of the still from world categories imaginaried connection get powered (transcendence, sensuousness, settlement by Heidegger, Merleau-Ponty, Schütz for example) to conceive the body as not inferable absolute origin being. Seen interdisciplinary there from results a new foundation for an evidence as constitution-comprehension, that can psychological like therapeutical the pathogenous for instance theoretical world/constitution/soul-distortions help over-power.

Constitutional Epi/Genetic Conditions: Genetic, Epigenetic, and Environmental Factors

PubMed Central

Schenkel, Laila C.; Rodenhiser, David; Siu, Victoria; McCready, Elizabeth; Ainsworth, Peter; Sadikovic, Bekim

2016-01-01

There are more than 4,000 phenotypes for which the molecular basis is at least partly known. Though defects in primary DNA structure constitute a major cause of these disorders, epigenetic disruption is emerging as an important alternative mechanism in the etiology of a broad range of congenital and developmental conditions. These include epigenetic defects caused by either localized (in cis) genetic alterations or more distant (in trans) genetic events but can also include environmental effects. Emerging evidence suggests interplay between genetic and environmental factors in the epigenetic etiology of several constitutional “epi/genetic” conditions. This review summarizes our broadening understanding of how epigenetics contributes to pediatric disease by exploring different classes of epigenomic disorders. It further challenges the simplistic dogma of “DNA encodes RNA encodes protein” to best understand the spectrum of factors that can influence genetic traits in a pediatric population. PMID:28180025

A constitutive theory of reacting electrolyte mixtures

NASA Astrophysics Data System (ADS)

Costa Reis, Martina; Wang, Yongqi; Bono Maurizio Sacchi Bassi, Adalberto

2013-11-01

A constitutive theory of reacting electrolyte mixtures is formulated. The intermolecular interactions among the constituents of the mixture are accounted for through additional freedom degrees to each constituent of the mixture. Balance equations for polar reacting continuum mixtures are accordingly formulated and a proper set of constitutive equations is derived with basis in the Müller-Liu formulation of the second law of thermodynamics. Moreover, the non-equilibrium and equilibrium responses of the reacting mixture are investigated in detail by emphasizing the inner and reactive structures of the medium. From the balance laws and constitutive relations, the effects of molecular structure of constituents upon the fluid flow are studied. It is also demonstrated that the local thermodynamic equilibrium state can be reached without imposing that the set of independent constitutive variables is time independent, neither spatially homogeneous nor null. The resulting constitutive relations presented throughout this work are of relevance to many practical applications, such as swelling of clays, developing of bio and polymeric membranes, and use of electrorheological fluids in industrial processes. The first author acknowledges financial support from National Counsel of Technological and Scientific Development (CNPq) and German Academic Exchange Service (DAAD).

Global Survey of National Constitutions: Mapping Constitutional Commitments to Sexual and Reproductive Health and Rights.

PubMed

Pizzarossa, Lucía Berro; Perehudoff, Katrina

2017-12-01

General Comment No. 22, issued in 2016 by the Committee on Economic, Social and Cultural Rights (CESCR), clarifies states' legal duties to respect, protect, and fulfill the right to sexual and reproductive health (SRH). Our study analyzes domestic constitutions around the world to investigate whether and to what extent the right to sexual and reproductive health is respected, protected, and fulfilled; to what extent these provisions are inclusive and non-discriminatory; and to what degree the interlinkages between this and other human rights are acknowledged. Of the 195 constitutions accessed, 27 enshrine sexual and/or reproductive health, and seven adopt restrictive approaches to this right. In the 27 constitutions, provisions most frequently enshrine respect of one's sexual health and family planning decisions, the protection of sexual health, and the provision of reproductive health care and family planning services (fulfillment). Most of the 27 constitutions fail to adequately respect reproductive health rights; to protect reproductive health, family planning, and abortion services from third-party interference; and to fulfill all dimensions of sexual health and access to abortion. Three of the 27 constitutions enshrine a universal right to SRH, and additional constitutions protect specific vulnerable groups (such as women, children) and/or restrict the scope of rights holders to couples. Among the 27 constitutions, nine explicitly link the right to sexual and reproductive health to the rights to education, science, and/or to make autonomous decisions about sexuality and reproduction. Our results can serve as a baseline measure to track constitutional reforms in pursuit of the realization of sexual and reproductive health and rights, and as building blocks for future lawmakers committed to realizing these rights through domestic legal reform.

Evidence-based educational pathway for the integration of first aid training in school curricula.

PubMed

De Buck, Emmy; Van Remoortel, Hans; Dieltjens, Tessa; Verstraeten, Hans; Clarysse, Matthieu; Moens, Olaf; Vandekerckhove, Philippe

2015-09-01

"Calling for help, performing first aid and providing Cardiopulmonary Resuscitation (CPR)" is part of the educational goals in secondary schools in Belgium (Flanders). However, for teachers it is not always clear at what age children can be taught which aspects of first aid. In addition, it is not clear what constitutes "performing first aid" and we strongly advocate that the first aid curriculum is broader than CPR training alone. To develop an evidence-based educational pathway to enable the integration of first aid into the school curriculum by defining the goals to be achieved for knowledge, skills and attitudes, for different age groups. Studies were identified through electronic databases research (The Cochrane Library, MEDLINE, Embase). We included studies on first aid education for children and adolescents up to 18 years old. A multidisciplinary expert panel formulated their practice experience and expert opinion and discussed the available evidence. We identified 5822 references and finally retained 30 studies (13 experimental and 17 observational studies), including studies concerning emergency call (7 studies), cardiopulmonary resuscitation (18 studies), AED (Automated External Defibrillator) use (6 studies), recovery position (5 studies), choking (2 studies), injuries (5 studies), and poisoning (2 studies). Recommendations (educational goals) were derived after carefully discussing the currently available evidence in the literature and balancing the skills and attitudes of children of different ages. An evidence-based educational pathway with educational goals concerning learning first aid for each age group was developed. This educational pathway can be used for the integration of first aid training in school curricula. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Mutations in PIK3CA are infrequent in neuroblastoma

PubMed Central

Dam, Vincent; Morgan, Brian T; Mazanek, Pavel; Hogarty, Michael D

2006-01-01

Background Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. Methods Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain "hot spots" where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. Results We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model. Conclusion These data suggest that activating mutations in the Ras/Raf-MAPK/PI3K signaling cascades occur infrequently in neuroblastoma. Further, despite compelling evidence for MYC and RAS cooperation in vitro and in vivo to promote tumourigenesis, activation of RAS signal transduction does not constitute a preferred secondary pathway in neuroblastomas with MYCN deregulation in either human tumors or murine models. PMID:16822308

78 FR 53174 - Agency Forms Submitted for OMB Review, Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... income such as vacation pay or pay for time lost shall constitute sufficient evidence unless there is...: Form No. Annual responses Time (minutes) Burden (hours) ID-5i 1,050 15 262 ID-5R (SUP) 400 10 67 UI-48...

Do Subject Matter Knowledge, and Pedagogical Content Knowledge Constitute the Ideal Gas Law of Science Teaching?

ERIC Educational Resources Information Center

Lederman, Norman G.; Gess-Newsome, Julie

1992-01-01

Describes Pedagogical Content Knowledge and focuses on the empirical research directly concerned with the relationship between science teachers' subject matter knowledge or structures and actual classroom practice. Concludes there is little evidence that a relationship exists. (PR)

The Idiom Principle Revisited

ERIC Educational Resources Information Center

Siyanova-Chanturia, Anna; Martinez, Ron

2015-01-01

John Sinclair's Idiom Principle famously posited that most texts are largely composed of multi-word expressions that "constitute single choices" in the mental lexicon. At the time that assertion was made, little actual psycholinguistic evidence existed in support of that holistic, "single choice," view of formulaic language. In…

Moving Research into Practice: Can We Make Dissemination Stick?

ERIC Educational Resources Information Center

Cook, Bryan G.; Cook, Lysandra; Landrum, Timothy J.

2013-01-01

Although researchers in special education have made significant advances in defining and identifying evidence-based practices, scholars often constitute an insular group that disseminates research findings primarily through outlets and venues targeting like-minded researchers using traditional approaches. Thus, despite tangible results in…

Juvenile curfews: are they an effective and constitutional means of combating juvenile violence?

PubMed

Fried, C S

2001-01-01

Curfew ordinances have become a popular way to attempt to combat juvenile crime and victimization. Although the Supreme Court has yet to hear a curfew case, several constitutional challenges have been brought in lower federal courts. The cases are replete with psychological assumptions for which there is limited empirical evidence. In applying the "strict scrutiny" standard, several courts have also questioned whether juvenile curfews are narrowly tailored to further the State's interest in reducing juvenile crime and victimization. While public opinion and reports from several police jurisdictions support the utility of juvenile curfews, recent empirical studies indicate that curfews are not effective at reducing juvenile offending or victimization. This paper argues that the emerging evidence does not support the use of juvenile curfews and urges policy makers and the courts to examine the efficacy of curfew legislation. Directions for future research that could be helpful to the courts in applying the Bellotti factors to curfew cases are also suggested. Copyright 2001 John Wiley & Sons, Ltd.

Variability in body size and shape of UK offshore workers: A cluster analysis approach.

PubMed

Stewart, Arthur; Ledingham, Robert; Williams, Hector

2017-01-01

Male UK offshore workers have enlarged dimensions compared with UK norms and knowledge of specific sizes and shapes typifying their physiques will assist a range of functions related to health and ergonomics. A representative sample of the UK offshore workforce (n = 588) underwent 3D photonic scanning, from which 19 extracted dimensional measures were used in k-means cluster analysis to characterise physique groups. Of the 11 resulting clusters four somatotype groups were expressed: one cluster was muscular and lean, four had greater muscularity than adiposity, three had equal adiposity and muscularity and three had greater adiposity than muscularity. Some clusters appeared constitutionally similar to others, differing only in absolute size. These cluster centroids represent an evidence-base for future designs in apparel and other applications where body size and proportions affect functional performance. They also constitute phenotypic evidence providing insight into the 'offshore culture' which may underpin the enlarged dimensions of offshore workers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obsessive-compulsive disorder: Insights from animal models☆

PubMed Central

Szechtman, Henry; Ahmari, Susanne E.; Beninger, Richard J.; Eilam, David; Harvey, Brian H.; Edemann-Callesen, Henriette; Winter, Christine

2017-01-01

Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. PMID:27168347

Antioxidative Activities of Both Oleic Acid and Camellia tenuifolia Seed Oil Are Regulated by the Transcription Factor DAF-16/FOXO in Caenorhabditis elegans

PubMed Central

Wei, Chia-Cheng; Yen, Pei-Ling; Chang, Shang-Tzen; Cheng, Pei-Ling; Lo, Yi-Chen; Liao, Vivian Hsiu-Chuan

2016-01-01

Background Tea seed oil is a high quality edible oil, yet lacking sufficient scientific evidences to support the nutritional and medical purposes. We identified major and minor components in Camellia tenuifolia seed oil and investigated the antioxidative activity and its underlying mechanisms in Caenorhabditis elegans. Principal Findings The results showed that the major constitutes in C. tenuifolia seed oil were unsaturated fatty acids (~78.4%). Moreover, two minor compounds, β-amyrin and β-sitosterol, were identified and their antioxidative activity was examined. We found that oleic acid was the major constitute in C. tenuifolia seed oil and plays a key role in the antioxidative activity of C. tenuifolia seed oil in C. elegans. Conclusions This study found evidences that the transcription factor DAF-16/FOXO was involved in both oleic acid- and C. tenuifolia seed oil-mediated oxidative stress resistance in C. elegans. This study suggests the potential of C. tenuifolia seed oil as nutrient or functional foods. PMID:27275864

Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and Exaggerated?

PubMed

Currie, Katharine D; Floras, John S; La Gerche, Andre; Goodman, Jack M

2018-03-24

Blood pressure responses to graded exercise testing can provide important diagnostic and prognostic information. While published guidelines outline what constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response to exercise testing, the widespread use of exaggerated blood pressure responses as a clinical tool is limited due to sparse and inconsistent data. A review of the original sources from these guidelines reveals an overall lack of empirical evidence to support both the normal blood pressure responses and their upper limits. In this current opinion, we critically evaluate the current exercise blood pressure guidelines including (1) the normal blood pressure responses to graded exercise testing; (2) the upper limits of this normal response; (3) the blood pressure criteria for test termination; and (4) the thresholds for exaggerated blood pressure responses. We provide evidence that exercise blood pressure responses vary according to subject characteristics, and subsequently a re-evaluation of what constitutes normal and abnormal responses is necessary to strengthen the clinical utility of this assessment.

Biodegradability of degradable plastic waste.

PubMed

Agamuthu, P; Faizura, Putri Nadzrul

2005-04-01

Plastic waste constitutes the third largest waste volume in Malaysian municipal solid waste (MSW), next to putrescible waste and paper. The plastic component in MSW from Kuala Lumpur averages 24% (by weight), whereas the national mean is about 15%. The 144 waste dumps in the country receive about 95% of the MSW, including plastic waste. The useful life of the landfills is fast diminishing as the plastic waste stays un-degraded for more than 50 years. In this study the compostability of polyethylene and pro-oxidant additive-based environmentally degradable plastics (EDP) was investigated. Linear low-density polyethylene (LLDPE) samples exposed hydrolytically or oxidatively at 60 degrees C showed that the abiotic degradation path was oxidative rather than hydrolytic. There was a weight loss of 8% and the plastic has been oxidized as shown by the additional carbonyl group exhibited in the Fourier transform infra red (FTIR) Spectrum. Oxidation rate seemed to be influenced by the amount of pro-oxidant additive, the chemical structure and morphology of the plastic samples, and the surface area. Composting studies during a 45-day experiment showed that the percentage elongation (reduction) was 20% for McD samples [high-density polyethylene, (HDPE) with 3% additive] and LL samples (LLDPE with 7% additive) and 18% reduction for totally degradable plastic (TDP) samples (HDPE with 3% additive). Lastly, microbial experiments using Pseudomonas aeroginosa on carbon-free media with degradable plastic samples as the sole carbon source, showed confirmatory results. A positive bacterial growth and a weight loss of 2.2% for degraded polyethylene samples were evident to show that the degradable plastic is biodegradable.

Anand constitutive model of lead-free solder joints in 3D IC device

NASA Astrophysics Data System (ADS)

Zhang, Liang; Liu, Zhi-quan; Ji, Yu-tong

2016-08-01

Anand constitutive relation of SnAgCu and SnAgCu-nano Al solders were studied under uniaxial tension, and the constitutive model was used in the finite element simulation to analyze the stress-strain response of lead-free solder joints in 3D IC devices. The results showed that the nine parameters of the Anand model can be determined from separated constitutive relations and experimental results. Based on Anand model, the finite element method was selected to calculate the stress-strain response of lead-free solder joints, it was found that in the 3D IC device the maximum stress-strain concentrated in the concern solder joints, the stress-strain of SnAgCu-nano Al solder joints was lower than that of SnAgCu solder joints, which represented that the addition of nano Al particles can enhance the reliability of lead-free solder joints in 3D IC devices.

A preliminary ferritic-martensitic stainless steel constitution diagram

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

Balmforth, M.C.; Lippold, J.C.

1998-01-01

This paper describes preliminary research to develop a constitution diagram that will more accurately predict the microstructure of ferritic and martensitic stainless steel weld deposits. A button melting technique was used to produce a wide range of compositions using mixtures of conventional ferritic and martensitic stainless steels, including types 403, 409, 410, 430, 439 and 444. These samples were prepared metallographically, and the vol-% ferrite and martensite was determined quantitatively. In addition, the hardness and ferrite number (FN) were measured. Using this data, a preliminary constitution diagram is proposed that provides a more accurate method for predicting the microstructures ofmore » arc welds in ferritic and martensitic stainless steels.« less

Quality performance measurement using the text of electronic medical records.

PubMed

Pakhomov, Serguei; Bjornsen, Susan; Hanson, Penny; Smith, Steven

2008-01-01

Annual foot examinations (FE) constitute a critical component of care for diabetes. Documented evidence of FE is central to quality-of-care reporting; however, manual abstraction of electronic medical records (EMR) is slow, expensive, and subject to error. The objective of this study was to test the hypothesis that text mining of the EMR results in ascertaining FE evidence with accuracy comparable to manual abstraction. The text of inpatient and outpatient clinical reports was searched with natural-language (NL) queries for evidence of neurological, vascular, and structural components of FE. A manual medical records audit was used for validation. The reference standard consisted of 3 independent sets used for development (n=200 ), validation (n=118), and reliability (n=80). The reliability of manual auditing was 91% (95% confidence interval [CI]= 85-97) and was determined by comparing the results of an additional audit to the original audit using the records in the reliability set. The accuracy of the NL query requiring 1 of 3 FE components was 89% (95% CI=83-95). The accuracy of the query requiring any 2 of 3 components was 88% (95% CI=82-94). The accuracy of the query requiring all 3 components was 75% (95% CI= 68- 83). The free text of the EMR is a viable source of information necessary for quality of health care reporting on the evidence of FE for patients with diabetes. The low-cost methodology is scalable to monitoring large numbers of patients and can be used to streamline quality-of-care reporting.

Great Holocene floods along Jokulsa a Fjollum, north Iceland

USGS Publications Warehouse

Waitt, R.B.

2002-01-01

Jokulsa a Fjollum, Iceland's largest glacial river, drains from Vatnajokull icecap northward to the sea along a broad low that includes an active volcanic belt. Geomorphic features along this path reveal an ancient discharge of water large enough to fill the river valley and spill among a plexus of lows in the volcanic landscape. Stratigraphy in most places reveals just one late Holocene great flood down Jokulsa a Fjollum, between 2500 and 2000 yr ago. Step-back water computation suggests its peak flow was 0.7 million m3/s or more. An early scabland-carving great flood had swept down the Asbyrgi area of lowermost Jokulsa just after deglaciation, 9000-8000 yr ago. Stratigraphy near Vesturdalur reveals at least 16 additional floods, perhaps of moderate discharge, between about 8000 and 4000 yr ago. Dispersed field evidence of the late Holocene great flood-anastomosing channels whose basalt surfaces are water fluted and half-potholed, in places plucked down to small-scale scabland replete with dry cataracts, huge boulders, long gravel bars, giant current dunes-is traced the length of Jokulsa valley. From Vatnajokull's north margin at Kverkfjoll, water anastomosed through diverse lows of a high-relief landscape. Thus swift release of meltwater from subglacial Kverkfjoll caldera must have been a source of flood. But even this catastrophic outflow was insufficient to constitute the huge discharges evident farther down-valley. Field evidence reveals a yet greater discharge directly from the large outlet glacier Dyngjujokull. There is no evidence that subglacial Baraoarbunga caldera was involved, but subglacial melting during eruption of a more eastern fissure system could be a source of flood.

Report of the first international workshop on onchocerciasis-associated epilepsy.

PubMed

Colebunders, Robert; Mandro, Michel; Njamnshi, Alfred K; Boussinesq, Michel; Hotterbeekx, An; Kamgno, Joseph; O'Neill, Sarah; Hopkins, Adrian; Suykerbuyk, Patrick; Basáñez, Maria-Gloria; Post, Rory J; Pedrique, Belén; Preux, Pierre-Marie; Stolk, Wilma A; Nutman, Thomas B; Idro, Richard

2018-03-22

Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic. On October 12-14 th 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3-18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for an association between onchocerciasis and epilepsy, 2) determine the burden of disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons with OAE and affected families, 5) identify the pathophysiological mechanism of OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence associated with OAE. An OAE Alliance was created to increase awareness about OAE and its public health importance, stimulate research and disseminate research findings, and create partnerships between OAE researchers, communities, advocacy groups, ministries of health, non-governmental organisations, the pharmaceutical industry and funding organizations. Although the exact pathophysiological mechanism underlying OAE remains unknown, there is increasing evidence that by controlling and eliminating onchocerciasis, OAE will also disappear. Therefore, OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts. Given the high numbers of people with epilepsy in O. volvulus-endemic regions, more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families.

First known EL5 chondrite - Evidence for dual genetic sequence for enstatite chondrites

NASA Technical Reports Server (NTRS)

Sears, D. W. G.; Weeks, K. S.; Rubin, A. E.

1984-01-01

The compositionally distinct EH and EL groups together with four (3-6) petrologic types which constitute the enstatite chondrites represent increasing degrees of metamorphic alteration. Although bulk composition variations preclude a simple conversion of EH4 into EL6 material, complex models which involve simultaneous bulk composition and petrologic type variations may be implied by other classification schemes in common use. Attention is presently given to the discovery of the first EL5 chondrite, which breaks the EH3,4-EH5-EL6 sequence and indicates that the enstatite chondrites constitute the two discrete, isochemical metamorphic sequences EH3-5 and EL5-6.

STUDY OF URANIUM-ALUMINUM-IRON TERNARY CONSTITUTION DIAGRAM. Progress Report for the Period Ending March 31, 1963

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

Russell, R.B.

The determination of the U--Al-- Fe constitution diagram up to about 1000 ppm each of aluminum and iron is now being implemented by a determination of the U--Al and U-- Fe binary systems. The techniques to be used for this study include optical, electron and x-ray metallography, microprobe analysis, electrical resistance, and hothardness measurements. It is expected that a combination of techniques will give evidence of the amount of solid solubility of aluminum and iron in alpha uranium from 300 to 660 deg C, and in beta uranium at selected higher temperatures. (N.W.R.)

Non-integer viscoelastic constitutive law to model soft biological tissues to in-vivo indentation.

PubMed

Demirci, Nagehan; Tönük, Ergin

2014-01-01

During the last decades, derivatives and integrals of non-integer orders are being more commonly used for the description of constitutive behavior of various viscoelastic materials including soft biological tissues. Compared to integer order constitutive relations, non-integer order viscoelastic material models of soft biological tissues are capable of capturing a wider range of viscoelastic behavior obtained from experiments. Although integer order models may yield comparably accurate results, non-integer order material models have less number of parameters to be identified in addition to description of an intermediate material that can monotonically and continuously be adjusted in between an ideal elastic solid and an ideal viscous fluid. In this work, starting with some preliminaries on non-integer (fractional) calculus, the "spring-pot", (intermediate mechanical element between a solid and a fluid), non-integer order three element (Zener) solid model, finally a user-defined large strain non-integer order viscoelastic constitutive model was constructed to be used in finite element simulations. Using the constitutive equation developed, by utilizing inverse finite element method and in vivo indentation experiments, soft tissue material identification was performed. The results indicate that material coefficients obtained from relaxation experiments, when optimized with creep experimental data could simulate relaxation, creep and cyclic loading and unloading experiments accurately. Non-integer calculus viscoelastic constitutive models, having physical interpretation and modeling experimental data accurately is a good alternative to classical phenomenological viscoelastic constitutive equations.

76 FR 19434 - Roni Dreszer, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... evidence under the [experience] * * * factor[] support[s]'' the revocation of his registration, is consistent with Agency precedent. Id. With respect to factor five, ``[s]uch other conduct which may threaten... factor requires some showing that the relevant conduct actually constituted a threat to public safety...

The Role of Metaphysical Naturalism in Science

ERIC Educational Resources Information Center

Mahner, Martin

2012-01-01

This paper defends the view that metaphysical naturalism is a constitutive ontological principle of science in that the general empirical methods of science, such as observation, measurement and experiment, and thus the very production of empirical evidence, presuppose a no-supernature principle. It examines the consequences of metaphysical…

Iran’s Economy

DTIC Science & Technology

2008-06-12

Agriculture Iran’s agriculture sector is substantial. Iran is a major source of caviar and pistachio nuts, which constitute significant non-oil exports for Iran...prepared meat and fish, and edible nuts and foods ( pistachios ). There is evidence that Iran is able to obtain embargoed U.S. goods through the re

Interaction in Bilingual Phonological Acquisition: Evidence from Phonetic Inventories

ERIC Educational Resources Information Center

Fabiano-Smith, Leah; Barlow, Jessica A.

2010-01-01

Purpose: To examine how interaction contributes to phonological acquisition in bilingual children in order to determine what constitutes typical development of bilingual speech sound inventories. Method: Twenty-four children, ages 3-4, were included: eight bilingual Spanish-English-speaking children, eight monolingual Spanish speakers, and eight…

The Semantic Processing of Motion Verbs: Coercion or Underspecification?

ERIC Educational Resources Information Center

Lukassek, Julia; Pryslopska, Anna; Hörnig, Robin; Maienborn, Claudia

2017-01-01

Underspecification and coercion are two prominent interpretive mechanisms to account for meaning variability beyond compositionality. While there is plentiful evidence that natural language meaning constitution exploits both mechanisms, it is an open issue whether a concrete phenomenon of meaning variability is an instance of underspecification or…

Legal Bibliography for Juvenile and Family Courts. Supplement 2.

ERIC Educational Resources Information Center

Sheridan, William H.; Freer, Alice B.

This bibliography provides a listing of journal articles on such topics as: the abused child, adoptions, case decisions, confessions, constitutional law, counsel, court administration and organization, courts, criminal law and procedure, custody, delinquency, domestic relations, due process for juveniles, evidence, family court and family law,…

[GRADE system: classification of quality of evidence and strength of recommendation].

PubMed

Aguayo-Albasini, José Luis; Flores-Pastor, Benito; Soria-Aledo, Víctor

2014-02-01

The acquisition and classification of scientific evidence, and subsequent formulation of recommendations constitute the basis for the development of clinical practice guidelines. There are several systems for the classification of evidence and strength of recommendations; the most commonly used nowadays is the Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The GRADE system initially classifies the evidence into high or low, coming from experimental or observational studies; subsequently and following a series of considerations, the evidence is classified into high, moderate, low or very low. The strength of recommendations is based not only on the quality of the evidence, but also on a series of factors such as the risk/benefit balance, values and preferences of the patients and professionals, and the use of resources or costs. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

Premature aging and cancer in nucleotide excision repair-disorders

PubMed Central

Diderich, K.; Alanazi, M.; Hoeijmakers, J.H.J.

2014-01-01

During past decades the major impact of DNA damage on cancer as ‘disease of the genes’ has become abundantly apparent. In addition to cancer recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair systems not only protect against cancer but equally against too fast aging has become evident from a systematic, integral analysis of a variety of mouse mutants carrying defects in e.g. transcription-coupled repair with or without an additional impairment of global genome nucleotide excision repair and the corresponding segmental premature aging syndromes in man. A striking correlation between the degree of the DNA repair deficiency and the acceleration of specific progeroid symptoms has been discovered for those repair systems that primarily protect from the cytotoxic and cytostatic effects of DNA damage. These observations are explained from the perspective of nucleotide excision repair mouse mutant and human syndromes. However, similar principles likely apply to other DNA repair pathways including interstrand crosslink repair and double strand break repair and genome maintenance systems in general, supporting the notion that DNA damage constitutes an important intermediate in the process of aging. PMID:21680258

Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts.

PubMed Central

Jeffrey, A M; Blobstein, S H; Weinstein, I B; Beland, F A; Harvey, R G; Kasai, H; Nakanishi, K

1976-01-01

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established. PMID:821053

[The HMPC monograph on Hypericum: Background, development, contents].

PubMed

Länger, Reinhard

2010-12-01

The adoption of the EU community monograph on Hypericum constitutes a milestone in the process of harmonisation of herbal medicinal products within the European Community. The assessment of the published clinical data revealed that for two types of extracts the evidence of the efficacy in mild to moderate depressive episodes compared to placebo or standard medication was found to be acceptable. Additionally, a sufficient efficacy in relapse prophylaxis could be demonstrated for these two herbal preparations. For some other dry extracts, the efficacy in the short-term treatment of symptoms in mild depressive disorders was found to be substantiated. Short-term treatment with preparations containing low amounts of hyperforin did not increase cytochrome P450 enzyme activity. Therefore the oral administration of traditional herbal preparations is restricted to two weeks. In the case that an applicant demonstrates that the daily intake of hyperforin is below 1 mg the warnings on interactions may be omitted in traditional herbal medicinal products. Additionally the cutaneous administration of traditional liquid herbal preparations for the traditional use in symptomatic treatment of minor inflammations of the skin and as an aid in healing minor wounds was included in the monograph.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males.

PubMed

Páez, David James; Bernatchez, Louis; Dodson, Julian J

2011-07-22

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males

PubMed Central

Páez, David James; Bernatchez, Louis; Dodson, Julian J.

2011-01-01

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance. PMID:21177685

[Social security law and evidence-based health care in Germany].

PubMed

Welti, Felix

2007-01-01

The present contribution examines whether German Social Security Law requires or allows the German health care system to follow the principles of evidence-based health care. The discussion will be based on the relevant example of statutory health insurance (Book of Social Code V-SGB V). According to Sect. 2 SGB V health care provision has to follow medical standards, acknowledging medical progress. It has to be effective and efficient. Special therapies are not outlawed, but also have to follow these principles. Efficiency is defined (Sect. 12 SGB V) by the benefits being sufficient and necessary. The responsibility for achieving these goals and supplying the benefits for all people according to need lies with the health care insurance funds along with the physicians' associations (Kassenirztliche Vereinigung) and the hospitals (Sect. 70 SGB V). These organisations cooperate in the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA, Sect. 92 SGB V), where they have to hear organisations of patients and of the disabled also. The G-BA is allowed by law to exclude therapies not meeting the SGB V criteria. The Institute for Quality and Efficiency in Health Care (IQWiG) advises the G-BA and is also responsible for generating evidence. A major political and constitutional controversy has been triggered on the legitimation of the Federal Joint Committee. In its statute the G-BA recurs on evidence-based health care. It examines therapies according to the degree of available evidence and the usability of the evidence in the respective supply setting. The Federal Social Court (Bundessozialgericht, BSG) decided that the decisions of the G-BA could not be challenged for being medically incorrect. In 2005, the Federal Constitutional Court (Bundesverfassungsgericht-BVerfG) decided that a stricter control over the G-BA by the social courts was needed and that in the case of serious disease a lower evidence level might be sufficient. BSG and G-BA will continue to accept the results and methods of Evidence-based Medicine.

Appraising the evidence for public health policy components using the quality and impact of component evidence assessment.

PubMed

Barbero, Colleen; Gilchrist, Siobhan; Schooley, Michael W; Chriqui, Jamie F; Luke, Douglas A; Eyler, Amy A

2015-03-01

An essential strategy expected to reduce the global burden of chronic and cardiovascular disease is evidence-based policy. However, it is often unknown what specific components should constitute an evidence-based policy intervention. We have developed an expedient method to appraise and compare the strengths of the evidence bases suggesting that individual components of a policy intervention will contribute to the positive public health impact of that intervention. Using a new definition of "best available evidence," the Quality and Impact of Component (QuIC) Evidence Assessment analyzes dimensions of evidence quality and evidence of public health impact to categorize multiple policy component evidence bases along a continuum of "emerging," "promising impact," "promising quality," and "best." QuIC was recently applied to components from 2 policy interventions to prevent and improve the outcomes of cardiovascular disease: public-access defibrillation and community health workers. Results illustrate QuIC's utility in international policy practice and research. Copyright © 2015 World Heart Federation (Geneva). All rights reserved.

Constitutive modeling and structural analysis considering simultaneous phase transformation and plastic yield in shape memory alloys

NASA Astrophysics Data System (ADS)

Hartl, D. J.; Lagoudas, D. C.

2009-10-01

The new developments summarized in this work represent both theoretical and experimental investigations of the effects of plastic strain generation in shape memory alloys (SMAs). Based on the results of SMA experimental characterization described in the literature and additional testing described in this work, a new 3D constitutive model is proposed. This phenomenological model captures both the conventional shape memory effects of pseudoelasticity and thermal strain recovery, and additionally considers the initiation and evolution of plastic strains. The model is numerically implemented in a finite element framework using a return mapping algorithm to solve the constitutive equations at each material point. This combination of theory and implementation is unique in its ability to capture the simultaneous evolution of recoverable transformation strains and irrecoverable plastic strains. The consideration of isotropic and kinematic plastic hardening allows the derivation of a theoretical framework capturing the interactions between irrecoverable plastic strain and recoverable strain due to martensitic transformation. Further, the numerical integration of the constitutive equations is formulated such that objectivity is maintained for SMA structures undergoing moderate strains and large displacements. The implemented model has been used to perform 3D analysis of SMA structural components under uniaxial and bending loads, including a case of local buckling behavior. Experimentally validated results considering simultaneous transformation and plasticity in a bending member are provided, illustrating the predictive accuracy of the model and its implementation.

The productive techniques and constitutive effects of 'evidence-based policy' and 'consumer participation' discourses in health policy processes.

PubMed

Lancaster, K; Seear, K; Treloar, C; Ritter, A

2017-03-01

For over twenty years there have been calls for greater 'consumer' participation in health decision-making. While it is recognised by governments and other stakeholders that 'consumer' participation is desirable, barriers to meaningful involvement nonetheless remain. It has been suggested that the reifying of 'evidence-based policy' may be limiting opportunities for participation, through the way this discourse legitimates particular voices to the exclusion of others. Others have suggested that assumptions underpinning the very notion of the 'affected community' or 'consumers' as fixed and bounded 'policy publics' need to be problematised. In this paper, drawing on interviews (n = 41) with individuals closely involved in Australian drug policy discussions, we critically interrogate the productive techniques and constitutive effects of 'evidence-based policy' and 'consumer participation' discourses in the context of drug policy processes. To inform our analysis, we draw on and combine a number of critical perspectives including Foucault's concept of subjugated knowledges, the work of feminist theorists, as well as recent work regarding conceptualisations of emergent policy publics. First, we explore how the subject position of 'consumer' might be seen as enacted in the material-discursive practices of 'evidence-based policy' and 'consumer participation' in drug policy processes. Secondly, we consider the centralising power-effects of the dominant 'evidence-based policy' paradigm, and how resistance may be thought about in this context. We suggest that such interrogation has potential to recast the call for 'consumer' participation in health policy decision-making and drug policy processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Global Survey of National Constitutions

PubMed Central

Perehudoff, Katrina

2017-01-01

Abstract General Comment No. 22, issued in 2016 by the Committee on Economic, Social and Cultural Rights (CESCR), clarifies states’ legal duties to respect, protect, and fulfill the right to sexual and reproductive health (SRH). Our study analyzes domestic constitutions around the world to investigate whether and to what extent the right to sexual and reproductive health is respected, protected, and fulfilled; to what extent these provisions are inclusive and non-discriminatory; and to what degree the interlinkages between this and other human rights are acknowledged. Of the 195 constitutions accessed, 27 enshrine sexual and/or reproductive health, and seven adopt restrictive approaches to this right. In the 27 constitutions, provisions most frequently enshrine respect of one’s sexual health and family planning decisions, the protection of sexual health, and the provision of reproductive health care and family planning services (fulfillment). Most of the 27 constitutions fail to adequately respect reproductive health rights; to protect reproductive health, family planning, and abortion services from third-party interference; and to fulfill all dimensions of sexual health and access to abortion. Three of the 27 constitutions enshrine a universal right to SRH, and additional constitutions protect specific vulnerable groups (such as women, children) and/or restrict the scope of rights holders to couples. Among the 27 constitutions, nine explicitly link the right to sexual and reproductive health to the rights to education, science, and/or to make autonomous decisions about sexuality and reproduction. Our results can serve as a baseline measure to track constitutional reforms in pursuit of the realization of sexual and reproductive health and rights, and as building blocks for future lawmakers committed to realizing these rights through domestic legal reform. PMID:29302182

Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles

PubMed Central

Cavolo, Samantha L.; Bulgari, Dinara; Deitcher, David L.

2016-01-01

Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. SIGNIFICANCE STATEMENT Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde transport. Here we show that activity stimulates further synaptic capture that is distinguished from basal capture by its selectivity for anterograde DCVs and its inhibition by overexpression of the fragile X retardation protein Fmr1. Fmr1 dramatically lowers DCV numbers in synaptic boutons. Therefore, activity-dependent anterograde capture is a major determinant of presynaptic peptide stores. PMID:27852784

Comparison of Gut Microbiota between Sasang Constitutions

PubMed Central

Bae, Hyo Sang; Lim, Chi-yeon; Kim, Mi Jeong; Seo, Jae-gu; Kim, Jong Yeol; Kim, Jai-eun

2013-01-01

The Sasang constitutional medicine has long been applied to diagnose and treat patients with various diseases. Studies have been conducted for establishment of scientific evidence supporting Sasang Constitutional (SC) diagnosis. Recent human microbiome studies have demonstrated individual variations of gut microbiota which can be dependent on lifestyle and health conditions. We hypothesized that gut microbial similarities and discrepancies may exist across SC types. We compared the difference of gut microbiota among three constitutions (So-Yang, So-Eum, and Tae-Eum), along with the investigation of anthropometric and biochemical parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types. The median plot analysis suggested that Firmicutes and Bacteroidetes appeared more abundant in SE and TE, respectively, in the male subjects of 20–29 years old. At the genus level, Bifidobacterium and Bacteroides manifested the difference between SE and TE types. For anthropometry, body weight, body mass index, and waist circumference of the TE type were significantly higher than those of the other types. Overall, findings indicated a possible link between SC types and gut microbiota within a narrow age range. Further investigations are deemed necessary to elucidate the influences of age, gender, and other factors in the context of SC types and gut microbiota. PMID:24454486

40 CFR 80.1506 - What penalties apply under this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Additional Requirements for Gasoline-Ethanol... pertains to the ethanol content of gasoline shall constitute a separate day of violation for each and every... that pertain to the ethanol content of gasoline. (2) For the purposes of this paragraph (b), the length...

40 CFR 80.1506 - What penalties apply under this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Additional Requirements for Gasoline-Ethanol... pertains to the ethanol content of gasoline shall constitute a separate day of violation for each and every... that pertain to the ethanol content of gasoline. (2) For the purposes of this paragraph (b), the length...

40 CFR 80.1506 - What penalties apply under this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Additional Requirements for Gasoline-Ethanol... pertains to the ethanol content of gasoline shall constitute a separate day of violation for each and every... that pertain to the ethanol content of gasoline. (2) For the purposes of this paragraph (b), the length...

CALYPSO: a new HF RADAR network to monitor sea surface currents in the Malta-Sicily channel (Mediterranean sea)

NASA Astrophysics Data System (ADS)

Cosoli, S.; Ciraolo, G.; Drago, A.; Capodici, F.; Maltese, A.; Gauci, A.; Galea, A.; Azzopardi, J.; Buscaino, G.; Raffa, F.; Mazzola, S.; Sinatra, R.

2016-12-01

Located in one of the main shipping lanes in the Mediterranean Sea, and in a strategic region for oil extraction platforms, the Malta-Sicily channel is exposed to significant oil spill risks. Shipping and extraction activities constitute a major threat for marine areas of relevant ecological value in the area, and impacts of oil spills on the local ecosystems and the economic activities, including tourism and fisheries, can be dramatic. Damages would be even more devastating for the Maltese archipelago, where marine resources represent important economic assets. Additionally, North Africa coastal areas are also under threat, due to their proximity to the Malta-Sicily Channel. Prevention and mitigation measures, together with rapid-response and decision-making in case of emergency situations, are fundamental steps that help accomplishing the tasks of minimizing risks and reducing impacts to the various compartments. Thanks to state-of-art technology for the monitoring of sea-surface currents in real-time under all sea-state conditions, the CALYPSO network of High-Frequency Radars represents an essential and invaluable tool for the specific purpose. HF radars technology provide a unique tool to track surface currents in near-real time, and as such the dispersion of pollutants can be monitored and forecasted and their origin backtracked, for instance through data assimilation into ocean circulation models or through short-term data-driven statistical forecasts of ocean currents. The network is constituted of four SeaSonde systems that work in the 13.5MHz frequency band. The network is operative since August 2012 and has been extensively validated using a variety of independent platforms and devices, including current meter data and drifting buoys. The latter provided clear evidences of the reliability of the collected data as for tracking the drifting objects. Additionally, data have provided a new insight into the oceanographic characteristics of the region, documenting the presence of a number of previously unreported features. The observing network represents an unique opportunity that exploit HF radar in coastal seas to meet Europe's needs for operational mapping of the surface ocean. Additionally, it provides expertise and support for a new generation of scientists and technical staff.

State-of-the-art office-based interventions to eliminate youth tobacco use: the past decade.

PubMed

Pbert, Lori; Farber, Harold; Horn, Kimberly; Lando, Harry A; Muramoto, Myra; O'Loughlin, Jennifer; Tanski, Susanne; Wellman, Robert J; Winickoff, Jonathan P; Klein, Jonathan D

2015-04-01

Tobacco use and tobacco smoke exposure are among the most important preventable causes of premature disease, disability, and death and therefore constitute a major pediatric health concern. The pediatric primary care setting offers excellent opportunities to prevent tobacco use in youth and to deliver cessation-related treatment to youth and parents who use tobacco. This report updates a "state-of-the-art" article published a decade ago on office-based interventions to address these issues. Since then there has been marked progress in understanding the nature, onset, and trajectories of tobacco use and nicotine addiction in youth with implications for clinical practice. In addition, clinicians need to remain abreast of emerging nicotine delivery systems, such as electronic cigarettes, that may influence uptake or continuation of smoking. Although evidence-based practice guidelines for treating nicotine addiction in youth are not yet available, research continues to build the evidence base toward that goal. In the interim, practical guidelines are available to assist clinicians in addressing nicotine addiction in the pediatric clinical setting. This article reports current practices in addressing tobacco in pediatric primary care settings. It reviews our increasing understanding of youth nicotine addiction, summarizes research efforts on intervention in the past decade and additional research needed going forward, and provides practical guidelines for pediatric health care providers to integrate tobacco use prevention and treatment into their clinical practice. Pediatric providers can and should play an important role in addressing tobacco use and dependence, both in the youth they care for and in parents who use tobacco. Copyright © 2015 by the American Academy of Pediatrics.

Aphasic variant of Alzheimer disease

PubMed Central

Sridhar, Jaiashre; Rader, Benjamin; Martersteck, Adam; Chen, Kewei; Cobia, Derin; Thompson, Cynthia K.; Weintraub, Sandra; Bigio, Eileen H.; Mesulam, M.-Marsel

2016-01-01

Objective: To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. Methods: A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Results: Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. Conclusions: There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. PMID:27566743

Constitutive β-catenin Activation Induces Male-Specific Tumorigenesis in the Bladder Urothelium

PubMed Central

Lin, Congxing; Yin, Yan; Stemler, Kristina; Humphrey, Peter; Kibel, Adam S.; Mysorekar, Indira U.; Ma, Liang

2013-01-01

The incidence for bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is about three times higher in men than in women. Although this gender difference has been primarily attributed to differential exposures, it is likely that underlying biological causes contribute to the gender inequality. In this study, we report a transgenic mouse bladder tumor model upon induction of constitutively activated β-catenin signaling in the adult urothelium. We showed that the histopathology of the tumors observed in our model closely resembled that of the human low grade urothelial carcinoma. Additionally, we provided evidence supporting the KRT5-positive;KRT7-negative basal cells as the putative cells-of-origin for β-catenin-induced luminal tumor. Intriguingly, the tumorigenesis in this model demonstrated a marked difference between opposite sexes; forty percent of males developed macroscopically detectable luminal tumors in twelve weeks, whereas only three percent of females developed tumors. We investigated the mechanisms underlying this sexual dimorphism in pathogenesis and demonstrated that nuclear translocation of the androgen receptor (AR) in the urothelial cells is a critical mechanism contributing to tumor development in male mice. Finally, we performed global gene profiling experiments and defined the molecular signature for the β-catenin-induced tumorigenesis in males. Altogether, we have established a model for investigating sexual dimorphism in UC development, and implicated synergy between β-catenin signaling and androgen/AR signaling in carcinogenesis of the basal urothelial cells. PMID:23928991

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding.

PubMed

Basagiannis, Dimitris; Christoforidis, Savvas

2016-08-05

VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding*

PubMed Central

Basagiannis, Dimitris; Christoforidis, Savvas

2016-01-01

VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors. PMID:27298320

50 CFR 300.5 - Facilitation of enforcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transmitted by flashing light directed at the vessel signaled. USCG units will normally use the flashing light..., flashing light, flags, whistle, horn or other means constitutes prima facie evidence of the offense of... International Code of Signals, may be sent by flashing light by an enforcement unit when conditions do not allow...

50 CFR 300.5 - Facilitation of enforcement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... transmitted by flashing light directed at the vessel signaled. USCG units will normally use the flashing light..., flashing light, flags, whistle, horn or other means constitutes prima facie evidence of the offense of... International Code of Signals, may be sent by flashing light by an enforcement unit when conditions do not allow...

Nonprofits' Expectations in PR Service-Learning Partnerships

ERIC Educational Resources Information Center

Rogers, Cathy; Andrews, Valerie

2016-01-01

Little scholarly evidence exists about the communication needs of nonprofit community partners and what they think constitutes an ideal service-learning (SL) relationship. This study seeks to fill this gap by identifying SL projects and relationships that best serve nonprofit community partners with communication needs. The researchers conducted a…

77 FR 20012 - Arbitration Panel Decision Under the Randolph-Sheppard Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... Complainant's claim is barred under the doctrine of sovereign immunity as alleged by Respondent; and (2... testimony and reviewing all of the evidence, the panel majority denied the SLA's claim of sovereign immunity... sovereign immunity rights. However, under the Kentucky constitution, the power to waive sovereign immunity...

Childhood Obesity: An Overview

ERIC Educational Resources Information Center

Reilly, John J.

2007-01-01

This article reviews recent research evidence, largely from systematic reviews, on a number of aspects of childhood obesity: its definition and prevalence; consequences; causes and prevention. The basis of the body mass index (BMI) as a means of defining obesity in children and adolescents is discussed: a high BMI for age constitutes obesity. In…

Tackling Noncommunicable Diseases in Africa: Caveat Lector

ERIC Educational Resources Information Center

Mensah, George A.

2016-01-01

Noncommunicable disease (NCD), principally cardiovascular diseases, cancer, chronic lung disease, and diabetes, constitutes the major cause of death worldwide. Evidence of a continuing increase in the global burden of these diseases has generated recent urgent calls for global action to tackle and reduce related death and disability. Because the…

Developments in the Law--Section 1981.

ERIC Educational Resources Information Center

Aguilar, Javier; And Others

1980-01-01

Reviews the history and current state of the law under Section 1981 of the Civil Rights Act of 1866. Suggests how it may be interpreted to maintain its vitality as a guarantee of racial equality. Considers actionable discrimination claims, protected interests, prima facie evidence, constitutional defenses, immunities, and procedural issues.…

The Ubiquity of Frequency Effects in First Language Acquisition

ERIC Educational Resources Information Center

Ambridge, Ben; Kidd, Evan; Rowland, Caroline F.; Theakston, Anna L.

2015-01-01

This review article presents evidence for the claim that frequency effects are pervasive in children's first language acquisition, and hence constitute a phenomenon that any successful account must explain. The article is organized around four key domains of research: children's acquisition of single words, inflectional morphology, simple…

Deliberate Imagery Practice: The Reliability of Using a Retrospective Recall Methodology

ERIC Educational Resources Information Center

Cumming, Jennifer; Hall, Craig; Starkes, Janet L.

2005-01-01

This study examined the reliability of a retrospective recall methodology for providing evidence of deliberate imagery practice. A secondary purpose was to determine which imagery activities constituted the sport-specific definition of deliberate practice (Starkes, Deakin, Allard, Hodges, & Hayes, 1996). Ninety-three Canadian athletes from one…

Dosage and Distribution in Morphosyntax Intervention: Current Evidence and Future Needs

ERIC Educational Resources Information Center

Proctor-Williams, Kerry

2009-01-01

This article reviews the effectiveness of dose forms and the efficacy of dosage and distribution in morphosyntax intervention for children. Dose forms include the commonly used techniques, procedures, and intervention contexts that constitute teaching episodes; dosage includes the quantitative measures of dose, dose frequency, total intervention…

Satiating the Appetite of the Sociologic Sponge: A Rejoinder to Mabbott.

ERIC Educational Resources Information Center

Sparks, Richard L.; And Others

1995-01-01

In response to a previous article, this article suggests that the differing viewpoints are the result of differences in opinion about what constitutes a foreign-language learning problem and a learning disability and whether evidence is provided to substantiate the claims presented by each side. (JL)

The Particle "ya" in Colloquial Singapore English

ERIC Educational Resources Information Center

Wee, Lionel

2010-01-01

It has been recently argued that the particles in Colloquial Singapore English (CSE) constitute a grammatical category that actively draws new members to it. Drawing on distributional and collocational evidence, this paper establishes that CSE has a new particle, "ya". The paper then proceeds to analyse the discourse pragmatic function…

Companies Can Apologize: Corporate Apologies and Legal Liability.

ERIC Educational Resources Information Center

Patel, Ameeta; Reinsch, Lamar

2003-01-01

Indicates that apologies generally do not constitute evidence of guilt and that, in fact, they sometimes have positive consequences for the apologist. Suggests that persons who practice (or teach) crisis communication should avoid the mistake of relying on an over-simplified and inaccurate understanding of the legal issues surrounding corporate…

Evidence - based medicine/practice in sports physical therapy.

PubMed

Manske, Robert C; Lehecka, B J

2012-10-01

A push for the use of evidence-based medicine and evidence-based practice patterns has permeated most health care disciplines. The use of evidence-based practice in sports physical therapy may improve health care quality, reduce medical errors, help balance known benefits and risks, challenge views based on beliefs rather than evidence, and help to integrate patient preferences into decision-making. In this era of health care utilization sports physical therapists are expected to integrate clinical experience with conscientious, explicit, and judicious use of research evidence in order to make clearly informed decisions in order to help maximize and optimize patient well-being. One of the more common reasons for not using evidence in clinical practice is the perceived lack of skills and knowledge when searching for or appraising research. This clinical commentary was developed to educate the readership on what constitutes evidence-based practice, and strategies used to seek evidence in the daily clinical practice of sports physical therapy.

A computer program for predicting nonlinear uniaxial material responses using viscoplastic models

NASA Technical Reports Server (NTRS)

Chang, T. Y.; Thompson, R. L.

1984-01-01

A computer program was developed for predicting nonlinear uniaxial material responses using viscoplastic constitutive models. Four specific models, i.e., those due to Miller, Walker, Krieg-Swearengen-Rhode, and Robinson, are included. Any other unified model is easily implemented into the program in the form of subroutines. Analysis features include stress-strain cycling, creep response, stress relaxation, thermomechanical fatigue loop, or any combination of these responses. An outline is given on the theoretical background of uniaxial constitutive models, analysis procedure, and numerical integration methods for solving the nonlinear constitutive equations. In addition, a discussion on the computer program implementation is also given. Finally, seven numerical examples are included to demonstrate the versatility of the computer program developed.

Vulvodynia: Assessment and Treatment.

PubMed

Goldstein, Andrew T; Pukall, Caroline F; Brown, Candace; Bergeron, Sophie; Stein, Amy; Kellogg-Spadt, Susan

2016-04-01

Vulvodynia constitutes a highly prevalent form of sexual pain in women, and current information regarding its assessment and treatment is needed. To update the scientific evidence published in 2010, from the Third International Consultation on Sexual Medicine, pertaining to the assessment and treatment of women's sexual pain. An expert committee, as part of the Fourth International Consultation on Sexual Medicine, was comprised of researchers and clinicians from biological and social science disciplines for the review of the scientific evidence on the assessment and treatment of women's genital pain. A review of assessment and treatment strategies involved in vulvodynia. We recommend the following treatments for the management of vulvodynia: psychological interventions, pelvic floor physical therapy, and vestibulectomy (for provoked vestibulodynia). We also support the use of multidisciplinary treatment approaches for the management of vulvodynia; however, more studies are needed to determine which components are most important. We recommend waiting for more empirical evidence before recommending alternative treatment options, anti-inflammatory agents, hormonal agents, and anticonvulsant medications. Although we do not recommend lidocaine, topical corticosteroids, or antidepressant medication for the management of vulvodynia, we suggest that capsaicin, botulinum toxin, and interferon be considered second-line avenues and that their recommendation be revisited once further research is conducted. A comprehensive assessment is needed to understand the pain experience of women presenting with vulvodynia. In addition, treatment typically progresses from less invasive to more invasive, and several treatment options are worth pursuing. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

[Cytokines and their role in reproductive system].

PubMed

Ianchiĭ, R I; Voznesens'ka, T Iu; Shepel', O A

2007-01-01

In this review we analyze the involvement of cytokines in regulation of ovarian function. A growing body of evidence suggests that the ovary is a site of inflammatory reactions. Immune-competent cells present within the ovary may constitute potential in-situ modulators of ovarian function that act through local secretion of regulatory soluble factors cytokines. In addition many over cell in the ovary also produce cytokines independently of the presence of leukocytes, thus ovaries are sites of cytokine action and production. There are many evidences that cytokines are involved in the ovarian control of follicular development and are surveyed as the important regulators of steroidogenesis and gamete production. It is established that cytokines generally inhibit gonadotropin-stimulated production of steroids. However ovarian steroids, in turn, reduce the cytokine production by immunecompetent cells. There are some data about participation of cytokines in regulating the proliferation and differentiation of granulose cells. Most cytokines appear in mammalian follicles only a short time before ovulation and play the important role in process of ovulation and luteinization. Thus a variety of clinical situations may be due to cytokine action in the gonads, and therapeutic manipulation of the immune system may affect reproductive function. Moreover the findings about the expression of some cytokines by oocytes and their presence in follicular fluid provide further evidence and substantiate the physiologic role for their in ovarian function, and may lead to clinical applications in programs of in vitro fertilization and in diagnosis and treatment of infertility in women, especially in cases attributed to ovarian dysfunction.

Cerebral misery perfusion due to carotid occlusive disease

PubMed Central

Maddula, Mohana; Sprigg, Nikola; Bath, Philip M; Munshi, Sunil

2017-01-01

Purpose Cerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand. We present an educational review of this important condition, which has a range of clinical manifestations. Method A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect. Findings Patients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors. Discussion The evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD. Conclusion Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment. PMID:28959496

Molecular phylogenetic evidence supports a new family of octocorals and a new genus of Alcyoniidae (Octocorallia, Alcyonacea)

PubMed Central

McFadden, Catherine S.; van Ofwegen, Leen P.

2013-01-01

Abstract Molecular phylogenetic evidence indicates that the octocoral family Alcyoniidae is highly polyphyletic, with genera distributed across Octocorallia in more than 10 separate clades. Most alcyoniid taxa belong to the large and poorly resolved Holaxonia–Alcyoniina clade of octocorals, but members of at least four genera of Alcyoniidae fall outside of that group. As a first step towards revision of the family, we describe a new genus, Parasphaerasclera gen. n., and family, Parasphaerascleridae fam. n., of Alcyonacea to accommodate species of Eleutherobia Pütter, 1900 and Alcyonium Linnaeus, 1758 that have digitiform to digitate or lobate growth forms, completely lack sclerites in the polyps, and have radiates or spheroidal sclerites in the colony surface and interior. Parasphaerascleridae fam. n. constitutes a well-supported clade that is phylogenetically distinct from all other octocoral taxa. We also describe a new genus of Alcyoniidae, Sphaerasclera gen. n., for a species of Eleutherobia with a unique capitate growth form. Sphaerasclera gen. n. is a member of the Anthomastus–Corallium clade of octocorals, but is morphologically and genetically distinct from Anthomastus Verrill, 1878 and Paraminabea Williams & Alderslade, 1999, two similar but dimorphic genera of Alcyoniidae that are its sister taxa. In addition, we have re-assigned two species of Eleutherobia that have clavate to capitate growth forms, polyp sclerites arranged to form a collaret and points, and spindles in the colony interior to Alcyonium, a move that is supported by both morphological and molecular phylogenetic evidence. PMID:24223488

Comorbidity ascertainment from the ESRD Medical Evidence Report and Medicare claims around dialysis initiation: a comparison using US Renal Data System data.

PubMed

Krishnan, Mahesh; Weinhandl, Eric D; Jackson, Scott; Gilbertson, David T; Lacson, Eduardo

2015-11-01

The end-stage renal disease Medical Evidence Report serves as a source of comorbid condition data for risk adjustment of quality metrics. We sought to compare comorbid condition data in the Medical Evidence Report around dialysis therapy initiation with diagnosis codes in Medicare claims. Observational cohort study using US Renal Data System data. Medicare-enrolled elderly (≥66 years) patients who initiated maintenance dialysis therapy July 1 to December 31, 2007, 2008, or 2009. 12 comorbid conditions ascertained from claims during the 6 months before dialysis therapy initiation, the Medical Evidence Report, and claims during the 3 months after dialysis therapy initiation. None. Comorbid condition prevalence according to claims before dialysis therapy initiation generally exceeded prevalence according to the Medical Evidence Report. The κ statistics for comorbid condition designations other than diabetes ranged from 0.06 to 0.43. Discordance of designations was associated with age, race, sex, and end-stage renal disease Network. During 23,930 patient-years of follow-up from 4 to 12 months after dialysis therapy initiation (8,930 deaths), designations from claims during the 3 months after initiation better discriminated risk of death than designations from the Medical Evidence Report (C statistics of 0.674 vs 0.616). Between the Medical Evidence Report and claims, standardized mortality ratios changed by >10% for more than half the dialysis facilities. Neither the Medical Evidence Report nor diagnosis codes in claims constitute a gold standard of comorbid condition data; results may not apply to nonelderly patients or patients without Medicare coverage. Discordance of comorbid condition designations from the Medical Evidence Report and claims around dialysis therapy initiation was substantial and significantly associated with patient characteristics, including location. These patterns may engender bias in risk-adjusted quality metrics. In lieu of the Medical Evidence Report, claims during the 3 months after dialysis therapy initiation may constitute a useful source of comorbid condition data. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Did the Navy Get Taken

DTIC Science & Technology

2015-10-01

into a museum , the Navy decided in 2010 that none of the applications to turn it into a public display was up to par. In addition to its pivotal role in...it formerly cost the Navy a bundle to turn around the Constitution. But then the winner of the competition started to advertise that it had won... Museum , which could not do so, but, referred me to the U.S. Navy’s Public Affairs Officer for the USS Constitution. He was unable to verify the

Possible Further Evidence of Low Genetic Diversity in the El Sidrón (Asturias, Spain) Neandertal Group: Congenital Clefts of the Atlas

PubMed Central

Ríos, Luis; Rosas, Antonio; Estalrrich, Almudena; García-Tabernero, Antonio; Bastir, Markus; Huguet, Rosa; Pastor, Francisco; Sanchís-Gimeno, Juan Alberto; de la Rasilla, Marco

2015-01-01

We present here the first cases in Neandertals of congenital clefts of the arch of the atlas. Two atlases from El Sidrón, northern Spain, present respectively a defect of the posterior (frequency in extant modern human populations ranging from 0.73% to 3.84%), and anterior (frequency in extant modern human populations ranging from 0.087% to 0.1%) arch, a condition in most cases not associated with any clinical manifestation. The fact that two out of three observable atlases present a low frequency congenital condition, together with previously reported evidence of retained deciduous mandibular canine in two out of ten dentitions from El Sidrón, supports the previous observation based on genetic evidence that these Neandertals constituted a group with close genetic relations. Some have proposed for humans and other species that the presence of skeletal congenital conditions, although without clinical significance, could be used as a signal of endogamy or inbreeding. In the present case this interpretation would fit the general scenario of high incidence of rare conditions among Pleistocene humans and the specific scenariothat emerges from Neandertal paleogenetics, which points to long-term small and decreasing population size with reduced and isolated groups. Adverse environmental factors affecting early pregnancies would constitute an alternative, non-exclusive, explanation for a high incidence of congenital conditions. Further support or rejection of these interpretations will come from new genetic and skeletal evidence from Neandertal remains. PMID:26418427

Possible Further Evidence of Low Genetic Diversity in the El Sidrón (Asturias, Spain) Neandertal Group: Congenital Clefts of the Atlas.

PubMed

Ríos, Luis; Rosas, Antonio; Estalrrich, Almudena; García-Tabernero, Antonio; Bastir, Markus; Huguet, Rosa; Pastor, Francisco; Sanchís-Gimeno, Juan Alberto; de la Rasilla, Marco

2015-01-01

We present here the first cases in Neandertals of congenital clefts of the arch of the atlas. Two atlases from El Sidrón, northern Spain, present respectively a defect of the posterior (frequency in extant modern human populations ranging from 0.73% to 3.84%), and anterior (frequency in extant modern human populations ranging from 0.087% to 0.1%) arch, a condition in most cases not associated with any clinical manifestation. The fact that two out of three observable atlases present a low frequency congenital condition, together with previously reported evidence of retained deciduous mandibular canine in two out of ten dentitions from El Sidrón, supports the previous observation based on genetic evidence that these Neandertals constituted a group with close genetic relations. Some have proposed for humans and other species that the presence of skeletal congenital conditions, although without clinical significance, could be used as a signal of endogamy or inbreeding. In the present case this interpretation would fit the general scenario of high incidence of rare conditions among Pleistocene humans and the specific scenariothat emerges from Neandertal paleogenetics, which points to long-term small and decreasing population size with reduced and isolated groups. Adverse environmental factors affecting early pregnancies would constitute an alternative, non-exclusive, explanation for a high incidence of congenital conditions. Further support or rejection of these interpretations will come from new genetic and skeletal evidence from Neandertal remains.

Genomic and metabolic characterisation of alkaloid biosynthesis by asexual Epichloë fungal endophytes of tall fescue pasture grasses.

PubMed

Ekanayake, Piyumi N; Kaur, Jatinder; Tian, Pei; Rochfort, Simone J; Guthridge, Kathryn M; Sawbridge, Timothy I; Spangenberg, German C; Forster, John W

2017-06-01

Symbiotic associations between tall fescue grasses and asexual Epichloë fungal endophytes exhibit biosynthesis of alkaloid compounds causing both beneficial and detrimental effects. Candidate novel endophytes with favourable chemotypic profiles have been identified in germplasm collections by screening for genetic diversity, followed by metabolite profile analysis in endogenous genetic backgrounds. A subset of candidates was subjected to genome survey sequencing to detect the presence or absence and structural status of known genes for biosynthesis of the major alkaloid classes. The capacity to produce specific metabolites was directly predictable from metabolic data. In addition, study of duplicated gene structure in heteroploid genomic constitutions provided further evidence for the origin of such endophytes. Selected strains were inoculated into meristem-derived callus cultures from specific tall fescue genotypes to perform isogenic comparisons of alkaloid profile in different host backgrounds, revealing evidence for host-specific quantitative control of metabolite production, consistent with previous studies. Certain strains were capable of both inoculation and formation of longer-term associations with a nonhost species, perennial ryegrass (Lolium perenne L.). Discovery and primary characterisation of novel endophytes by DNA analysis, followed by confirmatory metabolic studies, offers improvements of speed and efficiency and hence accelerated deployment in pasture grass improvement programs.

Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits.

PubMed

Sanchez, Mar M; McCormack, Kai M; Howell, Brittany R

2015-01-01

Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother-infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions.

Social Buffering of Stress Responses in Nonhuman Primates: Maternal Regulation of the Development of Emotional Regulatory Brain Circuits

PubMed Central

McCormack, Kai M.; Howell, Brittany R.

2015-01-01

Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses exists in different animal species, and has been examined in the context of the mother-infant relationship in addition to adults. Although it is a well-known effect, the biological mechanisms, which underlie it, as well as its developmental impact are not well understood. Here we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving we have shown that competent maternal care is critical for the development of healthy attachment, social behavior and emotional and stress regulation, as well as of neural circuits underlying these functions. PMID:26324227

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

Auerbach, Joshua D.; Ahn, Jaimo; Zgonis, Miltiadis H.; Reddy, Sudheer C.; Ecker, Malcolm L.

2008-01-01

The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18553213

Movement of Trace Elements During Residence in the Antarctic Ice: a Laboratory Simulation

NASA Technical Reports Server (NTRS)

Strait, Melissa M.

1991-01-01

Recent work has determined that differences in the trace element distribution between Antarctic eucrites and non-Antarctic eucrites may be due to weathering during residence in the ice, and samples that demonstrate trace element disturbances do not necessarily correspond to eucrites that appear badly weathered to the naked eye. This study constitutes a preliminary test of the idea that long-term residence in the ice is the cause of the trace element disturbances observed in the eucrites. Samples of a non-Antarctic eucrite were leached in water at room temperature conditions. Liquid samples were analyzed for rare earth element abundances using ion chromatography. The results for the short-term study showed little or no evidence that leaching had occurred. However, there were tantalizing hints that something may be happening. The residual solid samples are currently being analyzed for the unleached trace metals using instrumental neutron activation analysis and should show evidence of disturbance if the chromatography clues were real. In addition, another set of samples continues to be intermittently sampled for later analysis. The results should give us information about the movement of trace elements under our conditions and allow us to make some tentative extrapolations to what we observe in actual Antarctic eucrite samples.

Membrane-association of mRNA decapping factors is independent of stress in budding yeast

PubMed Central

Huch, Susanne; Gommlich, Jessie; Muppavarapu, Mridula; Beckham, Carla; Nissan, Tracy

2016-01-01

Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane flotation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation. PMID:27146487

Membrane-association of mRNA decapping factors is independent of stress in budding yeast.

PubMed

Huch, Susanne; Gommlich, Jessie; Muppavarapu, Mridula; Beckham, Carla; Nissan, Tracy

2016-05-05

Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane flotation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation.

Vitamin D, Calcium, and Cardiovascular Disease: a“D”vantageous or “D”etrimental? An era of uncertainty

PubMed Central

Chin, Kathleen; Appel, Lawrence J.; Michos, Erin D.

2017-01-01

While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of on-going large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes “sufficiency” across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation. PMID:28127710

Feature selection from a facial image for distinction of sasang constitution.

PubMed

Koo, Imhoi; Kim, Jong Yeol; Kim, Myoung Geun; Kim, Keun Ho

2009-09-01

Recently, oriental medicine has received attention for providing personalized medicine through consideration of the unique nature and constitution of individual patients. With the eventual goal of globalization, the current trend in oriental medicine research is the standardization by adopting western scientific methods, which could represent a scientific revolution. The purpose of this study is to establish methods for finding statistically significant features in a facial image with respect to distinguishing constitution and to show the meaning of those features. From facial photo images, facial elements are analyzed in terms of the distance, angle and the distance ratios, for which there are 1225, 61 250 and 749 700 features, respectively. Due to the very large number of facial features, it is quite difficult to determine truly meaningful features. We suggest a process for the efficient analysis of facial features including the removal of outliers, control for missing data to guarantee data confidence and calculation of statistical significance by applying ANOVA. We show the statistical properties of selected features according to different constitutions using the nine distances, 10 angles and 10 rates of distance features that are finally established. Additionally, the Sasang constitutional meaning of the selected features is shown here.

A blow to gender equality. Supreme Court judgement on Manushi's case on women's land rights.

PubMed

Reddy, V

1999-01-01

Many scholars take the view that personal laws of various communities are not subject to the constitution. Thus, the constitutional mandate of gender equality, which is to be found in articles 14 and 15 of the constitution, need not be taken into account by community-determined personal laws. The effect of such reasoning is that personal laws are given a free hand to discriminate against women. In the case of Madhu Kishwar against State of Bihar, the Apex Court decision caused a good deal of confusion on this aspect. A three-judge bench considered sections 7 and 8 of the Chotanagpur Tenancy Act, which is applicable to the Scheduled Tribes in Bihar and denies the right of succession to females in favor of males, as constitutional. This decision implies that general principles of equality as laid down in other succession laws cannot be applied to the laws of tribals. In addition, it reflects the general reluctance to let women be economically independent. However, it is proved that the decision is not in accordance with the constitution, making it clear that tribal women are entitled to equal succession rights, as are all women in India.

Feature Selection from a Facial Image for Distinction of Sasang Constitution

PubMed Central

Koo, Imhoi; Kim, Jong Yeol; Kim, Myoung Geun

2009-01-01

Recently, oriental medicine has received attention for providing personalized medicine through consideration of the unique nature and constitution of individual patients. With the eventual goal of globalization, the current trend in oriental medicine research is the standardization by adopting western scientific methods, which could represent a scientific revolution. The purpose of this study is to establish methods for finding statistically significant features in a facial image with respect to distinguishing constitution and to show the meaning of those features. From facial photo images, facial elements are analyzed in terms of the distance, angle and the distance ratios, for which there are 1225, 61 250 and 749 700 features, respectively. Due to the very large number of facial features, it is quite difficult to determine truly meaningful features. We suggest a process for the efficient analysis of facial features including the removal of outliers, control for missing data to guarantee data confidence and calculation of statistical significance by applying ANOVA. We show the statistical properties of selected features according to different constitutions using the nine distances, 10 angles and 10 rates of distance features that are finally established. Additionally, the Sasang constitutional meaning of the selected features is shown here. PMID:19745013

Relationship between traditional Chinese medicine constitutional types with chemotherapy-induced nausea and vomiting in patients with breast cancer: an observational study.

PubMed

Liu, Yi; Pan, Ting; Zou, Wenjing; Sun, Ye; Cai, Yun; Wang, Rui; Han, Pingping; Zhang, Zhe; He, Qunying; Ye, Feng

2016-11-09

The theory of traditional Chinese medicine (TCM) constitution involves genetic characteristics, psychological factors, organ functions, and many other aspects. Studies have shown that TCM constitution is associated with HLA polymorphisms and has a genetic basis. A large number of Chinese studies have suggested that the clinical evolution of breast cancer may differ among patients with different TCM constitutions. In addition, patients with breast cancer and different TCM constitutions may have different degrees of myelosuppression after chemotherapy. Some studies have revealed that some constitutions may become predictive factors for death and morbidity of some diseases. The study was to investigate the risk factors among TCM constitutions for chemotherapy-induced nausea and vomiting (CINV) in patients with primary breast cancer undergoing chemotherapy. From September 2008 to January 2014, 612 patients who underwent surgery and chemotherapy for breast cancer in three hospitals in Xi'an, Shanxi province, underwent TCM constitution assessment using the Nine Basic Constitutions in Chinese Medicine Questionnaire before chemotherapy. CINV was monitored during treatments. Patients were asked to complete the Functional Living Index-Emesis (FLIE) questionnaire. The most severe CINV grade during chemotherapy was recorded according to the WHO standard. The relationships between TCM constitutions, CINV, and clinical and pathological characteristics of the cancers were assessed. There were no differences in the incidence of CINV among breast cancer patients receiving different chemotherapy regimens, and among patients with different TCM constitutions. The wetness-heat score was an independent risk factor for severe CINV (grade III-IV) (OR = 1.012, 95 % CI: 1.007-1.021, P < 0.001). In-depth analyses of the wetness-heat constitution showed that bitter taste/smelly mouth was an independent risk factor for severe CINV (OR = 1.209, 95 % CI: 1.035-1.412, P = 0.017), as well as progesterone receptor-positive cancer (OR = 1.429, 95 % CI: 1.030-1.981, P = 0.032). Vomiting history was a protective factor against CINV (OR = 0.548, 95 % CI: 0.353-0.849, P = 0.007). Risk of grade III-IV nausea and vomiting was higher in breast cancer patients with TCM constitution of wetness-heat, especially bitter taste or smelly mouth.

Rothe Development Corporation v. Department of Defense: The Constitutionality of Federal Contracting Programs for Minority-Owned and Other Small Business

DTIC Science & Technology

2009-03-16

not have sufficient evidence to conclude that there was racial discrimination in defense contracting when it reauthorized the program in 2006. This...report examines the Rothe decision in detail; describes existing contracting programs for minority-owned and women -owned small businesses; and analyzes

Assessment and the Quality of Educational Programmes: What Constitutes Evidence?

ERIC Educational Resources Information Center

Shay, Sueellen; Jawitz, Jeff

2005-01-01

In a climate of growing accountability for Higher Education, there is an increased demand on assessment to play an evaluative role. National, professional and institutional quality assurance systems expect that the assessment of student performance can be used to evaluate the quality of teachers, learners, programmes and even institutions for the…

Construction and Validation of Textbook Analysis Grids for Ecology and Environmental Education

ERIC Educational Resources Information Center

Caravita, Silvia; Valente, Adriana; Luzi, Daniela; Pace, Paul; Valanides, Nicos; Khalil, Iman; Berthou, Guillemette; Kozan-Naumescu, Adrienne; Clement, Pierre

2008-01-01

Knowledge about ecology and environmental education (EE) constitutes a basic tool for promoting a sustainable future, and was a target area of the BIOHEAD-Citizen Project. School textbooks were considered as representative sources of evidence in terms of ecology and environmental education, and were used for comparison among the countries…

Visual Word Recognition by Bilinguals in a Sentence Context: Evidence for Nonselective Lexical Access

ERIC Educational Resources Information Center

Duyck, Wouter; Van Assche, Eva; Drieghe, Denis; Hartsuiker, Robert J.

2007-01-01

Recent research on bilingualism has shown that lexical access in visual word recognition by bilinguals is not selective with respect to language. In the present study, the authors investigated language-independent lexical access in bilinguals reading sentences, which constitutes a strong unilingual linguistic context. In the first experiment,…

Adapting Scale for Children: A Practical Model for Researchers

ERIC Educational Resources Information Center

Aydin, Selami; Harputlu, Leyla; Çelik, Seyda Savran; Ustuk, Özgehan; Güzel, Serhat; Genç, Deniz

2016-01-01

Measurement of children's behaviors in an educational and research context is a problematic and complex area. It is also evident that adapting scales to measure children's behaviors in an educational and research context is a complex process due to several reasons. First, cultural elements constitute a considerable problem. Second, it is difficult…

New Evidence on the Development of the Word "Big."

ERIC Educational Resources Information Center

Sena, Rhonda; Smith, Linda B.

1990-01-01

Results indicate that curvilinear trend in children's understanding of word "big" is not obtained in all stimulus contexts. This suggests that meaning and use of "big" is complex, and may not refer simply to larger objects in a set. Proposes that meaning of "big" constitutes a dynamic system driven by many perceptual,…

Evaluating the Diagnostic Validity of the Facet-Based Formative Assessment System

ERIC Educational Resources Information Center

DeBarger, Angela H.; DiBello, Louis; Minstrell, Jim; Stout, William; Pellegrino, James; Haertel, Geneva; Feng, Mingyu

2011-01-01

The research design and team constitute a multidisciplinary attack on problems of educational and assessment design in physics instruction. Components of the research include: (a) an Evidence-Centered Design analysis of Diagnoser instructional materials and assessments that provides a view of the evidentiary coherence of the existing system; (b)…

Ingraham v. Wright, 498 F.2d 248 (5th Cir. 1974)

ERIC Educational Resources Information Center

Federal Reporter, 2d. Series, 1974

1974-01-01

Text of a Federal Appeals Court case in which parents sought damages and injunctive relief as to use of corporal punishment in a county school system. The evidence established that use of corporal punishment at one school violated due process and the constitutional prohibition against cruel and unusual punishment. (JF)

Successful Collaboration between General Education and Special Education Teachers: A Case Study

ERIC Educational Resources Information Center

Simon, Barbara D.

2017-01-01

The study focused on the experiences of general and special education teachers on what constitutes successful collaboration since there is little evidence existing on the phenomenon. For collaboration to be successful, it must go beyond having two teachers in a classroom delivering instructions. It entails deliberate practices enabling teachers to…

Is BTZ a separate superselection sector of CTMG?

NASA Astrophysics Data System (ADS)

Deser, S.; Franklin, J.

2010-10-01

We exhibit exact solutions of (positive) matter coupled to original “wrong G-sign” cosmological TMG. They all evolve to conical singularity, rather than to black hole - here negative mass - BTZ. This provides evidence that the latter constitute a separate “superselection” sector, one that unlike in GR, is not reachable by physical sources.

Bridging the School-Home Divide in the Middle Grades: A Process for Strengthening School-Family Partnerships

ERIC Educational Resources Information Center

Kyzar, Kathleen; Jimerson, Jo Beth

2018-01-01

Evidence around adolescent learning and development is clear: School-family partnerships matter. However, traditional methods for engaging families that narrowly define who is involved and what constitutes involvement fall short of promoting optimal outcomes. Meaningful family engagement practices involve reciprocal, two-way interactions between…

Foray search: an effective systematic dispersal strategy in fragmented landscapes

Treesearch

L. Conradt; P.A. Zollner; T.J. Roper; C.D. Thomas

2003-01-01

In the absence of evidence to the contrary, population models generally assume that the dispersal trajectories of animals are random, but systematic dispersal could be more efficient at detecting new habitat and may therefore constitute a more realistic assumption. Here, we investigate, by means of simulations, the properties of a potentially widespread systematic...

Organic nitrogen in PM2.5 aerosol at a forest site in the Southeast US

EPA Science Inventory

There is growing evidence that organo-nitrogen compounds may constitute a significant fraction of the aerosol nitrogen (N) budget. In this study, the concentration of organic nitrogen (ON) and major inorganic ions in PM2.5 aerosol were measured at the Duke Forest Research Facilit...

Consensus Report on Impulsive Aggression as a Symptom across Diagnostic Categories in Child Psychiatry: Implications for Medication Studies

ERIC Educational Resources Information Center

Jensen, Peter S.; Youngstrom, Eric A.; Steiner, Hans; Findling, Robert L.; Meyer, Roger E.; Malone, Richard P.; Carlson, Gabrielle A.; Coccaro, Emil F.; Aman, Michael G.; Blair, James; Dougherty, Donald; Ferris, Craig; Flynn, Laurie; Green, Evelyn; Hoagwood, Kimberly; Hutchinson, Janice; Laughren, Tom; Leve, Leslie D.; Novins, Douglas K.; Vitiello, Benedetto

2007-01-01

Objective: To determine whether impulsive aggression (IA) is a meaningful clinical construct and to ascertain whether it is sufficiently similar across diagnostic categories, such that parallel studies across disorders might constitute appropriate evidence for pursuing indications. If so, how should IA be assessed, pharmacological studies…

Freeing Speech: Proverbial Wisdom and Faith Formation as Liberation

ERIC Educational Resources Information Center

Willhauck, Susan

2013-01-01

It is crucial to recover the practice of seeking and refining ways to speak of faith. Certain sayings, idioms, maxims, and proverbs constituting wisdom from various cultures help shape a faith that is liberative, particularly evident in undervalued and dominated cultures. This article examines proverbial wisdom and the patois of the street to…

39 CFR 501.6 - Suspension and revocation of authorization.

Code of Federal Regulations, 2014 CFR

2014-07-01

... decision of PT shall become a final decision of the Postal Service. The appeal may be filed with the Chief Information Officer of the Postal Service and must include all supporting evidence and state with specificity... Information Officer shall constitute a final decision of the Postal Service. (f) An order or final decision...

19 CFR 24.3 - Bills and accounts; receipts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Bills and accounts; receipts. 24.3 Section 24.3... TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.3 Bills and accounts; receipts. (a) Any bill or... document filed by the payer and the payer's cancelled check shall constitute evidence of payment. (c) A...

19 CFR 24.3 - Bills and accounts; receipts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Bills and accounts; receipts. 24.3 Section 24.3... TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.3 Bills and accounts; receipts. (a) Any bill or... document filed by the payer and the payer's cancelled check shall constitute evidence of payment. (c) A...

19 CFR 24.3 - Bills and accounts; receipts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Bills and accounts; receipts. 24.3 Section 24.3... TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.3 Bills and accounts; receipts. (a) Any bill or... document filed by the payer and the payer's cancelled check shall constitute evidence of payment. (c) A...

19 CFR 24.3 - Bills and accounts; receipts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Bills and accounts; receipts. 24.3 Section 24.3... TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.3 Bills and accounts; receipts. (a) Any bill or... document filed by the payer and the payer's cancelled check shall constitute evidence of payment. (c) A...

19 CFR 24.3 - Bills and accounts; receipts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Bills and accounts; receipts. 24.3 Section 24.3... TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.3 Bills and accounts; receipts. (a) Any bill or... document filed by the payer and the payer's cancelled check shall constitute evidence of payment. (c) A...

How to Kill a Journalism School: The Digital Sublime in the Discourse of Discontinuance

ERIC Educational Resources Information Center

McDevitt, Michael; Sindorf, Shannon

2012-01-01

The authors argue that journalism's uncertain identity in academia has made it vulnerable to unreflective instrumentalism in the digital era. They show how instrumentalism intertwined with the digital sublime constitutes a rhetorically resonate rationale for closing a journalism school. Evidence comes from documents and testimony associated with…

Comparisons of Self-Concept Scores of Children in America and in Taiwan.

ERIC Educational Resources Information Center

McDaniel, Ernest D.; Soong, Wanye

Traditional Chinese personality characteristics such as inner harmony, concern for others, submissiveness to authority, and respect for learning so pervade Chinese biographies that they constitute cultural themes. In order to determine whether such themes are more evident in Chinese than in Western youth, a cross-cultural study of self-concept was…

Extending brain-training to the affective domain: increasing cognitive and affective executive control through emotional working memory training.

PubMed

Schweizer, Susanne; Hampshire, Adam; Dalgleish, Tim

2011-01-01

So-called 'brain-training' programs are a huge commercial success. However, empirical evidence regarding their effectiveness and generalizability remains equivocal. This study investigated whether brain-training (working memory [WM] training) improves cognitive functions beyond the training task (transfer effects), especially regarding the control of emotional material since it constitutes much of the information we process daily. Forty-five participants received WM training using either emotional or neutral material, or an undemanding control task. WM training, regardless of training material, led to transfer gains on another WM task and in fluid intelligence. However, only brain-training with emotional material yielded transferable gains to improved control over affective information on an emotional Stroop task. The data support the reality of transferable benefits of demanding WM training and suggest that transferable gains across to affective contexts require training with material congruent to those contexts. These findings constitute preliminary evidence that intensive cognitively demanding brain-training can improve not only our abstract problem-solving capacity, but also ameliorate cognitive control processes (e.g. decision-making) in our daily emotive environments.

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

PubMed Central

Saumell, Sílvia; Solé, Francesc; Arenillas, Leonor; Montoro, Julia; Valcárcel, David; Pedro, Carme; Sanzo, Carmen; Luño, Elisa; Giménez, Teresa; Arnan, Montserrat; Pomares, Helena; De Paz, Raquel; Arrizabalaga, Beatriz; Jerez, Andrés; Martínez, Ana B.; Sánchez-Castro, Judith; Rodríguez-Gambarte, Juan D.; Raya, José M.; Ríos, Eduardo; Rodríguez-Rivera, María; Espinet, Blanca; Florensa, Lourdes

2015-01-01

Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS. PMID:26066831

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

PubMed

Saumell, Sílvia; Solé, Francesc; Arenillas, Leonor; Montoro, Julia; Valcárcel, David; Pedro, Carme; Sanzo, Carmen; Luño, Elisa; Giménez, Teresa; Arnan, Montserrat; Pomares, Helena; De Paz, Raquel; Arrizabalaga, Beatriz; Jerez, Andrés; Martínez, Ana B; Sánchez-Castro, Judith; Rodríguez-Gambarte, Juan D; Raya, José M; Ríos, Eduardo; Rodríguez-Rivera, María; Espinet, Blanca; Florensa, Lourdes

2015-01-01

Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

Enhancing Antitumor Efficacy of Chimeric Antigen Receptor T Cells Through Constitutive CD40L Expression

PubMed Central

Curran, Kevin J; Seinstra, Beatrijs A; Nikhamin, Yan; Yeh, Raymond; Usachenko, Yelena; van Leeuwen, Dayenne G; Purdon, Terence; Pegram, Hollie J; Brentjens, Renier J

2015-01-01

Adoptive cell therapy with genetically modified T cells expressing a chimeric antigen receptor (CAR) is a promising therapy for patients with B-cell acute lymphoblastic leukemia. However, CAR-modified T cells (CAR T cells) have mostly failed in patients with solid tumors or low-grade B-cell malignancies including chronic lymphocytic leukemia with bulky lymph node involvement. Herein, we enhance the antitumor efficacy of CAR T cells through the constitutive expression of CD40 ligand (CD40L, CD154). T cells genetically modified to constitutively express CD40L (CD40L-modified T cells) demonstrated increased proliferation and secretion of proinflammatory TH1 cytokines. Further, CD40L-modified T cells augmented the immunogenicity of CD40+ tumor cells by the upregulated surface expression of costimulatory molecules (CD80 and CD86), adhesion molecules (CD54, CD58, and CD70), human leukocyte antigen (HLA) molecules (Class I and HLA-DR), and the Fas-death receptor (CD95). Additionally, CD40L-modified T cells induced maturation and secretion of the proinflammatory cytokine interleukin-12 by monocyte-derived dendritic cells. Finally, tumor-targeted CD19-specific CAR/CD40L T cells exhibited increased cytotoxicity against CD40+ tumors and extended the survival of tumor-bearing mice in a xenotransplant model of CD19+ systemic lymphoma. This preclinical data supports the clinical application of CAR T cells additionally modified to constitutively express CD40L with anticipated enhanced antitumor efficacy. PMID:25582824

Motes v. Hall County.

PubMed

1983-09-07

In a challenge to Georgia's involuntary sterilization statute, the state Supreme Court ruled that the standard of evidence required by the statute before granting a state-initiated sterilization petition did not meet constitutional requirements. Recognizing procreation as a fundamental right, the court held that authorization of involuntary sterilization of mental incompetents must be based on the elevated standard of "clear and convincing evidence" that the person is irreversibly and incurably mentally incompetent, whether by mental retardation or brain damage, and is unable to care for a child without causing serious mental of physical harm to the child.

Directing bone marrow-derived stromal cell function with mechanics.

PubMed

Potier, E; Noailly, J; Ito, K

2010-03-22

Because bone marrow-derived stromal cells (BMSCs) are able to generate many cell types, they are envisioned as source of regenerative cells to repair numerous tissues, including bone, cartilage, and ligaments. Success of BMSC-based therapies, however, relies on a number of methodological improvements, among which better understanding and control of the BMSC differentiation pathways. Since many years, the biochemical environment is known to govern BMSC differentiation, but more recent evidences show that the biomechanical environment is also directing cell functions. Using in vitro systems that aim to reproduce selected components of the in vivo mechanical environment, it was demonstrated that mechanical loadings can affect BMSC proliferation and improve the osteogenic, chondrogenic, or myogenic phenotype of BMSCs. These effects, however, seem to be modulated by parameters other than mechanics, such as substrate nature or soluble biochemical environment. This paper reviews and discusses recent experimental data showing that despite some knowledge limitation, mechanical stimulation already constitutes an additional and efficient tool to drive BMSC differentiation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

The mysterious human epidermal cell cycle, or an oncogene-induced differentiation checkpoint

PubMed Central

Gandarillas, Alberto

2012-01-01

Fifteen years ago, we reported that proto-oncogene MYC promoted differentiation of human epidermal stem cells, a finding that was surprising to the MYC and the skin research communities. MYC was one of the first human oncogenes identified, and it had been strongly associated with proliferation. However, it was later shown that MYC could induce apoptosis under low survival conditions. Currently, the notion that MYC promotes epidermal differentiation is widely accepted, but the cell cycle mechanisms that elicit this function remain unresolved. We have recently reported that keratinocytes respond to cell cycle deregulation and DNA damage by triggering terminal differentiation. This mechanism might constitute a homeostatic protection face to cell cycle insults. Here, I discuss recent and not-so-recent evidence suggesting the existence of a largely unexplored oncogene-induced differentiation response (OID) analogous to oncogene-induced apoptosis (OIA) or senescence (OIS). In addition, I propose a model for the role of the cell cycle in skin homeostasis maintenance and for the dual role of MYC in differentiation. PMID:23114621

The Problem with Paradigms: Bateman's Worldview as a Case Study.

PubMed

Tang-Martinez, Zuleyma; Ryder, T Brandt

2005-11-01

Bateman's principles, their corollaries and predictions constitute a paradigm for the study of sexual selection theory, evolution of mating systems, parental investment theory, and sexual dimorphism in male and female behavior. Some aspects of this paradigm have been challenged in recent years, while others have been supported by empirical and theoretical research. We re-examine Bateman's 1948 paper in detail, including some methodological problems. Additionally, we review three areas in which an over-reliance on Bateman's predictions about sexual dynamics hindered our ability to understand the potential importance of certain behaviors: 1) male mate choice and sperm allocation; 2) the role of females in initiating and soliciting extra-pair copulations and fertilizations; and 3) the role of females in lekking systems, in which recent evidence suggests that copulations with multiple males (polyandrous behavior) may be common. We conclude this introduction to the symposium by emphasizing the heuristic value of Bateman's contributions, as well as the problems that arise when Bateman's paradigm is viewed through the lens of modern behavioral ecology and evolutionary theory.

Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment

DOE PAGES

An, F. P.; Balantekin, A. B.; Band, H. R.; ...

2016-10-07

Here this Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2 x 10 -4more » $$\\lesssim$$| Δ$$2\\atop{41}$$| $$\\lesssim$$ 0.3 eV 2 . The resulting limits on sin 2 $$2\\theta$$ 14 are improved by approximately a factor of two over previous results and constitute the most stringent constraints to date in the |Δm$$2\\atop{41}$$| $$\\lesssim$$ 0.2 eV 2 region.« less

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

Aartsen, M. G.; Ackermann, M.; Adams, J.

We present an all-sky search for muon neutrinos produced during the prompt γ -ray emission of 1172 gamma-ray bursts (GRBs) with the IceCube Neutrino Observatory. The detection of these neutrinos would constitute evidence for ultra-high-energy cosmic-ray (UHECR) production in GRBs, as interactions between accelerated protons and the prompt γ -ray field would yield charged pions, which decay to neutrinos. A previously reported search for muon neutrino tracks from northern hemisphere GRBs has been extended to include three additional years of IceCube data. A search for such tracks from southern hemisphere GRBs in five years of IceCube data has been introducedmore » to enhance our sensitivity to the highest energy neutrinos. No significant correlation between neutrino events and observed GRBs is seen in the new data. Combining this result with previous muon neutrino track searches and a search for cascade signature events from all neutrino flavors, we obtain new constraints for single-zone fireball models of GRB neutrino and UHECR production.« less

Validation of the Impostor Phenomenon among Managers

PubMed Central

Rohrmann, Sonja; Bechtoldt, Myriam N.; Leonhardt, Mona

2016-01-01

Following up on earlier investigations, the present research aims at validating the construct impostor phenomenon by taking other personality correlates into account and to examine whether the impostor phenomenon is a construct in its own right. In addition, gender effects as well as associations with dispositional working styles and strain are examined. In an online study we surveyed a sample of N = 242 individuals occupying leadership positions in different sectors. Confirmatory factor analyses provide empirical evidence for the discriminant validity of the impostor phenomenon. In accord with earlier studies we show that the impostor phenomenon is accompanied by higher levels of anxiety, dysphoric moods, emotional instability, a generally negative self-evaluation, and perfectionism. The study does not reveal any gender differences concerning the impostor phenomenon. With respect to working styles, persons with an impostor self-concept tend to show perfectionist as well as procrastinating behaviors. Moreover, they report being more stressed and strained by their work. In sum, the findings show that the impostor phenomenon constitutes a dysfunctional personality style. Practical implications are discussed. PMID:27313554

Automatic response activation in sequential affective priming: an ERP study

PubMed Central

Leuthold, Hartmut; Rothermund, Klaus; Schweinberger, Stefan R.

2012-01-01

Affective priming effects denote faster responses when two successively presented affective stimuli match in valence than when they mismatch. Two mechanisms have been proposed for their explanation: (i) Priming of affective information within a semantic network or distributed memory system (semantic priming). (ii) Automatic activation of the evaluative response through the affective prime (response priming). In this experiment, we sought more direct evidence for prime-induced response activations with measurement of the lateralized readiness potential (LRP). Onset of the stimulus-locked LRP was earlier in affectively congruent trials than in incongruent trials. In addition, priming modulated the LRP-amplitude of slow responses, indicating greater activation of the incorrect response hand in affectively incongruent trials. Onset of the response-locked LRP and peak latency of the P300 component were not modulated by priming but the amplitude of the N400 component was. In combination, these results suggest that both, semantic priming and response priming constitute affective priming effects in the evaluative categorization task. PMID:21642351

Resonant intersubband polariton-LO phonon scattering in an optically pumped polaritonic device

NASA Astrophysics Data System (ADS)

Manceau, J.-M.; Tran, N.-L.; Biasiol, G.; Laurent, T.; Sagnes, I.; Beaudoin, G.; De Liberato, S.; Carusotto, I.; Colombelli, R.

2018-05-01

We report experimental evidence of longitudinal optical (LO) phonon-intersubband polariton scattering processes under resonant injection of light. The scattering process is resonant with both the initial (upper polariton) and final (lower polariton) states and is induced by the interaction of confined electrons with longitudinal optical phonons. The system is optically pumped with a mid-IR laser tuned between 1094 cm-1 and 1134 cm-1 (λ = 9.14 μm and λ = 8.82 μm). The demonstration is provided for both GaAs/AlGaAs and InGaAs/AlInAs doped quantum well systems whose intersubband plasmon lies at a wavelength of ≈10 μm. In addition to elucidating the microscopic mechanism of the polariton-phonon scattering, it is found to differ substantially from the standard single particle electron-LO phonon scattering mechanism, and this work constitutes an important step towards the hopefully forthcoming demonstration of an intersubband polariton laser.

Long-Distance Interactions Regulate the Structure and Resilience of Coastal Ecosystems

NASA Astrophysics Data System (ADS)

van de Koppel, Johan; van der Heide, Tjisse; Altieri, Andrew H.; Eriksson, Britas Klemens; Bouma, Tjeerd J.; Olff, Han; Silliman, Brian R.

2015-01-01

Mounting evidence indicates that spatial interactions are important in structuring coastal ecosystems. Until recently, however, most of this work has been focused on seemingly exceptional systems that are characterized by regular, self-organized patterns. In this review, we document that interactions that operate at long distances, beyond the direct neighborhood of individual organisms, are more common and have much more far-reaching implications for coastal ecosystems than was previously realized. We review studies from a variety of ecosystem types—including cobble beaches, mussel beds, coral reefs, seagrass meadows, and mangrove forests—that reveal a startling interplay of positive and negative interactions between habitats across distances of up to a kilometer. In addition to classical feeding relations, alterations of physical conditions constitute an important part of these long-distance interactions. This entanglement of habitats has crucial implications for how humans manage coastal ecosystems, and evaluations of anthropogenic impact should explicitly address long-distance and system-wide effects before we deem these human activities to be causing little harm.

[Contextualized editorial practices: Maria Cecília de Souza Minayo and the journal Ciência & Saúde Coletiva].

PubMed

Spinelli, Hugo; Martinovich, Viviana

2016-01-01

This interview forms part of a series of dialogues that Salud Colectiva has been holding with key editors in the field, with the purpose of examining the similar difficulties confronted by Latin American journals and the diverse ways the journals have faced these difficulties as a likely starting point for uncovering contextualized solutions. In this interview, carried out in 2015 in the Instituto de Salud Colectiva of the Universidad Nacional de Lanús, Maria Cecília de Souza Minayo speaks to us about the context in which the journal Ciência & Saúde Coletiva emerged, the political disputes existing within the collective health field, and the relevance of debate as a constitutive process of science itself. Additionally, Minayo analyzes both the importance of funding to the growth of a journal and the problems and difficulties in obtaining funds, which puts into evidence the lack of policy regarding scientific publishing in Brazil.

Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts.

PubMed

Bosco, Joseph A; Bookman, Jared; Slover, James; Edusei, Emmanuel; Levine, Brett

2015-08-01

Infection is a rare, serious complication following total joint arthroplasty and constitutes a considerable emotional and financial burden for patients, surgeons, and healthcare systems. Prevention of surgical site and periprosthetic joint infections is crucial. This requires knowledge of the microorganisms that commonly cause these infections, including Staphylococcus species. Selection of the appropriate antibiotic regimen to treat infection remains controversial, but cefazolin and cefuroxime are the most commonly recommended antibiotics for prophylaxis. Appropriate timing of administration before surgery, with redosing performed as needed, can help to ensure optimal antibiotic concentration during surgery. Given the increasing evidence that S aureus colonization is a risk factor for periprosthetic joint infection, an exploration of the potential benefits of preoperative S aureus carrier screening and decolonization protocols is warranted. The use of antibiotic-loaded bone cement in primary total joint arthroplasty and antibiotic powder at wound closure are other controversial topics that require additional research. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

ER quality control components UGGT and STT3a are required for activation of defense responses in bir1-1.

PubMed

Zhang, Qian; Sun, Tongjun; Zhang, Yuelin

2015-01-01

The receptor-like kinase SUPPRESSOR OF BIR1, 1 (SOBIR1) functions as a critical regulator in plant immunity. It is required for activation of cell death and defense responses in Arabidopsis bak1-interacting receptor-like kinase 1,1 (bir1-1) mutant plants. Here we report that the ER quality control component UDP-glucose:glycoprotein glucosyltransferase (UGGT) is required for the biogenesis of SOBIR1 and mutations in UGGT suppress the spontaneous cell death and constitutive defense responses in bir1-1. Loss of function of STT3a, which encodes a subunit of the oligosaccharyltransferase complex, also suppresses the autoimmune phenotype in bir1-1. However, it has no effect on the accumulation of SOBIR1, suggesting that additional signaling components other than SOBIR1 may be regulated by ER quality control. Our study provides clear evidence that ER quality control play critical roles in regulating defense activation in bir1-1.

Extending the Search for Muon Neutrinos Coincident with Gamma-Ray Bursts in IceCube Data

NASA Astrophysics Data System (ADS)

Aartsen, M. G.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Samarai, I. Al; Altmann, D.; Andeen, K.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Argüelles, C.; Auffenberg, J.; Axani, S.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; BenZvi, S.; Berley, D.; Bernardini, E.; Besson, D. Z.; Binder, G.; Bindig, D.; Blaufuss, E.; Blot, S.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H.-P.; Bron, S.; Burgman, A.; Carver, T.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cross, R.; Day, M.; de André, J. P. A. M.; De Clercq, C.; del Pino Rosendo, E.; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Eller, P.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fösig, C.-C.; Franckowiak, A.; Friedman, E.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Giang, W.; Gladstone, L.; Glauch, T.; Glüsenkamp, T.; Goldschmidt, A.; Gonzalez, J. G.; Grant, D.; Griffith, Z.; Haack, C.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Hoshina, K.; Huang, F.; Huber, M.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Kang, W.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kheirandish, A.; Kim, J.; Kim, M.; Kintscher, T.; Kiryluk, J.; Kittler, T.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, M.; Krückl, G.; Krüger, C.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Kyriacou, A.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lauber, F.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mancina, S.; Mandelartz, M.; Maruyama, R.; Mase, K.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Micallef, J.; Momenté, G.; Montaruli, T.; Moulai, M.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke Pollmann, A.; Olivas, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Peiffer, P.; Penek, Ö.; Pepper, J. A.; Pérez de los Heros, C.; Pieloth, D.; Pinat, E.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relethford, B.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Rysewyk, D.; Sabbatini, L.; Sanchez Herrera, S. E.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Satalecka, K.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stachurska, J.; Stanev, T.; Stasik, A.; Stettner, J.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Tenholt, F.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Tung, C. F.; Turcati, A.; Unger, E.; Usner, M.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Rossem, M.; van Santen, J.; Vehring, M.; Voge, M.; Vogel, E.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Waza, A.; Weaver, Ch.; Weiss, M. J.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wickmann, S.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wolf, M.; Wood, T. R.; Woolsey, E.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; IceCube Collaboration

2017-07-01

We present an all-sky search for muon neutrinos produced during the prompt γ-ray emission of 1172 gamma-ray bursts (GRBs) with the IceCube Neutrino Observatory. The detection of these neutrinos would constitute evidence for ultra-high-energy cosmic-ray (UHECR) production in GRBs, as interactions between accelerated protons and the prompt γ-ray field would yield charged pions, which decay to neutrinos. A previously reported search for muon neutrino tracks from northern hemisphere GRBs has been extended to include three additional years of IceCube data. A search for such tracks from southern hemisphere GRBs in five years of IceCube data has been introduced to enhance our sensitivity to the highest energy neutrinos. No significant correlation between neutrino events and observed GRBs is seen in the new data. Combining this result with previous muon neutrino track searches and a search for cascade signature events from all neutrino flavors, we obtain new constraints for single-zone fireball models of GRB neutrino and UHECR production.

Kidney Response to the Spectrum of Diet-Induced Acid Stress

PubMed Central

Goraya, Nimrit; Wesson, Donald E.

2018-01-01

Chronic ingestion of the acid (H+)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H+ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H+ excretion is less than the cumulative increment in dietary H+, consistent with H+ retention. This H+ retention associated with the described high dietary H+ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H+ retention does not measurably change plasma acid–base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H+ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H+ injury, which we characterize as “H+ stress”, and the emerging evidence that high dietary H+ constitutes a threat to long-term kidney health. PMID:29751620

A General Reversible Hereditary Constitutive Model. Part 1; Theoretical Developments

NASA Technical Reports Server (NTRS)

Saleeb, A. F.; Arnold, S. M.

1997-01-01

Using an internal-variable formalism as a starting point, we describe the viscoelastic extension of a previously-developed viscoplasticity formulation of the complete potential structure type. It is mainly motivated by experimental evidence for the presence of rate/time effects in the so-called quasilinear, reversible, material response range. Several possible generalizations are described, in the general format of hereditary-integral representations for non-equilibrium, stress-type, state variables, both for isotropic as well as anisotropic materials. In particular, thorough discussions are given on the important issues of thermodynamic admissibility requirements for such general descriptions, resulting in a set of explicit mathematical constraints on the associated kernel (relaxation and creep compliance) functions. In addition, a number of explicit, integrated forms are derived, under stress and strain control to facilitate the parametric and qualitative response characteristic studies reported here, as well as to help identify critical factors in the actual experimental characterizations from test data that will be reported in Part II.

The complex pathophysiology of acquired aplastic anaemia

PubMed Central

Zeng, Y; Katsanis, E

2015-01-01

Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8+ cytotoxic T cells, CD4+ T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure. PMID:25683099

Small solar system bodies as granular systems

NASA Astrophysics Data System (ADS)

Hestroffer, Daniel; Campo Bagatín, Adriano; Losert, Wolfgang; Opsomer, Eric; Sánchez, Paul; Scheeres, Daniel J.; Staron, Lydie; Taberlet, Nicolas; Yano, Hajime; Eggl, Siegfried; Lecomte, Charles-Edouard; Murdoch, Naomi; Radjai, Fahrang; Richardson, Derek C.; Salazar, Marcos; Schwartz, Stephen R.; Tanga, Paolo

2017-06-01

Asteroids and other Small Solar System Bodies (SSSBs) are currently of great scientific and even industrial interest. Asteroids exist as the permanent record of the formation of the Solar System and therefore hold many clues to its understanding as a whole, as well as insights into the formation of planetary bodies. Additionally, SSSBs are being investigated in the context of impact risks for the Earth, space situational awareness and their possible industrial exploitation (asteroid mining). In all these aspects, the knowledge of the geophysical characteristics of SSSB surface and internal structure are of great importance. Given their size, constitution, and the evidence that many SSSBs are not simple monoliths, these bodies should be studied and modelled as self-gravitating granular systems in general, or as granular systems in micro-gravity environments in particular contexts. As such, the study of the geophysical characteristics of SSSBs is a multi-disciplinary effort that lies at the crossroads between Granular Mechanics, Celestial Mechanics, Soil Mechanics, Aerospace Engineering and Computer Sciences.

Self-Reflection and the Inner Voice: Activation of the Left Inferior Frontal Gyrus During Perceptual and Conceptual Self-Referential Thinking

PubMed Central

Morin, Alain; Hamper, Breanne

2012-01-01

Inner speech involvement in self-reflection was examined by reviewing 130 studies assessing brain activation during self-referential processing in key self-domains: agency, self-recognition, emotions, personality traits, autobiographical memory, and miscellaneous (e.g., prospection, judgments). The left inferior frontal gyrus (LIFG) has been shown to be reliably recruited during inner speech production. The percentage of studies reporting LIFG activity for each self-dimension was calculated. Fifty five percent of all studies reviewed indicated LIFG (and presumably inner speech) activity during self-reflection tasks; on average LIFG activation is observed 16% of the time during completion of non-self tasks (e.g., attention, perception). The highest LIFG activation rate was observed during retrieval of autobiographical information. The LIFG was significantly more recruited during conceptual tasks (e.g., prospection, traits) than during perceptual tasks (agency and self-recognition). This constitutes additional evidence supporting the idea of a participation of inner speech in self-related thinking. PMID:23049653

Self-reflection and the inner voice: activation of the left inferior frontal gyrus during perceptual and conceptual self-referential thinking.

PubMed

Morin, Alain; Hamper, Breanne

2012-01-01

Inner speech involvement in self-reflection was examined by reviewing 130 studies assessing brain activation during self-referential processing in key self-domains: agency, self-recognition, emotions, personality traits, autobiographical memory, and miscellaneous (e.g., prospection, judgments). The left inferior frontal gyrus (LIFG) has been shown to be reliably recruited during inner speech production. The percentage of studies reporting LIFG activity for each self-dimension was calculated. Fifty five percent of all studies reviewed indicated LIFG (and presumably inner speech) activity during self-reflection tasks; on average LIFG activation is observed 16% of the time during completion of non-self tasks (e.g., attention, perception). The highest LIFG activation rate was observed during retrieval of autobiographical information. The LIFG was significantly more recruited during conceptual tasks (e.g., prospection, traits) than during perceptual tasks (agency and self-recognition). This constitutes additional evidence supporting the idea of a participation of inner speech in self-related thinking.

The role of warning behaviors in threat assessment: an exploration and suggested typology.

PubMed

Reid Meloy, J; Hoffmann, Jens; Guldimann, Angela; James, David

2012-01-01

The concept of warning behaviors offers an additional perspective in threat assessment. Warning behaviors are acts which constitute evidence of increasing or accelerating risk. They are acute, dynamic, and particularly toxic changes in patterns of behavior which may aid in structuring a professional's judgment that an individual of concern now poses a threat - whether the actual target has been identified or not. They require an operational response. A typology of eight warning behaviors for assessing the threat of intended violence is proposed: pathway, fixation, identification, novel aggression, energy burst, leakage, directly communicated threat, and last resort warning behaviors. Previous research on risk factors associated with such warning behaviors is reviewed, and examples of each warning behavior from various intended violence cases are presented, including public figure assassination, adolescent and adult mass murder, corporate celebrity stalking, and both domestic and foreign acts of terrorism. Practical applications and future research into warning behaviors are suggested. Copyright © 2011 John Wiley & Sons, Ltd.

Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer.

PubMed

Osanai, Makoto; Lee, Gang-Hong

2011-06-01

Tobacco smoke influences cancer development in tissues that are not directly exposed, and epidemiological studies have indicated that smoking women might experience decreased risk of breast cancer as a result of antiestrogenic effects. However, it remains to be clarified whether nicotine, one of the major addictive and best-investigated constituents of tobacco smoke, has any effect on breast cancer. Our recent work demonstrated that the retinoic acid metabolizing enzyme CYP26A1 enhances oncogenic and cell survival properties of breast carcinoma cells, implying a role as an oncogene. Here, we present evidence that nicotine significantly suppresses constitutive expression of CYP26A1, and that cells treated with nicotine exhibit enhanced sensitivity to apoptosis. In addition, nicotine may inhibit anchorage independent growth, cellular invasiveness and motility. These data show that nicotine can limit CYP26A1-mediated oncogenic characteristics, and suggest mechanisms by which nicotine might inhibit breast cancer development. © 2011 Japanese Cancer Association.

Protected by fumigants: beetle perfumes in antimicrobial defense.

PubMed

Gross, Jürgen; Schumacher, Kerstin; Schmidtberg, Henrike; Vilcinskas, Andreas

2008-02-01

Beetles share with other eukaryotes an innate immune system that mediates endogenous defense against pathogens. In addition, larvae of some taxa produce fluid exocrine secretions that contain antimicrobial compounds. In this paper, we provide evidence that larvae of the brassy willow leaf beetle Phratora vitellinae constitutively release volatile glandular secretions that combat pathogens in their microenvironment. We identified salicylaldehyde as the major component of their enveloping perfume cloud, which is emitted by furrow-shaped openings of larval glandular reservoirs and which inhibits in vitro the growth of the bacterial entomopathogen Bacillus thuringiensis. The suggested role of salicylaldehyde as a fumigant in exogenous antimicrobial defense was confirmed in vivo by its removal from glandular reservoirs. This resulted in an enhanced susceptibility of the larvae to infection with the fungal entomopathogens Beauveria bassiana and Metarhizium anisopliae. Consequently, we established the hypothesis that antimicrobial defense in beetles can be expanded beyond innate immunity to include external disinfection of their microenvironment, and we report for the first time the contribution of fumigants to antimicrobial defense in animals.

Nitrogen isotope fractionation by alternative nitrogenases and past ocean anoxia

PubMed Central

Zhang, Xinning; Sigman, Daniel M.; Morel, François M. M.; Kraepiel, Anne M. L.

2014-01-01

Biological nitrogen fixation constitutes the main input of fixed nitrogen to Earth’s ecosystems, and its isotope effect is a key parameter in isotope-based interpretations of the N cycle. The nitrogen isotopic composition (δ15N) of newly fixed N is currently believed to be ∼–1‰, based on measurements of organic matter from diazotrophs using molybdenum (Mo)-nitrogenases. We show that the vanadium (V)- and iron (Fe)-only “alternative” nitrogenases produce fixed N with significantly lower δ15N (–6 to –7‰). An important contribution of alternative nitrogenases to N2 fixation provides a simple explanation for the anomalously low δ15N (<–2‰) in sediments from the Cretaceous Oceanic Anoxic Events and the Archean Eon. A significant role for the alternative nitrogenases over Mo-nitrogenase is also consistent with evidence of Mo scarcity during these geologic periods, suggesting an additional dimension to the coupling between the global cycles of trace elements and nitrogen. PMID:24639508

Thermodynamic, crystallographic, and dielectric study of the nature of glass transitions in cyclo-octanol

NASA Astrophysics Data System (ADS)

Puertas, Ricardo; Rute, Maria A.; Salud, Josep; López, David O.; Diez, Sergio; van Miltenburg, J. Kees; Pardo, Luis C.; Tamarit, Josep Ll.; Barrio, Maria; Pérez-Jubindo, Miguel A.; de La Fuente, Maria R.

2004-06-01

The stable solid polymorphism of cyclooctanol (C8H16O, for short C8 OH) is revealed to be a complex problem and only two stable solid phases, denoted on cooling from the liquid as phases I and II, are found using static (thermodynamic and x-ray diffraction) as well as dynamic (dielectric spectroscopy) experimental techniques. Both solid phases are known to exhibit glass transitions if they are cooled down fast enough to prevent transition to ordered crystalline states. Although glass transitions corresponding to both phases had been well documented by means of specific heat measurements, x-ray measurements constitute, as far as we know, the first evidence from the structural point of view. In addition, a great amount of dielectric works devoted to phase I and its glass transition, were published in the past but next to nothing relating to the dielectric properties of phase II and its glass transition. The nature of the disorder of phase II will be discussed.

Constitutional and occupational risk factors associated with bladder cancer

PubMed Central

Ferrís, J.; Garcia, J.; Berbel, O.; Ortega, J.A.

2016-01-01

Objective Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the etiology of BC. Material and methods Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. Results The main RF were (a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); (b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); (c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); (d) occupational, which represent 5–10% of BC RF; and (f) occupations with high BC risk, such as aluminum production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. Conclusions BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons. PMID:23664103

Tax-Independent Constitutive IκB Kinase Activation in Adult T-Cell Leukemia Cells1

PubMed Central

Hironaka, Noriko; Mochida, Kanako; Mori, Naoki; Maeda, Michiyuki; Yamamoto, Naoki; Yamaoka, Shoji

2004-01-01

Abstract Adult T-cell leukemia (ATL) is a fatal T-cell malignancy that arises long after infection with human T-cell leukemia virus type I (HTLV-I). We reported previously that nuclear factor-κB (NF-κB) was constitutively activated in ATL cells, although expression of the viral proteins was barely detectable, including Tax, which was known to persistently activate NF-κB. Here we demonstrate that ATL cells that do not express detectable Tax protein exhibit constitutive IκB kinase (IKK) activity. Transfection studies revealed that a dominant-negative form of IKK1, and not of IKK2 or NF-κB essential modulator (NEMO), suppressed constitutive NFκB activity in ATL cells. This IKK activity was accompanied by elevated expression of p52, suggesting that the recently described noncanonical pathway of NF-κB activation operates in ATL cells. We finally show that specific inhibition of NF-κB by a super-repressor form of IκBα (SR-IκBα) in HTLV-I-infected T cells results in cell death regardless of Tax expression, providing definitive evidence of an essential role for NF-κB in the survival of ATL cells. In conclusion, the IKK complex is constitutively activated in ATL cells through a cellular mechanism distinct from that of Tax-mediated IKK activation. Further elucidation of this cellular mechanism should contribute to establishing a rationale for treatment of ATL. PMID:15153339

Constitutional and occupational risk factors associated with bladder cancer.

PubMed

Ferrís, J; Garcia, J; Berbel, O; Ortega, J A

2013-09-01

Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the aetiology of BC. Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. The main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

PubMed Central

D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.

2013-01-01

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal. PMID:23221402

Non-convex dissipation potentials in multiscale non-equilibrium thermodynamics

NASA Astrophysics Data System (ADS)

Janečka, Adam; Pavelka, Michal

2018-04-01

Reformulating constitutive relation in terms of gradient dynamics (being derivative of a dissipation potential) brings additional information on stability, metastability and instability of the dynamics with respect to perturbations of the constitutive relation, called CR-stability. CR-instability is connected to the loss of convexity of the dissipation potential, which makes the Legendre-conjugate dissipation potential multivalued and causes dissipative phase transitions that are not induced by non-convexity of free energy, but by non-convexity of the dissipation potential. CR-stability of the constitutive relation with respect to perturbations is then manifested by constructing evolution equations for the perturbations in a thermodynamically sound way (CR-extension). As a result, interesting experimental observations of behavior of complex fluids under shear flow and supercritical boiling curve can be explained.

21 CFR 173.228 - Ethyl acetate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... incorporated by reference. 1 Copies may be obtained from: National Academy Press, 2101 Constitution Ave. NW.../federal_register/code_of_federal_regulations/ibr_locations.html. (b) The additive is used in accordance...

21 CFR 180.30 - Brominated vegetable oil.

Code of Federal Regulations, 2012 CFR

2012-04-01

... material incorporated by reference may be obtained from the National Academy Press, 2101 Constitution Ave...://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (b) The additive is...

21 CFR 173.228 - Ethyl acetate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... incorporated by reference. 1 Copies may be obtained from: National Academy Press, 2101 Constitution Ave. NW.../federal_register/code_of_federal_regulations/ibr_locations.html. (b) The additive is used in accordance...

Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease

PubMed Central

Carbonetto, Peter; Stephens, Matthew

2013-01-01

Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and “Measles” pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14, and FYN) constitute novel putative T1D loci for further study. PMID:24098138

Anisotropic Constitutive Relationships in Energetic Materials: Nitromethane and Rdx

NASA Astrophysics Data System (ADS)

Oleynik, I. I.; Conroy, M.; White, C. T.

2007-12-01

The anisotropic constitutive relationships in solid nitromethane (NM) and α-RDX were studied using first-principles density functional theory (DFT). In addition to hydrostatic compressions, we performed uniaxial compressions in the [100], [010], [001], [110], [101], [011], and [111] directions up to the compression ratio V/V0 = 0.70. Equilibrium properties, including lattice parameters and elastic constants, as well as hydrostatic EOS, are in good agreement with available experimental data. The shear stresses of uniaxially compressed NM and α-RDX were used to predict the relative shock sensitivity between different crystallographic directions.

On the thermodynamics of the Swift-Hohenberg theory

NASA Astrophysics Data System (ADS)

Espath, L. F. R.; Sarmiento, A. F.; Dalcin, L.; Calo, V. M.

2017-11-01

We present the microbalance including the microforces, the first- and second-order microstresses for the Swift-Hohenberg equation concomitantly with their constitutive equations, which are consistent with the free-energy imbalance. We provide an explicit form for the microstress structure for a free-energy functional endowed with second-order spatial derivatives. Additionally, we generalize the Swift-Hohenberg theory via a proper constitutive process. Finally, we present one highly resolved three-dimensional numerical simulation to demonstrate the particular form of the resulting microstresses and their interactions in the evolution of the Swift-Hohenberg equation.

Androgen therapy for delayed male puberty.

PubMed

Ambler, Geoffrey R

2009-06-01

Delayed puberty in men is a commonly presenting problem to paediatricians and an understanding of the available evidence on cause, treatments and outcomes is important to guide practice. Understanding of the regulation of the onset of puberty is gradually unfolding, although the genetic factors that dictate the timing of puberty in individuals and families remain poorly elucidated. Mutations and polymorphisms in candidate genes are being actively studied and it is likely that there is significant overlap between traditional diagnostic categories. Also, environmental endocrine disruptors may interact with the genetic regulation of puberty. Delayed puberty may not always be a benign condition, with increased risks of failing to achieve target height, adverse psychological and educational consequences, delayed sexual and psychosocial integration into society and effects on skeletal proportions and bone mass reported. Appropriate evaluation and follow-up is needed to guide clinical practice, particularly to distinguish constitutional delay in growth and puberty from that associated with other medical disease or permanent disorders. In milder cases of delayed puberty, treatment is often not required; however, considerable evidence exists for the efficacy and safety of short courses of low-dose testosterone therapy for appropriately selected individuals. This treatment is associated with high levels of patient satisfaction. There is not yet sufficient evidence for the routine use of other therapies (e.g. growth hormone, aromatase inhibitors) for constitutional delay in growth and puberty and better characterization of cause may lead to more targeted individual therapy.

Evidence-based medicine meets democracy: the role of evidence-based public health guidelines in local government.

PubMed

Kelly, M P; Atkins, L; Littleford, C; Leng, G; Michie, S

2017-12-01

In 2013, many public health functions transferred from the National Health Service to local government in England. From 2006 NICE had produced public health guidelines based on the principles of evidence-based medicine. This study explores how the guidelines were received in the new environment in local government and related issues raised relating to the use of evidence in local authoritites. In depth, interviews with 31 elected members and officers, including Directors of Public Health, from four very different local government organizations ('local authorities'). Participants reported that (i) there were tensions between evidence-based, and political decision-making; (ii) there were differences in views about what constituted 'good' evidence and (iii) that organizational life is an important mediator in the way evidence is used. Democratic political decision-making does not necessarily naturally align with decision-making based on evidence from the international scientific literature, and local knowledge and local evidence are very important in the ways that public health decisions are made. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health.

American Academy of Pediatrics v. Van de Kamp.

PubMed

1989-10-12

In 1987, the California legislature passed a bill prohibiting abortions on unemancipated minors unless they obtain parental consent, or unless a court determines them to be sufficiently mature to make their own decision. Health care providers challenged the bill's constitutionality, and obtained a preliminary injunction against its implementation. The state appealed the order. The appellate court held that since the California constitution expressly protects a right to privacy, and since California construes this right to cover abortion, to apply equally to minors and adults, and to afford more protection than the parallel federal right, the state must show some compelling interest to justify its bill. Evidence indicated that the state would not meet this burden, so the trial court properly granted a preliminary injunction.

Crater modification by gravity - A mechanical analysis of slumping. [on moon

NASA Technical Reports Server (NTRS)

Melosh, H. J.

1977-01-01

An analysis of the stability of a crater from a mechanical point of view indicates that the observed slumping of lunar craters requires a perfectly plastic constitutive relation for the lunar surface rock. The angle of internal friction of this material must be less than a few degrees. The evidence for a perfectly plastic constitutive relation is described, and a simplified model of a crater in a perfectly plastic medium is used to investigate the nature of its collapse. Crater stability is found to depend principally upon a dimensionless parameter equal to the product of the density, acceleration of gravity, and depth divided by the yield strength. Criteria for stability, 'slope failures', and 'floor failures' are reported.

Phase constitution and interface structure of nano-sized Ag-Cu/AlN multilayers: Experiment and ab initio modeling

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

Pigozzi, Giancarlo; Janczak-Rusch, Jolanta; Passerone, Daniele

2012-10-29

Nano-sized Ag-Cu{sub 8nm}/AlN{sub 10nm} multilayers were deposited by reactive DC sputtering on {alpha}-Al{sub 2}O{sub 3}(0001) substrates. Investigation of the phase constitution and interface structure of the multilayers evidences a phase separation of the alloy sublayers into nanosized grains of Ag and Cu. The interfaces between the Ag grains and the quasi-single-crystalline AlN sublayers are semi-coherent, whereas the corresponding Cu/AlN interfaces are incoherent. The orientation relationship between Ag and AlN is constant throughout the entire multilayer stack. These observations are consistent with atomistic models of the interfaces as obtained by ab initio calculations.

[Health-related strength and power training in seniors: Purpose and recommendations].

PubMed

Donath, Lars; Faude, Oliver; Bopp, Micha; Zahner, Lukas

2015-05-01

The proportion of older people in western societies rapidly increases. Aging-induced disease conditions accompanied with declines in cardiocirculatory and neuromuscular performance constitute a major individual and economic health burden. Besides decreasing vascular and cardiac function during the process of aging, a loss of skeletal muscle mass, muscle structure and function seem to mainly account for decreasing maximal strength, strength development and strength endurance. These findings adversely interfer with static and dynamic postural control and may lead to an increased risk of falling with impairments of autonomy and quality of life. Traditional strength training recommendations basing on health-related exercise prescriptions for elderly people have been proven to counteract or at least attenuate aging-induced declines of neuromuscular muscular function. Multimodal and combined strength and balance training deliver additional improvements of neuromuscular capacity. Recent evidence additionally underpin the need of trunk muscle training and claimed for regimes considering explosive and high-velocity strength training in seniors. High quality RCTs revealed notable strength training effects on mobility, autonomy, quality of life and the reduction of the risk of falling (up to 50%). Available evidence also indicates that various strength training regimes elicit preventive and therapeutic effects on osteoporosis, diabetes type 2 and other chronic diseases, with effect sizes comparable to medication intake. Thus, health care providers, health insurances, Employers' Liability Insurance Associations and politicians should promote infrastructural developments that enable feasible and cost-effective access to health-related fitness centers or other sport facilities (e. g. sport clubs). These environmental requirements should be embedded in multi-centric education programs and campaigns that might enable regularly conducted strength and endurance training perceived as beneficial and valuable from an individual health care perspective.

Methodology for senior-proof guidelines: A practice example from the Netherlands.

PubMed

van Munster, Barbara C; Portielje, Johanna E A; Maier, Andrea B; Arends, Arend J; de Beer, Johannes J A

2018-02-01

Evidence-based guidelines constitute a foundation for medical decision making. It is often unclear whether recommendations in general guidelines also apply to older people. This study aimed to develop a methodology to increase the focus on older people in the development of guidelines. The methodology distinguishes 4 groups of older people: (1) relatively healthy older people; (2) older people with 1 additional specific (interfering) comorbid condition; (3) older people with multimorbidity; and (4) vulnerable older people. The level of focus on older people required may be determined by the prevalence of the disease or condition, level of suffering, social relevance, and the expectation that a guideline may improve the quality of care. A specialist in geriatric medicine may be involved in the guideline process via participation, provision of feedback on drafts, or involvement in the analysis of problem areas. Regarding the patient perspective, it is advised to involve organisations for older people or informal carers in the inventory of problem areas, and additionally to perform literature research of patient values on the subject. If the guideline focuses on older people, then the relative importance of the various outcome measures for this target group needs to be explicitly stated. Search strategies for all the 4 groups are suggested. For clinical studies that focus on the treatment of diseases that frequently occur in older people, a check should be made regarding whether these studies produce the required evidence. This can be achieved by verifying if there is sufficient representation of older people in the studies and determining if there is a separate reporting of results applying to this age group. © 2017 John Wiley & Sons, Ltd.

HIV transmission law in the age of treatment-as-prevention.

PubMed

Haire, Bridget; Kaldor, John

2015-12-01

Evidence that treating people with HIV early in infection prevents transmission to sexual partners has reframed HIV prevention paradigms. The resulting emphasis on HIV testing as part of prevention strategies has rekindled the debate as to whether laws that criminalise HIV transmission are counterproductive to the human rights-based public health response. It also raises normative questions about what constitutes 'safe(r) sex' if a person with HIV has undetectable viral load, which has significant implications for sexual practice and health promotion. This paper discusses a recent high-profile Australian case where HIV transmission or exposure has been prosecuted, and considers how the interpretation of law in these instances impacts on HIV prevention paradigms. In addition, we consider the implications of an evolving medical understanding of HIV transmission, and particularly the ability to determine infectiousness through viral load tests, for laws that relate to HIV exposure (as distinct from transmission) offences. We conclude that defensible laws must relate to appreciable risk. Given the evidence that the transmissibility of HIV is reduced to negligible level where viral load is suppressed, this needs to be recognised in the framing, implementation and enforcement of the law. In addition, normative concepts of 'safe(r) sex' need to be expanded to include sex that is 'protected' by means of the positive person being virally suppressed. In jurisdictions where use of a condom has previously mitigated the duty of the person with HIV to disclose to a partner, this might logically also apply to sex that is 'protected' by undetectable viral load. 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/

Educational Mismatches and Labor Market Outcomes: Evidence from Both Vertical and Horizontal Mismatches in Thailand

ERIC Educational Resources Information Center

Pholphirul, Piriya

2017-01-01

Purpose: Educational mismatches constitute negative impacts on labor markets in most countries, Thailand is no exception. The purpose of this paper is to quantify the degree of educational mismatch in Thailand and its impacts on labor market outcomes. Design/methodology/approach: This study analyzes data obtained from Thailand's Labor Force Survey…

"Teach For"/"Teach First" Candidates: What Conclusions Do They Draw from Their Time in Teaching?

ERIC Educational Resources Information Center

Rice, Suzanne; Volkoff, Veronica; Dulfer, Nicky

2015-01-01

"Teach For" and "Teach First" programs now constitute a significant pathway into teaching in a number of countries. One criterion for selection into these programs is leadership capacity, and evidence indicates that many candidates do move into leadership roles in education, business, and policy in the years following their…

Critical Issues in Specific Learning Disability Identification: What We Need to Know about the PSW Model

ERIC Educational Resources Information Center

McGill, Ryan J.; Styck, Kara M.; Palomares, Ronald S.; Hass, Michael R.

2016-01-01

As a result of the upcoming Federal reauthorization of the Individuals With Disabilities Education Improvement Act (IDEA), practitioners and researchers have begun vigorously debating what constitutes evidence-based assessment for the identification of specific learning disability (SLD). This debate has resulted in strong support for a method that…

Biochemistry, Structure and Function of Non-Wheat Proteins: Case Study of Barley ß-Amylase

USDA-ARS?s Scientific Manuscript database

The importance of a protein is not always evident and may be due to its multifunctional nature. ß-Amylase in seeds of barley (Hordeum vulgare L.) constitutes approximately 2% of the total protein in mature seeds and is assumed to be important when storage proteins are mobilized to support protein s...

Teachers' Assumptions Regarding the Severity, Causes, and Outcomes of Behavioral Problems in Preschoolers: Implications for Referral.

ERIC Educational Resources Information Center

Walker, Elaine; And Others

1984-01-01

Asked preschool teachers (N=100) to rate severity, long-term outcome, stability, and importance of constitutional and environmental determinants for case vignettes describing three syndromes: aggression, hyperactivity, and withdrawal, and to judge the need for referral. Results indicated little evidence of sex bias in teachers' evaluations of the…

Perception vs. Evidence: An Analysis of "This" and "These" in Academic Prose

ERIC Educational Resources Information Center

Gray, Bethany; Cortes, Viviana

2011-01-01

This study investigates the use of "this" and "these" as pronouns versus determiners in a corpus of research articles in Applied Linguistics and Materials and Civil Engineering. The study reveals that authors in the two disciplines use both structures in a similar manner, with pronominal uses constituting one-fifth of all occurrences. Five types…

Does Research Degree Supervisor Training Work? The Impact of a Professional Development Induction Workshop on Supervision Practice

ERIC Educational Resources Information Center

McCulloch, Alistair; Loeser, Cassandra

2016-01-01

Supervisor induction and continued professional development programmes constitute good practice and are enshrined in institutional policies and national codes of practice. However, there is little evidence about whether they have an impact on either supervisors' learning or day-to-day practice. Set in a discussion of previous literature, this…

An Inquiry into the Impact of Admissions Policy that Diversifies the Selection of Pre-Service Teacher Education Candidates

ERIC Educational Resources Information Center

Stead, Virginia

2006-01-01

The world of educational quality in 2006 is infused with conflicting ecopolitical agendas that constitute evidence of social strain and what Cherry Banks (2006) calls the tension between unity and diversity. That tension is increasingly prevalent among growing multicultural communities where centuries of inadequate educational funding have created…

"Elven Elder LVL59 LFP/RB. Please PM Me": Immersion, Collaborative Tasks and Problem-Solving in Massively Multiplayer Online Games

ERIC Educational Resources Information Center

Voulgari, Iro; Komis, Vassilis

2010-01-01

Although there is strong evidence that massively multiplayer online games (MMOGs) constitute environments of social interactions and effective learning, we currently lack the tools for investigating the effectiveness of the social networks emerging as well as the cognitive aspects and knowledge acquisition such environments involve. Within this…

A Fool and His Money Are Soon Parted

ERIC Educational Resources Information Center

Manuel, Kate; Morony, Will

2011-01-01

There is persistent evidence of poor levels of financial literacy in a number of sectors of the Australian community. Young people, in particular, tend to fare badly in studies of financial literacy levels. A recent study commissioned by the Commonwealth Bank Foundation found that 16-25 year-olds constitute 42% of the bottom quartile, and only 4%…

Psychological Autopsy Studies as Diagnostic Tools: Are They Methodologically Flawed?

ERIC Educational Resources Information Center

Hjelmeland, Heidi; Dieserud, Gudrun; Dyregrov, Kari; Knizek, Birthe L.; Leenaars, Antoon A.

2012-01-01

One of the most established "truths" in suicidology is that almost all (90% or more) of those who kill themselves suffer from one or more mental disorders, and a causal link between the two is implied. Psychological autopsy (PA) studies constitute one main evidence base for this conclusion. However, there has been little reflection on the…

A Qualitative Analysis of Faculty and Student Perceptions of Effective Online Class Communities Using Herzberg's Motivator-Hygiene Factors

ERIC Educational Resources Information Center

Costello, Rebecca; Welch, S. A.

2014-01-01

This article describes a qualitative approach in understanding factors that are evident in effective online class communities. Instructors and students in the same class were asked about their perceptions regarding what constitutes an effective online experience. The analysis was done using both Herzberg's (1962, 1965) motivator-hygiene factors…

21 CFR 1140.32 - Format and content requirements for labeling and advertising.

Code of Federal Regulations, 2012 CFR

2012-04-01

...: (i) Whose readers younger than 18 years of age constitute 15 percent or less of the total readership... persons younger than 18 years of age as measured by competent and reliable survey evidence. (b) Labeling and advertising in an audio or video format shall be limited as follows: (1) Audio format shall be...

21 CFR 1140.32 - Format and content requirements for labeling and advertising.

Code of Federal Regulations, 2014 CFR

2014-04-01

...: (i) Whose readers younger than 18 years of age constitute 15 percent or less of the total readership... persons younger than 18 years of age as measured by competent and reliable survey evidence. (b) Labeling and advertising in an audio or video format shall be limited as follows: (1) Audio format shall be...

21 CFR 1140.32 - Format and content requirements for labeling and advertising.

Code of Federal Regulations, 2011 CFR

2011-04-01

...: (i) Whose readers younger than 18 years of age constitute 15 percent or less of the total readership... persons younger than 18 years of age as measured by competent and reliable survey evidence. (b) Labeling and advertising in an audio or video format shall be limited as follows: (1) Audio format shall be...

21 CFR 1140.32 - Format and content requirements for labeling and advertising.

Code of Federal Regulations, 2013 CFR

2013-04-01

...: (i) Whose readers younger than 18 years of age constitute 15 percent or less of the total readership... persons younger than 18 years of age as measured by competent and reliable survey evidence. (b) Labeling and advertising in an audio or video format shall be limited as follows: (1) Audio format shall be...

21 CFR 1140.32 - Format and content requirements for labeling and advertising.

Code of Federal Regulations, 2010 CFR

2010-04-01

...: (i) Whose readers younger than 18 years of age constitute 15 percent or less of the total readership... persons younger than 18 years of age as measured by competent and reliable survey evidence. (b) Labeling and advertising in an audio or video format shall be limited as follows: (1) Audio format shall be...

A-Z of management and finance in the NHS: outcomes and use of resources.

PubMed

Batstone, G

In general, clinical outcomes are the product of clinical practice and good outcomes are associated with the judicious application of the best available evidence of what constitutes good practice. From the patient's viewpoint this application needs to be tempered by personal choice, cultural beliefs, and questions of optimal time and location of treatment.

Tier 2 Interventions in Positive Behavior Support: A Survey of School Implementation

ERIC Educational Resources Information Center

Rodriguez, Billie Jo; Loman, Sheldon L.; Borgmeier, Christopher

2016-01-01

As increasing numbers of schools implement Multi-Tiered Systems of Support (MTSS), schools are looking for and implementing evidence-based practices for students whose needs are not fully met by Tier 1 supports. Although there is relative consistency and clarity in what constitutes Tier 1 behavior support within MTSS, Tier 2 supports may be more…

26 CFR 301.7425-4 - Discharge of liens; redemption by United States.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pursuant to paragraph (c)(1) of this section, shall constitute prima facie evidence of the regularity of... the holder of the lien being foreclosed, shall include the amount of the obligation secured by such... lien being foreclosed, the actual amount paid is the sum of (A) the amount of the obligation secured by...

Two new Liolaemus lizards from the Andean highlands of Southern Chile (Squamata, Iguania, Liolaemidae)

PubMed Central

Troncoso-Palacios, Jaime; Diaz, Hugo A.; Puas, German I.; Riveros-Riffo, Edvin; Elorza, Alvaro A.

2016-01-01

Abstract Liolaemus is a diverse genus of lizards, subdivided into two subgenera: Liolaemus (sensu stricto) and Eulaemus, distributed mainly in Chile and Argentina. The Liolaemus elongatus-kriegi complex is the most diverse group within Liolaemus (sensu stricto), especially the species closely related to Liolaemus elongatus, which form a clade currently comprising nine species. Several Chilean species of this group have been recently described, mainly from volcanoes and poorly explored mountains. Here molecular and morphological evidence are provided for a new species of the Liolaemus elongatus clade, which is characterized by its small size and lack of dorsal pattern, unusual features for the species of this group of lizards. Additionally, the lack of precloacal pores in males of Liolaemus (sensu stricto) is a trait found in few species, which do not constitute a monophyletic group. A second new southern Chilean species is also described, without precloacal pores and supported by molecular phylogenetics to be related to Liolaemus villaricensis. Both new species were found in the same locality, near a lake located in a pre-Andean zone with Araucaria and Nothofagus forest. The two species are dedicated to prominent Lonkos (tribal chiefs) of the Mapuche and Pehuenche people: Janequeo and Leftraru. Additionally, the phylogenetic results suggest that Liolaemus lonquimayensis is a synonym of Liolaemus elongatus. PMID:27920609

The Evolving Construct of Posttraumatic Stress Disorder (PTSD): DSM-5 Criteria Changes and Legal Implications

PubMed Central

Zoellner, Lori A.; Bedard-Gilligan, Michele A.; Jun, Janie J.; Marks, Libby H.; Garcia, Natalia M.

2014-01-01

In the DSM-5, the diagnosis of posttraumatic stress disorder (PTSD) has undergone multiple, albeit minor, changes. These changes include shifting PTSD placement from within the anxiety disorders into a new category of traumatic and stressor-related disorders, alterations in the definition of a traumatic event, shifting of the symptom cluster structure from three to four clusters, the addition of new symptoms including persistent negative beliefs and expectations about oneself or the world, persistent distorted blame of self or others, persistent negative trauma-related emotions, and risky or reckless behaviors, and the addition of a dissociative specifier. The evidence or lack thereof behind each of these changes is briefly reviewed. These changes, although not likely to change overall prevalence, have the potential to increase the heterogeneity of individuals receiving a PTSD diagnosis both by altering what qualifies as a traumatic event and by adding symptoms commonly occurring in other disorders such as depression, borderline personality disorder, and dissociative disorders. Legal implications of these changes include continued confusion regarding what constitutes a traumatic stressor, difficulties with differential diagnosis, increased ease in malingering, and improper linking of symptoms to causes of behavior. These PTSD changes are discussed within the broader context of DSM reliability and validity concerns. PMID:24470838

Abundant constitutive expression of the immediate-early 94K protein from cytomegalovirus (Colburn) in a DNA-transfected mouse cell line

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

Jeang, K.T.; Cho, M.S.; Hayward, G.S.

1984-10-01

A 94-kilodalton phosphoprotein known as IE94 is the only viral polypeptide synthesized in abundance under immediate-early conditions after infection by cytomegalovirus (CMV) strain Colburn in either permissive primate or nonpermissive rodent cells. The authors isolated a clonal Ltk/sup +/ cell line which expressed the /sup 35/methionine-labeled IE94 polypeptide in sufficient abundance to be visualized directly in autoradiographs after gel electrophoresis of total-cell-culture protein extracts. The IE94 polypeptide synthesized in the transfected cells was indistinguishable in size and overall net charge from that produced in virus-infected cells. In addition, the IE94 protein expressed in LH/sub 2/p198-3 cells was phosphorylated (presumably bymore » a cellular protein kinase) and generated similar phosphopeptide patterns after partial tryptic digestion to those obtained with the CMV IE94 protein from infected cells. The cell line contained two to four stably integrated copies of the IE94 gene and synthesized a single virus-specific mRNA of 2.5 kilobases detectable on Northern blots. A new antigen, detectable by indirect anticomplement immunofluorescence with monoclonal antibody against the human CMV IE68 protein, was present in the nuclei of more than 95% of the LH/sub 2/l198-3 cells. This evidence suggests that (unlike most herpesvirus genes) the CMV IE94 gene, together with its complex promoter and spliced mRNA structure, may contain all of the regulatory elements necessary for strong constitutive expression in mammalian cells in the absence of other viral factors.« less

Negative impact of urban habitat on immunity in the great tit Parus major.

PubMed

Bailly, Juliette; Scheifler, Renaud; Belvalette, Marie; Garnier, Stéphane; Boissier, Elena; Clément-Demange, Valérie-Anne; Gète, Maud; Leblond, Matthieu; Pasteur, Baptiste; Piget, Quentin; Sage, Mickaël; Faivre, Bruno

2016-12-01

Urban habitats are described as having an overall negative influence on many fitness-related traits in several bird species, but a vital function such as immunity remains poorly studied. The immune response is strongly linked to individual condition, which partly depends on resource availability and the parasitic context that often differ between urban and natural habitats. A difference between the immunity of populations dwelling in urban areas and populations from more natural habitats can, therefore, be hypothesized. We conducted a 2-year experimental study on great tits (Parus major) in urban and forest areas. We stimulated the constitutive immunity of nestlings and assessed both the inflammatory response by measuring the plasma levels of haptoglobin, an inflammatory marker, and its activation cost through the loss of body mass. In addition, we checked the nestlings for ectoparasites and assessed haemosporidian prevalence in adults. Nestlings from urban sites produced relatively less haptoglobin and lost more body mass than those from forest sites, which suggests that the activation of constitutive immunity is more costly for birds living in urban sites than for those living in the forest. We detected no ectoparasite in birds in both habitats. However, urban adults showed lower haemosporidian prevalence than forest ones, suggesting a reduced exposure to these parasites and their vectors in towns. Overall, our study provides evidence for an immune difference between urban and forest populations. Because immunity is crucial for organism fitness, it is of prime interest to identify causes and processes at the origin of this difference.

A Broad G Protein-Coupled Receptor Internalization Assay that Combines SNAP-Tag Labeling, Diffusion-Enhanced Resonance Energy Transfer, and a Highly Emissive Terbium Cryptate.

PubMed

Levoye, Angélique; Zwier, Jurriaan M; Jaracz-Ros, Agnieszka; Klipfel, Laurence; Cottet, Martin; Maurel, Damien; Bdioui, Sara; Balabanian, Karl; Prézeau, Laurent; Trinquet, Eric; Durroux, Thierry; Bachelerie, Françoise

2015-01-01

Although G protein-coupled receptor (GPCR) internalization has long been considered as a major aspect of the desensitization process that tunes ligand responsiveness, internalization is also involved in receptor resensitization and signaling, as well as the ligand scavenging function of some atypical receptors. Internalization thus contributes to the diversity of GPCR-dependent signaling, and its dynamics and quantification in living cells has generated considerable interest. We developed a robust and sensitive assay to follow and quantify ligand-induced and constitutive-induced GPCR internalization but also receptor recycling in living cells. This assay is based on diffusion-enhanced resonance energy transfer (DERET) between cell surface GPCRs labeled with a luminescent terbium cryptate donor and a fluorescein acceptor present in the culture medium. GPCR internalization results in a quantifiable reduction of energy transfer. This method yields a high signal-to-noise ratio due to time-resolved measurements. For various GPCRs belonging to different classes, we demonstrated that constitutive and ligand-induced internalization could be monitored as a function of time and ligand concentration, thus allowing accurate quantitative determination of kinetics of receptor internalization but also half-maximal effective or inhibitory concentrations of compounds. In addition to its selectivity and sensitivity, we provided evidence that DERET-based internalization assay is particularly suitable for characterizing biased ligands. Furthermore, the determination of a Z'-factor value of 0.45 indicates the quality and suitability of DERET-based internalization assay for high-throughput screening (HTS) of compounds that may modulate GPCRs internalization.

A Broad G Protein-Coupled Receptor Internalization Assay that Combines SNAP-Tag Labeling, Diffusion-Enhanced Resonance Energy Transfer, and a Highly Emissive Terbium Cryptate

PubMed Central

Levoye, Angélique; Zwier, Jurriaan M.; Jaracz-Ros, Agnieszka; Klipfel, Laurence; Cottet, Martin; Maurel, Damien; Bdioui, Sara; Balabanian, Karl; Prézeau, Laurent; Trinquet, Eric; Durroux, Thierry; Bachelerie, Françoise

2015-01-01

Although G protein-coupled receptor (GPCR) internalization has long been considered as a major aspect of the desensitization process that tunes ligand responsiveness, internalization is also involved in receptor resensitization and signaling, as well as the ligand scavenging function of some atypical receptors. Internalization thus contributes to the diversity of GPCR-dependent signaling, and its dynamics and quantification in living cells has generated considerable interest. We developed a robust and sensitive assay to follow and quantify ligand-induced and constitutive-induced GPCR internalization but also receptor recycling in living cells. This assay is based on diffusion-enhanced resonance energy transfer (DERET) between cell surface GPCRs labeled with a luminescent terbium cryptate donor and a fluorescein acceptor present in the culture medium. GPCR internalization results in a quantifiable reduction of energy transfer. This method yields a high signal-to-noise ratio due to time-resolved measurements. For various GPCRs belonging to different classes, we demonstrated that constitutive and ligand-induced internalization could be monitored as a function of time and ligand concentration, thus allowing accurate quantitative determination of kinetics of receptor internalization but also half-maximal effective or inhibitory concentrations of compounds. In addition to its selectivity and sensitivity, we provided evidence that DERET-based internalization assay is particularly suitable for characterizing biased ligands. Furthermore, the determination of a Z′-factor value of 0.45 indicates the quality and suitability of DERET-based internalization assay for high-throughput screening (HTS) of compounds that may modulate GPCRs internalization. PMID:26617570

Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.

PubMed

Rogalski, Emily; Sridhar, Jaiashre; Rader, Benjamin; Martersteck, Adam; Chen, Kewei; Cobia, Derin; Thompson, Cynthia K; Weintraub, Sandra; Bigio, Eileen H; Mesulam, M-Marsel

2016-09-27

To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. © 2016 American Academy of Neurology.

Flower-specific KNOX phenotype in the orchid Dactylorhiza fuchsii

PubMed Central

Box, Mathew S.; Glover, Beverley J.

2012-01-01

The KNOTTED1-like homeobox (KNOX) genes are best known for maintaining a pluripotent stem-cell population in the shoot apical meristem that underlies indeterminate vegetative growth, allowing plants to adapt their development to suit the prevailing environmental conditions. More recently, the function of the KNOX gene family has been expanded to include additional roles in lateral organ development such as complex leaf morphogenesis, which has come to dominate the KNOX literature. Despite several reports implicating KNOX genes in the development of carpels and floral elaborations such as petal spurs, few authors have investigated the role of KNOX genes in flower development. Evidence is presented here of a flower-specific KNOX function in the development of the elaborate flowers of the orchid Dactylorhiza fuchsii, which have a three-lobed labellum petal with a prominent spur. Using degenerate PCR, four Class I KNOX genes (DfKN1–4) have been isolated, one from each of the four major Class I KNOX subclades and by reverse transcription PCR (RT-PCR), it is demonstrated that DfKNOX transcripts are detectable in developing floral organs such as the spur-bearing labellum and inferior ovary. Although constitutive expression of the DfKN2 transcript in tobacco produces a wide range of floral abnormalities, including serrated petal margins, extra petal tissue, and fused organs, none of the vegetative phenotypes typical of constitutive KNOX expression were produced. These data are highly suggestive of a role for KNOX expression in floral development that may be especially important in taxa with elaborate flowers. PMID:22771852

Positive and Negative Consequences of Making Coffee among Breakfast Related Irrelevant Objects: Evidence from MCI, Dementia, and Healthy Ageing.

PubMed

Rodríguez-Bailón, María; García-Morán, Tamara; Montoro-Membila, Nuria; Ródenas-García, Estrella; Montoro, Marisa Arnedo; Funes Molina, María Jesús

2017-07-01

Previous studies have reported impairments in activities of daily living (ADL) performance in the presence of irrelevant but physically/functionally related objects in dementia patients. The aim of the present study was to increase our knowledge about the impact of the presence of contextually related non-target objects on ADL execution in patients with multi-domain mild cognitive impairment (MCI) and dementia. We compared ADL execution in patients with MCI, dementia, and healthy elderly participants under two experimental conditions: One in which the target objects were embedded with contextually related non-target items that constituted the object set necessary to complete two additional (but unrequired) ADL tasks related to the target task, and a second, control condition where target objects were surrounded by isolated objects (they never constituted a whole set needed to complete an alternative ADL task). Separate analysis of ADL errors associated with the target task versus errors involving the non-target objects revealed that, although the presence of contextually related objects facilitated the accomplishment of the target task, such a condition also led to errors involving the use of irrelevant objects in dementia and MCI. The presence of contextually related non-target items produces both positive and negative effects on ADL performance. These types of non-target objects might help to cue the retrieval of the action schema related to the target task, particularly in patients with MCI. In contrast, the presence of these objects might also lead to distraction in dementia and MCI. (JINS, 2017, 23, 481-492).

Molecular evidence of cryptic speciation in the "cosmopolitan" excavating sponge Cliona celata (Porifera, Clionaidae).

PubMed

Xavier, J R; Rachello-Dolmen, P G; Parra-Velandia, F; Schönberg, C H L; Breeuwer, J A J; van Soest, R W M

2010-07-01

Over the past several decades molecular tools have shown an enormous potential to aid in the clarification of species boundaries in the marine realm, particularly in morphologically simple groups. In this paper we report a case of cryptic speciation in an allegedly cosmopolitan and ecologically important species-the excavating sponge Cliona celata (Clionaidae, Hadromerida). In the Northeast Atlantic and Mediterranean C. celata displays a discontinuous distribution of its putative growth stages (boring, encrusting, and massive) leading us to investigate its specific status. Phylogenetic reconstructions of mitochondrial (COI, Atp8) and nuclear (28S) gene fragments revealed levels of genetic diversity and divergence compatible with interspecific relationships. We therefore demonstrate C. celata as constituting a species complex comprised of at least four morphologically indistinct species, each showing a far more restricted distribution: two species on the Atlantic European coasts and two on the Mediterranean and adjacent Atlantic coasts (Macaronesian islands). Our results provide further confirmation that the different morphotypes do indeed constitute either growth stages or ecologically adapted phenotypes as boring and massive forms were found in two of the four uncovered species. We additionally provide an overview of the cases of cryptic speciation which have been reported to date within the Porifera, and highlight how taxonomic crypsis may confound scientific interpretation and hamper biotechnological advancement. Our work together with previous studies suggests that overconservative systematic traditions but also morphological stasis have led to genetic complexity going undetected and that a DNA-assisted taxonomy may play a key role in uncovering the hidden diversity in this taxonomic group. Copyright 2010 Elsevier Inc. All rights reserved.

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors

PubMed Central

Lindeman, Neal I.; Cagle, Philip T.; Beasley, Mary Beth; Chitale, Dhananjay Arun; Dacic, Sanja; Giaccone, Giuseppe; Jenkins, Robert Brian; Kwiatkowski, David J.; Saldivar, Juan-Sebastian; Squire, Jeremy; Thunnissen, Erik; Ladanyi, Marc

2014-01-01

Objective To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Participants Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Evidence Three unbiased literature searches of electronic databases were performed to capture articles published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Consensus Process Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). Conclusions The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines. PMID:23551194

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors

PubMed Central

Lindeman, Neal I.; Cagle, Philip T.; Beasley, Mary Beth; Chitale, Dhananjay Arun; Dacic, Sanja; Giaccone, Giuseppe; Jenkins, Robert Brian; Kwiatkowski, David J.; Saldivar, Juan-Sebastian; Squire, Jeremy; Thunnissen, Erik; Ladanyi, Marc

2014-01-01

Objective To establish evidence-based recommendations for the molecular analysis of lung cancers that are that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Participants Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Evidence Three unbiased literature searches of electronic databases were performed to capture articles published published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Consensus Process Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). Conclusions The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines. PMID:23552377

Multidimensional Diagnostic Criteria for Chronic Pain: Introduction to the ACTTION-American Pain Society Pain Taxonomy (AAPT).

PubMed

Dworkin, Robert H; Bruehl, Stephen; Fillingim, Roger B; Loeser, John D; Terman, Gregory W; Turk, Dennis C

2016-09-01

A variety of approaches have been used to develop diagnostic criteria for chronic pain. The published evidence of the reliability and validity of existing diagnostic criteria is limited, and these criteria have typically not been used in clinical practice. The availability of a widely accepted, consistently applied, and evidence-based taxonomy of diagnostic criteria would improve the quality of clinical research on chronic pain and would be of great value in clinical practice. To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS) have collaborated on the development of the ACTTION-APS Pain Taxonomy (AAPT). AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. This article (1) describes the background and rationale for AAPT; (2) presents the AAPT taxonomy and the specific conditions for which diagnostic criteria have been developed (to be published separately); (3) briefly reviews the 5 dimensions that constitute the AAPT multidimensional framework and describes the 7 accompanying articles that discuss these dimensions and other important issues involving AAPT; and (4) provides an overview of next steps, specifically, the general processes by which the initial set of diagnostic criteria (for which the evidence base has been drawn from the literature, systematic reviews, and secondary analyses of existing databases) will undergo additional assessments of reliability and validity. To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. The long-term objective of AAPT is to advance the scientific understanding of chronic pain and its treatment. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Screen Violence and Youth Behavior.

PubMed

Anderson, Craig A; Bushman, Brad J; Bartholow, Bruce D; Cantor, Joanne; Christakis, Dimitri; Coyne, Sarah M; Donnerstein, Edward; Brockmyer, Jeanne Funk; Gentile, Douglas A; Green, C Shawn; Huesmann, Rowell; Hummer, Tom; Krahé, Barbara; Strasburger, Victor C; Warburton, Wayne; Wilson, Barbara J; Ybarra, Michele

2017-11-01

Violence in screen entertainment media (ie, television, film, video games, and the Internet), defined as depictions of characters (or players) trying to physically harm other characters (or players), is ubiquitous. The Workgroup on Media Violence and Violent Video Games reviewed numerous meta-analyses and other relevant research from the past 60 years, with an emphasis on violent video game research. Consistent with every major science organization review, the Workgroup found compelling evidence of short-term harmful effects, as well as evidence of long-term harmful effects. The vast majority of laboratory-based experimental studies have revealed that violent media exposure causes increased aggressive thoughts, angry feelings, physiologic arousal, hostile appraisals, aggressive behavior, and desensitization to violence and decreases prosocial behavior (eg, helping others) and empathy. Still, to more fully understand the potential for long-term harm from media violence exposure, the field is greatly in need of additional large-sample, high-quality, longitudinal studies that include validated measures of media violence exposure and measures of other known violence risk factors. Also, although several high-quality media violence intervention studies have been conducted, larger-scale studies with more comprehensive and longer-term assessments are needed to fully understand long-term effects and to inform the development of tools that will help to reduce problems associated with aggression and violence. The evidence that violent screen media constitutes a causal risk factor for increased aggression is compelling. Modern social-cognitive theories of social behavior provide useful frameworks for understanding how and why these effects occur. Copyright © 2017 by the American Academy of Pediatrics.

CD16b associates with high-density, detergent-resistant membranes in human neutrophils

PubMed Central

Fernandes, Maria J. G.; Rollet-Labelle, Emmanuelle; Paré, Guillaume; Marois, Sébastien; Tremblay, Marie-Lisane; Teillaud, Jean-Luc; Naccache, Paul H.

2005-01-01

CD16b is unique in that it is the only Fc receptor linked to the plasma membrane by a GPI (glycosylphosphatidylinositol) anchor. GPI-anchored proteins often preferentially localize to DRMs (detergent-resistant membranes) that are rich in sphingolipids and cholesterol and play an important role in signal transduction. Even though the responses to CD16b engagement have been intensively investigated, the importance of DRM integrity for CD16b signalling has not been characterized in human neutrophils. We provide direct evidence that CD16b constitutively partitions with both low- and high-density DRMs. Moreover, upon CD16b engagement, a significant increase in the amount of the receptor is observed in high-density DRMs. Similarly to CD16b, CD11b also resides in low- and high-density DRMs. In contrast with CD16b, the partitioning of CD11b in DRMs does not change in response to CD16b engagement. We also provide evidence for the implication of Syk in CD16b signalling and its partitioning to DRMs in resting and activated PMNs (polymorphonuclear neutrophils). Additionally, DRM-disrupting agents, such as nystatin and methyl-β-cyclodextrin, alter cellular responses to CD16b receptor ligation. Notably, a significant increase in the mobilization of intracellular Ca2+ and in tyrosine phosphorylation of intracellular substrates after CD16b engagement is observed. Altogether, the results of this study provide evidence that high-density DRMs play a role in CD16b signalling in human neutrophils. PMID:16171455

Bona fide evidence for natural vertical transmission of infectious salmon anemia virus in freshwater brood stocks of farmed Atlantic salmon (Salmo salar) in Southern Chile.

PubMed

Marshall, Sergio H; Ramírez, Ramón; Labra, Alvaro; Carmona, Marisela; Muñoz, Cristián

2014-06-01

Infectious salmon anemia (ISA) is a severe disease that affects farmed Atlantic salmon (Salmo salar), causing outbreaks in seawater in most salmon-producing countries worldwide, with particular aggressiveness in southern Chile. The etiological agent of this disease is a virus belonging to the Orthomyxoviridae family, named infectious salmon anemia virus (ISAV). Although it has been suggested that this virus can be vertically transmitted, even in freshwater, there is a lack of compelling experimental evidence to confirm this. Here we demonstrate significant putative viral loads in the ovarian fluid as well as in the eggs of two brood stock female adult specimens that harbored the virus systemically but without clinical signs. The target virus corresponded to a highly polymorphic region 3 (HPR-3) variant, which is known to be virulent in seawater and responsible for recent and past outbreaks of this disease in Chile. Additionally, the virus recovered from the fluid as well as from the interior of the eggs was fully infective to a susceptible fish cell line. To our knowledge, this is the first robust evidence demonstrating mother-to-offspring vertical transmission of the infective virus on the one hand and the asymptomatic transmission of a virulent form of the virus in freshwater fish on the other hand. The robustness of the data presented here will contribute to a better understanding of the biology of the virus but most importantly will constitute a key management tool in the control of an aggressive agent constantly threatening the sustainability of the global salmon industry.

Evidence for Loss of a Partial Flagellar Glycolytic Pathway during Trypanosomatid Evolution

PubMed Central

Brown, Robert W. B.; Collingridge, Peter W.; Gull, Keith; Rigden, Daniel J.; Ginger, Michael L.

2014-01-01

Classically viewed as a cytosolic pathway, glycolysis is increasingly recognized as a metabolic pathway exhibiting surprisingly wide-ranging variations in compartmentalization within eukaryotic cells. Trypanosomatid parasites provide an extreme view of glycolytic enzyme compartmentalization as several glycolytic enzymes are found exclusively in peroxisomes. Here, we characterize Trypanosoma brucei flagellar proteins resembling glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK): we show the latter associates with the axoneme and the former is a novel paraflagellar rod component. The paraflagellar rod is an essential extra-axonemal structure in trypanosomes and related protists, providing a platform into which metabolic activities can be built. Yet, bioinformatics interrogation and structural modelling indicate neither the trypanosome PGK-like nor the GAPDH-like protein is catalytically active. Orthologs are present in a free-living ancestor of the trypanosomatids, Bodo saltans: the PGK-like protein from B. saltans also lacks key catalytic residues, but its GAPDH-like protein is predicted to be catalytically competent. We discuss the likelihood that the trypanosome GAPDH-like and PGK-like proteins constitute molecular evidence for evolutionary loss of a flagellar glycolytic pathway, either as a consequence of niche adaptation or the re-localization of glycolytic enzymes to peroxisomes and the extensive changes to glycolytic flux regulation that accompanied this re-localization. Evidence indicating loss of localized ATP provision via glycolytic enzymes therefore provides a novel contribution to an emerging theme of hidden diversity with respect to compartmentalization of the ubiquitous glycolytic pathway in eukaryotes. A possibility that trypanosome GAPDH-like protein additionally represents a degenerate example of a moonlighting protein is also discussed. PMID:25050549

76 FR 71563 - Agency Information Collection Activities; Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... disclosures generally constitute only a small addition to the advertising for negative option plans. Because... Budget, Attention: Desk Officer for the Federal Trade Commission, New Executive Office Building, Docket...

Limited response of ponderosa pine bole defenses to wounding and fungi.

PubMed

Gaylord, Monica L; Hofstetter, Richard W; Kolb, Thomas E; Wagner, Michael R

2011-04-01

Tree defense against bark beetles (Curculionidae: Scolytinae) and their associated fungi generally comprises some combination of constitutive (primary) and induced (secondary) defenses. In pines, the primary constitutive defense against bark beetles consists of preformed resin stored in resin ducts. Induced defenses at the wound site (point of beetle entry) in pines may consist of an increase in resin flow and necrotic lesion formation. The quantity and quality of both induced and constitutive defenses can vary by species and season. The inducible defense response in ponderosa pine is not well understood. Our study examined the inducible defense response in ponderosa pine using traumatic mechanical wounding, and wounding with and without fungal inoculations with two different bark beetle-associated fungi (Ophiostoma minus and Grosmannia clavigera). Resin flow did not significantly increase in response to any treatment. In addition, necrotic lesion formation on the bole after fungal inoculation was minimal. Stand thinning, which has been shown to increase water availability, had no, or inconsistent, effects on inducible tree defense. Our results suggest that ponderosa pine bole defense against bark beetles and their associated fungi is primarily constitutive and not induced.

Elucidating the origin of chromosomal aberrations in IVF embryos by preimplantation genetic analysis.

PubMed

Frumkin, Tsvia; Malcov, Mira; Yaron, Yuval; Ben-Yosef, Dalit

2008-01-30

Preimplantation genetic screening (PGS) has been proposed as a method for improving success rates in patients with repeated IVF failures. This approach is based on the hypothesis that such failures are the result of aneuploid embryos. It has been suggested that FISH analysis of blastomeres removed from preimplantation embryos represent the chromosomal constitution of the entire embryo. However, it is not yet clear whether it also represents the chromosomal constitution of the implanted embryo. PGS reanalysis on day 5 of embryos designated as "aneuploid" on day 3 may demonstrate a high rate of mosaicism for chromosomal aberration. Some of these mosaic embryos are capable of developing into normal embryos by "self-correction". Others, however, may accumulate additional chromosomal anomalies. It is therefore concluded that the chromosomal constitution of a preimplantation embryo may evolve during early cleavages. Meiotic and post zygotic mitotic errors may account for these chromosomal aberrations. This review will focus on elucidating the origin of chromosomal changes during preimplantation embryo development by studying their chromosomal constitution at different stages.

From Colonies to Country. A History of US. Book Three.

ERIC Educational Resources Information Center

Hakim, Joy

This book covers U.S. history from the French and Indian War to the Constitutional Convention. The story of the United States is told in a form that is conversational and easily understandable to children. The book is divided into 41 brief chapters and an additional 5 features. A chronology of events, list of additional reading, picture credits,…

Short term feeding of a high fat diet exerts an additive effect on hepatocellular damage and steatosis in liver-specific PTEN knockout mice

USDA-ARS?s Scientific Manuscript database

Hepatospecific deletion of PTEN results in constitutive activation of Akt and increased lipogenesis. In mice, the addition of a high fat diet (HFD) downregulates lipogenesis. The aim of this study was to determine the effects of a HFD on hepatocellular damage induced by deletion of PTEN. Twelve-week...

Integrins in bone metastasis formation and potential therapeutic implications.

PubMed

Clëzardin, P

2009-11-01

Integrins constitute a family of cell surface receptors that are heterodimers composed of noncovalently associated alpha and beta subunits. Integrins bind to extracellular matrix proteins and immunogobulin superfamily molecules. They exert a stringent control on cell migration, survival and proliferation. However, their expression and functions are often deregulated in cancer, and many lines of evidence implicate them as key regulators during progression from primary tumor growth to metastasis. Here, we review the role of integrins in bone metastasis formation and present evidence that the use of integrin-targeted therapeutic agents may be an efficient strategy to block tumor metastasis.

Near infrared observations of S155. evidence of induced star formation?

NASA Astrophysics Data System (ADS)

Hunt, L. K.; Lisi, F.; Felli, M.; Tofani, G.

At the interface of the giant molecular cloud Cepheus OB3, S155 represents one of the most interesting examples of bright rim produced by the ionization of a nearby O-star. The interaction between the ionized HII region S155 and the hot molecular core Cepheus B may constitute the ideal site for new stars, according to the sequential star-formation theory. Past observations of molecular lines have shown the evidence of a hot spot in the cloud core, probably a compact region associated to a young stellar object. New J,H,K images recently obtained with the ARNICA array at the TIRGO telescope give evidence of stars with strong near-infrared excess, which must represent the newest generation of young stars.

Evidence for slowdown in stratospheric ozone loss: First stage of ozone recovery

NASA Technical Reports Server (NTRS)

Newchurch, M. J.; Yang, Eun-Su; Cunnold, D. M.; Reinsel, C.; Zawodny, J. M.; Russell, James M., III

2003-01-01

Global ozone trends derived from the Stratospheric Aerosol and Gas Experiment I and II (SAGE I/II) combined with the more recent Halogen Occultation Experiment (HALOE) observations provide evidence of a slowdown in stratospheric ozone losses since 1997. This evidence is quantified by the cumulative sum of residual differences from the predicted linear trend. The cumulative residuals indicate that the rate of ozone loss at 35- 45 km altitudes globally has diminished. These changes in loss rates are consistent with the slowdown of total stratospheric chlorine increases characterized by HALOE HCI measurements. These changes in the ozone loss rates in the upper stratosphere are significant and constitute the first stage of a recovery of the ozone layer.

Incompletely characterized incidental renal masses: emerging data support conservative management.

PubMed

Silverman, Stuart G; Israel, Gary M; Trinh, Quoc-Dien

2015-04-01

With imaging, most incidental renal masses can be diagnosed promptly and with confidence as being either benign or malignant. For those that cannot, management recommendations can be devised on the basis of a thorough evaluation of imaging features. However, most renal masses are either too small to characterize completely or are detected initially in imaging examinations that are not designed for full evaluation of them. These masses constitute a group of masses that are considered incompletely characterized. On the basis of current published guidelines, many masses warrant additional imaging. However, while the diagnosis of renal cancer at a curable stage remains the first priority, there is the additional need to reduce unnecessary healthcare costs and radiation exposure. As such, emerging data now support foregoing additional imaging for many incompletely characterized renal masses. These data include the low risk of progression to metastases or death for small renal masses that have undergone active surveillance (including biopsy-proven cancers) and a better understanding of how specific imaging features can be used to diagnose their origins. These developments support (a) avoidance of imaging entirely for those incompletely characterized renal masses that are highly likely to be benign cysts and (b) delay of further imaging of small solid masses in selected patients. Although more evidence-based data are needed and comprehensive management algorithms have yet to be defined, these recommendations are medically appropriate and practical, while limiting the imaging of many incompletely characterized incidental renal masses.

Fitness consequences of polymorphic inversions in the zebra finch genome.

PubMed

Knief, Ulrich; Hemmrich-Stanisak, Georg; Wittig, Michael; Franke, Andre; Griffith, Simon C; Kempenaers, Bart; Forstmeier, Wolfgang

2016-09-29

Inversion polymorphisms constitute an evolutionary puzzle: they should increase embryo mortality in heterokaryotypic individuals but still they are widespread in some taxa. Some insect species have evolved mechanisms to reduce the cost of embryo mortality but humans have not. In birds, a detailed analysis is missing although intraspecific inversion polymorphisms are regarded as common. In Australian zebra finches (Taeniopygia guttata), two polymorphic inversions are known cytogenetically and we set out to detect these two and potentially additional inversions using genomic tools and study their effects on embryo mortality and other fitness-related and morphological traits. Using whole-genome SNP data, we screened 948 wild zebra finches for polymorphic inversions and describe four large (12-63 Mb) intraspecific inversion polymorphisms with allele frequencies close to 50 %. Using additional data from 5229 birds and 9764 eggs from wild and three captive zebra finch populations, we show that only the largest inversions increase embryo mortality in heterokaryotypic males, with surprisingly small effect sizes. We test for a heterozygote advantage on other fitness components but find no evidence for heterosis for any of the inversions. Yet, we find strong additive effects on several morphological traits. The mechanism that has carried the derived inversion haplotypes to such high allele frequencies remains elusive. It appears that selection has effectively minimized the costs associated with inversions in zebra finches. The highly skewed distribution of recombination events towards the chromosome ends in zebra finches and other estrildid species may function to minimize crossovers in the inverted regions.

Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor

PubMed Central

Ramsay, Douglas; Bevan, Nicola; Rees, Stephen; Milligan, Graeme

2001-01-01

The wild-type β2-adrenoceptor and a constitutively active mutant of this receptor were C-terminally tagged with luciferase from the sea pansy Renilla reniformis. C-terminal addition of Renilla luciferase did not substantially alter the levels of expression of either form of the receptor, the elevated constitutive activity of the mutant β2-adrenoceptor nor the capacity of isoprenaline to elevate cyclic AMP levels in intact cells expressing these constructs. Treatment of cells expressing constitutively active mutant β2-adrenoceptor-Renilla luciferase with antagonist/inverse agonist ligands resulted in upregulation of levels of this polypeptide which could be monitored by the elevated luciferase activity. The pEC50 for ligand-induced luciferase upregulation and ligand affinity to bind the receptor were highly correlated. Similar upregulation could be observed following sustained treatment with agonist ligands. These effects were only observed at a constitutively active mutant of the β2-adrenoceptor. Co-expression of the wild-type β2-adrenoceptor C-terminally tagged with the luciferase from Photinus pyralis did not result in ligand-induced upregulation of the levels of activity of this luciferase. Co-expression of the constitutively active mutant β2-adrenoceptor-Renilla luciferase and an equivalent mutant of the α1b-adrenoceptor C-terminally tagged with green fluorescent protein allowed pharmacological selectivity of adrenoceptor antagonists to be demonstrated. This approach offers a sensitive and convenient means, which is amenable to high throughput analysis, to monitor ligand binding to a constitutively active mutant receptor. As no prior knowledge of receptor ligands is required this approach may be suitable to identify ligands at orphan G protein-coupled receptors. PMID:11350868

The whole set of the constitutive promoters recognized by four minor sigma subunits of Escherichia coli RNA polymerase

PubMed Central

Shimada, Tomohiro; Tanaka, Kan

2017-01-01

The promoter selectivity of Escherichia coli RNA polymerase (RNAP) is determined by the sigma subunit. The model prokaryote Escherichia coli K-12 contains seven species of the sigma subunit, each recognizing a specific set of promoters. For identification of the “constitutive promoters” that are recognized by each RNAP holoenzyme alone in the absence of other supporting factors, we have performed the genomic SELEX screening in vitro for their binding sites along the E. coli K-12 W3110 genome using each of the reconstituted RNAP holoenzymes and a collection of genome DNA segments of E. coli K-12. The whole set of constitutive promoters for each RNAP holoenzyme was then estimated based on the location of RNAP-binding sites. The first successful screening of the constitutive promoters was achieved for RpoD (σ70), the principal sigma for transcription of growth-related genes. As an extension, we performed in this study the screening of constitutive promoters for four minor sigma subunits, stationary-phase specific RpoS (σ38), heat-shock specific RpoH (σ32), flagellar-chemotaxis specific RpoF (σ28) and extra-cytoplasmic stress-response RpoE (σ24). The total number of constitutive promoters were: 129~179 for RpoS; 101~142 for RpoH; 34~41 for RpoF; and 77~106 for RpoE. The list of constitutive promoters were compared with that of known promoters identified in vivo under various conditions and using varieties of E. coli strains, altogether allowing the estimation of “inducible promoters” in the presence of additional supporting factors. PMID:28666008

NR2A contributes to genesis and propagation of cortical spreading depression in rats.

PubMed

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-03-22

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile.

NR2A contributes to genesis and propagation of cortical spreading depression in rats

PubMed Central

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-01-01

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID:27001011

Morphologic and seismic evidence of rapid submergence offshore Cide-Sinop in the southern Black Sea shelf

NASA Astrophysics Data System (ADS)

Ocakoğlu, Neslihan; İşcan, Yeliz; Kılıç, Fatmagül; Özel, Oğuz

2018-06-01

Multi-beam bathymetric and multi-channel seismic reflection data obtained offshore Cide-Sinop have revealed important records on the latest transgression of the Black Sea for the first time. A relatively large shelf plain within the narrow southern continental shelf characterized by a flat seafloor morphology at -100 water depth followed by a steep continental slope leading to -500 m depth. This area is widely covered by submerged morphological features such as dunes, lagoons, possible aeolianites, an eroded anticline and small channels that developed by aeolian and fluvial processes. These morphological features sit upon an erosional surface that truncates the top of all seismic units and constitutes the seafloor over the whole shelf. The recent prograded delta deposits around the shelf break are also truncated by the similar erosional surface. These results indicate that offshore Cide-Sinop was once a terrestrial landscape that was then submerged. The interpreted paleoshoreline varies from -100 to -120 m. This variation can be explained by not only sea level changes but also the active faults observed on the seismic section. The effective protection of morphological features on the seafloor is the evidence of abrupt submergence rather than gradual. In addition, the absence of coastal onlaps suggests that these morphological features should have developed at low sea level before the latest sea level rise in the Black Sea.

Nitrergic system and plasmatic methylarginines: Evidence of their role in the perinatal programming of cardiovascular diseases.

PubMed

Bassareo, Pier Paolo; Mussap, Michele; Bassareo, Valentina; Flore, Giovanna; Mercuro, Giuseppe

2015-12-07

Atherosclerosis, in turn preceded by endothelial dysfunction, underlies a series of important cardiovascular diseases. Reduced bioavailability of endothelial nitric oxide, by increasing vascular tone and promoting platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, plays a key role in the onset of the majority of cardiovascular diseases. In addition, high blood levels of asymmetric dimethylarginine, a potent inhibitor of nitric oxide synthesis, are associated with future development of adverse cardiovascular events and cardiac death. Recent reports have demonstrated that another methylarginine, i.e., symmetric dimethylarginine, is also involved in the onset of endothelial dysfunction and hypertension. Almost a decade ago, prematurity at birth and intrauterine growth retardation were first associated with a potential negative influence on the cardiovascular apparatus, thus constituting risk factors or leading to early onset of cardiovascular diseases. This condition is referred to as cardiovascular perinatal programming. Accordingly, cardiovascular morbidity and mortality are higher among former preterm adults than in those born at term. The aim of this paper was to undertake a comprehensive literature review focusing on cellular and biochemical mechanisms resulting in both reduced nitric oxide bioavailability and increased methylarginine levels in subjects born preterm. Evidence of the involvement of these compounds in the perinatal programming of cardiovascular risk are also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of spatial and temporal heterogeneity and competition in structuring trematode communities in the great pond snail, Lymnaea stagnalis (L.)

USGS Publications Warehouse

Soldánová, Miroslava; Kuris, Armand M.; Scholz, Tomáš; Lafferty, Kevin D.

2012-01-01

We assessed how spatial and temporal heterogeneity and competition structure larval trematode communities in the pulmonate snail Lymnaea stagnalis. To postulate a dominance hierarchy, mark-release-recapture was used to monitor replacements of trematode species within snails over time. In addition, we sampled the trematode community in snails in different ponds in 3 consecutive years. A total of 7,623 snails (10,382 capture events) was sampled in 7 fishponds in the Jindřichův Hradec and Třeboň areas in South Bohemia (Czech Republic) from August 2006 to October 2008. Overall, 39% of snails were infected by a community of 14 trematode species; 7% of snails were infected with more than 1 trematode species (constituting 16 double- and 4 triple-species combinations). Results of the null-model analyses suggested that spatial heterogeneity in recruitment among ponds isolated trematode species from each other, whereas seasonal pulses in recruitment increased species interactions in some ponds. Competitive exclusion among trematodes led to a rarity of multiple infections compared to null-model expectations. Competitive relationships among trematode species were hypothesized as a dominance hierarchy based on direct evidence of replacement and invasion and on indirect evidence. Seven top dominant species with putatively similar competitive abilities (6 rediae and 1 sporocyst species) reduced the prevalence of the other trematode species developing in sporocysts only.

Sulfate-rich eolian and wet interdune deposits, erebus crater, meridiani Planum, Mars

USGS Publications Warehouse

Metz, J.M.; Grotzinger, J.P.; Rubin, D.M.; Lewis, K.W.; Squyres, S. W.; Bell, J.F.

2009-01-01

This study investigates three bedrock exposures at Erebus crater, an ?? 300 m diameter crater approximately 4 km south of Endurance crater on Mars. These outcrops, called Olympia, Payson, and Yavapai, provide additional evidence in support of the dune-interdune model proposed for the formation of the deposits at the Opportunity landing site in Meridiani Planum. There is evidence for greater involvement of liquid water in the Olympia outcrop exposures than was observed in Eagle or Endurance craters. The Olympia outcrop likely formed in a wet interdune and sand sheet environment. The facies observed within the Payson outcrop, which is likely stratigraphically above the Olympia outcrop, indicate that it was deposited in a damp-wet interdune, sand sheet, and eolian dune environment. The Yavapai outcrop, which likely stratigraphically overlies the Payson outcrop, indicates that it was deposited in primarily a sand sheet environment and also potentially in an eolian dune environment. These three outcrop exposures may indicate an overall drying-upward trend spanning the stratigraphic section from its base at the Olympia outcrop to its top at the Yavapai outcrop. This contrasts with the wetting-upward trend seen in Endurance and Eagle craters. Thus, the series of outcrops seen at Meridiani by Opportunity may constitute a full climatic cycle, evolving from dry to wet to dry conditions. ?? 2009, SEPM (Society for Sedimentary Geology).

Micropolar continuum modelling of bi-dimensional tetrachiral lattices

PubMed Central

Chen, Y.; Liu, X. N.; Hu, G. K.; Sun, Q. P.; Zheng, Q. S.

2014-01-01

The in-plane behaviour of tetrachiral lattices should be characterized by bi-dimensional orthotropic material owing to the existence of two orthogonal axes of rotational symmetry. Moreover, the constitutive model must also represent the chirality inherent in the lattices. To this end, a bi-dimensional orthotropic chiral micropolar model is developed based on the theory of irreducible orthogonal tensor decomposition. The obtained constitutive tensors display a hierarchy structure depending on the symmetry of the underlying microstructure. Eight additional material constants, in addition to five for the hemitropic case, are introduced to characterize the anisotropy under Z2 invariance. The developed continuum model is then applied to a tetrachiral lattice, and the material constants of the continuum model are analytically derived by a homogenization process. By comparing with numerical simulations for the discrete lattice, it is found that the proposed continuum model can correctly characterize the static and wave properties of the tetrachiral lattice. PMID:24808754

Decommissioning of eight surplus production reactors at the Hanford Site, Richland, Washington. Addendum (Final Environmental Impact Statement)

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

Not Available

1992-12-01

The first section of this volume summarizes the content of the draft environmental impact statement (DEIS) and this Addendum, which together constitute the final environmental impact statement (FEIS) prepared on the decommissioning of eight surplus plutonium production reactors at Hanford. The FEIS consists of two volumes. The first volume is the DEIS as written. The second volume (this Addendum) consists of a summary; Chapter 9, which contains comments on the DEIS and provides DOE`s responses to the comments; Appendix F, which provides additional health effects information; Appendix K, which contains costs of decommissioning in 1990 dollars; Appendix L, which containsmore » additional graphite leaching data; Appendix M, which contains a discussion of accident scenarios; Appendix N, which contains errata; and Appendix 0, which contains reproductions of the letters, transcripts, and exhibits that constitute the record for the public comment period.« less

Effects of cerium on the hydrogen absorption-desorption properties of rare earth-Mg-Ni hydrogen-absorbing alloys

NASA Astrophysics Data System (ADS)

Yasuoka, Shigekazu; Ishida, Jun; Kishida, Kyosuke; Inui, Haruyuki

2017-04-01

The influence of Ce addition on the phase constitution, microstructure, hydrogen absorption/desorption properties and battery performances of newly developed rare earth (RE)-Mg-Ni hydrogen-absorbing superlattice alloys for negative electrode materials in Ni-metal hydride (MH) batteries were investigated. The partial substitution of RE (La and Nd) with Ce results in a higher discharge performance and a lower cycle life in the battery. The Ce addition greatly affects the phase constitution, which is mainly characterized by increased formation of the AB2 phase (A = RE or Mg and B = Ni or Al). The existence of the AB2 phase is found to accelerate alloy pulverization and oxidation when the alloys are used as negative electrode materials in Ni-MH model cells. The accelerated pulverization and oxidation are considered to be responsible for the observed higher discharge performance and lower cycle life in the batteries, respectively.

Review of "The Impact of a Universal Class-Size Reduction Policy: Evidence from Florida's Statewide Mandate"

ERIC Educational Resources Information Center

Finn, Jeremy D.

2010-01-01

In 2002, voters in Florida approved a constitutional amendment limiting class sizes in public schools to 18 students in the elementary grades, 22 students in middle grades, and 25 in high school grades. Analyzing statewide achievement data for school districts from 2004-2006 and for schools in 2007, this study purports to find that "mandated…

Preventing School Shootings: A Public Health Approach to Gun Violence

DTIC Science & Technology

2013-03-01

Neither did the 17th Century English jurist and judge, William Blackstone , nor philosopher and physician, John Locke, known as the Father of Classical...Liberalism. The writings of Blackstone and Locke, both of whom wrote extensively about constitutional traditions and natural rights, respectively...provide considerable evidence for the collective interpretation as opposed to the individual interpretation of the Second Amendment. Blackstone

Defining Educational Research: A Perspective of/on Presidential Addresses and the Australian Association for Research in Education

ERIC Educational Resources Information Center

Lingard, Bob; Gale, Trevor

2010-01-01

This paper is concerned with the definition of the field of educational research and the changing and developing role of the Australian Association for Research in Education (AARE) in representing and constituting this field. The evidence for the argument is derived from AARE Presidential Addresses across its 40-year history. The paper documents…

Allostasis and the Human Brain: Integrating Models of Stress from the Social and Life Sciences

ERIC Educational Resources Information Center

Ganzel, Barbara L.; Morris, Pamela A.; Wethington, Elaine

2010-01-01

We draw on the theory of allostasis to develop an integrative model of the current stress process that highlights the brain as a dynamically adapting interface between the changing environment and the biological self. We review evidence that the core emotional regions of the brain constitute the primary mediator of the well-established association…

Synaptic Plasticity and Memory Formation

DTIC Science & Technology

1993-06-30

transmission that constitutes LTP. Positive evidence that induction of LTP alters receptors was then obtained: first, aniracetam , a drug which modulates...waveform distortion associated with LTP also reproduces the percent increase in slope and amplitude found with potentiation. The effects of aniracetam ...interaction very much like that found between aniracetam and LTP in physiological experiments. Thus, we have arrived at the very specific hypothesis that

Evidence-Based Practice in Autism Educational Research: Can We Bridge the Research and Practice Gap?

ERIC Educational Resources Information Center

Guldberg, Karen

2017-01-01

In order to develop deeper and better understandings of what constitutes effective educational practices, and to bridge the gap between research and practice, there is a need for a paradigm shift in autism educational research. The contribution of this paper is to examine the key methodological challenges that stand in the way of autism…

38 CFR 1.10 - Eligibility for and disposition of the United States flag for burial purposes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... request to a close friend or associate of the deceased veteran. Such action will constitute final and... phrase close friend or associate for the purpose of disposing of the burial flag means any person who... establishes by evidence that he or she was a close friend or associate of the veteran may be furnished the...

Students' Expectations about Earnings and Employment and the Experience of Recent University Graduates: Evidence from Cyprus

ERIC Educational Resources Information Center

Menon, Maria Eliophotou; Pashourtidou, Nicoletta; Polycarpou, Alexandros; Pashardes, Panos

2012-01-01

The employability of university graduates constitutes a major policy concern in both developed and developing nations. In this context, the present study uses self-reported data to compare the earnings and employment expectations of university students, and the realised earnings and employment paths of recent graduates. The sample consisted of 476…

Application of Evidence-Centered Assessment Design to the Advanced Placement Redesign: A Graphic Restatement

ERIC Educational Resources Information Center

Bejar, Isaac I.

2010-01-01

The foregoing articles constitute what I consider a comprehensive and clear description of the redesign process of a major assessment. The articles serve to illustrate the problems that will need to be addressed by large-scale assessments in the twenty-first century. Primary among them is how to organize the development of such assessments to meet…

A Social Science Review of Evidence Cited in Litigation on Corporal Punishment in the Schools.

ERIC Educational Resources Information Center

Hyman, Irwin A.

In the case of Ingraham vs. Wright, the United States Supreme Court ruled that under the eighth amendment school children do not have constitutional protection from the use of corporal punishment. The majority decision relies heavily on assumptions concerning the tradition and effectiveness of the use of corporal punishment in education. In an…

Implementing Geographical Key Concepts: Design of a Symbiotic Teacher Training Course Based on Empirical and Theoretical Evidence

ERIC Educational Resources Information Center

Fögele, Janis; Mehren, Rainer

2015-01-01

A central desideratum for the professionalization of qualified teachers is an improved practice of further teacher education. The present work constitutes a course of in-service training, which is built upon both a review of empirical findings concerning the efficacy of in-service training courses for teachers and theoretical assumptions about the…

Comparison of polyphenol concentration and composition between genetically diverse cacao (Theobroma cacao L.) accessions selected for high yield and disease resistance

USDA-ARS?s Scientific Manuscript database

There is abundant evidence that consumption of cacao and dark chocolate promotes human health and that the main cacao components contributing positive health effects are polyphenols. The polyphenols in cacao bean constitute 12–18% dry weight of the whole bean and are predominantly catechins (37% w/w...

Psychological Autopsy Studies as Diagnostic Tools: Are they Methodologically Flawed?

PubMed Central

Hjelmeland, Heidi; Dieserud, Gudrun; Dyregrov, Kari; Knizek, Birthe L.; Leenaars, Antoon A.

2012-01-01

One of the most established “truths” in suicidology is that almost all (90 % or more) of those who kill themselves suffer from one or more mental disorders, and a causal link between the two is implied. Psychological autopsy (PA) studies constitute one main evidence base for this conclusion. However, there has been little reflection on the reliability and validity of this method. For example, psychiatric diagnoses are assigned to people who have died by suicide by interviewing a few of the relatives and/or friends, often many years after the suicide. In this article, we scrutinize PA studies with particular focus on the diagnostic process and demonstrate that they cannot constitute a valid evidence base for a strong relationship between mental disorders and suicide. We show that most questions asked to assign a diagnosis are impossible to answer reliably by proxies, and thus, one cannot validly make conclusions. Thus, as a diagnostic tool psychological autopsies should now be abandoned. Instead, we recommend qualitative approaches focusing on the understanding of suicide beyond mental disorders, where narratives from a relatively high number of informants around each suicide are systematically analyzed in terms of the informants’ relationships with the deceased. PMID:24563941

Constitutive expression of the xylanase inhibitor TAXI-III delays Fusarium head blight symptoms in durum wheat transgenic plants.

PubMed

Moscetti, Ilaria; Tundo, Silvio; Janni, Michela; Sella, Luca; Gazzetti, Katia; Tauzin, Alexandra; Giardina, Thierry; Masci, Stefania; Favaron, Francesco; D'Ovidio, Renato

2013-12-01

Cereals contain xylanase inhibitor (XI) proteins which inhibit microbial xylanases and are considered part of the defense mechanisms to counteract microbial pathogens. Nevertheless, in planta evidence for this role has not been reported yet. Therefore, we produced a number of transgenic plants constitutively overexpressing TAXI-III, a member of the TAXI type XI that is induced by pathogen infection. Results showed that TAXI-III endows the transgenic wheat with new inhibition capacities. We also showed that TAXI-III is correctly secreted into the apoplast and possesses the expected inhibition parameters against microbial xylanases. The new inhibition properties of the transgenic plants correlate with a significant delay of Fusarium head blight disease symptoms caused by Fusarium graminearum but do not significantly influence leaf spot symptoms caused by Bipolaris sorokiniana. We showed that this contrasting result can be due to the different capacity of TAXI-III to inhibit the xylanase activity of these two fungal pathogens. These results provide, for the first time, clear evidence in planta that XI are involved in plant defense against fungal pathogens and show the potential to manipulate TAXI-III accumulation to improve wheat resistance against F. graminearum.

Experimental evidence of massive-scale emotional contagion through social networks

PubMed Central

Kramer, Adam D. I.; Guillory, Jamie E.; Hancock, Jeffrey T.

2014-01-01

Emotional states can be transferred to others via emotional contagion, leading people to experience the same emotions without their awareness. Emotional contagion is well established in laboratory experiments, with people transferring positive and negative emotions to others. Data from a large real-world social network, collected over a 20-y period suggests that longer-lasting moods (e.g., depression, happiness) can be transferred through networks [Fowler JH, Christakis NA (2008) BMJ 337:a2338], although the results are controversial. In an experiment with people who use Facebook, we test whether emotional contagion occurs outside of in-person interaction between individuals by reducing the amount of emotional content in the News Feed. When positive expressions were reduced, people produced fewer positive posts and more negative posts; when negative expressions were reduced, the opposite pattern occurred. These results indicate that emotions expressed by others on Facebook influence our own emotions, constituting experimental evidence for massive-scale contagion via social networks. This work also suggests that, in contrast to prevailing assumptions, in-person interaction and nonverbal cues are not strictly necessary for emotional contagion, and that the observation of others’ positive experiences constitutes a positive experience for people. PMID:24889601

Visioning services for children affected by HIV and AIDS through a family lens.

PubMed

Richter, Linda; Beyrer, Chris; Kippax, Susan; Heidari, Shirin

2010-06-23

The HIV epidemic continues to place a great burden on children, from loss of parents and income to severe disruptions of their homes and families. Underpinned by the understanding that a healthy family constitutes the foundation for a child's wellbeing, the importance of family-centred care and services for children is increasingly recognized. It is not enough to merely provide antiretrovirals: it is of pivotal importance that treatment and care for children are integrated into the broader context of family-support schemes. However, despite growing evidence of the benefits of family-centred services, reforms in favour of family oriented HIV interventions have been slow to emerge. Treatment, prevention and care interventions often target individuals, and not families and communities.For the first time, this supplement to the Journal of the International AIDS Society brings together in one place the rationale for family-centred services for children affected by HIV and AIDS and some of the available evidence for the effectiveness of doing so. We hope this constitutes a beginning of what could be a groundswell of interest in family-centred services for children affected by HIV and AIDS.

Experimental evidence of massive-scale emotional contagion through social networks.

PubMed

Kramer, Adam D I; Guillory, Jamie E; Hancock, Jeffrey T

2014-06-17

Emotional states can be transferred to others via emotional contagion, leading people to experience the same emotions without their awareness. Emotional contagion is well established in laboratory experiments, with people transferring positive and negative emotions to others. Data from a large real-world social network, collected over a 20-y period suggests that longer-lasting moods (e.g., depression, happiness) can be transferred through networks [Fowler JH, Christakis NA (2008) BMJ 337:a2338], although the results are controversial. In an experiment with people who use Facebook, we test whether emotional contagion occurs outside of in-person interaction between individuals by reducing the amount of emotional content in the News Feed. When positive expressions were reduced, people produced fewer positive posts and more negative posts; when negative expressions were reduced, the opposite pattern occurred. These results indicate that emotions expressed by others on Facebook influence our own emotions, constituting experimental evidence for massive-scale contagion via social networks. This work also suggests that, in contrast to prevailing assumptions, in-person interaction and nonverbal cues are not strictly necessary for emotional contagion, and that the observation of others' positive experiences constitutes a positive experience for people.

Visioning services for children affected by HIV and AIDS through a family lens

PubMed Central

2010-01-01

The HIV epidemic continues to place a great burden on children, from loss of parents and income to severe disruptions of their homes and families. Underpinned by the understanding that a healthy family constitutes the foundation for a child's wellbeing, the importance of family-centred care and services for children is increasingly recognized. It is not enough to merely provide antiretrovirals: it is of pivotal importance that treatment and care for children are integrated into the broader context of family-support schemes. However, despite growing evidence of the benefits of family-centred services, reforms in favour of family oriented HIV interventions have been slow to emerge. Treatment, prevention and care interventions often target individuals, and not families and communities. For the first time, this supplement to the Journal of the International AIDS Society brings together in one place the rationale for family-centred services for children affected by HIV and AIDS and some of the available evidence for the effectiveness of doing so. We hope this constitutes a beginning of what could be a groundswell of interest in family-centred services for children affected by HIV and AIDS. PMID:20573282

Association of Sasang Constitutional Type with Sarcopenia

PubMed Central

Lee, Seung Ku; Yoon, Dae Wui; Choi, Kyung-Mee; Lee, Si Woo; Kim, Jong Yeol; Kim, Jin Kwan; Shin, Chol

2015-01-01

Sasang constitutional medicine (SCM) is a unique Korean traditional medicine that classifies human beings as four distinct types named Sasang constitutional types (SCTs), based on physiologic, physical, and psychological traits. Accumulating evidence has demonstrated that specific constitutional types are associated with chronic diseases, but no study has investigated the relationship between SCTs and sarcopenia. The aim of this study was to examine the association in a large population-based study. Data from 1,204 participants who completed questionnaires for life style, anthropometric evaluation, and biochemical analysis were analyzed. Classification of the SCTs was done using an integrated diagnostic method. Sarcopenia was defined as appendicular skeletal muscle mass/height2 less than one standard deviation below the gender-specific normal mean of a younger group. Dual-energy X-ray absorptiometry was used to assess whole body composition. The prevalence of sarcopenia was 8.6% in the Tae-eum (TE) type, 44.7% in the So-eum (SE) type, and 20.7% in the So-yang (SY) type. Multivariate analysis revealed that the SE and SY types had 9.22 (5.06–16.81; P < 0.0001) and 2.90 (1.76–4.76; P < 0.0001) greater odds of sarcopenia compared to the TE type, respectively. Our results show that the SE and SY types are significantly associated with increased prevalence of sarcopenia. PMID:26649062

Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.

PubMed

Gri, G; Savio, D; Trinchieri, G; Ma, X

1998-03-13

Monocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two essential cis elements, the NFkappaB site and the Ets site. The NFkappaB site was shown to interact with members of the NFkappaB family: p50 and c-Rel. The Ets site constitutively bound a multi-component Ets-2-containing complex. While the NFkappaB and Ets sites appear equally critical for inducible p40 promoter activity in macrophage cell lines, NFkappaB plays a more dominant role in the constitutive p40 promoter activity in EBV+ B cells. Transient expression of Ets-2 and c-Rel in B, T, and monocytic cell lines synergistically activated the IL-12 p40 promoter, apparently overcoming the requirement for cell type- or stimulant-specific transcription factors. These data provide new evidence that full activation of the human IL-12 p40 promoter may result primarily from the interplay between NFkappaB and Ets family members.

The incompetent developmentally disabled person's right of self-determination: right-to-die, sterilization and institutionalization.

PubMed

Krais, W A

1989-01-01

The developmentally disabled, specifically those mentally incompetent from birth, are entitled to a full panoply of constitutional rights and protections. These rights include the right to terminate life-sustaining treatment, the right of procreative integrity and the right not to be involuntarily institutionalized. However, the mentally incompetent developmentally disabled are generally unable to exercise these rights. This Note asserts first that proper procedural safeguards are necessary to guarantee the exercise of these constitutional rights by the incompetent disabled individual. Second, the Note focuses upon how best to preserve the disabled person's autonomy. The Note subsequently rejects the substituted judgment standard as a legal fiction, and endorses the best interest test which necessarily comports with the evidence, and properly accounts for the disabled person's incompetency.

[The role of local government in the development of health policies].

PubMed

Dallari, S G

1991-10-01

Analysing the evidences for local concern with health in the various historical phases of the organization of social life, especially relating to the discussion of the efficacy of the social rights written into some contemporary constitutions, the attempt is made to define the responsibility for the guarantee of the right to health. The possibility of defining the responsibility for the guarantee of social rights arises directly from the legal definition of such rights, practicable at the level of local government. Thus, after a thorough examination of the Brazilian constitutional organization in search of the guarantee of health for all, it is concluded that the promotion of the said responsibility is greatly favored, since Municipal competence regarding issues related to health are listed and discussed there in detail.

Phenotypic Checkpoints Regulate Neuronal Development

PubMed Central

Ben-Ari, Yehezkel; Spitzer, Nicholas C.

2010-01-01

Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and may constitute presymptomatic signatures of neurological disorders when they go awry. PMID:20864191

Effect of high temperature yoga exercise on improving physical and mental well-being of overweight middle-aged and young women

PubMed Central

Guo, Yan-Hua; Wang, Feng; Hu, Jian-Ping; Wang, Yi; Zhang, Li-Yan

2014-01-01

Objective: To explore the effect of high temperature yoga exercise on improving physical and psychological well-being of overweight middle-aged and young women. Design: 50 overweight middle-aged and young women from yoga clubs were selected. The indexes of their constitution, physiological functions, psychological adaptation were measured and compared before and after one year of uninterrupted high temperature yoga exercise. Results: The indexes of the subjects’ constitution and physiological functions were remarkably uplifted (P < 0.05); their psychological adaptation was improved as well. Conclusion: Aerobics represented by high temperature yoga can improve body shape, lower lipid, reduce weight, and exert an evident therapeutic effect on improving physiological functions and boosting psychological well-being. PMID:25664117

Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility

PubMed Central

Núnez-Ollé, Marc; Jung, Carole; Terré, Berta; Balsiger, Norman A.; Plata, Cristina; Roset, Ramon; Pardo-Pastor, Carlos; Garrido, Marta; Rojas, Santiago; Alameda, Francesc; Lloreta, Josep; Martín-Caballero, Juan; Flores, Juana M.; Stracker, Travis H.; Valverde, Miguel A.; Muñoz, Francisco J.; Gil-Gómez, Gabriel

2017-01-01

Cyclin O (encoded by CCNO) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous CCNO mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of Ccno in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the development of motile cilia and hydrocephalus. To further investigate the functions of Ccno in vivo, we have generated a new mouse model characterized by the constitutive loss of Ccno in all tissues and followed a cohort during ageing. Ccno-/- mice were growth impaired and developed hydrocephalus with high penetrance. In addition, some Ccno+/- mice also developed hydrocephalus and affected Ccno-/- and Ccno+/- mice exhibited additional CNS defects including cortical thinning and hippocampal abnormalities. In addition to the CNS defects, both male and female Ccno-/- mice were infertile and female mice exhibited few motile cilia in the oviduct. Our results further establish CCNO as an important gene for normal development and suggest that heterozygous CCNO mutations could underlie hydrocephalus or diminished fertility in some human patients. PMID:29245899

Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility.

PubMed

Núnez-Ollé, Marc; Jung, Carole; Terré, Berta; Balsiger, Norman A; Plata, Cristina; Roset, Ramon; Pardo-Pastor, Carlos; Garrido, Marta; Rojas, Santiago; Alameda, Francesc; Lloreta, Josep; Martín-Caballero, Juan; Flores, Juana M; Stracker, Travis H; Valverde, Miguel A; Muñoz, Francisco J; Gil-Gómez, Gabriel

2017-11-21

Cyclin O (encoded by CCNO ) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous CCNO mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of Ccno in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the development of motile cilia and hydrocephalus. To further investigate the functions of Ccno in vivo , we have generated a new mouse model characterized by the constitutive loss of Ccno in all tissues and followed a cohort during ageing. Ccno -/- mice were growth impaired and developed hydrocephalus with high penetrance. In addition, some Ccno +/- mice also developed hydrocephalus and affected Ccno -/- and Ccno +/- mice exhibited additional CNS defects including cortical thinning and hippocampal abnormalities. In addition to the CNS defects, both male and female Ccno -/- mice were infertile and female mice exhibited few motile cilia in the oviduct. Our results further establish CCNO as an important gene for normal development and suggest that heterozygous CCNO mutations could underlie hydrocephalus or diminished fertility in some human patients.

Permethrin induction of multiple cytochrome P450 genes in insecticide resistant mosquitoes, Culex quinquefasciatus.

PubMed

Gong, Youhui; Li, Ting; Zhang, Lee; Gao, Xiwu; Liu, Nannan

2013-01-01

The expression of some insect P450 genes can be induced by both exogenous and endogenous compounds and there is evidence to suggest that multiple constitutively overexpressed P450 genes are co-responsible for the development of resistance to permethrin in resistant mosquitoes. This study characterized the permethrin induction profiles of P450 genes known to be constitutively overexpressed in resistant mosquitoes, Culex quinquefasciatus. The gene expression in 7 of the 19 P450 genes CYP325K3v1, CYP4D42v2, CYP9J45, (CYP) CPIJ000926, CYP325G4, CYP4C38, CYP4H40 in the HAmCqG8 strain, increased more than 2-fold after exposure to permethrin at an LC50 concentration (10 ppm) compared to their acetone treated counterpart; no significant differences in the expression of these P450 genes in susceptible S-Lab mosquitoes were observed after permethrin treatment. Eleven of the fourteen P450 genes overexpressed in the MAmCqG6 strain, CYP9M10, CYP6Z12, CYP9J33, CYP9J43, CYP9J34, CYP306A1, CYP6Z15, CYP9J45, CYPPAL1, CYP4C52v1, CYP9J39, were also induced more than doubled after exposure to an LC50 (0.7 ppm) dose of permethrin. No significant induction in P450 gene expression was observed in the susceptible S-Lab mosquitoes after permethrin treatment except for CYP6Z15 and CYP9J39, suggesting that permethrin induction of these two P450 genes are common to both susceptible and resistant mosquitoes while the induction of the others are specific to insecticide resistant mosquitoes. These results demonstrate that multiple P450 genes are co-up-regulated in insecticide resistant mosquitoes through both constitutive overexpression and induction mechanisms, providing additional support for their involvement in the detoxification of insecticides and the development of insecticide resistance.

Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles.

PubMed

Cavolo, Samantha L; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

2016-11-16

Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde transport. Here we show that activity stimulates further synaptic capture that is distinguished from basal capture by its selectivity for anterograde DCVs and its inhibition by overexpression of the fragile X retardation protein Fmr1. Fmr1 dramatically lowers DCV numbers in synaptic boutons. Therefore, activity-dependent anterograde capture is a major determinant of presynaptic peptide stores. Copyright © 2016 the authors 0270-6474/16/3611781-07$15.00/0.

Participation of the arcRACME protein in self-activation of the arc operon located in the arginine catabolism mobile element in pandemic clone USA300.

PubMed

Rozo, Zayda Lorena Corredor; Márquez-Ortiz, Ricaurte Alejandro; Castro, Betsy Esperanza; Gómez, Natasha Vanegas; Escobar-Pérez, Javier

2017-07-01

Staphylococcus aureus pandemic clone USA300 has, in addition to its constitutive arginine catabolism (arc) gene cluster, an arginine catabolism mobile element (ACME) carrying another such cluster, which gives this clone advantages in colonisation and infection. Gene arcR, which encodes an oxygen-sensitive transcriptional regulator, is inside ACME and downstream of the constitutive arc gene cluster, and this situation may have an impact on its activation. Different relative expression behaviours are proven here for arcRACME and the arcACME operon compared to the constitutive ones. We also show that the artificially expressed recombinant ArcRACME protein binds to the promoter region of the arcACME operon; this mechanism can be related to a positive feedback model, which may be responsible for increased anaerobic survival of the USA300 clone during infection-related processes.

On 3D inelastic analysis methods for hot section components

NASA Technical Reports Server (NTRS)

Mcknight, R. L.; Chen, P. C.; Dame, L. T.; Holt, R. V.; Huang, H.; Hartle, M.; Gellin, S.; Allen, D. H.; Haisler, W. E.

1986-01-01

Accomplishments are described for the 2-year program, to develop advanced 3-D inelastic structural stress analysis methods and solution strategies for more accurate and cost effective analysis of combustors, turbine blades and vanes. The approach was to develop a matrix of formulation elements and constitutive models. Three constitutive models were developed in conjunction with optimized iterating techniques, accelerators, and convergence criteria within a framework of dynamic time incrementing. Three formulations models were developed; an eight-noded mid-surface shell element, a nine-noded mid-surface shell element and a twenty-noded isoparametric solid element. A separate computer program was developed for each combination of constitutive model-formulation model. Each program provides a functional stand alone capability for performing cyclic nonlinear structural analysis. In addition, the analysis capabilities incorporated into each program can be abstracted in subroutine form for incorporation into other codes or to form new combinations.

The 3D inelastic analysis methods for hot section components

NASA Technical Reports Server (NTRS)

Mcknight, R. L.; Maffeo, R. J.; Tipton, M. T.; Weber, G.

1992-01-01

A two-year program to develop advanced 3D inelastic structural stress analysis methods and solution strategies for more accurate and cost effective analysis of combustors, turbine blades, and vanes is described. The approach was to develop a matrix of formulation elements and constitutive models. Three constitutive models were developed in conjunction with optimized iterating techniques, accelerators, and convergence criteria within a framework of dynamic time incrementing. Three formulation models were developed: an eight-noded midsurface shell element; a nine-noded midsurface shell element; and a twenty-noded isoparametric solid element. A separate computer program has been developed for each combination of constitutive model-formulation model. Each program provides a functional stand alone capability for performing cyclic nonlinear structural analysis. In addition, the analysis capabilities incorporated into each program can be abstracted in subroutine form for incorporation into other codes or to form new combinations.

Constitutive gene expression and specification of tissue identity in adult planarian biology

PubMed Central

Reddien, Peter W.

2011-01-01

Planarians are flatworms that constitutively maintain adult tissues through cell turnover and can regenerate entire organisms from tiny body fragments. In addition to requiring new cells (from neoblasts), these feats require mechanisms that specify tissue identity in the adult. Critical roles for Wnt and BMP signaling in regeneration and maintenance of the body axes have been uncovered, among other regulatory factors. Available data indicate that genes involved in positional identity regulation at key embryonic stages in other animals display persisting regionalized expression in adult planarians. These expression patterns suggest that a constitutively active gene expression map exists for maintenance of the planarian body. Planarians therefore present a fertile ground for identification of factors regulating regionalization of the metazoan body plan and for study of the attributes of these factors that can lead to maintenance and regeneration of adult tissues. PMID:21680047

3, 3′- DIINDOLYLMETHANE ENHANCES CHEMOSENSITIVITY OF MULTIPLE CHEMOTHERAPEUTIC AGENTS IN PANCREATIC CANCER

PubMed Central

Banerjee, Sanjeev; Wang, Zhiwei; Kong, Dejuan; Sarkar, Fazlul H.

2009-01-01

Clinical management of pancreatic cancer (PC) is a major problem, which is in part due to both de novo and acquired resistance to conventional therapeutics. Here, we present in vitro and in vivo preclinical evidence in support of chemo-sensitization of PC cells by DIM, a natural compound that can be easily obtained by consuming cruciferous vegetables. DIM pretreatment of PC cells led to a significantly increased apoptosis (p<0.01) with suboptimal concentrations of chemotherapeutic agents (cisplatin, gemcitabine and oxaliplatin) compared to monotherapy. It is known that resistance to chemotherapy in PC is associated with constitutively activated NF-κB, which becomes further activated by chemotherapeutic drugs. Our data provide mechanistic evidence for the first time showing that DIM potentiates the killing of PC cells by down-regulation of constitutive as well as drug induced activation of NF-κB and its downstream genes (Bcl-xL, XIAP, c-IAP, survivin). Most importantly, using an orthotopic animal model, we found reduction in tumor size (p<0.001) when DIM was given in combination with oxaliplatin compared to monotherapy. This was accompanied by loss of phospho p-65, down-regulation of NF-κB activity and its downstream genes (Bcl-xL, survivin and XIAP), which correlated with reduced cell proliferation (as assessed by Ki-67 immunostaining of tumor specimens) and evidence of apoptosis (as assessed by PARP cleavage and TUNEL staining). These results provide strong in vivo evidence in support of our hypothesis that DIM could abrogate chemotherapeutic drug (cisplatin, gemcitabine and/or oxaliplatin) induced activation of NF-κB, resulting in the chemo-sensitization of pancreatic tumors to conventional therapeutics. PMID:19531648

78 FR 63247 - Agency Information Collection Activities: Proposed Collection, Comments Requested; Extension of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... allow for an additional 30 days for public comment until November 22, 2013. This process is conducted in..., Justice Management Division, United States Department of Justice, Two Constitutional Square, 145 N Street...

Bioluminescence Resonance Energy Transfer Studies Reveal Constitutive Dimerization of the Human Lutropin Receptor and a Lack of Correlation between Receptor Activation and the Propensity for Dimerization*

PubMed Central

Guan, Rongbin; Feng, Xiuyan; Wu, Xueqing; Zhang, Meilin; Zhang, Xuesen; Hébert, Terence E.; Segaloff, Deborah L.

2009-01-01

Previous studies from our laboratory using co-immunoprecipitation techniques suggested that the human lutropin receptor (hLHR) constitutively self-associates into dimers/oligomers and that agonist treatment of cells either increased hLHR dimerization/oligomerization and/or stabilized hLHR dimers/oligomers to detergent solubilization (Tao, Y. X., Johnson, N. B., and Segaloff, D. L. (2004) J. Biol. Chem. 279, 5904–5914). In this study, bioluminescence resonance energy transfer (BRET2) analyses confirmed that the hLHR constitutively self-associates in living cells. After subcellular fractionation, hLHR dimers/oligomers were detected in both the plasma membrane and endoplasmic reticulum (ER). Further evidence supporting the constitutive formation of hLHR dimer/oligomers in the ER is provided by data showing homodimerization of misfolded hLHR mutants that are retained in the ER. These mutants, when co-expressed with wild-type receptor, are shown by BRET2 to heterodimerize, accounting for their dominant-negative effects on cell surface receptor expression. Hormone desorption assays using intact cells demonstrate allosterism between hLHR protomers, indicating functional cell surface hLHR dimers. However, quantitative BRET2 analyses in intact cells indicate a lack of effect of agonist on the propensity of the hLHR to dimerize. Using purified plasma membranes, human chorionic gonadotropin was similarly observed to have no effect on the BRET2 signal. An examination of the propensity for constitutively active and signaling inactive hLHR mutants to dimerize further showed no correlation between dimerization and the activation state of the hLHR. Taken altogether, our data suggest that hLHR dimers/oligomers are formed early in the biosynthetic pathway in the ER, are constitutively expressed on the plasma membrane, and are not affected by the activation state of the hLHR. PMID:19147490

Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells

PubMed Central

Frigault, Matthew J; Lee, Jihyun; Basil, Maria Ciocca; Carpenito, Carmine; Motohashi, Shinichiro; Scholler, John; Kawalekar, Omkar U.; Guedan, Sonia; McGettigan, Shannon E.; Posey, Avery D.; Ang, Sonny; Cooper, Laurence J. N.; Platt, Jesse M.; Johnson, F. Brad; Paulos, Chrystal M; Zhao, Yangbing; Kalos, Michael; Milone, Michael C.; June, Carl H.

2015-01-01

This study compared second generation chimeric antigen receptors encoding signaling domains composed of CD28, ICOS and 4-1BB. Here we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T-cell with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to three months following a single stimulation through the TCR. Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28. Results from gene array and functional assays linked sustained cytokine secretion and expression of T-bet, EOMES and GATA-3 to the effect. Sustained expression of the endogenous IL2 locus has not been reported in primary T cells. Sustained proliferation was dependent on CAR structure and high expression, the latter of which was necessary but not sufficient. The mechanism involves constitutive signaling through NF-kB, Akt, Erk and NFAT. The propagated CAR T cells retained a diverse TCR repertoire and cellular transformation was not observed. The CARs with a constitutive growth phenotype displayed inferior antitumor effects and engraftment in vivo. Therefore the design of CARs that have a non-constitutive growth phenotype may be a strategy to improve efficacy and engraftment of CAR T cells. The identification of CARs that confer constitutive or non-constitutive growth patterns may explain observations that CAR T cells have differential survival patterns in clinical trials. PMID:25600436

Anatomical, histological and immunohistochemical study of testicular development in Columba livia (Aves: Columbiformes).

PubMed

Olea, G B; Aguirre, M V; Lombardo, D M

2018-07-01

In this work, testicular ontogeny is analyzed at the anatomical, histological and immunohistochemical levels; the latter through the detection of GnRHR and PCNA in the testicles of embryos, neonates and juveniles of Columba livia. We analyzed 150 embryos, 25 neonates and 5 juveniles by means of observations under a stereoscopic magnifying glass and scanning electron microscope (SEM). The histological analysis was performed using hematoxylin-eosin staining techniques and the PAS reaction. For the immunohistochemical analysis, the expression of GnRHR and PCNA in embryos corresponding to stages 41, 43 and in neonates of 2, 5, 7 and 75 days post-hatch was revealed in testicular histological preparations. That gonadal outline is evident in stage 18. In stage 29, the testes are constituted of a medulla in which the PGCs are surrounded by the Sertoli cells, constituting the seminiferous tubules. From stage 37 a greater organization of the tubules is visualized and at the time of hatching the testicle is constituted of the closed seminiferous tubules, formed of the PGCs and Sertoli cells. The Leydig cells are evident outside the tubules. In the juvenile stages, the differentiation of germline cells and the organization of small vessels that irrigate the developing testicle begin to be visible. In the analyzed stages, the immunodetection of the GnRHR receptor and PCNA revealed specific marking in the plasma membrane and in the perinuclear zone for GnRHR and in the nucleus of the germline cells in juvenile testicles for PCNA. These results can be used as a basis for further study of endocrine regulation events during testicular ontogeny in avian species. Copyright © 2018 Elsevier GmbH. All rights reserved.

What does meaningful look like? A qualitative study of patient engagement at the Pan-Canadian Oncology Drug Review: perspectives of reviewers and payers.

PubMed

Rozmovits, Linda; Mai, Helen; Chambers, Alexandra; Chan, Kelvin

2018-04-01

Objectives While there is wide support for patient engagement in health technology assessment, determining what constitutes meaningful (as opposed to tokenistic) engagement is complex. This paper explores reviewer and payer perceptions of what constitutes meaningful patient engagement in the Pan-Canadian Oncology Drug Review process. Methods Qualitative interview study comprising 24 semi-structured telephone interviews. A qualitative descriptive approach, employing the technique of constant comparison, was used to produce a thematic analysis. Results Submissions from patient advocacy groups were seen as meaningful when they provided information unavailable from other sources. This included information not collected in clinical trials, information relevant to clinical trade-offs and information about aspects of lived experience such as geographic differences and patient and carer priorities. In contrast, patient submissions that relied on emotional appeals or lacked transparency about their own methods were seen as detracting from the meaningfulness of patient engagement by conflating health technology assessment with other functions of patient advocacy groups such as fundraising or public awareness campaigns, and by failing to provide credible information relevant to deliberations. Conclusions This study suggests that misalignment of stakeholder expectations remains an issue even for a well-regarded health technology assessment process that has promoted patient engagement since its inception. Support for the technical capacity of patient groups to participate in health technology assessment is necessary but not sufficient to address this issue fully. There is a fundamental tension between the evidence-based nature of health technology assessment and the experientially oriented culture of patient advocacy. Divergent notions of what constitutes evidence and how it should be used must also be addressed.

G protein-gated K+ channel ablation in forebrain pyramidal neurons selectively impairs fear learning

PubMed Central

Victoria, Nicole C.; de Velasco, Ezequiel Marron Fernandez; Ostrovskaya, Olga; Metzger, Stefania; Xia, Zhilian; Kotecki, Lydia; Benneyworth, Michael A.; Zink, Anastasia N.; Martemyanov, Kirill A.; Wickman, Kevin

2015-01-01

Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders. PMID:26612516

ADHD-Derived Coding Variation in the Dopamine Transporter Disrupts Microdomain Targeting and Trafficking Regulation

PubMed Central

Sakrikar, Dhananjay; Mazei-Robison, Michelle S.; Mergy, Marc A.; Richtand, Nathan W.; Han, Qiao; Hamilton, Peter J.; Bowton, Erica; Galli, Aurelio; Veenstra-VanderWeele, Jeremy; Gill, Michael; Blakely, Randy D.

2012-01-01

Attention-Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed disorder of school-age children. Although genetic and brain imaging studies suggest a contribution of altered dopamine (DA) signaling in ADHD, evidence of signaling perturbations contributing to risk is largely circumstantial. The presynaptic, cocaine and amphetamine (AMPH)-sensitive DA transporter (DAT) constrains DA availability at pre- and post-synaptic receptors following vesicular release and is targeted by the most commonly prescribed ADHD therapeutics. Using polymorphism discovery approaches with an ADHD cohort, we identified a human DAT (hDAT) coding variant, R615C, located in the transporter’s distal C-terminus, a region previously implicated in constitutive and regulated transporter trafficking. Here we demonstrate that whereas wildtype DAT proteins traffic in a highly regulated manner, DAT 615C proteins recycle constitutively, and demonstrate insensitivity to the endocytic effects of AMPH and protein kinase C (PKC) activation. The disrupted regulation of DAT 615C parallels a redistribution of the transporter variant away from GM1 ganglioside- and flotillin1-enriched membranes, and is accompanied by altered calcium/calmodulin-dependent protein kinase II (CaMKII) and flotillin-1 interactions. Using C-terminal peptides derived from wildtype DAT and the R615C variant, we establish that the DAT 615C C-terminus can act dominantly to preclude AMPH regulation of wildtype DAT. Mutagenesis of DAT C-terminal sequences suggest that phosphorylation of T613 may be important in sorting DAT between constitutive and regulated pathways. Together, our studies support a coupling of DAT microdomain localization with transporter regulation and provide evidence of perturbed DAT activity and DA signaling as a risk determinant for ADHD. PMID:22514303

Constitutive and Companion Cell-Specific Overexpression of AVP1, Encoding a Proton-Pumping Pyrophosphatase, Enhances Biomass Accumulation, Phloem Loading, and Long-Distance Transport1[OPEN

PubMed Central

Shulaev, Vladimir; Paez-Valencia, Julio

2016-01-01

Plant productivity is determined in large part by the partitioning of assimilates between the sites of production and the sites of utilization. Proton-pumping pyrophosphatases (H+-PPases) are shown to participate in many energetic plant processes, including general growth and biomass accumulation, CO2 fixation, nutrient acquisition, and stress responses. H+-PPases have a well-documented role in hydrolyzing pyrophosphate (PPi) and capturing the released energy to pump H+ across the tonoplast and endomembranes to create proton motive force (pmf). Recently, an additional role for H+-PPases in phloem loading and biomass partitioning was proposed. In companion cells (CCs) of the phloem, H+-PPases localize to the plasma membrane rather than endomembranes, and rather than hydrolyzing PPi to create pmf, pmf is utilized to synthesize PPi. Additional PPi in the CCs promotes sucrose oxidation and ATP synthesis, which the plasma membrane P-type ATPase in turn uses to create more pmf for phloem loading of sucrose via sucrose-H+ symporters. To test this model, transgenic Arabidopsis (Arabidopsis thaliana) plants were generated with constitutive and CC-specific overexpression of AVP1, encoding type 1 ARABIDOPSIS VACUOLAR PYROPHOSPHATASE1. Plants with both constitutive and CC-specific overexpression accumulated more biomass in shoot and root systems. 14C-labeling experiments showed enhanced photosynthesis, phloem loading, phloem transport, and delivery to sink organs. The results obtained with constitutive and CC-specific promoters were very similar, such that the growth enhancement mediated by AVP1 overexpression can be attributed to its role in phloem CCs. This supports the model for H+-PPases functioning as PPi synthases in the phloem by arguing that the increases in biomass observed with AVP1 overexpression stem from improved phloem loading and transport. PMID:26530315

Constitutive Behavior of Mixed Sn-Pb/Sn-3.0Ag-0.5Cu Solder Alloys

NASA Astrophysics Data System (ADS)

Tucker, J. P.; Chan, D. K.; Subbarayan, G.; Handwerker, C. A.

2012-03-01

During the transition from Pb-containing solders to Pb-free solders, joints composed of a mixture of Sn-Pb and Sn-Ag-Cu often result from either mixed assemblies or rework. Comprehensive characterization of the mechanical behavior of these mixed solder alloys resulting in a deformationally complete constitutive description is necessary to predict failure of mixed alloy solder joints. Three alloys with 1 wt.%, 5 wt.%, and 20 wt.% Pb were selected so as to represent reasonable ranges of Pb contamination expected from different 63Sn-37Pb components mixed with Sn-3.0Ag-0.5Cu. Creep and displacement-controlled tests were performed on specially designed assemblies at temperatures of 25°C, 75°C, and 125°C using a double lap shear test setup that ensures a nearly homogeneous state of plastic strain at the joint interface. The observed changes in creep and tensile behavior with Pb additions were related to phase equilibria and microstructure differences observed through differential scanning calorimetric and scanning electron microscopic cross-sectional analysis. As Pb content increased, the steady-state creep strain rates increased, and primary creep decreased. Even 1 wt.% Pb addition was sufficient to induce substantially large creep strains relative to the Sn-3.0Ag-0.5Cu alloy. We describe rate-dependent constitutive models for Pb-contaminated Sn-Ag-Cu solder alloys, ranging from the traditional time-hardening creep model to the viscoplastic Anand model. We illustrate the utility of these constitutive models by examining the inelastic response of a chip-scale package (CSP) under thermomechanical loading through finite-element analysis. The models predict that, as Pb content increases, total inelastic dissipation decreases.

EVIDENCE – BASED MEDICINE/PRACTICE IN SPORTS PHYSICAL THERAPY

PubMed Central

Lehecka, B.J.

2012-01-01

A push for the use of evidence‐based medicine and evidence‐based practice patterns has permeated most health care disciplines. The use of evidence‐based practice in sports physical therapy may improve health care quality, reduce medical errors, help balance known benefits and risks, challenge views based on beliefs rather than evidence, and help to integrate patient preferences into decision‐making. In this era of health care utilization sports physical therapists are expected to integrate clinical experience with conscientious, explicit, and judicious use of research evidence in order to make clearly informed decisions in order to help maximize and optimize patient well‐being. One of the more common reasons for not using evidence in clinical practice is the perceived lack of skills and knowledge when searching for or appraising research. This clinical commentary was developed to educate the readership on what constitutes evidence‐based practice, and strategies used to seek evidence in the daily clinical practice of sports physical therapy. PMID:23091778

[Evidence based medicine. A new paradigm for medical practice].

PubMed

Carneiro, A V

1998-01-01

Modern medical practice is an ever-changing process, and the doctor's need for information has been partially met by continuous medical education (CME) activities. It has been shown that CME activities have not prevented clinical knowledge, as well as medical practice, from deteriorating with time. When faced with the need to get the most recent and relevant information possible, the busy clinician has two major problems: most of the published medical literature is either irrelevant or not useful; and there is little time to read it. Evidence-based medicine constitutes a new paradigm for medical practice in the sense that it tries to transform clinical problems into well formulated clinical questions, selecting and critically appraising scientific evidence with predefined and rigorous rules. It combines the expertise of the individual clinician with the best external evidence from clinical research for rational, ethical and efficacious practice. Evidence-based medicine can be taught and practiced by physicians with different degrees of autonomy, with several subspecialties, working in the hospital or in outpatient clinics, alone or in groups.

Characteristics of TCM constitutions of adult Chinese women in Hong Kong and identification of related influencing factors: a cross-sectional survey.

PubMed

Sun, Youzhi; Liu, Pei; Zhao, Yi; Jia, Lei; He, Yanhua; Xue, Steve An; Zheng, Xiao; Wang, Zhiyu; Wang, Neng; Chen, Jianping

2014-05-21

Traditional Chinese Medicine Constitution (TCMC) refers to an integrated, metastable and natural specialty of individual in morphosis, physiological functions and psychological conditions. It is formed on the basis of innate and acquired endowments in the human life process, which can be divided into normal constitution and unbalanced ones. The aim of this study was to investigate the distribution of TCMCs of Chinese women in Hong Kong and its acquired influencing factors. Local Chinese women between 30 to 65 years old, were recruited from 18 districts of Hong Kong (n=944), and were assessed using the Traditional Chinese Medicine Physical Constitution Scale for their TCMC types. Social-demographic, reproductive, lifestyle, systemic health and emotional status information were collected through structured questionnaire. The associations between different independent factors and each TCMC type, as well as the complex unbalanced TCMC types were tested individually. Significant factors related to unbalanced TCMC types were identified in final models using multiple factor analysis. A total of 764 (80.9%) participants were diagnosed with unbalanced TCMCs. The most common TCMC type was Qi-deficiency constitution (53.9%), followed by Phlegm-wetness (38.9%), Yang-deficiency (38.2%), Yin-deficiency (35.5), Blood-stasis (35.4) and Qi-depressed (31%) constitution. Six hundred and eleven participants (64.7%) had at least two types of combined and unbalanced constitutions. Stepwise logistic analysis indicated that poor systemic health condition (OR, 1.76-2.89), negative emotions (OR=1.39), overweight (OR=1.58), high educational level (OR=1.18) and mental work (OR=1.44) were significantly positively correlated with certain unbalanced TCMCs. Meanwhile, aging (OR, 0.59-0.73), exercise habit (OR, 0.61-0.79) and reproductive history (OR=0.72) showed inverse associations with unbalanced constitutions. In addition, systemic health condition and emotional status, exercise habit and age were significantly associated with the combined unbalanced TCMC types. The majority of middle-aged Chinese women in Hong Kong had unbalanced and complex TCMCs. Qi-deficiency, Phlegm-wetness and Yang-deficiency constitutions are the most common constitutions. Poor systemic health condition, less-than-satisfactory emotional life, overweight and mental work are associated with and may be contributors for the formation of unbalanced TCMCs, while regular physical exercise was found to be a potential protective factor for unbalanced TCMCs.

The Australian government's review of positron emission tomography: evidence-based policy-making in action.

PubMed

Ware, Robert E; Francis, Hilton W; Read, Kenneth E

2004-06-21

The Commonwealth Government constituted the Medicare Services Advisory Committee (MSAC) to implement its commitment to entrench the principles of evidence-based medicine in Australian clinical practice. With its recent review of positron emission tomography (PETReview), the Commonwealth intervened in an established MSAC process, and sanctioned the stated objective to restrict expenditure on the technology. In our opinion: The evaluation of evidence by PETReview was fundamentally compromised by a failure to meet the terms of reference, poor science, poor process and unique decision-making benchmarks. By accepting the recommendations of PETReview, the Commonwealth is propagating information which is not of the highest quality. The use of inferior-quality information for decision-making by doctors, patients and policy-makers is likely to harm rather than enhance healthcare outcomes.

Culturally Adapting an Evidence-Based Parenting Intervention for Latino Immigrants: The Need to Integrate Fidelity and Cultural Relevance1

PubMed Central

Cardona, Jose Ruben Parra; Domenech-Rodriguez, Melanie; Forgatch, Marion; Sullivan, Cris; Bybee, Deborah; Holtrop, Kendal; Escobar-Chew, Ana Rocio; Tams, Lisa; Dates, Brian; Bernal, Guillermo

2011-01-01

Latinos constitute the largest ethnic minority group in the US. However, the cultural adaptation and dissemination of evidence-based parenting interventions among Latino populations continues to be scarce in spite of extensive research that demonstrates the long-term positive effects of these interventions. The purpose of this article is threefold: (a) justify the importance of cultural adaptation research as a key strategy to disseminate efficacious interventions among Latinos, (b) describe the initial steps of a program of prevention research with Latino immigrants aimed at culturally adapting an evidence-based intervention informed by parent management training (PMT) principles, and (c) discuss implications for advancing cultural adaptation prevention practice and research, based on the initial feasibility and cultural acceptability findings of the current investigation. PMID:22428711

Constitutive expression of the nifA gene activates associative nitrogen fixation of Enterobacter gergoviae 57-7, an opportunistic endophytic diazotroph.

PubMed

An, Q; Dong, Y; Wang, W; Li, Y; Li, J

2007-09-01

This study was undertaken to investigate whether a nitrogen-fixing bacterium Enterobacter gergoviae 57-7, which was isolated from surface-sterilized maize (Zea mays L.) roots, can colonize in roots and whether constitutive expression of the nifA gene encoding the transcriptional activator of nitrogenase genes can activate nif gene expression in planta. Maize seedlings grown in an agar medium were inoculated with Ent. gergoviae strains containing the green fluorescent protein reporter gene. Root colonization and expression of the dinitrogenase reductase gene (nifH) by Ent. gergoviae were observed by confocal laser scanning microscopy. gfp-tagged Ent. gergoviae was observed to colonize predominantly in cortical aerenchyma of primary and lateral roots and in stellar parenchyma cells and xylem vessels of primary roots. In planta nifH :: gfp expression was not detected but after a constitutively expressed nifA gene was introduced into Ent. gergoviae. Enterobacter gergoviae 57-7 is an opportunistic endophyte because it can live in soil and colonize in maize roots in the gnotobiotic agar culture. In agreement with previous (15)N-dilution evidence that Ent. gergoviae 57-7 did not fix N(2) in association with maize in pots whereas a derivative E7 containing a constitutively expressed nifA gene promoted plant growth partly through associative nitrogen fixation, constitutive expression of the nifA gene can activate bacterial nif gene expression in planta. This study and our previous studies suggest that manipulation of the promoter of the nifA gene in a nitrogen-fixing bacterium having a high colonization competence is a practical and promising approach to achieve a stable associative nitrogen fixation for cereals.

Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

PubMed

Pezzolo, Annalisa; Sementa, Angela Rita; Lerone, Margherita; Morini, Martina; Ognibene, Marzia; Defferrari, Raffaella; Mazzocco, Katia; Conte, Massimo; Gigliotti, Anna Rita; Garaventa, Alberto; Pistoia, Vito; Varesio, Luigi

2017-05-04

Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥ 10 y. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival. We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence. Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control. This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.

Novel Gal3 proteins showing altered Gal80p binding cause constitutive transcription of Gal4p-activated genes in Saccharomyces cerevisiae.

PubMed Central

Blank, T E; Woods, M P; Lebo, C M; Xin, P; Hopper, J E

1997-01-01

Gal4p-mediated activation of galactose gene expression in Saccharomyces cerevisiae normally requires both galactose and the activity of Gal3p. Recent evidence suggests that in cells exposed to galactose, Gal3p binds to and inhibits Ga180p, an inhibitor of the transcriptional activator Gal4p. Here, we report on the isolation and characterization of novel mutant forms of Gal3p that can induce Gal4p activity independently of galactose. Five mutant GAL3(c) alleles were isolated by using a selection demanding constitutive expression of a GAL1 promoter-driven HIS3 gene. This constitutive effect is not due to overproduction of Gal3p. The level of constitutive GAL gene expression in cells bearing different GAL3(c) alleles varies over more than a fourfold range and increases in response to galactose. Utilizing glutathione S-transferase-Gal3p fusions, we determined that the mutant Gal3p proteins show altered Gal80p-binding characteristics. The Gal3p mutant proteins differ in their requirements for galactose and ATP for their Gal80p-binding ability. The behavior of the novel Gal3p proteins provides strong support for a model wherein galactose causes an alteration in Gal3p that increases either its ability to bind to Gal80p or its access to Gal80p. With the Gal3p-Gal80p interaction being a critical step in the induction process, the Gal3p proteins constitute an important new reagent for studying the induction mechanism through both in vivo and in vitro methods. PMID:9111326

Handbook for Military Justice and Civil Law

DTIC Science & Technology

2000-09-01

In most cases, however, to an individual to identify himself is not an "interrogation," and production of the identification is not a "statement...mind, the most productive approach for the reader is to develop a thorough knowledge of what actions are legally permissible (producing admissible...activities that constitute reasonable searches, and other command activities which, although permissible and productive of admissible evidence, are not

The Bacillus subtilis ywjI (glpX) gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the class III Fbp enzyme.

PubMed

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-05-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions.

The Bacillus subtilis ywjI (glpX) Gene Encodes a Class II Fructose-1,6-Bisphosphatase, Functionally Equivalent to the Class III Fbp Enzyme▿

PubMed Central

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-01-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions. PMID:19270101

Status Report on Power System Transformation: A 21st Century Power Partnership Report

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

Miller, Mackay; Martinot, Eric; Cox, Sadie

This report has three primary goals: (1) to articulate the concept of power system transformation; (2) to explore the current global landscape of ‘innovations’ that constitute power system transformation and provide evidence of how these innovations are emerging; and (3) to suggest an analytical framework for assessing the status of power system transformation on an on-going basis.

East European Military Establishments: The Warsaw Pact Northern Tier.

DTIC Science & Technology

1980-12-01

grant is contributing to student fellowships for dissertation preparation, curriculum development, work- shops and tutorials, and a series of visiting...assistance is a source of consid- erable professional satisfaction for the Polish militarv officer and as such constitutes a source of solidaritv...with the Soviet military. Yet there is clear evidence that in the mid-1960s considerable dis- satisfaction existed within the Polish officer corns

Teacher and Principal Perceptions of Student Victimization and the Schools' Response to Violence: The Contributions of Context on Staff Congruence

ERIC Educational Resources Information Center

Stone, Susan; Astor, Ron; Benbenishty, Rami

2009-01-01

Consistency in staff awareness and response is a key programmatic centerpiece in most school violence prevention and intervention programs. Staff consensus on the definition of violence, the behaviors that constitute violence, the extent of the problem, and how to deal with violent situations are often the cornerstone of evidence-based programs.…

Autofrecuencias de las ecuaciones de Helmholtz y Liouville para un modelo de tierra tipo Jeffreys simplificado.

NASA Astrophysics Data System (ADS)

Sevilla, M. J.; González-Camacho, A.

The authors obtain expressions for the free frequencies of polar motion for an ellipsoidal, rotating and perturbed earth model constituted by an elastic mantle with an homogeneous liquid core of additional simple motion.

Teaching with Secondary Data.

ERIC Educational Resources Information Center

Sobol, Jeff

1981-01-01

Presents a general overview of the use of secondary data in teaching sociology on the college level. Topics discussed include potential for additional applications, sources which constitute secondary data, reasons for using secondary data in the classroom, information about computing, and potential problems. (Author/DB)

Gene mapping study for constitutive skin color in an isolated Mongolian population.

PubMed

Paik, Seung Hwan; Kim, Hyun-Jin; Son, Ho-Young; Lee, Seungbok; Im, Sun-Wha; Ju, Young Seok; Yeon, Je Ho; Jo, Seong Jin; Eun, Hee Chul; Seo, Jeong-Sun; Kwon, Oh Sang; Kim, Jong-Il

2012-03-31

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

Gene mapping study for constitutive skin color in an isolated Mongolian population

PubMed Central

Paik, Seung Hwan; Kim, Hyun-Jin; Son, Ho-Young; Lee, Seungbok; Im, Sun-Wha; Ju, Young Seok; Yeon, Je Ho; Jo, Seong Jin; Eun, Hee Chul; Seo, Jeong-Sun

2012-01-01

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC. PMID:22198297

Configurational and constitutional information storage: multiple dynamics in systems based on pyridyl and acyl hydrazones.

PubMed

Chaur, Manuel N; Collado, Daniel; Lehn, Jean-Marie

2011-01-03

The C=N group of hydrazones can undergo E/Z isomerization both photochemically and thermally, allowing the generation of a closed process that can be tuned by either of these two physical stimuli. On the other hand, hydrazine-exchange reactions enable a constitutional change in a given hydrazone. The two classes of processes: 1) configurational (physically stimulated) and 2) constitutional (chemically stimulated) give access to short-term and long-term information storage, respectively. Such transformations are reported herein for two hydrazones (bis-pyridyl hydrazone and 2-pyridinecarboxaldehyde phenylhydrazone) that undergo a closed, chemically or physically driven process, and, in addition, can be locked or unlocked at will by metal-ion coordination or removal. These features also extend to acyl hydrazones derived from 2-pyridinecarboxaldehyde. Similarly to the terpydine-like hydrazones, such acyl hydrazones can undergo both constitutional and configurational changes, as well as metal-ion coordination. All these types of hydrazones represent dynamic systems capable of acting as multiple state molecular devices, in which the presence of coordination sites furthermore allows the metal ion-controlled locking and unlocking of the interconversion of the different states. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

State and Municipal Innovations in Obesity Policy: Why Localities Remain a Necessary Laboratory for Innovation

PubMed Central

Ashe, Marice; Farias, Ruben; Gostin, Lawrence

2015-01-01

Municipal and state governments are surging ahead in obesity prevention, providing a testing ground for innovative policies and shifting social norms in the process. Though high-profile measures such as New York City’s soda portion rule attract significant media attention, we catalog the broader array of initiatives in less-known localities. Local innovation advances prevention policy, but faces legal and political constraints—constitutional challenges, preemption, charges of paternalism, lack of evidence, and widening health inequalities. These arguments can be met with astute framing, empirical evidence, and policy design, enabling local governments to remain at the forefront in transforming obesogenic environments. PMID:25602886

Natural representations: diagram and text in Darwin's "On the origin of species".

PubMed

Brink-Roby, Heather

2009-01-01

This article examines Darwin's use of diagram and text in the "Origin" by focusing on their interacting roles in his discussion of natural relations, extinction, and time. Each medium presented opportunities and challenges that depend on the topic in question; indeed, a medium's dimensionality could undermine one claim and make self-evident another. While Darwin divides representational labor between diagram and text, he also creates a constitutive interplay between media. The resulting dynamic alliance of form and content recalls his early evolutionary reflections on representation; image and word could be used not simply to argue for, but also as evidence of, his theory.

Facts and values in psychotherapy-A critique of the empirical reduction of psychotherapy within evidence-based practice.

PubMed

Berg, Henrik; Slaattelid, Rasmus

2017-10-01

This paper addresses an implicit presupposition in research-supported psychological treatments and evidence-based practice in psychology. It argues that the notion of research-supported psychological treatments is based on a reductive conceptualisation of psychotherapy. Research-supported psychological treatments hinge upon an empirical reduction where psychotherapy schools become conceptualized as mere collections of empirical propositions. However, this paper argues that the different psychotherapy schools have distinct ethoses that are constituted by normative claims. Consequently, the evaluation of the different psychotherapy schools and the practice of psychotherapy should include the underlying normative claims of these ethoses. © 2017 John Wiley & Sons, Ltd.

Social Security And Mental Illness: Reducing Disability With Supported Employment

PubMed Central

Drake, Robert E.; Skinner, Jonathan S.; Bond, Gary R.; Goldman, Howard H.

2010-01-01

Social Security Administration disability programs are expensive, growing, and headed toward bankruptcy. People with psychiatric disabilities now constitute the largest and most rapidly expanding subgroup of program beneficiaries. Evidence-based supported employment is a well-defined, rigorously tested service model that helps people with psychiatric disabilities obtain and succeed in competitive employment. Providing evidence-based supported employment and mental health services to this population could reduce the growing rates of disability and enable those already disabled to contribute positively to the workforce and to their own welfare, at little or no cost (and, depending on assumptions, a possible savings) to the government. PMID:19414885

The modality-specific organization of grammatical categories: evidence from impaired spoken and written sentence production.

PubMed

Rapp, B; Caramazza, A

1997-02-01

We describe the case of a brain-damaged individual whose speech is characterized by difficulty with practically all words except for elements of the closed class vocabulary. In contrast, his written sentence production exhibits a complementary impairment involving the omission of closed class vocabulary items and the relative sparing of nouns. On the basis of these differences we argue: (1) that grammatical categories constitute an organizing parameter of representation and/or processing for each of the independent, modality-specific lexicons, and (2) that these observations contribute to the growing evidence that access to the orthographic and phonological forms of words can occur independently.

The "olfactory mirror" and other recent attempts to demonstrate self-recognition in non-primate species.

PubMed

Gallup, Gordon G; Anderson, James R

2018-03-01

The recent attempt by Horowitz (2017) to develop an "olfactory mirror" test of self-recognition in domestic dogs raises some important questions about the kinds of data that are required to provide definitive evidence for self-recognition in dogs and other species. We conclude that the "olfactory mirror" constitutes a compelling analog to the mark test for mirror self-recognition in primates, but despite claims to the contrary neither dogs, elephants, dolphins, magpies, horses, manta rays, squid, nor ants have shown compelling, reproducible evidence for self-recognition in any modality. Copyright © 2017 Elsevier B.V. All rights reserved.