Science.gov

Sample records for admixing sufficient molybdate-reagent

  1. Pharmacogenomics in admixed populations.

    PubMed

    Suarez-Kurtz, Guilherme

    2005-04-01

    Personalized drug therapy proffered by pharmacogenomics must be based on the recognition of inherent genetic individuality, rather than relying on inter-ethnic differences in the frequency of polymorphisms that affect the pharmacokinetics and targets of drugs. This is particularly significant in admixed populations, in which the substructure created by inter-ethnic crosses further increases the fluidity of racial and/or ethnic labels. Inter-ethnic admixture is either common or increasing quickly in many, if not most, populations, and so extrapolation on a global scale of pharmacogenomic data from well-defined ethnic groups is plagued with uncertainty. To impact positively on global health, pharmacogenomics must broaden its scope of investigation with respect to both target and population diversity, and avoid the risk of contributing to the creation of a genomics divide between regions and nations. In this review, I examine the challenges and advantages of studying pharmacogenomics in admixed populations, drawing examples mainly from the trihybrid populations of the Americas. PMID:15808344

  2. MaCH-admix: genotype imputation for admixed populations.

    PubMed

    Liu, Eric Yi; Li, Mingyao; Wang, Wei; Li, Yun

    2013-01-01

    Imputation in admixed populations is an important problem but challenging due to the complex linkage disequilibrium (LD) pattern. The emergence of large reference panels such as that from the 1,000 Genomes Project enables more accurate imputation in general, and in particular for admixed populations and for uncommon variants. To efficiently benefit from these large reference panels, one key issue to consider in modern genotype imputation framework is the selection of effective reference panels. In this work, we consider a number of methods for effective reference panel construction inside a hidden Markov model and specific to each target individual. These methods fall into two categories: identity-by-state (IBS) based and ancestry-weighted approach. We evaluated the performance on individuals from recently admixed populations. Our target samples include 8,421 African Americans and 3,587 Hispanic Americans from the Women' Health Initiative, which allow assessment of imputation quality for uncommon variants. Our experiments include both large and small reference panels; large, medium, and small target samples; and in genome regions of varying levels of LD. We also include BEAGLE and IMPUTE2 for comparison. Experiment results with large reference panel suggest that our novel piecewise IBS method yields consistently higher imputation quality than other methods/software. The advantage is particularly noteworthy among uncommon variants where we observe up to 5.1% information gain with the difference being highly significant (Wilcoxon signed rank test P-value < 0.0001). Our work is the first that considers various sensible approaches for imputation in admixed populations and presents a comprehensive comparison. PMID:23074066

  3. Determining epistatic selection in admixed populations.

    PubMed

    Schumer, Molly; Brandvain, Yaniv

    2016-06-01

    When two diverging species begin hybridizing, selection against hybridization is likely driven not by single substitutions, but by interactions between incompatible mutations. To identify these incompatibilities in natural populations, researchers examine the extent of nonrandom associations between ancestry at physically unlinked loci in admixed populations. In this approach, which we call 'AD scans', locus pairs with significantly positive 'ancestry disequilibrium' (AD, i.e. locus pairs that positively covary by ancestry) represent incompatible alleles. Past research has uniformly revealed an excess of locus pairs with significantly positive AD, suggesting that dozens to hundreds of incompatibilities separate species. With forward simulations, we show that many realistic demographic scenarios, including recent and/or ongoing hybridization, generate a bias towards positive ancestry disequilibrium. We suggest steps that researchers can take to avoid pitfalls in interpreting AD scans, and present a novel measure of AD, which minimizes but does not fully eliminate bias in the AD distribution. We also show, by simulation, that the tail of the AD distribution is enriched for true incompatibilities. To illustrate the potential power and appropriate caution in interpretation of AD scans, we reanalyse previously published data from two admixed populations of Xiphophorus fishes. Our results imply that the prevalence of positive LD in admixed populations does not in itself support the idea that two-locus incompatibilities are widespread, but the co-enrichment of top AD hits across the two Xiphophorus populations supports the idea that AD scans can identify candidate interspecific incompatibilities. PMID:27061282

  4. Dark-matter admixed neutron stars

    NASA Astrophysics Data System (ADS)

    Leung, S.-C.; Chu, M.-C.; Lin, L.-M.

    2011-11-01

    We study the hydrostatic equilibrium configuration of an admixture of degenerate dark matter and normal nuclear matter by using a general relativistic two-fluid formalism. We consider non-self-annihilating dark matter particles of mass ˜1GeV. The mass-radius relations and moments of inertia of these dark-matter admixed neutron stars are investigated and the stability of these stars is demonstrated by performing a radial perturbation analysis. We find a new class of compact stars which consists of a small normal matter core with radius of a few kilometers embedded in a ten-kilometer-sized dark matter halo. These stellar objects may be observed as extraordinarily small neutron stars that are incompatible with realistic nuclear matter models.

  5. Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma.

    PubMed

    Jukes, Alistair; Allan, Rodney; Rawson, Robert; Buckland, Michael E

    2016-09-01

    Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7-15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called 'collision tumour'. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis. PMID:27068013

  6. Enhanced Methods for Local Ancestry Assignment in Sequenced Admixed Individuals

    PubMed Central

    Brown, Robert; Pasaniuc, Bogdan

    2014-01-01

    Inferring the ancestry at each locus in the genome of recently admixed individuals (e.g., Latino Americans) plays a major role in medical and population genetic inferences, ranging from finding disease-risk loci, to inferring recombination rates, to mapping missing contigs in the human genome. Although many methods for local ancestry inference have been proposed, most are designed for use with genotyping arrays and fail to make use of the full spectrum of data available from sequencing. In addition, current haplotype-based approaches are very computationally demanding, requiring large computational time for moderately large sample sizes. Here we present new methods for local ancestry inference that leverage continent-specific variants (CSVs) to attain increased performance over existing approaches in sequenced admixed genomes. A key feature of our approach is that it incorporates the admixed genomes themselves jointly with public datasets, such as 1000 Genomes, to improve the accuracy of CSV calling. We use simulations to show that our approach attains accuracy similar to widely used computationally intensive haplotype-based approaches with large decreases in runtime. Most importantly, we show that our method recovers comparable local ancestries, as the 1000 Genomes consensus local ancestry calls in the real admixed individuals from the 1000 Genomes Project. We extend our approach to account for low-coverage sequencing and show that accurate local ancestry inference can be attained at low sequencing coverage. Finally, we generalize CSVs to sub-continental population-specific variants (sCSVs) and show that in some cases it is possible to determine the sub-continental ancestry for short chromosomal segments on the basis of sCSVs. PMID:24743331

  7. Mapping asthma-associated variants in admixed populations

    PubMed Central

    Mersha, Tesfaye B.

    2015-01-01

    Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease–associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges

  8. Unravelling the hidden ancestry of American admixed populations

    PubMed Central

    Montinaro, Francesco; Busby, George B.J.; Pascali, Vincenzo L.; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-01-01

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations. PMID:25803618

  9. Accurate inference of local phased ancestry of modern admixed populations.

    PubMed

    Ma, Yamin; Zhao, Jian; Wong, Jian-Syuan; Ma, Li; Li, Wenzhi; Fu, Guoxing; Xu, Wei; Zhang, Kui; Kittles, Rick A; Li, Yun; Song, Qing

    2014-01-01

    Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis. PMID:25052506

  10. Mapping Genes that Predict Treatment Outcome in Admixed Populations

    PubMed Central

    Baye, Tesfaye M.; Wilke, Russell A.

    2010-01-01

    There is great interest in characterizing the genetic architecture underlying drug response. For many drugs, gene-based dosing models explain a considerable amount of the overall variation in treatment outcome. As such, prescription drug labels are increasingly being modified to contain pharmacogenetic information. Genetic data must, however, be interpreted within the context of relevant clinical covariates. Even the most predictive models improve with the addition of data related to biogeographical ancestry. The current review explores analytical strategies that leverage population structure to more fully characterize genetic determinants of outcome in large clinical practice-based cohorts. The success of this approach will depend upon several key factors: (1) the availability of outcome data from groups of admixed individuals (i.e., populations recombined over multiple generations), (2) a measurable difference in treatment outcome (i.e., efficacy and toxicity endpoints), and (3) a measurable difference in allele frequency between the ancestral populations. PMID:20921971

  11. Practical considerations for imputation of untyped markers in admixed populations.

    PubMed

    Shriner, Daniel; Adeyemo, Adebowale; Chen, Guanjie; Rotimi, Charles N

    2010-04-01

    Imputation of genotypes for markers untyped in a study sample has become a standard approach to increase genome coverage in genome-wide association studies at practically zero cost. Most methods for imputing missing genotypes extend previously described algorithms for inferring haplotype phase. These algorithms generally fall into three classes based on the underlying model for estimating the conditional distribution of haplotype frequencies: a cluster-based model, a multinomial model, or a population genetics-based model. We compared BEAGLE, PLINK, and MACH, representing the three classes of models, respectively, with specific attention to measures of imputation success and selection of the reference panel for an admixed study sample of African Americans. Based on analysis of chromosome 22 and after calibration to a fixed level of 90% concordance between experimentally determined and imputed genotypes, MACH yielded the largest absolute number of successfully imputed markers and the largest gain in coverage of the variation captured by HapMap reference panels. Following the common practice of performing imputation once, the Yoruba in Ibadan, Nigeria (YRI) reference panel outperformed other HapMap reference panels, including (1) African ancestry from Southwest USA (ASW) data, (2) an unweighted combination of the Northern and Western Europe (CEU) and YRI data into a single reference panel, and (3) a combination of the CEU and YRI data into a single reference panel with weights matching estimates of admixture proportions. For our admixed study sample, the optimal strategy involved imputing twice with the HapMap CEU and YRI reference panels separately and then merging the data sets. PMID:19918757

  12. Facial asymmetry and genetic ancestry in Latin American admixed populations.

    PubMed

    Quinto-Sánchez, Mirsha; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Cintas, Celia; Silva de Cerqueira, Caio Cesar; Ramallo, Virginia; Castillo, Lucia; Farrera, Arodi; Jaramillo, Claudia; Arias, Williams; Fuentes, Macarena; Everardo, Paola; de Avila, Francisco; Gomez-Valdés, Jorge; Hünemeier, Tábita; Gibbon, Shara; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Ruiz-Linares, Andres; González-José, Rolando

    2015-05-01

    Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. PMID:25582401

  13. The role of local ancestry adjustment in association studies using admixed populations.

    PubMed

    Zhang, Jianqi; Stram, Daniel O

    2014-09-01

    Association analysis using admixed populations imposes challenges and opportunities for disease mapping. By developing some explicit results for the variance of an allele of interest conditional on either local or global ancestry and by simulation of recently admixed genomes we evaluate power and false-positive rates under a variety of scenarios concerning linkage disequilibrium (LD) and the presence of unmeasured variants. Pairwise LD patterns were compared between admixed and nonadmixed populations using the HapMap phase 3 data. Based on the above, we showed that as follows: For causal variants with similar effect size in all populations, power is generally higher in a study using admixed population than using nonadmixed population, especially for highly differentiated SNPs. This gain of power is achieved with adjustment of global ancestry, which completely removes any cross-chromosome inflation of type I error rates, and addresses much of the intrachromosome inflation. If reliably estimated, adjusting for local ancestry precisely recovers the localization that could have been achieved in a stratified analysis of source populations. Improved localization is most evident for highly differentiated SNPs; however, the advantage of higher power is lost on exactly the same differentiated SNPs. In the real admixed populations such as African Americans and Latinos, the expansion of LD is not as dramatic as in our simulation. While adjustment for global ancestry is required prior to announcing a novel association seen in an admixed population, local ancestry adjustment may best be regarded as a localization tool not strictly required for discovery purposes. PMID:25043967

  14. Exploring iris colour prediction and ancestry inference in admixed populations of South America.

    PubMed

    Freire-Aradas, A; Ruiz, Y; Phillips, C; Maroñas, O; Söchtig, J; Tato, A Gómez; Dios, J Álvarez; de Cal, M Casares; Silbiger, V N; Luchessi, A D; Luchessi, A D; Chiurillo, M A; Carracedo, Á; Lareu, M V

    2014-11-01

    New DNA-based predictive tests for physical characteristics and inference of ancestry are highly informative tools that are being increasingly used in forensic genetic analysis. Two eye colour prediction models: a Bayesian classifier - Snipper and a multinomial logistic regression (MLR) system for the Irisplex assay, have been described for the analysis of unadmixed European populations. Since multiple SNPs in combination contribute in varying degrees to eye colour predictability in Europeans, it is likely that these predictive tests will perform in different ways amongst admixed populations that have European co-ancestry, compared to unadmixed Europeans. In this study we examined 99 individuals from two admixed South American populations comparing eye colour versus ancestry in order to reveal a direct correlation of light eye colour phenotypes with European co-ancestry in admixed individuals. Additionally, eye colour prediction following six prediction models, using varying numbers of SNPs and based on Snipper and MLR, were applied to the study populations. Furthermore, patterns of eye colour prediction have been inferred for a set of publicly available admixed and globally distributed populations from the HGDP-CEPH panel and 1000 Genomes databases with a special emphasis on admixed American populations similar to those of the study samples. PMID:25051225

  15. Necessary, but also Sufficient?

    PubMed

    Martens, Sascha

    2016-07-01

    Cell biologists are equipped with a plethora of techniques and approaches to unravel the fascinating inner working of the cell. Among these, biochemistry has the ability to define the machinery that is both necessary and sufficient for a given process and, therefore, to define its core mechanism. PMID:27142894

  16. When is Testing Sufficient

    NASA Technical Reports Server (NTRS)

    Rosenberg, Linda H.; Arthur, James D.; Stapko, Ruth K.; Davani, Darush

    1999-01-01

    The Software Assurance Technology Center (SATC) at NASA Goddard Space Flight Center has been investigating how projects can determine when sufficient testing has been completed. For most projects, schedules are underestimated, and the last phase of the software development, testing, must be decreased. Two questions are frequently asked: "To what extent is the software error-free? " and "How much time and effort is required to detect and remove the remaining errors? " Clearly, neither question can be answered with absolute certainty. Nonetheless, the ability to answer these questions with some acceptable level of confidence is highly desirable. First, knowing the extent to which a product is error-free, we can judge when it is time to terminate testing. Secondly, if errors are judged to be present, we can perform a cost/benefit trade-off analysis to estimate when the software will be ready for use and at what cost. This paper explains the efforts of the SATC to help projects determine what is sufficient testing and when is the most cost-effective time to stop testing.

  17. Impact of Population Stratification on Family-Based Association in an Admixed Population.

    PubMed

    Mersha, T B; Ding, L; He, H; Alexander, E S; Zhang, X; Kurowski, B G; Pilipenko, V; Kottyan, L; Martin, L J; Fardo, D W

    2015-01-01

    Population substructure is a well-known confounder in population-based case-control genetic studies, but its impact in family-based studies is unclear. We performed population substructure analysis using extended families of admixed population to evaluate power and Type I error in an association study framework. Our analysis shows that power was improved by 1.5% after principal components adjustment. Type I error was also reduced by 2.2% after adjusting for family substratification. The presence of population substructure was underscored by discriminant analysis, in which over 92% of individuals were correctly assigned to their actual family using only 100 principal components. This study demonstrates the importance of adjusting for population substructure in family-based studies of admixed populations. PMID:26064873

  18. Admixture Aberration Analysis: Application to Mapping in Admixed Population Using Pooled DNA

    NASA Astrophysics Data System (ADS)

    Bercovici, Sivan; Geiger, Dan

    Admixture mapping is a gene mapping approach used for the identification of genomic regions harboring disease susceptibility genes in the case of recently admixed populations such as African Americans. We present a novel method for admixture mapping, called admixture aberration analysis (AAA), that uses a DNA pool of affected admixed individuals. We demonstrate through simulations that AAA is a powerful and economical mapping method under a range of scenarios, capturing complex human diseases such as hypertension and end stage kidney disease. The method has a low false-positive rate and is robust to deviation from model assumptions. Finally, we apply AAA on 600 prostate cancer-affected African Americans, replicating a known risk locus. Simulation results indicate that the method can yield over 96% reduction in genotyping. Our method is implemented as a Java program called AAAmap and is freely available.

  19. A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations

    PubMed Central

    Gompert, Zachariah

    2016-01-01

    Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20) SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure), particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur) and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among chromosomes in the Uyghur

  20. A melting pot of multicontinental mtDNA lineages in admixed Venezuelans.

    PubMed

    Gómez-Carballa, Alberto; Ignacio-Veiga, Ana; Alvarez-Iglesias, Vanesa; Pastoriza-Mourelle, Ana; Ruíz, Yarimar; Pineda, Lennie; Carracedo, Angel; Salas, Antonio

    2012-01-01

    The arrival of Europeans in Colonial and post-Colonial times coupled with the forced introduction of sub-Saharan Africans have dramatically changed the genetic background of Venezuela. The main aim of the present study was to evaluate, through the study of mitochondrial DNA (mtDNA) variation, the extent of admixture and the characterization of the most likely continental ancestral sources of present-day urban Venezuelans. We analyzed two admixed populations that have experienced different demographic histories, namely, Caracas (n = 131) and Pueblo Llano (n = 219). The native American component of admixed Venezuelans accounted for 80% (46% haplogroup [hg] A2, 7% hg B2, 21% hg C1, and 6% hg D1) of all mtDNAs; while the sub-Saharan and European contributions made up ∼10% each, indicating that Trans-Atlantic immigrants have only partially erased the native American nature of Venezuelans. A Bayesian-based model allowed the different contributions of European countries to admixed Venezuelans to be disentangled (Spain: ∼38.4%, Portugal: ∼35.5%, Italy: ∼27.0%), in good agreement with the documented history. Seventeen entire mtDNA genomes were sequenced, which allowed five new native American branches to be discovered. B2j and B2k, are supported by two different haplotypes and control region data, and their coalescence ages are 3.9 k.y. (95% C.I. 0-7.8) and 2.6 k.y. (95% C.I. 0.1-5.2), respectively. The other clades were exclusively observed in Pueblo Llano and they show the fingerprint of strong recent genetic drift coupled with severe historical consanguinity episodes that might explain the high prevalence of certain Mendelian and complex multi-factorial diseases in this region. PMID:22120584

  1. Becoming pure: identifying generational classes of admixed individuals within lesser and greater scaup populations.

    PubMed

    Lavretsky, Philip; Peters, Jeffrey L; Winker, Kevin; Bahn, Volker; Kulikova, Irina; Zhuravlev, Yuri N; Wilson, Robert E; Barger, Chris; Gurney, Kirsty; McCracken, Kevin G

    2016-02-01

    Estimating the frequency of hybridization is important to understand its evolutionary consequences and its effects on conservation efforts. In this study, we examined the extent of hybridization in two sister species of ducks that hybridize. We used mitochondrial control region sequences and 3589 double-digest restriction-associated DNA sequences (ddRADseq) to identify admixture between wild lesser scaup (Aythya affinis) and greater scaup (A. marila). Among 111 individuals, we found one introgressed mitochondrial DNA haplotype in lesser scaup and four in greater scaup. Likewise, based on the site-frequency spectrum from autosomal DNA, gene flow was asymmetrical, with higher rates from lesser into greater scaup. However, using ddRADseq nuclear DNA, all individuals were assigned to their respective species with >0.95 posterior assignment probability. To examine the power for detecting admixture, we simulated a breeding experiment in which empirical data were used to create F1 hybrids and nine generations (F2-F10) of backcrossing. F1 hybrids and F2, F3 and most F4 backcrosses were clearly distinguishable from pure individuals, but evidence of admixed histories was effectively lost after the fourth generation. Thus, we conclude that low interspecific assignment probabilities (0.011-0.043) for two lesser and nineteen greater scaup were consistent with admixed histories beyond the F3 generation. These results indicate that the propensity of these species to hybridize in the wild is low and largely asymmetric. When applied to species-specific cases, our approach offers powerful utility for examining concerns of hybridization in conservation efforts, especially for determining the generational time until admixed histories are effectively lost through backcrossing. PMID:26833858

  2. Autosomal admixture levels are informative about sex bias in admixed populations.

    PubMed

    Goldberg, Amy; Verdu, Paul; Rosenberg, Noah A

    2014-11-01

    Sex-biased admixture has been observed in a wide variety of admixed populations. Genetic variation in sex chromosomes and functions of quantities computed from sex chromosomes and autosomes have often been examined to infer patterns of sex-biased admixture, typically using statistical approaches that do not mechanistically model the complexity of a sex-specific history of admixture. Here, expanding on a model of Verdu and Rosenberg (2011) that did not include sex specificity, we develop a model that mechanistically examines sex-specific admixture histories. Under the model, multiple source populations contribute to an admixed population, potentially with their male and female contributions varying over time. In an admixed population descended from two source groups, we derive the moments of the distribution of the autosomal admixture fraction from a specific source population as a function of sex-specific introgression parameters and time. Considering admixture processes that are constant in time, we demonstrate that surprisingly, although the mean autosomal admixture fraction from a specific source population does not reveal a sex bias in the admixture history, the variance of autosomal admixture is informative about sex bias. Specifically, the long-term variance decreases as the sex bias from a contributing source population increases. This result can be viewed as analogous to the reduction in effective population size for populations with an unequal number of breeding males and females. Our approach suggests that it may be possible to use the effect of sex-biased admixture on autosomal DNA to assist with methods for inference of the history of complex sex-biased admixture processes. PMID:25194159

  3. Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations.

    PubMed

    McHugh, Caitlin; Brown, Lisa; Thornton, Timothy A

    2016-09-01

    The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African-Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and nonrandom mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD can incorporate either local or chromosome-wide ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican-American (MXL) and African-American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions, assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample ([Formula: see text]), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample. PMID:27440868

  4. Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method.

    PubMed

    Tagashira, E; Izumi, T; Yanaura, S

    1978-04-28

    A method for testing a rat's physical-dependence liability to sedaditive-hypnotic agents and for evaluating that dependence was studied by using the method. Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days. Manifestations of CNS-suppressing action of either drug (e.g., systemic muscle relaxation, motor incoordination, staggering gait, and ptosis) persisted day and night during the drug medication. Twenty-four to 48 h after withdrawal of either drug, abstinence symptoms (e.g., muscle fasciculation, nuchal twitching, vocalization, increased irritability, ataxia, hyperthermia, and clonic-tonic and grand mal-type convulsions) were evidenced in all animals (N = 6), some of which died after convulsions. These withdrawal signs in rats were classified and found to be closely correlated with the magnitude of weight loss during the withdrawal. The calssification provides a basis for quantitatively assessing physical-dependence liability. The data obtained in the present study suggest that rats, like dogs and monkeys, are suitable experimental animals for tests in early stages of dependence liability, and that the administration of drug-admixed food is a useful method of developing dependence on both barbiturate and morphine-type drugs. PMID:418446

  5. Gravel admix, vegetation, and soil water interactions in protective barriers: Experimental design, construction, and initial conditions

    SciTech Connect

    Waugh, W.J.

    1989-05-01

    The purpose of this study is to measure the interactive effects of gravel admix and greater precipitation on soil water storage and plant abundance. The study is one of many tasks in the Protective Barrier Development Program for the disposal of Hanford defense waste. A factorial field-plot experiment was set up at the site selected as the borrow area for barrier topsoil. Gravel admix, vegetation, and enhanced precipitation treatments were randomly assigned to the plots using a split-split plot design structure. Changes in soil water storage and plant cover were monitored using neutron probe and point intercept methods, respectively. The first-year results suggest that water extraction by plants will offset gravel-caused increases in soil water storage. Near-surface soil water contents were much lower in graveled plots with plants than in nongraveled plots without plants. Large inherent variability in deep soil water storage masked any effects gravel may have had on water content below the root zone. In the future, this source of variation will be removed by differencing monthly data series and testing for changes in soil water storage. Tests of the effects of greater precipitation on soil water storage were inconclusive. A telling test will be possible in the spring of 1988, following the first wet season during which normal precipitation is doubled. 26 refs., 9 figs., 9 tabs.

  6. Concurrent release of admixed antimicrobials and salicylic acid from salicylate-based poly(anhydride-esters)

    PubMed Central

    Johnson, Michelle L.; Uhrich, Kathryn E.

    2008-01-01

    A polymer blend consisting of antimicrobials (chlorhexidine, clindamycin, and minocycline) physically admixed at 10% by weight into a salicylic acid-based poly (anhydride-ester) (SA-based PAE) was developed as an adjunct treatment for periodontal disease. The SA-based PAE/antimicrobial blends were characterized by multiple methods, including contact angle measurements and differential scanning calorimetry. Static contact angle measurements showed no significant differences in hydrophobicity between the polymer and antimicrobial matrix surfaces. Notable decreases in the polymer glass transition temperature (Tg) and the antimicrobials' melting points (Tm) were observed indicating that the antimicrobials act as plasticizers within the polymer matrix. In vitro drug release of salicylic acid from the polymer matrix and for each physically admixed antimicrobial was concurrently monitored by high pressure liquid chromatography during the course of polymer degradation and erosion. Although the polymer/antimicrobial blends were immiscible, the initial 24 h of drug release correlated to the erosion profiles. The SA-based PAE/antimicrobial blends are being investigated as an improvement on current localized drug therapies used to treat periodontal disease. PMID:19180627

  7. Genomic prediction in an admixed population of Atlantic salmon (Salmo salar)

    PubMed Central

    Ødegård, Jørgen; Moen, Thomas; Santi, Nina; Korsvoll, Sven A.; Kjøglum, Sissel; Meuwissen, Theo H. E.

    2014-01-01

    Reliability of genomic selection (GS) models was tested in an admixed population of Atlantic salmon, originating from crossing of several wild subpopulations. The models included ordinary genomic BLUP models (GBLUP), using genome-wide SNP markers of varying densities (1–220 k), a genomic identity-by-descent model (IBD-GS), using linkage analysis of sparse genome-wide markers, as well as a classical pedigree-based model. Reliabilities of the models were compared through 5-fold cross-validation. The traits studied were salmon lice (Lepeophtheirus salmonis) resistance (LR), measured as (log) density on the skin and fillet color (FC), with respective estimated heritabilities of 0.14 and 0.43. All genomic models outperformed the classical pedigree-based model, for both traits and at all marker densities. However, the relative improvement differed considerably between traits, models and marker densities. For the highly heritable FC, the IBD-GS had similar reliability as GBLUP at high marker densities (>22 k). In contrast, for the lowly heritable LR, IBD-GS was clearly inferior to GBLUP, irrespective of marker density. Hence, GBLUP was robust to marker density for the lowly heritable LR, but sensitive to marker density for the highly heritable FC. We hypothesize that this phenomenon may be explained by historical admixture of different founder populations, expected to reduce short-range lice density (LD) and induce long-range LD. The relative importance of LD/relationship information is expected to decrease/increase with increasing heritability of the trait. Still, using the ordinary GBLUP, the typical long-range LD of an admixed population may be effectively captured by sparse markers, while efficient utilization of relationship information may require denser markers (e.g., 22 k or more). PMID:25484890

  8. Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico

    PubMed Central

    Gomez-Rubio, Paulina; Klimentidis, Yann C.; Cantu-Soto, Ernesto; Meza-Montenegro, Maria M.; Billheimer, Dean; Lu, Zhenqiang; Chen, Zhao; Klimecki, Walter T.

    2013-01-01

    Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high % urinary monomethylarsonic acid (MMA(V)), with several arsenic-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic arsenic metabolite. Some epidemiological studies have suggested that indigenous Americans (AME) methylate As more efficiently, however data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and arsenic methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to arsenic in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3–1053.5 μg/L, while %AME mean and range were 72.4 and 23–100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index (BMI), and TAs) multiple regression model showed that higher AME ancestry is associated with lower %uMMA excretion in this population (p <0.01). The data also showed a significant interaction between BMI and gender indicating negative association between BMI and %uMMA, stronger in women than men (p <0.01). Moreover age and the AS3MT variants 7388 (intronic) and M287T (non-synonymous) were also significantly associated with As methylation efficiency (p = 0.01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations. PMID:22047162

  9. Working toward Self-Sufficiency.

    ERIC Educational Resources Information Center

    Caplan, Nathan

    1985-01-01

    Upon arrival in the United States, the Southeast Asian "Boat People" faced a multitude of problems that would seem to have hindered their achieving economic self-sufficiency. Nonetheless, by the time of a 1982 research study which interviewed nearly 1,400 refugee households, 25 percent of all the households in the sample had achieved economic…

  10. Repulsive Casimir force: Sufficient conditions

    SciTech Connect

    Rosa, Luigi; Lambrecht, Astrid

    2010-09-15

    In this paper the Casimir energy of two parallel plates made by materials of different penetration depth and no medium in between is derived. We study the Casimir force density and derive analytical constraints on the two penetration depths which are sufficient conditions to ensure repulsion. Compared to other methods our approach needs no specific model for dielectric or magnetic material properties and constitutes a complementary analysis.

  11. Natural selection for the Duffy-null allele in the recently admixed people of Madagascar.

    PubMed

    Hodgson, Jason A; Pickrell, Joseph K; Pearson, Laurel N; Quillen, Ellen E; Prista, António; Rocha, Jorge; Soodyall, Himla; Shriver, Mark D; Perry, George H

    2014-08-22

    While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa. PMID:24990677

  12. Natural selection for the Duffy-null allele in the recently admixed people of Madagascar

    PubMed Central

    Hodgson, Jason A.; Pickrell, Joseph K.; Pearson, Laurel N.; Quillen, Ellen E.; Prista, António; Rocha, Jorge; Soodyall, Himla; Shriver, Mark D.; Perry, George H.

    2014-01-01

    While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa. PMID:24990677

  13. Properties of thermal air plasma with admixing of copper and carbon

    NASA Astrophysics Data System (ADS)

    Fesenko, S.; Veklich, A.; Boretskij, V.; Cressault, Y.; Gleizes, A.; Teulet, Ph

    2014-11-01

    This paper deals with investigations of air plasma with admixing of copper and carbon. Model plasma source unit with real breaking arc was used for the simulation of real discharges, which can be occurred during sliding of Cu-C composite electrodes on copper wire at electromotive vehicles. The complex technique of plasma property studies is developed. From one hand, the radial profiles of temperature and electron density in plasma of electric arc discharge in air between Cu-C composite and copper electrodes in air flow were measured by optical spectroscopy techniques. From another hand, the radial profiles of electric conductivity of plasma mixture were calculated by solution of energy balance equation. It was assumed that the thermal conductivity of air plasma is not depending on copper or carbon vapor admixtures. The electron density is obtained from electric conductivity profiles by calculation in assumption of local thermodynamic equilibrium in plasma. Computed in such way radial profiles of electron density in plasma of electric arc discharge in air between copper electrodes were compared with experimentally measured profiles. It is concluded that developed techniques of plasma diagnostics can be reasonably used in investigations of thermal plasma with copper and carbon vapors.

  14. Genetic architecture of skin and eye color in an African-European admixed population.

    PubMed

    Beleza, Sandra; Johnson, Nicholas A; Candille, Sophie I; Absher, Devin M; Coram, Marc A; Lopes, Jailson; Campos, Joana; Araújo, Isabel Inês; Anderson, Tovi M; Vilhjálmsson, Bjarni J; Nordborg, Magnus; Correia E Silva, António; Shriver, Mark D; Rocha, Jorge; Barsh, Gregory S; Tang, Hua

    2013-03-01

    Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62), SLC24A5 P = 9.6 × 10(-9)) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27), TYR P = 1.1 × 10(-9), APBA2[OCA2] P = 1.5 × 10(-8), SLC45A2 P = 6 × 10(-9)) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability. PMID:23555287

  15. mStruct: Inference of Population Structure in Light of Both Genetic Admixing and Allele Mutations

    PubMed Central

    Shringarpure, Suyash; Xing, Eric P.

    2009-01-01

    Traditional methods for analyzing population structure, such as the Structure program, ignore the influence of the effect of allele mutations between the ancestral and current alleles of genetic markers, which can dramatically influence the accuracy of the structural estimation of current populations. Studying these effects can also reveal additional information about population evolution such as the divergence time and migration history of admixed populations. We propose mStruct, an admixture of population-specific mixtures of inheritance models that addresses the task of structure inference and mutation estimation jointly through a hierarchical Bayesian framework, and a variational algorithm for inference. We validated our method on synthetic data and used it to analyze the Human Genome Diversity Project–Centre d'Etude du Polymorphisme Humain (HGDP–CEPH) cell line panel of microsatellites and HGDP single-nucleotide polymorphism (SNP) data. A comparison of the structural maps of world populations estimated by mStruct and Structure is presented, and we also report potentially interesting mutation patterns in world populations estimated by mStruct. PMID:19363128

  16. Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

    PubMed Central

    Beleza, Sandra; Johnson, Nicholas A.; Candille, Sophie I.; Absher, Devin M.; Coram, Marc A.; Lopes, Jailson; Campos, Joana; Araújo, Isabel Inês; Anderson, Tovi M.; Vilhjálmsson, Bjarni J.; Nordborg, Magnus; Correia e Silva, António; Shriver, Mark D.; Rocha, Jorge

    2013-01-01

    Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10−62, SLC24A5 P = 9.6×10−9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10−27, TYR P = 1.1×10−9, APBA2[OCA2] P = 1.5×10−8, SLC45A2 P = 6×10−9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (∼44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ∼70% of the estimated heritability. PMID:23555287

  17. Energy Strategic Planning & Sufficiency Project

    SciTech Connect

    Retziaff, Greg

    2005-03-30

    This report provides information regarding options available, their advantages and disadvantages, and the costs for pursuing activities to advance Smith River Rancheria toward an energy program that reduces their energy costs, allows greater self-sufficiency and stimulates economic development and employment opportunities within and around the reservation. The primary subjects addressed in this report are as follows: (1) Baseline Assessment of Current Energy Costs--An evaluation of the historical energy costs for Smith River was conducted to identify the costs for each component of their energy supply to better assess changes that can be considered for energy cost reductions. (2) Research Viable Energy Options--This includes a general description of many power generation technologies and identification of their relative costs, advantages and disadvantages. Through this research the generation technology options that are most suited for this application were identified. (3) Project Development Considerations--The basic steps and associated challenges of developing a generation project utilizing the selected technologies are identified and discussed. This included items like selling to third parties, wheeling, electrical interconnections, fuel supply, permitting, standby power, and transmission studies. (4) Energy Conservation--The myriad of federal, state and utility programs offered for low-income weatherization and utility bill payment assistance are identified, their qualification requirements discussed, and the subsequent benefits outlined. (5) Establishing an Energy Organization--The report includes a high level discussion of formation of a utility to serve the Tribal membership. The value or advantages of such action is discussed along with some of the challenges. (6) Training--Training opportunities available to the Tribal membership are identified.

  18. High specific activity silicon-32

    DOEpatents

    Phillips, D.R.; Brzezinski, M.A.

    1996-06-11

    A process for preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidation state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  19. High specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1996-01-01

    A process for preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  20. Production of high specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1994-01-01

    A process for preparation of silicon-32 is provide and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  1. Production of high specific activity silicon-32

    SciTech Connect

    Phillips, D.R.; Brzezinski, M.A.

    1994-09-13

    A process for the preparation of silicon-32 is provided and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  2. Evidence that a West-East admixed population lived in the Tarim Basin as early as the early Bronze Age

    PubMed Central

    2010-01-01

    Background The Tarim Basin, located on the ancient Silk Road, played a very important role in the history of human migration and cultural communications between the West and the East. However, both the exact period at which the relevant events occurred and the origins of the people in the area remain very obscure. In this paper, we present data from the analyses of both Y chromosomal and mitochondrial DNA (mtDNA) derived from human remains excavated from the Xiaohe cemetery, the oldest archeological site with human remains discovered in the Tarim Basin thus far. Results Mitochondrial DNA analysis showed that the Xiaohe people carried both the East Eurasian haplogroup (C) and the West Eurasian haplogroups (H and K), whereas Y chromosomal DNA analysis revealed only the West Eurasian haplogroup R1a1a in the male individuals. Conclusion Our results demonstrated that the Xiaohe people were an admixture from populations originating from both the West and the East, implying that the Tarim Basin had been occupied by an admixed population since the early Bronze Age. To our knowledge, this is the earliest genetic evidence of an admixed population settled in the Tarim Basin. PMID:20163704

  3. Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

    PubMed Central

    Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H.; Gilissen, Christian; Reader, Rose H.; Jara, Lillian; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O’Hare, Anne; Bolton, Patrick F.; Hennessy, Elizabeth R.; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A.; Cazier, Jean-Baptiste; De Barbieri, Zulema

    2015-01-01

    Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model. PMID:25781923

  4. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

    PubMed

    Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H; Gilissen, Christian; Reader, Rose H; Jara, Lillian; Echeverry, María Magdalena; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O'Hare, Anne; Bolton, Patrick F; Hennessy, Elizabeth R; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A; Cazier, Jean-Baptiste; De Barbieri, Zulema; Fisher, Simon E; Newbury, Dianne F

    2015-03-01

    Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model. PMID:25781923

  5. Hypoplastic model for simulation of compressibility characteristics of cement-admixed Bangkok soft clay at high water content

    NASA Astrophysics Data System (ADS)

    Chattonjai, Piyachat

    2016-06-01

    The developed hypoplastic model for simulation of compressibility characteristics of cement-admixed Bangkok soft clay at high water content was proposed in this paper. By using unique equation, the model is able to predict the relationship between void ratio and vertical effective stress of different water and cement content of soil cement. For practically convenient utilization and understanding, the parameters of Q1 which represented to initial cement bonding of soil (the initial value of structure tensor at time = 0) and C2 which effected to the model stiffness on isotropic consolidation direction, at 45° for loading and 225° for unloading of stress response envelope, were proposed as the function of cement and water content by comparing with dry weight of soil. By numerical integration that satisfied one-dimensional settlement, the simulation results were directly compared with fifteen experimental results to verify the accuracy of the proposed model.

  6. Several different lactase persistence associated alleles and high diversity of the lactase gene in the admixed Brazilian population.

    PubMed

    Friedrich, Deise C; Santos, Sidney E B; Ribeiro-dos-Santos, Ândrea K C; Hutz, Mara H

    2012-01-01

    Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The -13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The -13779*C,-13910*T, -13937*A, -14010*C, -14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was -13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The -13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the -13910*T allele is an oversimplification. PMID:23029545

  7. Genomic Ancestry, Self-Reported “Color” and Quantitative Measures of Skin Pigmentation in Brazilian Admixed Siblings

    PubMed Central

    Leite, Tailce K. M.; Fonseca, Rômulo M. C.; de França, Nanci M.; Parra, Esteban J.; Pereira, Rinaldo W.

    2011-01-01

    A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported “color”, but several studies have demonstrated that stratifying according to “color” is not a useful strategy to control for population structure, due to the dissociation between self-reported “color” and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported “color”, according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported “color” and skin pigmentation, self-reported “color” and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three “color” groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the “color” categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different “color”, and in some cases, the sibling reporting the darker “color” category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported “color” and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported “color”, such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with

  8. Evaluating Whole Chemical Mixtures and Sufficient Similarity

    EPA Science Inventory

    This powerpoint presentation supports apresentation describing dose-response assessment for complex chemical mixtures including deriving reference doses for mixtures evaluating sufficient similarity among chemical mixtures.

  9. Some existence and sufficient conditions of optimality

    NASA Technical Reports Server (NTRS)

    Assefi, T.

    1976-01-01

    The role of the existence and sufficiency conditions in the field of optimal control was briefly described. The existence theorems are discussed for general nonlinear systems. However, the sufficiency conditions pertain to "nearly" linear systems with integral convex costs. Moreover, a brief discussion of linear systems with multiple-cost functions is presented.

  10. Exploring the applicability of analysing X chromosome STRs in Brazilian admixed population.

    PubMed

    Auler-Bittencourt, Eloisa; Iwamura, Edna Sadayo Miazato; Lima, Maria Jenny Mitraud; da Silva, Ismael Dale Cotrim Guerreiro; dos Santos, Sidney Emannuel Batista

    2015-09-01

    Kinship and parentage analyses always involve one sample being compared to another sample or a few samples with a specific relationship question in mind. In most cases, the analysis of autosomal STR markers is sufficient to determine the genetic kinship. However, when genetic profiles are reconstructed from supposed relatives, for whom the family configuration available for analysis is deficient, the examination may be inconclusive. This study reports practical examples of actual cases analysing the efficiency of the chromosome X STR (STR-ChrX) markers. Three cases with different degrees of efficiency and impact were selected as follows: the identification of two charred bodies in a traffic accident, in which the family setting available was not complete, and one filiation analysis resulting from rape. This is the first paper reporting the use of the multiplex STR 12 ChrX in actual cases using the software Familias 1.8 and Brazilian regional frequency data. Our study clarifies the complex analysis using this powerful tool for professionals in the forensic science community, for both civil and criminal justice. We also discuss state-of-the-art ChrX STR markers and its implications and applications for legal procedures. The data presented here should be used in other studies of complex cases to improve the progress of the current justice system. PMID:26385714

  11. Comparison of genome-wide association methods in analyses of admixed populations with complex familial relationships.

    PubMed

    Kadri, Naveen K; Guldbrandtsen, Bernt; Sørensen, Peter; Sahana, Goutam

    2014-01-01

    Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic markers. Linear models that ignored K were also tested. Correction for P was performed using principal component or structured association analysis. In analyses of simulated and real data, linear mixed models that corrected for K were able to control for type-I error, regardless of whether they also corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships derived from either pedigree or from genetic markers. PMID:24662750

  12. Comparison of Genome-Wide Association Methods in Analyses of Admixed Populations with Complex Familial Relationships

    PubMed Central

    Kadri, Naveen K.; Guldbrandtsen, Bernt; Sørensen, Peter; Sahana, Goutam

    2014-01-01

    Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic markers. Linear models that ignored K were also tested. Correction for P was performed using principal component or structured association analysis. In analyses of simulated and real data, linear mixed models that corrected for K were able to control for type-I error, regardless of whether they also corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships derived from either pedigree or from genetic markers. PMID:24662750

  13. Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice

    PubMed Central

    Kang, Myung Joo; Eum, Jae Yoon; Jeong, Mi Sook; Park, Sang Han; Moon, Ki Young; Kang, Mean Hyung; Kim, Min Soo; Choi, Sun Eun; Lee, Min Won; Lee, Do Ik; Bang, Hyoweon; Lee, Chung Soo; Joo, Seong Soo; Li, Kapsok; Lee, Mi-Kyung; Seo, Seong Jun; Choi, Young Wook

    2011-01-01

    Background The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T). Methods HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed. Results EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils. Conclusion A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD. PMID:22072881

  14. Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

    PubMed Central

    Lins, Tulio C.; Vieira, Rodrigo G.; Grattapaglia, Dario; Pereira, Rinaldo W.

    2011-01-01

    The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5′ and 3′ gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations. PMID:21931507

  15. HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations

    PubMed Central

    Ohashi, Marina; Lebedeva, Tatiana; Acuña-Alonzo, Víctor; Yunis, María; Granados-Montiel, Julio; Cruz-Lagunas, Alfredo; Vargas-Alarcón, Gilberto; Rodríguez-Reyna, Tatiana S.; Fernandez-Viña, Marcelo; Granados, Julio; Yunis, Edmond J.

    2013-01-01

    Major histocompatibility complex (MHC) genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence based typing (SBT) method and we structured the blocks and conserved extended haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes) by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs) and HLA-B that correlated with the frequency of most probable ancestral HLA-C/−B and -DRB1/−DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations. PMID:24086347

  16. Semiparametric tests for sufficient cause interaction

    PubMed Central

    Vansteelandt, Stijn; VanderWeele, Tyler J.; Robins, James M.

    2014-01-01

    A sufficient cause interaction between two exposures signals the presence of individuals for whom the outcome would occur only under certain values of the two exposures. When the outcome is dichotomous and all exposures are categorical, then under certain no confounding assumptions, empirical conditions for sufficient cause interactions can be constructed based on the sign of linear contrasts of conditional outcome probabilities between differently exposed subgroups, given confounders. It is argued that logistic regression models are unsatisfactory for evaluating such contrasts, and that Bernoulli regression models with linear link are prone to misspecification. We therefore develop semiparametric tests for sufficient cause interactions under models which postulate probability contrasts in terms of a finite-dimensional parameter, but which are otherwise unspecified. Estimation is often not feasible in these models because it would require nonparametric estimation of auxiliary conditional expectations given high-dimensional variables. We therefore develop ‘multiply robust tests’ under a union model that assumes at least one of several working submodels holds. In the special case of a randomized experiment or a family-based genetic study in which the joint exposure distribution is known by design or Mendelian inheritance, the procedure leads to asymptotically distribution-free tests of the null hypothesis of no sufficient cause interaction. PMID:25558182

  17. Sufficiency, Intimacy and the Good Life.

    ERIC Educational Resources Information Center

    Taylor, Donald L.

    Our capacity to provide food and shelter is freeing us from the constant burden of keeping the wolf away from the door. We are increasingly able to give our attention to other values. This type of sufficiency provides time and circumstances for developing intimate relationships. Intimate relationships are characterized by revelation of one's…

  18. Modeling of microwave discharges of H{sub 2} admixed with CH{sub 4} for diamond deposition

    SciTech Connect

    Lombardi, G.; Hassouni, K.; Stancu, G.-D.; Mechold, L.; Roepcke, J.; Gicquel, A.

    2005-09-01

    Microwave discharges of H{sub 2} admixed with CH{sub 4} in a moderate-pressure quartz bell jar reactor used for diamond deposition are studied numerically. Special attention was devoted to high-power densities which provide the most effective way for producing high-quality diamond films. First, a one-dimensional radial model describing the coupled phenomena of chemistry, energy transfer, as well as species and energy transport along the reactor's radial coordinate was developed. Species densities predicted with the model were compared with measurements with infrared tunable diode laser spectroscopy, resulting in validation of the model. Second, a one-dimensional axial model was used to describe the plasma flow along the reactor axis in a region between the reactor end wall and the substrate surface. This model was particularly useful for studying the plasma behavior in the vicinity of the substrate surface, where thermal and composition gradients are large. Both the radial and axial transport models are based on the same discharge model in which the plasma is described as a thermochemically nonequilibrium flow with different energy distributions for heavy species and electrons. The chemistry was described with a model containing 28 species and 131 reactions. The electron temperature, the gas temperature, and the species concentration were determined by solving a coupled set of equations. A wide range of experimental conditions used for diamond deposition was simulated, from low microwave power density (9 W cm{sup -3}, i.e., 600 W, 2500 Pa, and T{sub g}{approx}2200 K) to high-power density (30 W cm{sup -3}, i.e., 2 kW, 12 000 Pa, and T{sub g}{approx}3200 K). The main chemical paths were identified, and the major species, transport effects, and reaction pathways that govern diamond deposition plasmas are discussed.

  19. HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population

    PubMed Central

    Cuellar-Giraldo, David; Díaz-Cruz, Camilo; Burbano, Lisseth-Estefania; Guío, Claudia-Marcela; Reyes, Saúl; Cortes, Fabián; Cárdenas-Robledo, Simón; Narváez, Diana M.; Cárdenas, Wilmer; Porras, Alexandra; Lattig, María-Claudia; Groot de Restrepo, Helena

    2015-01-01

    Objective: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia. Methods: In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR. Mitochondrial hypervariable region 1 was amplified and haplogroups were determined using HaploGrep software. Genomic ancestry was estimated by genotyping a panel of ancestry informative markers. To test the association of HLA polymorphisms and MS, we ran separate multivariate logistic regression models. Bonferroni correction was used to account for multiple regression tests. Results: A total of 100 patients with MS (mean age 40.4 ± 12 years; 70% females) and 200 healthy controls (mean age 37.6 ± 11 years; 83.5% females) were included in the analysis. Ancestry proportions and haplogroup frequencies did not differ between patients and controls. HLA-DRB1*15 was present in 31% of cases and 13.5% of controls, whereas HLA-DRB1*14 was present in 5% of cases and 15.5% of controls. In the multivariate model, HLA-DRB1*15 was significantly associated with MS (odds ratio [OR] = 3.05, p < 0.001), whereas HLA-DRB1*14 was confirmed as a protective factor in our population (OR = 0.16, p = 0.001). Conclusions: This study provides evidence indicating that HLA-DRB1*15 allele confers susceptibility to MS and HLA-DRB1*14 allele exerts resistance to MS in a highly admixed population. This latter finding could partially explain the low prevalence of MS in Bogotá, Colombia. PMID:26740965

  20. Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

    PubMed Central

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C.; Cok, Jaime; Combe, Juan M.; Vargas, Gloria; Prado, William A.; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R.; Chanock, Stephen J.; Berg, Douglas E.; Gilman, Robert H.; Tarazona-Santos, Eduardo

    2012-01-01

    Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group. PMID:22870209

  1. Sufficient separability criteria and linear maps

    NASA Astrophysics Data System (ADS)

    Lewenstein, Maciej; Augusiak, Remigiusz; Chruściński, Dariusz; Rana, Swapan; Samsonowicz, Jan

    2016-04-01

    We study families of positive and completely positive maps acting on a bipartite system CM⊗CN (with M ≤N ). The maps have a property that, when applied to any state (of a given entanglement class), result in a separable state or, more generally, a state of another certain entanglement class (e.g., Schmidt number ≤k ). This allows us to derive useful families of sufficient separability criteria. Explicit examples of such criteria have been constructed for arbitrary M ,N , with a special emphasis on M =2 . Our results can be viewed as generalizations of the known facts that in the sufficiently close vicinity of the completely depolarized state (the normalized identity matrix), all states are separable (belong to "weakly" entangled classes). Alternatively, some of our results can be viewed as an entanglement classification for a certain family of states, corresponding to mixtures of the completely polarized state with pure states, partial transposes, and/or local transformations thereof.

  2. Policy Capacity Is Necessary but Not Sufficient

    PubMed Central

    Gen, Sheldon; Wright, Amy Conley

    2015-01-01

    Policy capacity focuses on the managerial and organizational abilities to inform policy decisions with sound research and analysis, and facilitate policy implementation with operational efficiency. It stems from a view of the policy process that is rational and positivistic, in which optimal policy choices can be identified, selected, and implemented with objectivity. By itself, however, policy capacity neglects the political aspects of policy-making that can dominate the process, even in health policies. These technical capabilities are certainly needed to advance reforms in health policies, but they are not sufficient. Instead, they must be complemented with public engagement and policy advocacy to ensure support from the public that policies are meant to serve. PMID:26673469

  3. Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents?

    PubMed Central

    Shaw, Christopher A.; Höglinger, Günter U.

    2008-01-01

    A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these numbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death pathways as those activated by environmental factors that trigger most sporadic disease cases. In this article we present a countervailing view that environmental neurotoxins may be the sole sufficient factor in at least three neurological disease clusters. For each, neurotoxins have been isolated and characterized that, at least in animal models, faithfully reproduce each disorder without the need for genetic co-factors. Based on these data, we will propose a set of principles that would enable any potential toxin to be evaluated as an etiological factor in a given neurodegenerative disease. Finally, we will attempt to put environmental toxins into the context of possible genetically-determined susceptibility. PMID:17985252

  4. Sufficient dimension reduction with additional information.

    PubMed

    Hung, Hung; Liu, Chih-Yen; Horng-Shing Lu, Henry

    2016-07-01

    Sufficient dimension reduction is widely applied to help model building between the response [Formula: see text] and covariate [Formula: see text] In some situations, we also collect additional covariate [Formula: see text] that has better performance in predicting [Formula: see text], but has a higher obtaining cost, than [Formula: see text] While constructing a predictive model for [Formula: see text] based on [Formula: see text] is straightforward, this strategy is not applicable since [Formula: see text] is not available for future observations in which the constructed model is to be applied. As a result, the aim of the study is to build a predictive model for [Formula: see text] based on [Formula: see text] only, where the available data is [Formula: see text] A naive method is to conduct analysis using [Formula: see text] directly, but ignoring [Formula: see text] can cause the problem of inefficiency. On the other hand, it is not trivial to utilize the information of [Formula: see text] to infer [Formula: see text], either. In this article, we propose a two-stage dimension reduction method for [Formula: see text] that is able to utilize the information of [Formula: see text] In the breast cancer data, the risk score constructed from the two-stage method can well separate patients with different survival experiences. In the Pima data, the two-stage method requires fewer components to infer the diabetes status, while achieving higher classification accuracy than the conventional method. PMID:26704765

  5. Energy Strategic Planning & Self-Sufficiency Project

    SciTech Connect

    Greg Retzlaff

    2005-03-30

    This report provides information regarding options available, their advantages and disadvantages, and the costs for pursuing activities to advance Smith River Rancheria toward an energy program that reduces their energy costs, allows greater self-sufficiency and stimulates economic development and employment opportunities within and around the reservation. The primary subjects addressed in this report are as follow: (1) Baseline Assessment of Current Energy Costs--An evaluation of the historical energy costs for Smith River was conducted to identify the costs for each component of their energy supply to better assess changes that can be considered for energy cost reductions. (2) Research Viable Energy Options--This includes a general description of many power generation technologies and identification of their relative costs, advantages and disadvantages. Through this research the generation technology options that are most suited for this application were identified. (3) Project Development Considerations--The basic steps and associated challenges of developing a generation project utilizing the selected technologies are identified and discussed. This included items like selling to third parties, wheeling, electrical interconnections, fuel supply, permitting, standby power, and transmission studies. (4) Energy Conservation--The myriad of federal, state and utility programs offered for low-income weatherization and utility bill payment assistance are identified, their qualification requirements discussed, and the subsequent benefits outlined. (5) Establishing an Energy Organization--The report includes a high level discussion of formation of a utility to serve the Tribal membership. The value or advantages of such action is discussed along with some of the challenges. (6) Training--Training opportunities available to the Tribal membership are identified.

  6. Recovery of Native Genetic Background in Admixed Populations Using Haplotypes, Phenotypes, and Pedigree Information – Using Cika Cattle as a Case Breed

    PubMed Central

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  7. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    PubMed

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  8. Research on Necessary and Sufficient Condition for Hamilton Graph

    NASA Astrophysics Data System (ADS)

    Cui, Yan; Cui, Chao-Dong

    An important concept, "closed domain" is proposed in this paper. In the same time, necessary and sufficient lemma for closed domain, R, is proved on which necessary and sufficient theorem for judging whether a general graph G is a Hamilton graph is proposed and proved. All instances in this paper are judged by comparatively using the theorem proposed herein and the original necessary condition theorem and sufficient condition theorem to prove the correctness of the method proposed in this paper.

  9. 24 CFR 242.2 - Program financial self-sufficiency.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Program financial self-sufficiency... self-sufficiency and actuarial soundness; i.e., to avoid mortgage defaults and claims for insurance... AUTHORITIES MORTGAGE INSURANCE FOR HOSPITALS General Eligibility Requirements § 242.2 Program financial...

  10. 39 CFR 491.3 - Sufficient legal form.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... or an authorized official pursuant to an order of such a court or pursuant to federal, state or...

  11. 39 CFR 491.3 - Sufficient legal form.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... or an authorized official pursuant to an order of such a court or pursuant to federal, state or...

  12. 39 CFR 491.3 - Sufficient legal form.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... or an authorized official pursuant to an order of such a court or pursuant to federal, state or...

  13. Southeast Asian Refugee Self-Sufficiency Study. Final Report.

    ERIC Educational Resources Information Center

    Caplan, Nathan; And Others

    This study on the economic self-sufficiency of the Southeast Asian refugee household was conducted in order to gather information on the economic status of these refugees, the factors that contribute to self-sufficiency, and refugees' needs for services. A survey of 1,384 households of Vietnamese, Sino-Vietnamese, and Lao refugees who arrived in…

  14. 27 CFR 25.174 - Bond not sufficient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When...

  15. 27 CFR 25.174 - Bond not sufficient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When...

  16. 27 CFR 25.174 - Bond not sufficient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When...

  17. 27 CFR 25.174 - Bond not sufficient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When...

  18. 27 CFR 25.174 - Bond not sufficient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When...

  19. 39 CFR 491.3 - Sufficient legal form.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... is legal process in the nature of garnishment; that it is issued by a court of competent...

  20. 39 CFR 491.3 - Sufficient legal form.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... is legal process in the nature of garnishment; that it is issued by a court of competent...

  1. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Torres-Mejia, Gabriella; John, Esther M; Giuliano, Anna R; Hines, Lisa M; Stern, Mariana C; Baumgartner, Kathy B; Presson, Angela P; Wolff, Roger K

    2014-08-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process. PMID:24670917

  2. Kicking Triturus arntzeni when it's down: large-scale nuclear genetic data confirm that newts from the type locality are genetically admixed.

    PubMed

    Wielstra, B; Arntzen, J W

    2014-01-01

    We collected nuclear DNA data (52 markers) with next-generation sequencing for nine Triturus newt specimens, including the holotype and two of the paratypes of T. arntzeni, from the type locality at Vrtovać in eastern Serbia. We compare these data to a reference set composed of the four crested newt species distributed in eastern Serbia namely T. cristatus, T. dobrogicus, T. ivanbureschi and T. macedonicus to determine to which of these species the newts from the type locality of T. arntzeni should be attributed. The majority of alleles in individuals from Vrtovać is derived from T. macedonicus, but a considerable number of T. ivanbureschi alleles is also present; alleles typical for T. cristatus and T. dobrogicus are found at low frequency. Accordingly, we interpret Vrtovać as a T. macedonicus - T. ivanbureschi hybrid population, albeit not composed of F1 hybrids but of genetically admixed individuals derived through multiple generations of backcrossing. The data support the notion that the name T. arntzeni should not be applied to a species newly distinguished in T. karelinii sensu lato (to which the name T. ivanbureschi has been given). We conclude that because of the hybrid nature of the individuals from Vrtovać, the name T. arntzeni should be placed not only in the synonymy of T. macedonicus but also in the synonymy of T. ivanbureschi. In this study we demonstrate that next-generation sequencing can provide high quality data for type material with degraded DNA and therefore can play an important role in taxonomy. PMID:24871018

  3. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study

    PubMed Central

    Slattery, Martha L.; Herrick, Jennifer S.; Torres-Mejia, Gabriella; John, Esther M.; Giuliano, Anna R.; Hines, Lisa M.; Stern, Mariana C.; Baumgartner, Kathy B.; Presson, Angela P.; Wolff, Roger K.

    2014-01-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P ARTP = 0.01), for premenopausal women (P ARTP = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P ARTP = 0.03) and ER−/PR− tumors (P ARTP = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process. PMID:24670917

  4. Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

    PubMed Central

    Pappas, Derek James; Gourraud, Pierre-Antoine; Le Gall, Caroline; Laurent, Julie; Trounson, Alan; DeWitt, Natalie; Talib, Sohel

    2015-01-01

    Summary The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed the admixed nature of populations like that of California nor evaluated the benefit to the population as a whole. We developed a new model for evaluating an iPSC haplobank based on demographic and immunogenetic characteristics reflecting California. The model evaluates haplolines or cell lines from donors homozygous for a single HLA-A, HLA-B, HLA-DRB1 haplotype. We generated estimates of the percentage of the population matched under various combinations of haplolines derived from six ancestries (black/African American, American Indian, Asian/Pacific Islander, Hispanic, and white/not Hispanic) and data available from the U.S. Census Bureau, the California Institute for Regenerative Medicine, and the National Marrow Donor Program. The model included both cis (haplotype-level) and trans (genotype-level) matching between a modeled iPSC haplobank and the recipient population following resampling simulations. We showed that serving a majority (>50%) of a simulated California population through cis matching would require the creation, redundant storage, and maintenance of almost 207 different haplolines representing the top 60 most frequent haplotypes from each ancestry group. Allowances for trans matching reduced the haplobank to fewer than 141 haplolines found among the top 40 most frequent haplotypes. Finally, we showed that a model optimized, custom haplobank was able to serve a majority of the California population with fewer than 80 haplolines. PMID:25926330

  5. Quantification is Neither Necessary Nor Sufficient for Measurement

    NASA Astrophysics Data System (ADS)

    Mari, Luca; Maul, Andrew; Torres Irribarra, David; Wilson, Mark

    2013-09-01

    Being an infrastructural, widespread activity, measurement is laden with stereotypes. Some of these concern the role of measurement in the relation between quality and quantity. In particular, it is sometimes argued or assumed that quantification is necessary for measurement; it is also sometimes argued or assumed that quantification is sufficient for or synonymous with measurement. To assess the validity of these positions the concepts of measurement and quantitative evaluation should be independently defined and their relationship analyzed. We contend that the defining characteristic of measurement should be the structure of the process, not a feature of its results. Under this perspective, quantitative evaluation is neither sufficient nor necessary for measurement.

  6. Is the Supply of Mathematics and Science Teachers Sufficient?

    ERIC Educational Resources Information Center

    Ingersoll, Richard M.; Perda, David

    2010-01-01

    This study seeks to empirically ground the debate over mathematics and science teacher shortages and evaluate the extent to which there is, or is not, sufficient supply of teachers in these fields. The authors' analyses of nationally representative data from multiple sources show that math and science are the fields most difficult to staff, but…

  7. Online Learning in Higher Education: Necessary and Sufficient Conditions

    ERIC Educational Resources Information Center

    Lim, Cher Ping

    2005-01-01

    The spectacular development of information and communication technologies through the Internet has provided opportunities for students to explore the virtual world of information. In this article, the author discusses the necessary and sufficient conditions for successful online learning in educational institutions. The necessary conditions…

  8. Sufficient observables for large-scale structure in galaxy surveys

    NASA Astrophysics Data System (ADS)

    Carron, J.; Szapudi, I.

    2014-03-01

    Beyond the linear regime, the power spectrum and higher order moments of the matter field no longer capture all cosmological information encoded in density fluctuations. While non-linear transforms have been proposed to extract this information lost to traditional methods, up to now, the way to generalize these techniques to discrete processes was unclear; ad hoc extensions had some success. We pointed out in Carron and Szapudi's paper that the logarithmic transform approximates extremely well the optimal `sufficient statistics', observables that extract all information from the (continuous) matter field. Building on these results, we generalize optimal transforms to discrete galaxy fields. We focus our calculations on the Poisson sampling of an underlying lognormal density field. We solve and test the one-point case in detail, and sketch out the sufficient observables for the multipoint case. Moreover, we present an accurate approximation to the sufficient observables in terms of the mean and spectrum of a non-linearly transformed field. We find that the corresponding optimal non-linear transformation is directly related to the maximum a posteriori Bayesian reconstruction of the underlying continuous field with a lognormal prior as put forward in the paper of Kitaura et al.. Thus, simple recipes for realizing the sufficient observables can be built on previously proposed algorithms that have been successfully implemented and tested in simulations.

  9. Housing Policy and Family Self-Sufficiency. Background Briefing Report.

    ERIC Educational Resources Information Center

    Bratt, Rachel

    The relationship between housing and family well-being and self-sufficiency are explored in this paper's three major sections. The first section provides background information on the relationship between housing and the physical and social well-being of individuals and families and describes the major federal housing initiatives that have been…

  10. Leadership, the Logic of Sufficiency and the Sustainability of Education

    ERIC Educational Resources Information Center

    Bottery, Mike

    2012-01-01

    The notion of sufficiency has not yet entered mainstream educational thinking, and it still has to make its mark upon educational leadership. However, a number of related concepts--particularly those of sustainability and complexity theory--are beginning to be noticed. This article examines these two concepts and uses them to critique the…

  11. Hawaii's energy self-sufficiency program from renewable energy sources

    SciTech Connect

    Neill, D.R.

    1981-01-01

    The need for public support for incentives to accelerate commercialization of renewable energy sources is discussed from the viewpoint of the Hawaiian program to use the state's wind, solar, geothermal, and OTEC resources to achieve energy self-sufficiency. The objectives and major events in the research, development and demonstration and implementation programs and related activities are described. (LEW)

  12. Intellectual Freedom and Economic Sufficiency as Educational Entitlements.

    ERIC Educational Resources Information Center

    Morse, Jane Fowler

    2001-01-01

    Using the theories of John Stuart Mill and Karl Marx, this article supports the educational entitlements of intellectual freedom and economic sufficiency. Explores these issues in reference to their implications for teaching, the teaching profession and its training. Concludes that ideas cannot be controlled by the interests of the dominant class.…

  13. The Indochinese in America: Progress Towards Self Sufficiency.

    ERIC Educational Resources Information Center

    Finck, John

    Despite suspicion in some quarters that refugee resettlement has been unduly expensive, evidence indicates that the Indochinese have made steady progress toward self-sufficiency. The majority of Hmong refugees in Providence, Rhode Island, for example, which has been "heavily impacted" by the large number of Indochinese who have become its newest…

  14. Exploring Necessary and Sufficient Conditions in Dynamic Geometry Environments

    ERIC Educational Resources Information Center

    Leung, Allen; Chan, Yip-Cheung

    2006-01-01

    This paper describes a possible dragging experiment in a dynamic geometry environment (DGE) that explores a necessary and sufficient condition for cyclic quadrilateral. The dragging modalities identified by Arzarello, Olivero, Paola, and Robutti (2002) and the functions of variation realized in DGE discussed by Leung (2003) will be used as tools…

  15. Recent Widows' Kin Support and Orientations to Self-Sufficiency.

    ERIC Educational Resources Information Center

    O'Bryant, Shirley L.; Morgan, Leslie A.

    1990-01-01

    Data on recently widowed women suggest that many are quite self-sufficient; however, in areas where support is needed, they largely rely on children. Widows' past experiences and attitudes toward independence influenced amount of overall help they received, whereas income, number of children, and perceived willingness of children to help affected…

  16. Entrepreneurship by any other name: self-sufficiency versus innovation.

    PubMed

    Parker Harris, Sarah; Caldwell, Kate; Renko, Maija

    2014-01-01

    Entrepreneurship has been promoted as an innovative strategy to address the employment of people with disabilities. Research has predominantly focused on the self-sufficiency aspect without fully integrating entrepreneurship literature in the areas of theory, systems change, and demonstration projects. Subsequently there are gaps in services, policies, and research in this field that, in turn, have limited our understanding of the support needs and barriers or facilitators of entrepreneurs with disabilities. A thorough analysis of the literature in these areas led to the development of two core concepts that need to be addressed in integrating entrepreneurship into disability employment research and policy: clarity in operational definitions and better disability statistics and outcome measures. This article interrogates existing research and policy efforts in this regard to argue for a necessary shift in the field from focusing on entrepreneurship as self-sufficiency to understanding entrepreneurship as innovation. PMID:25225770

  17. Retinal flow is sufficient for steering during observer rotation

    NASA Technical Reports Server (NTRS)

    Li, Li; Warren, William H Jr

    2002-01-01

    How do people control locomotion while their eyes are simultaneously rotating? A previous study found that during simulated rotation, they can perceive a straight path of self-motion from the retinal flow pattern, despite conflicting extraretinal information, on the basis of dense motion parallax and reference objects. Here we report that the same information is sufficient for active control ofjoystick steering. Participants steered toward a target in displays that simulated a pursuit eye movement. Steering was highly inaccurate with a textured ground plane (motion parallax alone), but quite accurate when an array of posts was added (motion parallax plus reference objects). This result is consistent with the theory that instantaneous heading is determined from motion parallax, and the path of self-motion is determined by updating heading relative to environmental objects. Retinal flow is thus sufficient for both perceiving self-motion and controlling self-motion with a joystick; extraretinal and positional information can also contribute, but are not necessary.

  18. Efficiency, sufficiency, and recent change in Newfoundland subsistence horticulture

    SciTech Connect

    Omohundro, J.T.

    1986-09-01

    Traditional Newfoundland horticulture has been a subordinate and compensatory element of the subsistence sphere in a plural economy centered on fishing. Criticized as inefficient and ruinous to the land, this tuber-rootbrassica gardening has in fact been a valuable contribution to diet, is relatively efficient, and compensates for the inadequacies of land and weather. Field data from the Great Northern Peninsula, where some traditional practices persist, demonstrate that the practices conserve time and labor, and substitute massive applications of materials to assure a yield sufficient for household needs. The inefficiency in the tradition may be understood as a response to the constraints upon household labor and follows a kind of Leibig's law of the minimum. Recent changes in gardening practices reveal the dynamics of horticulture in the household's mixed economic strategy. As cash and land have become more common, they have been used to further reduce time while maintaining sufficiency.

  19. Predictive sufficiency and the use of stored internal state

    NASA Technical Reports Server (NTRS)

    Musliner, David J.; Durfee, Edmund H.; Shin, Kang G.

    1994-01-01

    In all embedded computing systems, some delay exists between sensing and acting. By choosing an action based on sensed data, a system is essentially predicting that there will be no significant changes in the world during this delay. However, the dynamic and uncertain nature of the real world can make these predictions incorrect, and thus, a system may execute inappropriate actions. Making systems more reactive by decreasing the gap between sensing and action leaves less time for predictions to err, but still provides no principled assurance that they will be correct. Using the concept of predictive sufficiency described in this paper, a system can prove that its predictions are valid, and that it will never execute inappropriate actions. In the context of our CIRCA system, we also show how predictive sufficiency allows a system to guarantee worst-case response times to changes in its environment. Using predictive sufficiency, CIRCA is able to build real-time reactive control plans which provide a sound basis for performance guarantees that are unavailable with other reactive systems.

  20. Technology for human self-sufficiency in space

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1988-01-01

    A proposed Pathfinder program would determine the critical human and technology requirements for human self-sufficiency and productivity on manned and long-duration missions to the moon and Mars. Human health would require countermeasures against weightlessness, protection from space radiation and habitats conducive to psychological well-being. Life support systems would need regeneration of expendable resources, power systems for plant life support and processing; and microbial contaminant control. Operational performance requirements include extravehicular activities suit, interactive systems for shared control between humans and computers, and human-centered semi-autonomous systems.

  1. Is recurrent processing necessary and/or sufficient for consciousness?

    PubMed

    Tsuchiya, Naotsugu; van Boxtel, Jeroen J A

    2010-09-01

    Abstract Abstract While we agree with Lamme's general framework, we are not so convinced by his mapping between psychological concepts with their underlying neuronal mechanisms. Specifically, we doubt if recurrent processing is either necessary or sufficient for consciousness. A gist of a scene may be consciously perceived by purely feedforward, without recurrent, processing. Neurophysiological studies of perceptual suppression show recurrent processing in visual cortex for consciously invisible objects. While the neuronal correlates of attention and consciousness remain to be clarified, we agree with Lamme that these two processes are independent, evinced by our recent demonstration of opposing effects of attention and consciousness. PMID:24168345

  2. Vitamin D sufficiency and Staphylococcus aureus infection in children.

    PubMed

    Wang, Jeffrey W; Hogan, Patrick G; Hunstad, David A; Fritz, Stephanie A

    2015-05-01

    Vitamin D promotes epithelial immunity by upregulating antimicrobial peptides, including LL-37, which have bactericidal activity against Staphylococcus aureus. We found that children with vitamin D deficiency or insufficiency [25-hydroxyvitamin D <30 ng/mL] were more likely to present with recurrent, rather than primary, S. aureus skin or soft tissue infection. Vitamin D sufficiency may be one of a myriad of host and environmental factors that can be directly impacted to reduce the frequency of S. aureus skin and soft tissue infection. PMID:25860535

  3. Photon underproduction crisis: Are QSOs sufficient to resolve it?

    NASA Astrophysics Data System (ADS)

    Khaire, Vikram; Srianand, Raghunathan

    2015-07-01

    We investigate the recent claim of `photon underproduction crisis' by Kollmeier et al. which suggests that the known sources of ultraviolet (UV) radiation may not be sufficient to generate the inferred H I photoionization rate (Γ _{H I}) in the low-redshift intergalactic medium. Using the updated QSO emissivities from the recent studies and our cosmological radiative transfer code developed to estimate the UV background, we show that the QSO contributions to Γ _{H I} is higher by a factor ˜2 as compared to the previous estimates. Using self-consistently computed combinations of star formation rate density and dust attenuation, we show that a typical UV escape fraction of 4 per cent from star-forming galaxies should be sufficient to explain the inferred Γ _{H I} by Kollmeier et al. Interestingly, we find that the contribution from QSOs alone can explain the recently inferred Γ _{H I} by Shull et al. which used the same observational data but different simulation. Therefore, we conclude that the crisis is not as severe as it was perceived before and there seems no need to look for alternate explanations such as low luminosity hidden QSOs or decaying dark matter particles.

  4. Variational necessary and sufficient stability conditions for inviscid shear flow

    PubMed Central

    Hirota, M.; Morrison, P. J.; Hattori, Y.

    2014-01-01

    A necessary and sufficient condition for linear stability of inviscid parallel shear flow is formulated by developing a novel variational principle, where the velocity profile is assumed to be monotonic and analytic. It is shown that unstable eigenvalues of Rayleigh's equation (which is a non-self-adjoint eigenvalue problem) can be associated with positive eigenvalues of a certain self-adjoint operator. The stability is therefore determined by maximizing a quadratic form, which is theoretically and numerically more tractable than directly solving Rayleigh's equation. This variational stability criterion is based on the understanding of Kreĭn signature for continuous spectra and is applicable to other stability problems of infinite-dimensional Hamiltonian systems. PMID:25484600

  5. Geothermal resource requirements for an energy self-sufficient spaceport

    SciTech Connect

    Kruger, P.; Fioravanti, M.; Duchane, D.; Vaughan, A.

    1997-01-01

    Geothermal resources in the southwestern United States provide an opportunity for development of isolated spaceports with local energy self-sufficiency. Geothermal resources can provide both thermal energy and electrical energy for the spaceport facility infrastructure and production of hydrogen fuel for the space vehicles. In contrast to hydrothermal resources by which electric power is generated for sale to utilities, hot dry rock (HDR) geothermal resources are more wide-spread and can be more readily developed at desired spaceport locations. This paper reviews a dynamic model used to quantify the HDR resources requirements for a generic spaceport and estimate the necessary reservoir size and heat extraction rate. The paper reviews the distribution of HDR resources in southern California and southern New Mexico, two regions where a first developmental spaceport is likely to be located. Finally, the paper discusses the design of a HDR facility for the generic spaceport and estimates the cost of the locally produced power.

  6. [Vitamin-antioxidant sufficiency of winter sports athletes].

    PubMed

    Beketova, N A; Kosheleva, O V; Pereverzeva, O G; Vrzhesinskaia, O A; Kodentsova, V M; Solntseva, T N; Khanfer'ian, R A

    2013-01-01

    The sufficiency of 169 athletes (six disciplines: bullet shooting, biathlon, bobsleigh, skeleton, freestyle skiing, snowboarding) with vitamins A, E, C, B2, and beta-carotene has been investigated in April-September 2013. All athletes (102 juniors, mean age--18.5 +/- 0.3 years, and 67 adult high-performance athletes, mean age--26.8 +/- 0.7 years) were sufficiently supplied with vitamin A (70.7 +/- 1.7 mcg/dl). Mean blood serum retinol level was 15% higher the upper limit of the norm (80 mcg/dl) in biathletes while median reached 90.9 mcg/dl. Blood serum level of tocopherols (1.22 +/- 0.03 mg/dl), ascorbic acid (1.06 +/- 0.03 mg/dl), riboflavin (7.1 +/- 0.4 ng/ml), and beta-carotene (25.1 +/- 1.7 mcg/dl) was in within normal range, but the incidence of insufficiency of vitamins E, C, B2, and carotenoid among athletes varied in the range of 0-25, 0-17, 15-67 and 42-75%, respectively. 95% of adults and 80% of younger athletes were sufficiently provided with vitamin E. Vitamin E level in blood serum of juniors involved in skeleton and biathlon was lower by 51 and 72% (p < 0.05), than this parameter in adult athletes. Vitamin A, C and B2, and beta-carotene blood serum level did not significantly differ in junior and adult athletes. Women were better supplied with vitamins C, B2, and beta-carotene: a reduced blood serum level of these micronutrients in women was detected 2-3 fold rare (p < 0.10) than among men. Blood serum concentration of vitamin C (1.20 +/- 0.05 mg/dl) and beta-carotene (32.0 +/- 3.9 mcg/dl) in women was greater by 15 and 54% (p < 0.05) than in men. In general, the biathletes were better provided with vitamins compared with other athletes. The vast majority (80%) were optimally provided by all three antioxidants (beta-carotene and vitamins E and C). In other sports, the relative quantity of athletes sufficiently supplied with these essential nutrients did not exceed 56%. The quota of supplied with all antioxidants among bullet shooters (31.1%) and

  7. Nonpetroleum mobility fuels and military-energy self-sufficiency

    SciTech Connect

    Freiwald, D.A.; Barattino, W.J.

    1981-01-01

    Nonpetroleum hydrocarbon fuels will likely serve as transition fuels for a few decades after petroleum sources become scarce. But nonpetroleum hydrocarbon fuels are ultimately either nonrenewable (e.g., coal and oil shale synfuels) or are inefficient to produce. Nuclear sources (supplemented by solar, geothermal, etc., as available) for electric power generation and hydrogen production provide a combination that can be used for military energy needs including mobility fuels, namely liquid hydrogen. This approach can give the military energy self-sufficiency for stationary needs as well as ground vehicles, ships, and aircraft. System integration concepts are discussed, and concepts for a methodology to evaluate source-to-use pathways for different classes of military bases are outlined.

  8. Sufficient and necessary condition of separability for generalized Werner states

    SciTech Connect

    Deng Dongling; Chen Jingling

    2009-02-15

    In a celebrated paper [Optics Communications 179, 447, 2000], A.O. Pittenger and M.H. Rubin presented for the first time a sufficient and necessary condition of separability for the generalized Werner states. Inspired by their ideas, we generalized their method to a more general case. We obtain a sufficient and necessary condition for the separability of a specific class of N d-dimensional system (qudits) states, namely special generalized Werner state (SGWS): W{sup [d{sup N}]}(v)=(1-v)(I{sup (N)})/(d{sup N}) +v|{psi}{sub d}{sup N}><{psi}{sub d}{sup N}|, where |{psi}{sub d}{sup N}>={sigma}{sub i=0}{sup d-1}{alpha}{sub i}|i...i> is an entangled pure state of N qudits system and {alpha}{sub i} satisfies two restrictions: (i) {sigma}{sub i=0}{sup d-1}{alpha}{sub i}{alpha}{sub i}*=1; (ii) Matrix 1/d (I{sup (1)}+T{sigma}{sub i{ne}}{sub j}{alpha}{sub i}|i>

  9. Using scientifically and statistically sufficient statistics in comparing image segmentations.

    PubMed

    Chi, Yueh-Yun; Muller, Keith E

    2010-01-01

    Automatic computer segmentation in three dimensions creates opportunity to reduce the cost of three-dimensional treatment planning of radiotherapy for cancer treatment. Comparisons between human and computer accuracy in segmenting kidneys in CT scans generate distance values far larger in number than the number of CT scans. Such high dimension, low sample size (HDLSS) data present a grand challenge to statisticians: how do we find good estimates and make credible inference? We recommend discovering and using scientifically and statistically sufficient statistics as an additional strategy for overcoming the curse of dimensionality. First, we reduced the three-dimensional array of distances for each image comparison to a histogram to be modeled individually. Second, we used non-parametric kernel density estimation to explore distributional patterns and assess multi-modality. Third, a systematic exploratory search for parametric distributions and truncated variations led to choosing a Gaussian form as approximating the distribution of a cube root transformation of distance. Fourth, representing each histogram by an individually estimated distribution eliminated the HDLSS problem by reducing on average 26,000 distances per histogram to just 2 parameter estimates. In the fifth and final step we used classical statistical methods to demonstrate that the two human observers disagreed significantly less with each other than with the computer segmentation. Nevertheless, the size of all disagreements was clinically unimportant relative to the size of a kidney. The hierarchal modeling approach to object-oriented data created response variables deemed sufficient by both the scientists and statisticians. We believe the same strategy provides a useful addition to the imaging toolkit and will succeed with many other high throughput technologies in genetics, metabolomics and chemical analysis. PMID:24967000

  10. Oral immunization of mice with a glycoconjugate vaccine containing the O157 antigen of Escherichia coli O157:H7 admixed with cholera toxin fails to elicit protection against subsequent colonization by the pathogen.

    PubMed

    Conlan, J W; KuoLee, R; Webb, A; Cox, A D; Perry, M B

    2000-03-01

    It has been postulated that a humoral immune response directed against the O157 antigen of Escherichia coli O157:H7, and expressed in the intestine, might afford protection from colonization and consequent infection by this enteric pathogen. The present study was conducted to determine whether such an immune response can be experimentally generated in mice. To this end, mice were orally immunized with a glycoconjugate vaccine consisting of horse serum albumin and the O157 polysaccharide admixed with the mucosal adjuvant, cholera toxin. Mice consistently developed robust local and systemic immune responses to the cholera toxin adjuvant, but were far from uniformly reactive to the test vaccine. Moreover, vaccinated mice were as susceptible to transient intestinal colonization following challenge with an isolate of E. coli O157:H7 as unvaccinated control mice. These results indicate that this vaccination approach is unlikely to be straightforward in target bovine or human hosts. PMID:10749542

  11. India's baseline plan for nuclear energy self-sufficiency.

    SciTech Connect

    Bucher, R .G.; Nuclear Engineering Division

    2009-01-01

    India's nuclear energy strategy has traditionally strived for energy self-sufficiency, driven largely by necessity following trade restrictions imposed by the Nuclear Suppliers Group (NSG) following India's 'peaceful nuclear explosion' of 1974. On September 6, 2008, the NSG agreed to create an exception opening nuclear trade with India, which may create opportunities for India to modify its baseline strategy. The purpose of this document is to describe India's 'baseline plan,' which was developed under constrained trade conditions, as a basis for understanding changes in India's path as a result of the opening of nuclear commerce. Note that this treatise is based upon publicly available information. No attempt is made to judge whether India can meet specified goals either in scope or schedule. In fact, the reader is warned a priori that India's delivery of stated goals has often fallen short or taken a significantly longer period to accomplish. It has been evident since the early days of nuclear power that India's natural resources would determine the direction of its civil nuclear power program. It's modest uranium but vast thorium reserves dictated that the country's primary objective would be thorium utilization. Estimates of India's natural deposits vary appreciably, but its uranium reserves are known to be extremely limited, totaling approximately 80,000 tons, on the order of 1% of the world's deposits; and nominally one-third of this ore is of very low uranium concentration. However, India's roughly 300,000 tons of thorium reserves account for approximately 30% of the world's total. Confronted with this reality, the future of India's nuclear power industry is strongly dependent on the development of a thorium-based nuclear fuel cycle as the only way to insure a stable, sustainable, and autonomous program. The path to India's nuclear energy self-sufficiency was first outlined in a seminal paper by Drs. H. J. Bhabha and N. B. Prasad presented at the Second

  12. On necessity and sufficiency in counseling and psychotherapy (revisited).

    PubMed

    Lazarus, Arnold A

    2007-09-01

    It seems to me that Carl Rogers (see record 2007-14639-002) was far too ambitious in trying to specify general conditions of necessity and sufficiency that would be relevant to the entire spectrum of problems and the diverse expectancies and personalities of the people who seek our help. Rogers' position and orientation almost totally overlook the array of problems under the rubric of "response deficits" that stem from misinformation and missing information and call for active correction, training, and retraining. Rogers also paid scant attention to problems with significant biological determinants. Nevertheless, as exemplified by his seminal 1957 article and many other articles and books, Rogers made major contributions within the domain of the therapeutic alliance. Today, the scientific emphasis looks at accountability, the need to establish various treatments of choice, and the need to understand their presumed mechanisms. Treatment efficacy and generalizability across different methodologies are now considered key issues. The efficacy narrowing and clinically self-limiting consequences of adhering to one particular school of thought are now self-evident to most. (PsycINFO Database Record (c) 2010 APA, all rights reserved). PMID:22122247

  13. The Generalized Asymptotic Equipartition Property: Necessary and Sufficient Conditions

    PubMed Central

    Harrison, Matthew T.

    2011-01-01

    Suppose a string X1n=(X1,X2,…,Xn) generated by a memoryless source (Xn)n≥1 with distribution P is to be compressed with distortion no greater than D ≥ 0, using a memoryless random codebook with distribution Q. The compression performance is determined by the “generalized asymptotic equipartition property” (AEP), which states that the probability of finding a D-close match between X1n and any given codeword Y1n, is approximately 2−nR(P, Q, D), where the rate function R(P, Q, D) can be expressed as an infimum of relative entropies. The main purpose here is to remove various restrictive assumptions on the validity of this result that have appeared in the recent literature. Necessary and sufficient conditions for the generalized AEP are provided in the general setting of abstract alphabets and unbounded distortion measures. All possible distortion levels D ≥ 0 are considered; the source (Xn)n≥1 can be stationary and ergodic; and the codebook distribution can have memory. Moreover, the behavior of the matching probability is precisely characterized, even when the generalized AEP is not valid. Natural characterizations of the rate function R(P, Q, D) are established under equally general conditions. PMID:21614133

  14. Manual curation is not sufficient for annotation of genomic databases

    PubMed Central

    Baumgartner, William A.; Cohen, K. Bretonnel; Fox, Lynne M.; Acquaah-Mensah, George; Hunter, Lawrence

    2008-01-01

    Motivation Knowledge base construction has been an area of intense activity and great importance in the growth of computational biology. However, there is little or no history of work on the subject of evaluation of knowledge bases, either with respect to their contents or with respect to the processes by which they are constructed. This article proposes the application of a metric from software engineering known as the found/fixed graph to the problem of evaluating the processes by which genomic knowledge bases are built, as well as the completeness of their contents. Results Well-understood patterns of change in the found/fixed graph are found to occur in two large publicly available knowledge bases. These patterns suggest that the current manual curation processes will take far too long to complete the annotations of even just the most important model organisms, and that at their current rate of production, they will never be sufficient for completing the annotation of all currently available proteomes. Contact larry.hunter@uchsc.edu PMID:17646325

  15. [Effect of vitamin sufficiency on adaptation syndrome in growing rats].

    PubMed

    Sidorova, Iu S; Beketova, N A; Vrzhesinskaia, O A; Kodentsova, V M; Kosheleva, O V; Zorin, S N; Selifanov, A V; Mazo, V K

    2014-01-01

    The influence of vitamin supply of growing male -Wistar rats (n=21) with an initial body weight 53,5±0,9 g on their resistance to a single distress induced by the electric shock has been investigated. Control rats within 21 days received a complete semisynthetic diet,providingadequate amounts of vitamins. Combined vitamin deficiency in experimental rats was caused by 5-fold decrease of vitamin mixture amount in the feed and the total vitamin E exclusion from the mixture. On the 21st day, one day before the end of the experiment, both groups of rats were subjected to stress impact (electrocutaneous irritation on paws, 0,4 mA for 8 sec) and then animals were placed in metabolic cages to collect urine. By the end of the experiment, the animals with the combined vitamin deficiency lag behind in growth. Vitamin B2, A, B1 and E liver content decreased in experimental rats by 1,6, 2,3, 4,4 and 15 fold accordingly. Retinol plasma concentration was significantly reduced by 18%, α-tocopherol level - by 5 fold, urinary excretionof riboflavin and 4-pyridoxic acid (vitamin B6 metabolite) was significantly reduced by 6,5 and 2,46 times accordingly. MDA blood plasma concentration and the urinary ratio of oxidized and not oxidized form of 8-hydroxy-2'-deoxy-guanosine did not differ in both groups of rats. Urinary excretion of stress biomarker corticosterone in rats with combined vitamin deficit was 2,5-fold higher than in control rats. Thus, reducing of vitamins supply resulted in an increase of urine corticosterone in stressed rats, that characterized the intensity of general adaptation syndrome. This fact shows the importance of optimal sufficiency with vitamins in nonspecific (general) resistance to stress. PMID:25816622

  16. Greater learnability is not sufficient to produce cultural universals.

    PubMed

    Rafferty, Anna N; Griffiths, Thomas L; Ettlinger, Marc

    2013-10-01

    Looking across human societies reveals regularities in the languages that people speak and the concepts that they use. One explanation that has been proposed for these "cultural universals" is differences in the ease with which people learn particular languages and concepts. A difference in learnability means that languages and concepts possessing a particular property are more likely to be accurately transmitted from one generation of learners to the next. Intuitively, this difference could allow languages and concepts that are more learnable to become more prevalent after multiple generations of cultural transmission. If this is the case, the prevalence of languages and concepts with particular properties can be explained simply by demonstrating empirically that they are more learnable. We evaluate this argument using mathematical analysis and behavioral experiments. Specifically, we provide two counter-examples that show how greater learnability need not result in a property becoming prevalent. First, more learnable languages and concepts can nonetheless be less likely to be produced spontaneously as a result of transmission failures. We simulated cultural transmission in the laboratory to show that this can occur for memory of distinctive items: these items are more likely to be remembered, but not generated spontaneously once they have been forgotten. Second, when there are many languages or concepts that lack the more learnable property, sheer numbers can swamp the benefit produced by greater learnability. We demonstrate this using a second series of experiments involving artificial language learning. Both of these counter-examples show that simply finding a learnability bias experimentally is not sufficient to explain why a particular property is prevalent in the languages or concepts used in human societies: explanations for cultural universals based on cultural transmission need to consider the full set of hypotheses a learner could entertain and all of

  17. EFFICIENCY OF PREPARED BAITS OF LONE OR/AND ADMIXED FOUR BOTANICAL OILS ON THE VIABILITY OF SUCCESSIVE RAISED GENERATIONS OF AGROTIS IPSILON (HUFNAGEL) (INSECTA: LEPIDOPTERA: NOCTUIDAE) AFTER TREATING THE PARENT ONES.

    PubMed

    Mesbah, H A; El-Sayed, Nagda A; El-Kady, Magda B; Tayeb, E H; Mourad, A K; Kordy, A M; Henaidy, Zeinab M

    2014-01-01

    The present study is initiated to determine the toxic and delayed effects of four botanical oils on the greasy cutworm A. ipsilon, aiming to attain an alternative environmentally safe and effective phytochemicals against the insect-pest. Four botanical oils (camphor, red basil, menthol and rose oil) were added at rates of 0.5 and 1.0% (v/w). The tested oils were added alone, and/or admixed at proportional rate of 1:1 in the prepared baits against the exposed 4th instar till the 6th instar larvae of the insect. The study was run under the laboratory higrothermic conditions of 25±2°C and 65±5% R.H. The results showed that the tested baits of camphor, red basil and menthol oils at concentration rates of 0.5 and 1.0% (v/w) adversely affected the inspected parameters of fitness components of the treated individuals of parent (p) generation. They gave more or less fewer numbers of weak unviable adult-moths, which were either sterile or they laid few numbers of infertile eggs and died before the induction of (F1) progeny. That failure could be elucidated by the rapid occurrence of drastic effects on the biological performance of both the influenced sexes of adult-moths along the period of parent's development. Finally it ended by the inhibited induction of (F1) progeny. A delayed effect of the prepared baits of rose oil at 0.5 and 1.0% (v/w), was assessed on the following raised F1, F2, F3 and F4 generations after parent's treatment. The delayed effect was detected as less efficient latent effect on each of these consequently raised generations; characterized by the gradual decrease of the number of alive immatures and adult-moths. The effect was recorded as gradual increase of dead and malformed individuals and adult-moths. In addition to the gradual decrease of deposited and/or hatched eggs up to the 4th generation, which ended by the complete failure of the development. That failure could be also attributed to the cumulated effects of the induced recessive lethal

  18. 76 FR 39115 - Notice of Proposed Information Collection: Transformation Initiative Family Self-Sufficiency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... Family Self-Sufficiency Demonstration Small Grants. Description of the need for information and proposed... URBAN DEVELOPMENT Notice of Proposed Information Collection: Transformation Initiative Family Self-Sufficiency Demonstration Small Grants AGENCY: Office of Policy Development and Research, HUD. ACTION:...

  19. 24 CFR 960.255 - Self-sufficiency incentives-Disallowance of increase in annual income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Self-sufficiency incentives... and Reexamination § 960.255 Self-sufficiency incentives—Disallowance of increase in annual income. (a... participation in any economic self-sufficiency or other job training program; or (iii) Whose annual...

  20. Sufficiency of Longitudinal Moment of Inertia for Haptic Cylinder Length Judgments

    ERIC Educational Resources Information Center

    Cabe, Patrick A.

    2010-01-01

    Many studies invoke moment of inertia (I[subscript ii]) as necessary and sufficient information to perceive cylinder length via wielding, yet some assert that I[subscript ii] is neither necessary (weight, "m", or static moment, M, are sufficient) nor sufficient for length judgments ("m" or M is necessary). Mathematical expressions for I[subscript…

  1. Minimal sufficient positive-operator valued measure on a separable Hilbert space

    SciTech Connect

    Kuramochi, Yui

    2015-10-15

    We introduce a concept of a minimal sufficient positive-operator valued measure (POVM), which is the least redundant POVM among the POVMs that have the equivalent information about the measured quantum system. Assuming the system Hilbert space to be separable, we show that for a given POVM, a sufficient statistic called a Lehmann-Scheffé-Bahadur statistic induces a minimal sufficient POVM. We also show that every POVM has an equivalent minimal sufficient POVM and that such a minimal sufficient POVM is unique up to relabeling neglecting null sets. We apply these results to discrete POVMs and information conservation conditions proposed by the author.

  2. Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

    PubMed Central

    Lima-Costa, M. Fernanda; Macinko, James; Mambrini, Juliana Vaz de Melo; Cesar, Cibele C.; Peixoto, Sérgio V.; Magalhães, Wagner C. S.; Horta, Bernardo L.; Barreto, Mauricio; Castro-Costa, Erico; Firmo, Josélia O. A.; Proietti, Fernando A.; Leal, Thiago Peixoto; Rodrigues, Maira R.; Pereira, Alexandre; Tarazona-Santos, Eduardo

    2015-01-01

    Background Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. Materials/Methods We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. Results European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. Conclusions Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality. PMID:26680774

  3. Dark Matter Admixed Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Leung, S.-C.; Chu, M.-C.; Lin, L.-M.

    2015-10-01

    We perform two-dimensional hydrodynamic simulations for the thermonuclear explosion of Chandrasekhar-mass white dwarfs with dark matter (DM) cores in Newtonian gravity. We include a 19-isotope nuclear reaction network and make use of the pure turbulent deflagration model as the explosion mechanism in our simulations. Our numerical results show that the general properties of the explosion depend quite sensitively on the mass of the DM core M DM: a larger M DM generally leads to a weaker explosion and a lower mass of synthesized iron-peaked elements. In particular, the total mass of produced can drop from about 0.3 to 0.03 M ⊙ as M DM increases from 0.01 to 0.03 M ⊙. We have also constructed the bolometric light curves obtained from our simulations and found that our results match well with the observational data of sub-luminous Type Ia supernovae.

  4. 33 CFR 115.30 - Sufficiency of State authority for bridges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of...

  5. 33 CFR 115.30 - Sufficiency of State authority for bridges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of...

  6. 33 CFR 115.30 - Sufficiency of State authority for bridges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of...

  7. 33 CFR 115.30 - Sufficiency of State authority for bridges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of...

  8. 33 CFR 115.30 - Sufficiency of State authority for bridges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of...

  9. Dorsal Hippocampal CREB Is Both Necessary and Sufficient for Spatial Memory

    ERIC Educational Resources Information Center

    Sekeres, Melanie J.; Neve, Rachael L.; Frankland, Paul W.; Josselyn, Sheena A.

    2010-01-01

    Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust…

  10. Sufficiency and Conditional Estimation of Person Parameters in the Polytomous Rasch Model

    ERIC Educational Resources Information Center

    Andrich, David

    2010-01-01

    Rasch models are characterised by sufficient statistics for all parameters. In the Rasch unidimensional model for two ordered categories, the parameterisation of the person and item is symmetrical and it is readily established that the total scores of a person and item are sufficient statistics for their respective parameters. In contrast, in the…

  11. Role of sufficient phosphorus in biodiesel production from diatom Phaeodactylum tricornutum.

    PubMed

    Yu, Shi-Jin; Shen, Xiao-Fei; Ge, Huo-Qing; Zheng, Hang; Chu, Fei-Fei; Hu, Hao; Zeng, Raymond J

    2016-08-01

    In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N-P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality. PMID:27260287

  12. Assessing sufficiency of thermal riverscapes for resilient salmon and steelhead populations

    EPA Science Inventory

    Resilient salmon populations require river networks that provide water temperature regimes sufficient to support a diversity of salmonid life histories across space and time. Efforts to protect, enhance and restore watershed thermal regimes for salmon may target specific location...

  13. Necessary and sufficient conditions for self-focusing of short ultraintense laser pulse in underdense plasma

    SciTech Connect

    Chen, X.L.; Sudan, R.N. )

    1993-04-05

    We analyze the propagation of a short intense laser pulse in underdense cold plasma. When no electron cavitation is present, a global invariant [ital H] is obtained, and its relation with self-focusing is studied. For relativistic self-focusing, [ital H][lt]0 is a sufficient and necessary condition. For relativistic and ponderomotive self-focusing, [ital H][lt]0 is sufficient but not necessary. Numerical simulations are performed to confirm the above points.

  14. Correlation, necessity, and sufficiency: Common errors in the scientific reasoning of undergraduate students for interpreting experiments.

    PubMed

    Coleman, Aaron B; Lam, Diane P; Soowal, Lara N

    2015-01-01

    Gaining an understanding of how science works is central to an undergraduate education in biology and biochemistry. The reasoning required to design or interpret experiments that ask specific questions does not come naturally, and is an essential part of the science process skills that must be learned for an understanding of how scientists conduct research. Gaps in these reasoning skills make it difficult for students to become proficient in reading primary scientific literature. In this study, we assessed the ability of students in an upper-division biochemistry laboratory class to use the concepts of correlation, necessity, and sufficiency in interpreting experiments presented in a format and context that is similar to what they would encounter when reading a journal article. The students were assessed before and after completion of a laboratory module where necessary vs. sufficient reasoning was used to design and interpret experiments. The assessment identified two types of errors that were commonly committed by students when interpreting experimental data. When presented with an experiment that only establishes a correlation between a potential intermediate and a known effect, students frequently interpreted the intermediate as being sufficient (causative) for the effect. Also, when presented with an experiment that tests only necessity for an intermediate, they frequently made unsupported conclusions about sufficiency, and vice versa. Completion of the laboratory module and instruction in necessary vs. sufficient reasoning showed some promise for addressing these common errors. PMID:26146931

  15. A necessary and sufficient condition for deadlock-free adaptive routing in wormhole networks

    SciTech Connect

    Duato, J.

    1994-12-31

    Deadlock avoidance is a key issue in wormhole networks. A first approach consists of removing the cyclic dependencies between channels. Although this is a necessary and sufficient condition for deadlock-free deterministic routing, it is only a sufficient condition for deadlock-free adaptive routing. A more powerful approach only requires the absence of cyclic dependencies on a connected channel subset. The remaining channels can be used in almost any way. In this paper, we propose a necessary and sufficient condition for deadlock-free adaptive routing. This condition is the key for the design of maximally adaptive routing algorithms with minimum restrictions. Some examples are given, showing the application of the new theory. In particular, we propose a partially adaptive routing algorithm for k-ary n-cubes which doubles the throughput without increasing the hardware complexity significantly.

  16. Understanding Self-Sufficiency of Welfare Leavers in Illinois: Elaborating Models with Psychosocial Factors.

    ERIC Educational Resources Information Center

    Julnes, George; Fan, Xitao; Hayashi, Kentaro

    2001-01-01

    Used survey (for 1,001 adults) and administrative data (for 137,330 first-exit cases) in structural equation modeling to examine psychological and social factors as determinants of welfare dependency and self-sufficiency. Findings show well-being to be a predictor of low recidivism and high employment. (SLD)

  17. Sufficient conditions of optimality for control of hydro-electric power stations

    NASA Astrophysics Data System (ADS)

    Ferreira, M. M. A.; Ribeiro, A. F.; Smirnov, G. V.

    2013-10-01

    In this paper we consider a control problem for a cascade of hydro-electric power stations where some of the stations have reversible turbines. The objective of our work is to optimize the profit of power production satisfying restrictions on the water level in the reservoirs. We obtain sufficient conditions of optimality and illustrate them with a simple example.

  18. Validation of the Employment Hope Scale: Measuring Psychological Self-Sufficiency among Low-Income Jobseekers

    ERIC Educational Resources Information Center

    Hong, Philip Young P.; Polanin, Joshua R.; Pigott, Therese D.

    2012-01-01

    Objectives: The Employment Hope scale (EHS) was designed to measure the empowerment-based self-sufficiency (SS) outcome among low-income job-seeking clients. This measure captures the psychological SS dimension as opposed to the more commonly used economic SS in workforce development and employment support practice. The study validates the EHS and…

  19. Investigation of Professional Self Sufficiency Levels of Physical Education and Sports Teachers

    ERIC Educational Resources Information Center

    Saracaoglu, Asuman Seda; Ozsaker, Murat; Varol, Rana

    2012-01-01

    The present research aimed at detecting professional self sufficiency levels of physical education and sports teachers who worked in Izmir Province and at investigating them in terms of some variables. For data collection, Teacher's Sense of Efficacy Scale-developed by Moran and Woolfolk-Hoy (2001) and Turkish validity and reliability studies…

  20. Designing and Managing Public Housing Self-Sufficiency Programs: The Youngs Lake Commons Program

    ERIC Educational Resources Information Center

    Kleit, Rachel Garshick

    2004-01-01

    This article evaluates an experimental public housing self-sufficiency program that encourages home ownership among low-income families. A quasi-experimental design, in combination with focus groups, records review, and key informant interviews, provides data to focus on four questions: (a) Do these programs simply accelerate move-outs for those…

  1. 75 FR 39035 - Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

    ... URBAN DEVELOPMENT Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program AGENCY: Office of... Voucher Program) with public and private resources to enable eligible families to achieve economic...; enter into a Contract of Participation with each eligible family that opts to participate in the...

  2. A class of group covariant signal sets and its necessary and sufficient condition

    SciTech Connect

    Usuda, Tsuyoshi Sasaki; Ishikawa, Yoshihiro; Shiromoto, Keisuke

    2014-12-04

    (G,χ-hat)-covariant quantum state signals, which is a generalization of the narrow sense group covariant signals, are defined. Then a necessary and sufficient condition for (G,χ-hat)-covariant signals is given and examples of the signals are shown.

  3. Book, Film, Television: An International Comparison of National Self-Sufficiency in Three Media.

    ERIC Educational Resources Information Center

    Jokela, Mikko

    This study was conducted to compare national self-sufficiency in two media--book and film--to determine to what extent books and films in 39 countries are of domestic and foreign origin, and to find the direction of flow. Statistical findings are compared with findings from a 1973 study on the structure and origin of television programmes in 51…

  4. Sufficient Condition on the Fractional Integral for the Convergence of a Function

    PubMed Central

    Duarte-Mermoud, Manuel A.; Aguila-Camacho, Norelys; Gallegos, Javier A.

    2013-01-01

    A sufficient condition on the fractional integral of the absolute value of a function is given in this paper, which allows to assure the convergence of the function to zero. This result can be useful to assure the convergence of a function when it is hard to know its exact evolution, but conditions on its fractional integral can be stated. PMID:24453850

  5. A Classroom Note on a Sufficient, but Unsatisfied, Condition for Goldbach's Conjecture to Be True

    ERIC Educational Resources Information Center

    Skurnick, Ronald

    2011-01-01

    This classroom note is presented as a suggested exercise--not to have the class prove or disprove Goldbach's Conjecture, but to stimulate student discussions in the classroom regarding proof, as well as necessary, sufficient, satisfied, and unsatisfied conditions. Goldbach's Conjecture is one of the oldest unsolved problems in the field of number…

  6. 42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations §...

  7. 42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations §...

  8. 42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial...

  9. 42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial...

  10. 42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial...

  11. 42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations §...

  12. 42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations §...

  13. 42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial...

  14. 42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations §...

  15. Response to Teriparatide in Patients with Baseline 25-Hydroxyvitamin D Insufficiency or Sufficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serum 25-hydroxyvitamin D (25OHD) concentrations >30 ng/ml have been recommended for lowering fracture risk. The objective of this study was to determine if 25OHD sufficiency is a prerequisite for effective response to teriparatide (TPTD). Study data came from 1620 osteoporotic postmenopausal wome...

  16. TAXONOMIC LEVEL AND SAMPLE SIZE SUFFICIENT FOR ASSESSING POLLUTION IMPACTS ON THE SOUTHERN CALIFORNIA BIGHT MACROBENTHOS

    EPA Science Inventory

    Macrobenthic data from samples taken in 1980, 1983 and 1985 along a pollution gradient in the Southern California Bight (USA) were analyzed at 5 taxonomic levels (species, genus, family, order, phylum) to determIne the taxon and sample size sufficient for assessing pollution impa...

  17. Pathway to Self-Sufficiency: Social and Economic Development Strategies of Native American Communities.

    ERIC Educational Resources Information Center

    Office of Human Development Services (DHHS), Washington, DC.

    In fiscal year (FY) 1984 the Administration for Native Americans awarded 227 grants for social and economic development strategies (SEDS) which would help Native American communities move toward self-sufficiency. More than half the grants were primarily for economic development; approximately one-third were for improving tribal governments, and…

  18. The Family Self-Sufficiency Program: HUD's Best Kept Secret for Promoting Employment and Asset Growth.

    ERIC Educational Resources Information Center

    Sard, Barbara

    This paper describes the Family Self-Sufficiency (FSS) program, an employment and savings incentive program for low-income families that have Section 8 vouchers or live in public housing. It consists of both case management services to help participants pursue employment and other goals and escrow accounts into which the public housing agency…

  19. Sufficient Stochastic Maximum Principle in a Regime-Switching Diffusion Model

    SciTech Connect

    Donnelly, Catherine

    2011-10-15

    We prove a sufficient stochastic maximum principle for the optimal control of a regime-switching diffusion model. We show the connection to dynamic programming and we apply the result to a quadratic loss minimization problem, which can be used to solve a mean-variance portfolio selection problem.

  20. Struggle for Self-Sufficiency: Impact of Welfare Reform on Families with Children in Kansas.

    ERIC Educational Resources Information Center

    Kansas Action for Children, Inc., Topeka.

    Since Congress passed the Personal Responsibility and Work Opportunity Reconciliation Act in 1996, Kansas has dramatically reduced its welfare roles. Noting that achieving self-sufficiency is the real measure of success in combating poverty, this study examines welfare reform efforts in Kansas. To gather information, United Way member agencies and…

  1. Public and Private Incentives for Investment in Higher Education: Are They Sufficient, Especially for Black Males?

    ERIC Educational Resources Information Center

    Appiah, Elizabeth N.

    2013-01-01

    The institutional costs of higher education have been rising. With diminishing public support per student, tuition and fees private costs have also been rising. But so have the real earnings of college graduates. Are there still sufficient incentives on efficiency grounds for additional public investment in higher education? And in particular,…

  2. 25 CFR 26.23 - What is an Individual Self-Sufficiency Plan (ISP)?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 26.23 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM General Applicability § 26.23 What is an Individual Self-Sufficiency Plan (ISP...; (3) Identifies all financial resources and defines the employment or training objective...

  3. Rhetorically self-sufficient arguments in Western Australian parliamentary debates on Lesbian and Gay Law Reform.

    PubMed

    Summers, Mark

    2007-12-01

    Western Australia's Acts Amendment (Lesbian and Gay Law Reform) Bill 2001 delivered a measure of legal equality in such areas as property transfer, superannuation, inheritance and discrimination, and more controversially, adoption, lesbian access to IVF, lowering the age of consent for sex between men from 21 to 16, and incorporating information on homosexuality into high school sex education classes. This paper examines the use of various moral principles within parliamentary speeches supporting or opposing the legislation, and the extent to which they were treated by members as beyond question, or 'rhetorically self-sufficient'. The resources of 'equality', 'human rights', 'democracy', 'the interests of the majority' and 'the interests of children' were given a kind of beyond-question, self-sufficient status, but their use was able to be undermined in a number of ways, relating to members' management of what the Bill was 'about', and the flexibility of these social constructs. It is argued that rather than pitting one set of resources against another, members on both sides of the debate faced a rhetorical pressure to adopt and mobilize all of the same self-sufficient moral resources, due to the flexible, constructed and non-hierarchical, yet often rhetorically self-sufficient nature of common-sense moral principles. PMID:17535460

  4. Necessary and sufficient conditions for the entanglement sudden death under amplitude damping and phase damping

    SciTech Connect

    Huang Jiehui; Zhu Shiyao

    2007-12-15

    By using principal minor method, which is developed from the Peres-Horodecki criterion for the separability of a quantum state, we derive the necessary and sufficient conditions for the entanglement sudden death of a two-qubit state under amplitude damping and phase damping.

  5. Investigating the Factor Structure and Measurement Invariance of Phonological Abilities in a Sufficiently Transparent Language

    ERIC Educational Resources Information Center

    Papadopoulos, Timothy C.; Kendeou, Panayiota; Spanoudis, George

    2012-01-01

    Theory-driven conceptualizations of phonological abilities in a sufficiently transparent language (Greek) were examined in children ages 5 years 8 months to 7 years 7 months, by comparing a set of a priori models. Specifically, the fit of 9 different models was evaluated, as defined by the Number of Factors (1 to 3; represented by rhymes,…

  6. Food self-sufficiency across scales: how local can we go?

    PubMed

    Pradhan, Prajal; Lüdeke, Matthias K B; Reusser, Dominik E; Kropp, Juergen P

    2014-08-19

    This study explores the potential for regions to shift to a local food supply using food self-sufficiency (FSS) as an indicator. We considered a region food self-sufficient when its total calorie production is enough to meet its demand. For future scenarios, we considered population growth, dietary changes, improved feed conversion efficiency, climate change, and crop yield increments. Starting at the 5' resolution, we investigated FSS from the lowest administrative levels to continents. Globally, about 1.9 billion people are self-sufficient within their 5' grid, while about 1 billion people from Asia and Africa require cross-continental agricultural trade in 2000. By closing yield gaps, these regions can achieve FSS, which also reduces international trade and increases a self-sufficient population in a 5' grid to 2.9 billion. The number of people depending on international trade will vary between 1.5 and 6 billion by 2050. Climate change may increase the need for international agricultural trade by 4% to 16%. PMID:25062356

  7. Community Service and University Roles: An Action Research Based on the Philosophy of Sufficiency Economy

    ERIC Educational Resources Information Center

    Nuangchalerm, Prasart; Chansirisira, Pacharawit

    2012-01-01

    This study employs action research to develop community service through university roles by applying the philosophy of sufficiency economy of His Majesty the King Bhumibol Adulyadej to fulfill villagers' way of life. Participatory learning, seminar, field trip and supervision were employed for strategic plan. Data were collected by participatory…

  8. Faculty Sufficiency and AACSB Accreditation Compliance within a Global University: A Mathematical Modeling Approach

    ERIC Educational Resources Information Center

    Boronico, Jess; Murdy, Jim; Kong, Xinlu

    2014-01-01

    This manuscript proposes a mathematical model to address faculty sufficiency requirements towards assuring overall high quality management education at a global university. Constraining elements include full-time faculty coverage by discipline, location, and program, across multiple campus locations subject to stated service quality standards of…

  9. Role of input self-sufficiency in the economic and environmental sustainability of specialised dairy farms.

    PubMed

    Lebacq, T; Baret, P V; Stilmant, D

    2015-03-01

    Increasing input self-sufficiency is often viewed as a target to improve sustainability of dairy farms. However, few studies have specifically analysed input self-sufficiency, by including several technical inputs and without only focussing on animal feeding, in order to explore its impact on farm sustainability. To address this gap, our work has three objectives as follows: (1) identifying the structural characteristics required by specialised dairy farms located in the grassland area to be self-sufficient; (2) analysing the relationships between input self-sufficiency, environmental and economic sustainability; and (3) studying how the farms react to a decrease in milk price according to their self-sufficiency degree. Based on farm accounting databases, we categorised 335 Walloon specialised conventional dairy farms into four classes according to their level of input self-sufficiency. To this end, we used as proxy the indicator of economic autonomy - that is, the ratio between costs of inputs related to animal production, crop production and energy use and the total gross product. Classes were then compared using multiple comparison tests and canonical discriminant analysis. A total of 30 organic farms - among which 63% had a high level of economic autonomy - were considered separately and compared with the most autonomous class. We showed that a high degree of economic autonomy is associated, in conventional farms, with a high proportion of permanent grassland in the agricultural area. The most autonomous farms used less input - especially animal feeding - for a same output level, and therefore combined good environmental and economic performances. Our results also underlined that, in a situation of decrease in milk price, the least autonomous farms had more latitude to decrease their input-related costs without decreasing milk production. Their incomes per work unit were, therefore, less impacted by falling prices, but remained lower than those of more

  10. Portfolio of Research in Welfare and Family Self-Sufficiency: FY 2014. OPRE Report 2015-15

    ERIC Educational Resources Information Center

    Administration for Children & Families, 2015

    2015-01-01

    The Division of Economic Independence within the Office of Planning, Research and Evaluation (OPRE) has primary responsibility for welfare and family self-sufficiency research. OPRE's research in the area of welfare and family self-sufficiency is designed to expand knowledge about effective programs to promote employment, self-sufficiency, and…

  11. Stable dynamics in forced systems with sufficiently high/low forcing frequency.

    PubMed

    Bartuccelli, M; Gentile, G; Wright, J A

    2016-08-01

    We consider parametrically forced Hamiltonian systems with one-and-a-half degrees of freedom and study the stability of the dynamics when the frequency of the forcing is relatively high or low. We show that, provided the frequency is sufficiently high, Kolmogorov-Arnold-Moser (KAM) theorem may be applied even when the forcing amplitude is far away from the perturbation regime. A similar result is obtained for sufficiently low frequency, but in that case we need the amplitude of the forcing to be not too large; however, we are still able to consider amplitudes which are outside of the perturbation regime. In addition, we find numerically that the dynamics may be stable even when the forcing amplitude is very large, well beyond the range of validity of the analytical results, provided the frequency of the forcing is taken correspondingly low. PMID:27586604

  12. Colocalization of Sensors Is Sufficient to Activate the DNA Damage Checkpoint in the Absence of Damage

    PubMed Central

    Bonilla, Carla Yaneth; Melo, Justine Amy

    2010-01-01

    Summary Previous work on the DNA damage checkpoint in Saccharomyces cerevisiae has shown that two complexes independently sense DNA lesions: the kinase Mec1-Ddc2 and the PCNA-like 9-1-1 complex. To test whether colocalization of these components is sufficient for checkpoint activation, we fused these checkpoint proteins to the LacI repressor and artificially colocalized these fusions by expressing them in cells harboring Lac operator arrays. We observed Rad53 and Rad9 phosphorylation, Sml1 degradation, and metaphase delay, demonstrating that colocalization of these sensors is sufficient to activate the checkpoint in the absence of DNA damage. Our tethering system allowed us to establish that CDK functions in the checkpoint pathway downstream of damage processing and checkpoint protein recruitment. This CDK dependence is likely, at least in part, through Rad9, since mutation of CDK consensus sites compromised its checkpoint function. PMID:18471973

  13. Children's Sleep Needs: Is There Sufficient Evidence to Recommend Optimal Sleep for Children?

    PubMed Central

    Matricciani, Lisa; Blunden, Sarah; Rigney, Gabrielle; Williams, Marie T.; Olds, Tim S.

    2013-01-01

    It is widely recognized that sleep is important for children's health and well-being and that short sleep duration is associated with a wide range of negative health outcomes. Recently, there has been much interest in whether or not there are sufficient data to support the specific recommendations made for how much sleep children need. In this article we explore concepts related to children's sleep need, discuss the theory, rationale, and empirical evidence for contemporary sleep recommendations, and outline future research directions for sleep recommendations. If sleep is to be treated as a therapeutic intervention, then consensus guidelines, statements, and evidence-based best-practice documents are needed to underpin sleep recommendations for children. Citation: Matricciani L; Blunden S; Rigney G; Williams MT; Olds TS. Children's sleep needs: is there sufficient evidence to recommend optimal sleep for children? SLEEP 2013;36(4):527-534. PMID:23564999

  14. Featural information is sufficient to produce a left cheek bias for happiness perception.

    PubMed

    Low, Jia Y; Lindell, Annukka K

    2016-08-01

    People perceive the left cheek as more emotionally expressive than the right. Both configural and featural information enable the evaluation of emotional expressions; whether they make equivalent contributions to the left cheek bias is undetermined. As scrambling faces disrupts configural processing whilst leaving featural information intact, we investigated whether configural information is necessary, or featural information is sufficient, to induce a left cheek bias for emotion perception. Eighty-one participants (65 F, 16 M) viewed two types of left and right cheek image pairs - normal, scrambled - and indicated which image appeared happier (half mirror-reversed to control for perceptual biases). Results indicated a left cheek bias for both normal and scrambled faces, irrespective of mirror reversal. As scrambling faces disrupts configural processing, the fact that the left cheek was perceived as more expressive even when scrambled confirms that differences between the cheeks' featural information are sufficient to induce the left cheek bias. PMID:27363004

  15. Linear stable unity-feedback system - Necessary and sufficient conditions for stability under nonlinear plant perturbations

    NASA Technical Reports Server (NTRS)

    Desoer, C. A.; Kabuli, M. G.

    1989-01-01

    The authors consider a linear (not necessarily time-invariant) stable unity-feedback system, where the plant and the compensator have normalized right-coprime factorizations. They study two cases of nonlinear plant perturbations (additive and feedback), with four subcases resulting from: (1) allowing exogenous input to Delta P or not; 2) allowing the observation of the output of Delta P or not. The plant perturbation Delta P is not required to be stable. Using the factorization approach, the authors obtain necessary and sufficient conditions for all cases in terms of two pairs of nonlinear pseudostate maps. Simple physical considerations explain the form of these necessary and sufficient conditions. Finally, the authors obtain the characterization of all perturbations Delta P for which the perturbed system remains stable.

  16. Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction.

    PubMed

    Pascoli, Vincent; Terrier, Jean; Hiver, Agnès; Lüscher, Christian

    2015-12-01

    The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease. PMID:26586182

  17. Retrocausal Effects as a Consequence of Quantum Mechanics Refined to Accommodate the Principle of Sufficient Reason

    SciTech Connect

    Stapp, Henry P.

    2011-05-10

    The principle of sufficient reason asserts that anything that happens does so for a reason: no definite state of affairs can come into being unless there is a sufficient reason why that particular thing should happen. This principle is usually attributed to Leibniz, although the first recorded Western philosopher to use it was Anaximander of Miletus. The demand that nature be rational, in the sense that it be compatible with the principle of sufficient reason, conflicts with a basic feature of contemporary orthodox physical theory, namely the notion that nature's response to the probing action of an observer is determined by pure chance, and hence on the basis of absolutely no reason at all. This appeal to pure chance can be deemed to have no rational fundamental place in reason-based Western science. It is argued here, on the basis of the other basic principles of quantum physics, that in a world that conforms to the principle of sufficient reason, the usual quantum statistical rules will naturally emerge at the pragmatic level, in cases where the reason behind nature's choice of response is unknown, but that the usual statistics can become biased in an empirically manifest way when the reason for the choice is empirically identifiable. It is shown here that if the statistical laws of quantum mechanics were to be biased in this way then the basically forward-in-time unfolding of empirical reality described by orthodox quantum mechanics would generate the appearances of backward-time-effects of the kind that have been reported in the scientific literature.

  18. Sleep budgets in a globalizing world: biocultural interactions influence sleep sufficiency among Egyptian families.

    PubMed

    Worthman, Carol M; Brown, Ryan A

    2013-02-01

    Declines in self-reported sleep quotas with globalizing lifestyle changes have focused attention on their possible role in rising global health problems such as obesity or depression. Cultural factors that act across the life course and support sleep sufficiency have received scant attention, nor have the potential interactions of cultural and biological factors in age-related changes in sleep behavior been systematically investigated. This study examines the effects of cultural norms for napping and sleeping arrangements along with sleep schedules, age, and gender on sleep budgets among Egyptian households. Data were collected in 2000 from 16 households with 78 members aged 3-56 years at two sites in Egypt (Cairo and an agrarian village). Each participant provided one week of continuous activity records and details of each sleep event. Records showed that nighttime sleep onsets were late and highly variable. Napping was common and, along with wake time flexibility, played a key role in maintaining sleep sufficiency throughout the life course into later middle age. Cosleeping was prevalent and exhibited contrasting associations with reduced duration and sufficiency of both nocturnal and total sleep, and with earlier, more regular, and less disrupted sleep. Daily sleep quotas met published guidelines and showed age-related changes similar to existing reports, but differed in how they were achieved. Cultural norms organizing sleep practices by age and gender appear to tap their intrinsic biological properties as well. Moreover, flexibility in how sleep was achieved contributed to sleep sufficiency. The findings suggest how biocultural dynamics can play key roles in sleep patterns that sustain favorable sleep quotas from infancy onwards in populations pursuing globalizing contemporary lifestyles. PMID:22651897

  19. 75 FR 21022 - Announcement of Funding Awards for the Housing Choice Voucher Family Self-Sufficiency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ...In accordance with Section 102(a)(4)(C) of the Department of Housing and Urban Development Reform Act of 1989, this announcement notifies the public of funding decisions made by the Department for funding under Notice PIH 2009-40 (HA) for the Housing Choice Voucher Family Self-Sufficiency (HCV/FSS) Administrative Fee funding. This announcement contains the consolidated names and addresses of......

  20. Usefulness of High Suction Pressure for Sufficient Tissue Collection During Endobronchial Ultrasound Guided Transbronchial Needle Aspiration

    PubMed Central

    Shiroyama, Takayuki; Okamoto, Norio; Suzuki, Hidekazu; Tamiya, Motohiro; Yamadori, Tadahiro; Morishita, Naoko; Otsuka, Tomoyuki; Morita, Satomu; Kurata, Kanako; Okimura, Akira; Kawahara, Kunimitsu; Sasada, Shinji; Hirashima, Tomonori; Kawase, Ichiro

    2013-01-01

    Introduction The optimal suction pressure during endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) remains to be determined. The aim of this study was to compare suction pressures for performance in collecting sufficient tissue specimens from mediastinal and hilar lymph nodes during EBUS-TBNA. Methods Retrospective analysis of consecutive patients with mediastinal and hilar lymphadenopathy who underwent EBUS-TBNA over a 3-year period. Results from patients who underwent EBUS-TBNA using a dedicated 20-mL VacLoc (Merit Medical Systems, Inc, South Jordan, UT) syringe (conventional method, group C) were compared with results from patients in whom a disposable 30-mL syringe (high pressure group, group H) was used. The yield for sufficient histologic specimen retrieval and amount of tissue obtained were compared between the 2 groups. Results Of 178 patients who underwent EBUS-TBNA, 131 had lung cancer confirmed by EBUS-TBNA: 35 in group C and 96 in group H. There were 7 patients in group C and 6 in group H who received final diagnoses by cytology alone. There were 28 in group C and 90 in group H who were diagnosed by both cytology and histology. There was a statistically significant difference between the groups in terms of the rate of sufficient sampling for histological specimens (p = 0.04). The H group revealed a tissue area approximately twice that of the C group (p = 0.003). There were no major procedure-related complications in either group. Conclusion Higher suction pressures with larger syringe volumes during EBUS-TBNA may be useful for safely collecting sufficient tissue specimens. PMID:24340058

  1. Self-sufficient electronic control for nonlinear, frequency tunable, piezoelectric vibration harvesters

    NASA Astrophysics Data System (ADS)

    Heller, S.; Neiss, S.; Kroener, M.; Woias, P.

    2015-12-01

    Research in vibration energy harvesting focuses increasingly on nonlinear harvesters. In comparison to linear harvesters they show an inherent larger bandwidth through hardening or softening effects and higher conversion efficiency. A further increase of the bandwidth and thus a higher energy yield can be achieved by controlled tuning of such a nonlinear system. In this paper a self-sufficient tuning control electronic, which is directly powered by the harvester, is presented.

  2. Necessary and sufficient conditions for discrete and differential inclusions of elliptic type

    NASA Astrophysics Data System (ADS)

    Mahmudov, E. N.

    2006-11-01

    This paper deals for the first time with the Dirichlet problem for discrete (PD), discrete approximation problem on a uniform grid and differential (PC) inclusions of elliptic type. In the form of Euler-Lagrange inclusion necessary and sufficient conditions for optimality are derived for the problems under consideration on the basis of new concepts of locally adjoint mappings. The results obtained are generalized to the multidimensional case with a second order elliptic operator.

  3. MSEBAG: a dynamic classifier ensemble generation based on `minimum-sufficient ensemble' and bagging

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Kamel, Mohamed S.

    2016-01-01

    In this paper, we propose a dynamic classifier system, MSEBAG, which is characterised by searching for the 'minimum-sufficient ensemble' and bagging at the ensemble level. It adopts an 'over-generation and selection' strategy and aims to achieve a good bias-variance trade-off. In the training phase, MSEBAG first searches for the 'minimum-sufficient ensemble', which maximises the in-sample fitness with the minimal number of base classifiers. Then, starting from the 'minimum-sufficient ensemble', a backward stepwise algorithm is employed to generate a collection of ensembles. The objective is to create a collection of ensembles with a descending fitness on the data, as well as a descending complexity in the structure. MSEBAG dynamically selects the ensembles from the collection for the decision aggregation. The extended adaptive aggregation (EAA) approach, a bagging-style algorithm performed at the ensemble level, is employed for this task. EAA searches for the competent ensembles using a score function, which takes into consideration both the in-sample fitness and the confidence of the statistical inference, and averages the decisions of the selected ensembles to label the test pattern. The experimental results show that the proposed MSEBAG outperforms the benchmarks on average.

  4. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary.

    PubMed

    Ma, Qing; de Cuevas, Margaret; Matunis, Erika L

    2016-03-01

    Sexual identity is continuously maintained in specific differentiated cell types long after sex determination occurs during development. In the adult Drosophila testis, the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo) acts with the canonical male sex determinant DoublesexM (Dsx(M)) to maintain the male identity of somatic cyst stem cells and their progeny. Here we find that ectopic expression of chinmo is sufficient to induce a male identity in adult ovarian somatic cells, but it acts through a Dsx(M)-independent mechanism. Conversely, the feminization of the testis somatic stem cell lineage caused by loss of chinmo is enhanced by expression of the canonical female sex determinant Dsx(F), indicating that chinmo acts in parallel with the canonical sex determination pathway to maintain the male identity of testis somatic cells. Consistent with this finding, ectopic expression of female sex determinants in the adult testis disrupts tissue morphology. The miRNA let-7 downregulates chinmo in many contexts, and ectopic expression of let-7 in the adult testis is sufficient to recapitulate the chinmo loss-of-function phenotype, but we find no apparent phenotypes upon removal of let-7 in the adult ovary or testis. Our finding that chinmo is necessary and sufficient to promote a male identity in adult gonadal somatic cells suggests that the sexual identity of somatic cells can be reprogrammed in the adult Drosophila ovary as well as in the testis. PMID:26811385

  5. Quantum Markov chains, sufficiency of quantum channels, and Rényi information measures

    NASA Astrophysics Data System (ADS)

    Datta, Nilanjana; Wilde, Mark M.

    2015-12-01

    A short quantum Markov chain is a tripartite state {ρ }{ABC} such that system A can be recovered perfectly by acting on system C of the reduced state {ρ }{BC}. Such states have conditional mutual information I(A;B| C) equal to zero and are the only states with this property. A quantum channel {N} is sufficient for two states ρ and σ if there exists a recovery channel using which one can perfectly recover ρ from {N}(ρ ) and σ from {N}(σ ). The relative entropy difference D(ρ \\parallel σ )-D({N}(ρ )\\parallel {N}(σ )) is equal to zero if and only if {N} is sufficient for ρ and σ. In this paper, we show that these properties extend to Rényi generalizations of these information measures which were proposed in (Berta et al 2015 J. Math. Phys. 56 022205; Seshadreesan et al 2015 J. Phys. A: Math. Theor. 48 395303), thus providing an alternate characterization of short quantum Markov chains and sufficient quantum channels. These results give further support to these quantities as being legitimate Rényi generalizations of the conditional mutual information and the relative entropy difference. Along the way, we solve some open questions of Ruskai and Zhang, regarding the trace of particular matrices that arise in the study of monotonicity of relative entropy under quantum operations and strong subadditivity of the von Neumann entropy.

  6. Resource Utilization and Site Selection for a Self-Sufficient Martian Outpost

    NASA Technical Reports Server (NTRS)

    Barker, Donald; Chamitoff, Gregory; James, George

    1998-01-01

    As a planet with striking similarities to Earth, Mars is an important focus for scientific research aimed at understanding the processes of planetary evolution and the formation of our solar system. Fortunately, Mars is also a planet with abundant natural resources, including assessible materials that can be used to support human life and to sustain a self-sufficient martian outpost. Resources required include water, breathable air, food, shelter, energy, and fuel. Through a mission design based on in situ resource development, we can establish a permanent outpost on Mars beginning with the first manned mission. This paper examines the potential for supporting the first manned mission with the objective of achieving self-sufficiency through well-understood resource development and a program of rigorous scientific research aimed at extending that capability. We examine the potential for initially extracting critical resources from the martian environment, and discuss the scientific investigations required to identify additional resources in the atmosphere, on the surface, and within the subsurface. We also discuss our current state of knowledge of Mars, technical considerations of resource utilization, and using unmanned missions' data for selecting an optimal site. The primary goal of achieving self-sufficiency on Mars would accelerate the development of human colonization beyond Earth, while providing a robust and permanent martian base from which humans can explore and conduct long-term research on planetary evolution, the solar system, and life itself.

  7. On the role of budget sufficiency, cost efficiency, and uncertainty in species management

    USGS Publications Warehouse

    van der Burg, Max Post; Bly, Bartholomew B.; Vercauteren, Tammy; Grand, James B.; Tyre, Andrew J.

    2014-01-01

    Many conservation planning frameworks rely on the assumption that one should prioritize locations for management actions based on the highest predicted conservation value (i.e., abundance, occupancy). This strategy may underperform relative to the expected outcome if one is working with a limited budget or the predicted responses are uncertain. Yet, cost and tolerance to uncertainty rarely become part of species management plans. We used field data and predictive models to simulate a decision problem involving western burrowing owls (Athene cunicularia hypugaea) using prairie dog colonies (Cynomys ludovicianus) in western Nebraska. We considered 2 species management strategies: one maximized abundance and the other maximized abundance in a cost-efficient way. We then used heuristic decision algorithms to compare the 2 strategies in terms of how well they met a hypothetical conservation objective. Finally, we performed an info-gap decision analysis to determine how these strategies performed under different budget constraints and uncertainty about owl response. Our results suggested that when budgets were sufficient to manage all sites, the maximizing strategy was optimal and suggested investing more in expensive actions. This pattern persisted for restricted budgets up to approximately 50% of the sufficient budget. Below this budget, the cost-efficient strategy was optimal and suggested investing in cheaper actions. When uncertainty in the expected responses was introduced, the strategy that maximized abundance remained robust under a sufficient budget. Reducing the budget induced a slight trade-off between expected performance and robustness, which suggested that the most robust strategy depended both on one's budget and tolerance to uncertainty. Our results suggest that wildlife managers should explicitly account for budget limitations and be realistic about their expected levels of performance.

  8. Stability boundaries and sufficient stability conditions for stably stratified, monotonic shear flows

    NASA Astrophysics Data System (ADS)

    Hirota, Makoto; Morrison, Philip J.

    2016-05-01

    Linear stability of inviscid, parallel, and stably stratified shear flow is studied under the assumption of smooth strictly monotonic profiles of shear flow and density, so that the local Richardson number is positive everywhere. The marginally unstable modes are systematically found by solving a one-parameter family of regular Sturm-Liouville problems, which can determine the stability boundaries more efficiently than solving the Taylor-Goldstein equation directly. By arguing for the non-existence of a marginally unstable mode, we derive new sufficient conditions for stability, which generalize the Rayleigh-Fjørtoft criterion for unstratified shear flows.

  9. The Autonomous House: A Bio-Hydrogen Based Energy Self-Sufficient Approach

    PubMed Central

    Chen, Shang-Yuan; Chu, Chen-Yeon; Cheng, Ming-jen; Lin, Chiu-Yue

    2009-01-01

    In the wake of the greenhouse effect and global energy crisis, finding sources of clean, alternative energy and developing everyday life applications have become urgent tasks. This study proposes the development of an “autonomous house” emphasizing the use of modern green energy technology to reduce environmental load, achieve energy autonomy and use energy intelligently in order to create a sustainable, comfortable living environment. The houses’ two attributes are: (1) a self-sufficient energy cycle and (2) autonomous energy control to maintain environmental comfort. The autonomous house thus combines energy-conserving, carbon emission-reducing passive design with active elements needed to maintain a comfortable environment. PMID:19440531

  10. The autonomous house: a bio-hydrogen based energy self-sufficient approach.

    PubMed

    Chen, Shang-Yuan; Chu, Chen-Yeon; Cheng, Ming-Jen; Lin, Chiu-Yue

    2009-04-01

    In the wake of the greenhouse effect and global energy crisis, finding sources of clean, alternative energy and developing everyday life applications have become urgent tasks. This study proposes the development of an "autonomous house" emphasizing the use of modern green energy technology to reduce environmental load, achieve energy autonomy and use energy intelligently in order to create a sustainable, comfortable living environment. The houses' two attributes are: (1) a self-sufficient energy cycle and (2) autonomous energy control to maintain environmental comfort. The autonomous house thus combines energy-conserving, carbon emission-reducing passive design with active elements needed to maintain a comfortable environment. PMID:19440531

  11. Sufficient conditions for rate-independent hysteresis in autoregressive identified models

    NASA Astrophysics Data System (ADS)

    Martins, Samir Angelo Milani; Aguirre, Luis Antonio

    2016-06-01

    This paper shows how hysteresis can be described using polynomial models and what are the sufficient conditions to be met by the model in order to have hysteresis. Such conditions are related to the model equilibria, to the forcing function and to certain term clusters in the polynomial models. The main results of the paper are used in the identification and analysis of nonlinear models estimated from data produced by a magneto-rheological damper (MRD) model with Bouc-Wen rate-independent hysteresis. A striking feature of the identified model is its simplicity and this could turn out to be a key factor in controller design.

  12. Designing and managing public housing self-sufficiency programs: the Youngs Lake Commons Program.

    PubMed

    Kleit, Rachel Garshick

    2004-10-01

    This article evaluates an experimental public housing self-sufficiency program that encourages home ownership among low-income families. A quasi-experimental design, in combination with focus groups, records review, and key informant interviews, provides data to focus on four questions: (a) Do these programs simply accelerate move-outs for those who would have left without intervention? (b) Are program elements replicable given the importance of the local context in public housing move-outs? (c) How do housing authorities resolve tensions that arise between housing management and social service delivery? (d) What should housing authority response be to those who fail? PMID:15358903

  13. Self sufficient wireless transmitter powered by foot-pumped urine operating wearable MFC.

    PubMed

    Taghavi, M; Stinchcombe, A; Greenman, J; Mattoli, V; Beccai, L; Mazzolai, B; Melhuish, C; Ieropoulos, I A

    2016-02-01

    The first self-sufficient system, powered by a wearable energy generator based on microbial fuel cell (MFC) technology is introduced. MFCs made from compliant material were developed in the frame of a pair of socks, which was fed by urine via a manual gaiting pump. The simple and single loop cardiovascular fish circulatory system was used as the inspiration for the design of the manual pump. A wireless programmable communication module, engineered to operate within the range of the generated electricity, was employed, which opens a new avenue for research in the utilisation of waste products for powering portable as well as wearable electronics. PMID:26657063

  14. A computation using mutually exclusive processing is sufficient to identify specific Hedgehog signaling components

    PubMed Central

    Spratt, Spencer J.

    2013-01-01

    A system of more than one part can be deciphered by observing differences between the parts. A simple way to do this is by recording something absolute displaying a trait in one part and not in another: in other words, mutually exclusive computation. Conditional directed expression in vivo offers processing in more than one part of the system giving increased computation power for biological systems analysis. Here, I report the consideration of these aspects in the development of an in vivo screening assay that appears sufficient to identify components specific to a system. PMID:24391661

  15. Self-Sufficient Formaldehyde-to-Methanol Conversion by Organometallic Formaldehyde Dismutase Mimic.

    PubMed

    van der Waals, Dominic; Heim, Leo E; Vallazza, Simona; Gedig, Christian; Deska, Jan; Prechtl, Martin H G

    2016-08-01

    The catalytic networks of methylotrophic organisms, featuring redox enzymes for the activation of one-carbon moieties, can serve as great inspiration in the development of novel homogeneously catalyzed pathways for the interconversion of C1 molecules at ambient conditions. An imidazolium-tagged arene-ruthenium complex was identified as an effective functional mimic of the bacterial formaldehyde dismutase, which provides a new and highly selective route for the conversion of formaldehyde to methanol in absence of any external reducing agents. Moreover, secondary amines are reductively methylated by the organometallic dismutase mimic in a redox self-sufficient manner with formaldehyde acting both as carbon source and reducing agent. PMID:27380865

  16. Necessary and sufficient condition for quantum adiabatic evolution by unitary control fields

    NASA Astrophysics Data System (ADS)

    Wang, Zhen-Yu; Plenio, Martin B.

    2016-05-01

    We decompose the quantum adiabatic evolution as the products of gauge invariant unitary operators and obtain the exact nonadiabatic correction in the adiabatic approximation. A necessary and sufficient condition that leads to adiabatic evolution with geometric phases is provided, and we determine that in the adiabatic evolution, while the eigenstates are slowly varying, the eigenenergies and degeneracy of the Hamiltonian can change rapidly. We exemplify this result by the example of the adiabatic evolution driven by parametrized pulse sequences. For driving fields that are rotating slowly with the same average energy and evolution path, fast modulation fields can have smaller nonadiabatic errors than obtained under the traditional approach with a constant amplitude.

  17. Necessary and Sufficient Process leading to Work Smart Standards. Final report

    SciTech Connect

    1996-11-01

    The Necessary and Sufficient Process leading to Work Smart Standards is a Department of Energy initiative to assure adequate protection for workers, the public, and the environment. The Work Smart Standards initiative directs the Laboratory to develop a set of ES and H standards based on the work performed at the Laboratory and the hazards associated with the work. Berkeley Lab`s set of Work Smart Standards includes required Federal, State and local laws and, additionally, national and international standards which represent the highest operating standards of industrial and commercial institutions.

  18. Domain 3 of Hepatitis C Core Protein is Sufficient for Intracellular Lipid Accumulation

    PubMed Central

    Jhaveri, Ravi; Qiang, Guan; Diehl, Anna Mae

    2009-01-01

    Background Hepatitis C virus (HCV) is a major cause of liver disease worldwide with steatosis, or “fatty liver”, being a frequent histologic finding. In previous work, we identified sequence polymorphisms within domain 3 (d3) of genotype 3 HCV Core protein that correlated with steatosis and in vitro lipid accumulation. In this study, we investigated the sufficiency of d3 to promote lipid accumulation, the role of HCV genotype in d3 lipid accumulation and the subcellular distribution of d3. Methods Stable cell lines expressing green fluorescent protein (GFP) fusions with HCV Core d3 from genotype 3 steatosis (d3S), non-steatosis (d3NS) and genotype 1 (d3G1) isolates were analyzed by immunofluorescence (IF), Oil Red O (ORO) staining and triglyceride (TG) quantitation Results Cells expressing d3S had significantly more ORO than d3NS or d3G1 cells (p values: 0.02 and <0.0001 respectively) as well as TG (p=0.03 and 0.003 respectively). IF analysis showed domain 3 does not co-localize to lipid droplets but partially co-localizes to the Golgi. Conclusions Our results suggest that HCV Core d3 is sufficient to mediate the accumulation of lipid by a mechanism that is independent of domains 1 and 2. Our results also suggest that altered lipid trafficking may be involved. PMID:19852667

  19. Spindle assembly checkpoint is sufficient for complete Cdc20 sequestering in mitotic control.

    PubMed

    Ibrahim, Bashar

    2015-01-01

    The spindle checkpoint assembly (SAC) ensures genome fidelity by temporarily delaying anaphase onset, until all chromosomes are properly attached to the mitotic spindle. The SAC delays mitotic progression by preventing activation of the ubiquitin ligase anaphase-promoting complex (APC/C) or cyclosome; whose activation by Cdc20 is required for sister-chromatid separation marking the transition into anaphase. The mitotic checkpoint complex (MCC), which contains Cdc20 as a subunit, binds stably to the APC/C. Compelling evidence by Izawa and Pines (Nature 2014; 10.1038/nature13911) indicates that the MCC can inhibit a second Cdc20 that has already bound and activated the APC/C. Whether or not MCC per se is sufficient to fully sequester Cdc20 and inhibit APC/C remains unclear. Here, a dynamic model for SAC regulation in which the MCC binds a second Cdc20 was constructed. This model is compared to the MCC, and the MCC-and-BubR1 (dual inhibition of APC) core model variants and subsequently validated with experimental data from the literature. By using ordinary nonlinear differential equations and spatial simulations, it is shown that the SAC works sufficiently to fully sequester Cdc20 and completely inhibit APC/C activity. This study highlights the principle that a systems biology approach is vital for molecular biology and could also be used for creating hypotheses to design future experiments. PMID:25977749

  20. Non-self-sufficiency as a primary outcome measure in ALS trials.

    PubMed

    Marin, Benoît; Bianchi, Elisa; Pupillo, Elisabetta; Lunetta, Christian; Tremolizzo, Lucio; Logroscino, Giancarlo; Chiò, Adriano; Preux, Pierre Marie; Beghi, Ettore

    2015-01-01

    Our objective was to assess non-self-sufficiency (NSS) in ALS as an outcome measure in therapeutic trials. Using data from the control arm of two randomized trials and an observational study, associations between NSS (score ≤2 in the ALSFRS-R items for swallowing, cutting food and handling utensils, or walking) and the total ALSFRS-R score, forced vital capacity (FVC), and survival at selected time-points until death or 48 weeks, were assessed. These measures were used as surrogates of relevant functional impairment. Of 82 self-sufficient (SS) patients at baseline, 32 (39.0%) became NSS at four weeks and increased to 72 (87.8%) at the end of follow-up. A significant association was found between NSS, ALSFRS-R score and FVC at 24, 36 and 48 weeks. Thirty-four subjects died (41.5%). Compared to SS patients (median survival, 27.9 months), individuals becoming NSS at four weeks were at increased risk to die (median survival, 23.6 months, p = 0.02). NSS status at four weeks predicted survival even after adjustment for ALSFRS-R total score, age, gender, site of onset, disease duration, BMI, and FVC. 'Walking' was the only predictor of survival when adjusting for all covariates. In conclusion, NSS status is a possible endpoint to investigate short-term efficacy of treatments of ALS. PMID:26470831

  1. Sufficient oxygen for animal respiration 1,400 million years ago

    PubMed Central

    Zhang, Shuichang; Wang, Xiaomei; Wang, Huajian; Bjerrum, Christian J.; Hammarlund, Emma U.; Costa, M. Mafalda; Connelly, James N.; Zhang, Baomin; Su, Jin; Canfield, Donald E.

    2016-01-01

    The Mesoproterozoic Eon [1,600–1,000 million years ago (Ma)] is emerging as a key interval in Earth history, with a unique geochemical history that might have influenced the course of biological evolution on Earth. Indeed, although this time interval is rather poorly understood, recent chromium isotope results suggest that atmospheric oxygen levels were <0.1% of present levels, sufficiently low to have inhibited the evolution of animal life. In contrast, using a different approach, we explore the distribution and enrichments of redox-sensitive trace metals in the 1,400 Ma sediments of Unit 3 of the Xiamaling Formation, North China Block. Patterns of trace metal enrichments reveal oxygenated bottom waters during deposition of the sediments, and biomarker results demonstrate the presence of green sulfur bacteria in the water column. Thus, we document an ancient oxygen minimum zone. We develop a simple, yet comprehensive, model of marine carbon−oxygen cycle dynamics to show that our geochemical results are consistent with atmospheric oxygen levels >4% of present-day levels. Therefore, in contrast to previous suggestions, we show that there was sufficient oxygen to fuel animal respiration long before the evolution of animals themselves. PMID:26729865

  2. Plasma membrane restricted RhoGEF activity is sufficient for RhoA-mediated actin polymerization

    PubMed Central

    van Unen, Jakobus; Reinhard, Nathalie R.; Yin, Taofei; Wu, Yi I.; Postma, Marten; Gadella, Theodorus W.J.; Goedhart, Joachim

    2015-01-01

    The small GTPase RhoA is involved in cell morphology and migration. RhoA activity is tightly regulated in time and space and depends on guanine exchange factors (GEFs). However, the kinetics and subcellular localization of GEF activity towards RhoA are poorly defined. To study the mechanism underlying the spatiotemporal control of RhoA activity by GEFs, we performed single cell imaging with an improved FRET sensor reporting on the nucleotide loading state of RhoA. By employing the FRET sensor we show that a plasma membrane located RhoGEF, p63RhoGEF, can rapidly activate RhoA through endogenous GPCRs and that localized RhoA activity at the cell periphery correlates with actin polymerization. Moreover, synthetic recruitment of the catalytic domain derived from p63RhoGEF to the plasma membrane, but not to the Golgi apparatus, is sufficient to activate RhoA. The synthetic system enables local activation of endogenous RhoA and effectively induces actin polymerization and changes in cellular morphology. Together, our data demonstrate that GEF activity at the plasma membrane is sufficient for actin polymerization via local RhoA signaling. PMID:26435194

  3. Attended but unseen: visual attention is not sufficient for visual awareness.

    PubMed

    Kentridge, R W; Nijboer, T C W; Heywood, C A

    2008-02-12

    Does any one psychological process give rise to visual awareness? One candidate is selective attention-when we attend to something it seems we always see it. But if attention can selectively enhance our response to an unseen stimulus then attention cannot be a sufficient precondition for awareness. Kentridge, Heywood & Weiskrantz [Kentridge, R. W., Heywood, C. A., & Weiskrantz, L. (1999). Attention without awareness in blindsight. Proceedings of the Royal Society of London, Series B, 266, 1805-1811; Kentridge, R. W., Heywood, C. A., & Weiskrantz, L. (2004). Spatial attention speeds discrimination without awareness in blindsight. Neuropsychologia, 42, 831-835.] demonstrated just such a dissociation in the blindsight subject GY. Here, we test whether the dissociation generalizes to the normal population. We presented observers with pairs of coloured discs, each masked by the subsequent presentation of a coloured annulus. The discs acted as primes, speeding discrimination of the colour of the annulus when they matched in colour and slowing it when they differed. We show that the location of attention modulated the size of this priming effect. However, the primes were rendered invisible by metacontrast-masking and remained unseen despite being attended. Visual attention could therefore facilitate processing of an invisible target and cannot, therefore, be a sufficient precondition for visual awareness. PMID:18237752

  4. The Promoter of the Cereal VERNALIZATION1 Gene Is Sufficient for Transcriptional Induction by Prolonged Cold

    PubMed Central

    Casao, M. Cristina; Greenup, Aaron A.; Trevaskis, Ben

    2011-01-01

    The VERNALIZATION1 (VRN1) gene of temperate cereals is transcriptionally activated by prolonged cold during winter (vernalization) to promote flowering. To investigate the mechanisms controlling induction of VRN1 by prolonged cold, different regions of the VRN1 gene were fused to the GREEN FLUORESCENT PROTEIN (GFP) reporter and expression of the resulting gene constructs was assayed in transgenic barley (Hordeum vulgare). A 2 kb segment of the promoter of VRN1 was sufficient for GFP expression in the leaves and shoot apex of transgenic barley plants. Fluorescence increased at the shoot apex prior to inflorescence initiation and was subsequently maintained in the developing inflorescence. The promoter was also sufficient for low-temperature induction of GFP expression. A naturally occurring insertion in the proximal promoter, which is associated with elevated VRN1 expression and early flowering in some spring wheats, did not abolish induction of VRN1 transcription by prolonged cold, however. A translational fusion of the promoter and transcribed regions of VRN1 to GFP, VRN1::GFP, was localised to nuclei of cells at the shoot apex of transgenic barley plants. The distribution of VRN1::GFP at the shoot apex was similar to the expression pattern of the VRN1 promoter-GFP reporter gene. Fluorescence from the VRN1::GFP fusion protein increased in the developing leaves after prolonged cold treatment. These observations suggest that the promoter of VRN1 is targeted by mechanisms that trigger vernalization-induced flowering in economically important temperate cereal crops. PMID:22242122

  5. Application of nitrogen sufficiency conversion strategy for microalgae-based ammonium-rich wastewater treatment.

    PubMed

    Wang, Jinghan; Zhou, Wenguang; Yang, Haizhen; Ruan, Roger

    2016-10-01

    Ammonium ([Formula: see text]-N)-rich wastewater, a main cause for eutrophication, can serve as a promising medium for fast microalgae cultivation with efficient [Formula: see text]-N removal. To achieve this goal, a well-controlled three-stage treatment process was developed. Two trophic modes (mixotrophy and heterotrophy) in Stage 1 and Stage 2, with two nitrogen availability conditions (N sufficient and N deprived) in Stage 2, and different [Formula: see text]-N concentrations in Stage 3 were compared to investigate the effects of nitrogen sufficiency conversion on indigenous strain UMN266 for [Formula: see text]-N removal. Results showed that mixotrophic cultures in the first two stages with N deprivation in Stage 2 was the optimum treatment strategy, and higher [Formula: see text]-N concentration in Stage 3 facilitated both microalgal growth and [Formula: see text]-N removal, with average and maximum biomass productivity of 55.3 and 161.0 mg L(-1) d(-1), and corresponding removal rates of 4.2 and 15.0 mg L(-1) d(-1), respectively, superior to previously published results. Observations of intracellular compositions confirmed the optimum treatment strategy, discovering excellent starch accumulating property of strain UMN266 as well. Combination of bioethanol production with the proposed three-stage process using various real wastewater streams at corresponding stages was suggested for future application. PMID:26979571

  6. Measuring what latent fingerprint examiners consider sufficient information for individualization determinations.

    PubMed

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2014-01-01

    Latent print examiners use their expertise to determine whether the information present in a comparison of two fingerprints (or palmprints) is sufficient to conclude that the prints were from the same source (individualization). When fingerprint evidence is presented in court, it is the examiner's determination--not an objective metric--that is presented. This study was designed to ascertain the factors that explain examiners' determinations of sufficiency for individualization. Volunteer latent print examiners (n = 170) were each assigned 22 pairs of latent and exemplar prints for examination, and annotated features, correspondence of features, and clarity. The 320 image pairs were selected specifically to control clarity and quantity of features. The predominant factor differentiating annotations associated with individualization and inconclusive determinations is the count of corresponding minutiae; other factors such as clarity provided minimal additional discriminative value. Examiners' counts of corresponding minutiae were strongly associated with their own determinations; however, due to substantial variation of both annotations and determinations among examiners, one examiner's annotation and determination on a given comparison is a relatively weak predictor of whether another examiner would individualize. The extensive variability in annotations also means that we must treat any individual examiner's minutia counts as interpretations of the (unknowable) information content of the prints: saying "the prints had N corresponding minutiae marked" is not the same as "the prints had N corresponding minutiae." More consistency in annotations, which could be achieved through standardization and training, should lead to process improvements and provide greater transparency in casework. PMID:25372036

  7. Sufficient oxygen for animal respiration 1,400 million years ago.

    PubMed

    Zhang, Shuichang; Wang, Xiaomei; Wang, Huajian; Bjerrum, Christian J; Hammarlund, Emma U; Costa, M Mafalda; Connelly, James N; Zhang, Baomin; Su, Jin; Canfield, Donald E

    2016-02-16

    The Mesoproterozoic Eon [1,600-1,000 million years ago (Ma)] is emerging as a key interval in Earth history, with a unique geochemical history that might have influenced the course of biological evolution on Earth. Indeed, although this time interval is rather poorly understood, recent chromium isotope results suggest that atmospheric oxygen levels were <0.1% of present levels, sufficiently low to have inhibited the evolution of animal life. In contrast, using a different approach, we explore the distribution and enrichments of redox-sensitive trace metals in the 1,400 Ma sediments of Unit 3 of the Xiamaling Formation, North China Block. Patterns of trace metal enrichments reveal oxygenated bottom waters during deposition of the sediments, and biomarker results demonstrate the presence of green sulfur bacteria in the water column. Thus, we document an ancient oxygen minimum zone. We develop a simple, yet comprehensive, model of marine carbon-oxygen cycle dynamics to show that our geochemical results are consistent with atmospheric oxygen levels >4% of present-day levels. Therefore, in contrast to previous suggestions, we show that there was sufficient oxygen to fuel animal respiration long before the evolution of animals themselves. PMID:26729865

  8. Knowledge of response location alone is not sufficient to generate social inhibition of return.

    PubMed

    Welsh, Timothy N; Manzone, Joseph; McDougall, Laura

    2014-11-01

    Previous research has revealed that the inhibition of return (IOR) effect emerges when individuals respond to a target at the same location as their own previous response or the previous response of a co-actor. The latter social IOR effect is thought to occur because the observation of co-actor's response evokes a representation of that action in the observer and that the observation-evoked response code subsequently activates the inhibitory mechanisms underlying IOR. The present study was conducted to determine if knowledge of the co-actor's response alone is sufficient to evoke social IOR. Pairs of participants completed responses to targets that appeared at different button locations. Button contact generated location-contingent auditory stimuli (high and low tones in Experiment 1 and colour words in Experiment 2). In the Full condition, the observer saw the response and heard the auditory stimuli. In the Auditory Only condition, the observer did not see the co-actor's response, but heard the auditory stimuli generated via button contact to indicate response endpoint. It was found that, although significant individual and social IOR effects emerged in the Full conditions, there were no social IOR effects in the Auditory Only conditions. These findings suggest that knowledge of the co-actor's response alone via auditory information is not sufficient to activate the inhibitory processes leading to IOR. The activation of the mechanisms that lead to social IOR seems to be dependent on processing channels that code the spatial characteristics of action. PMID:25463556

  9. Epidermal jasmonate perception is sufficient for all aspects of jasmonate-mediated male fertility in Arabidopsis.

    PubMed

    Jewell, Jeremy B; Browse, John

    2016-03-01

    Jasmonate (JA) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana, the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI1-YFP transgene in the coi1-1 mutant background. As COI1 is an essential component of the JA co-receptor complex, the null coi1-1 mutant is male sterile due to lack of JA perception. We show that expression of COI1-YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA-dependent non-autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation. PMID:26833563

  10. Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination.

    PubMed

    Bonaud, Amélie; Lechouane, Fabien; Le Noir, Sandrine; Monestier, Olivier; Cogné, Michel; Sirac, Christophe

    2015-01-01

    Antibody affinity maturation relies on activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) of immunoglobulin (Ig) loci. Class switch recombination (CSR) can in parallel occur between AID-targeted, transcribed, spliced and repetitive switch (S) regions. AID thus initiates not only mutations but also double-strand breaks (DSBs). What governs the choice between those two outcomes remains uncertain. Here we explore whether insertion of transcribed intronic S regions in a locus (Igκ) strongly recruiting AID is sufficient for efficient CSR. Although strongly targeted by AID and carrying internal deletions, the knocked-in S regions only undergo rare CSR-like events. This model confirms S regions as exquisite SHM targets, extending AID activity far from transcription initiation sites, and shows that such spliced and repetitive AID targets are not sufficient by themselves for CSR. Beyond transcription and AID recruitment, additional IgH elements are thus needed for CSR, restricting this hazardous gene remodelling to IgH loci. PMID:26146363

  11. Entropy of Quantum Dynamical Systems and Sufficient Families in Orthomodular Lattices with Bayessian State

    NASA Astrophysics Data System (ADS)

    Mona, Khare; Shraddha, Roy

    2008-09-01

    The purpose of the present paper is to study the entropy hs(Φ) of a quantum dynamical systems Φ = (L,s,phi), where s is a bayessian state on an orthomodular lattice L. Having introduced the notion of entropy hs(phi,Script A) of partition Script A of a Boolean algebra B with respect to a state s and a state preserving homomorphism phi, we prove a few results on that, define the entropy of a dynamical system hs(Φ), and show its invariance. The concept of sufficient families is also given and we establish that hs(Φ) comes out to be equal to the supremum of hs(phi,Script A), where Script A varies over any sufficient family. The present theory has then been extended to the quantum dynamical system (L,s,phi), which as an effect of the theory of commutators and Bell inequalities can equivalently be replaced by the dynamical system (B,s0,phi), where B is a Boolean algebra and s0 is a state on B.

  12. The promoter of the cereal VERNALIZATION1 gene is sufficient for transcriptional induction by prolonged cold.

    PubMed

    Alonso-Peral, Maria M; Oliver, Sandra N; Casao, M Cristina; Greenup, Aaron A; Trevaskis, Ben

    2011-01-01

    The VERNALIZATION1 (VRN1) gene of temperate cereals is transcriptionally activated by prolonged cold during winter (vernalization) to promote flowering. To investigate the mechanisms controlling induction of VRN1 by prolonged cold, different regions of the VRN1 gene were fused to the GREEN FLUORESCENT PROTEIN (GFP) reporter and expression of the resulting gene constructs was assayed in transgenic barley (Hordeum vulgare). A 2 kb segment of the promoter of VRN1 was sufficient for GFP expression in the leaves and shoot apex of transgenic barley plants. Fluorescence increased at the shoot apex prior to inflorescence initiation and was subsequently maintained in the developing inflorescence. The promoter was also sufficient for low-temperature induction of GFP expression. A naturally occurring insertion in the proximal promoter, which is associated with elevated VRN1 expression and early flowering in some spring wheats, did not abolish induction of VRN1 transcription by prolonged cold, however. A translational fusion of the promoter and transcribed regions of VRN1 to GFP, VRN1::GFP, was localised to nuclei of cells at the shoot apex of transgenic barley plants. The distribution of VRN1::GFP at the shoot apex was similar to the expression pattern of the VRN1 promoter-GFP reporter gene. Fluorescence from the VRN1::GFP fusion protein increased in the developing leaves after prolonged cold treatment. These observations suggest that the promoter of VRN1 is targeted by mechanisms that trigger vernalization-induced flowering in economically important temperate cereal crops. PMID:22242122

  13. Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

    PubMed

    Hill, Alexis S; Sahay, Amar; Hen, René

    2015-09-01

    Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects. PMID:25833129

  14. Spindle assembly checkpoint is sufficient for complete Cdc20 sequestering in mitotic control

    PubMed Central

    Ibrahim, Bashar

    2015-01-01

    The spindle checkpoint assembly (SAC) ensures genome fidelity by temporarily delaying anaphase onset, until all chromosomes are properly attached to the mitotic spindle. The SAC delays mitotic progression by preventing activation of the ubiquitin ligase anaphase-promoting complex (APC/C) or cyclosome; whose activation by Cdc20 is required for sister-chromatid separation marking the transition into anaphase. The mitotic checkpoint complex (MCC), which contains Cdc20 as a subunit, binds stably to the APC/C. Compelling evidence by Izawa and Pines (Nature 2014; 10.1038/nature13911) indicates that the MCC can inhibit a second Cdc20 that has already bound and activated the APC/C. Whether or not MCC per se is sufficient to fully sequester Cdc20 and inhibit APC/C remains unclear. Here, a dynamic model for SAC regulation in which the MCC binds a second Cdc20 was constructed. This model is compared to the MCC, and the MCC-and-BubR1 (dual inhibition of APC) core model variants and subsequently validated with experimental data from the literature. By using ordinary nonlinear differential equations and spatial simulations, it is shown that the SAC works sufficiently to fully sequester Cdc20 and completely inhibit APC/C activity. This study highlights the principle that a systems biology approach is vital for molecular biology and could also be used for creating hypotheses to design future experiments. PMID:25977749

  15. High-rate nitrogen removal by the Anammox process with a sufficient inorganic carbon source.

    PubMed

    Yang, Jiachun; Zhang, Li; Fukuzaki, Yasuhiro; Hira, Daisuke; Furukawa, Kenji

    2010-12-01

    This study focused on high-rate nitrogen removal by the anaerobic ammonium oxidation (Anammox) process with a sufficient inorganic carbon (IC) source. Experiments were carried out in an up-flow column Anammox reactor fed with synthetic inorganic wastewater for 110 days. The IC source was added into the influent tank in the form of bicarbonate. The results confirmed the positive impact of inorganic matter on stimulating Anammox activity. After the addition of sufficient IC, the nitrogen removal rate sharply increased from 5.2 to 11.8 kg-Nm(-3)day(-1) within only 32 days. NO(2)-N inhibition was not observed even at NO(2)-N concentrations greater than 460 mgN/L, indicating the enriched Anammox consortium adapted to high NO(2)-N concentrations. The ratio of NO(2)-N removal, NO(3)-N production and NH(4)-N removal for the reactor was correspondingly changed from 1.21:0.21:1 to 1.24:0.18:1. Simultaneously, the sludge volume index of the Anammox granules decreased markedly from 36.8 to 21.5 mL/g, which was attributed to the implementation of proper operational strategy. In addition, DNA analysis revealed that a shift from the KSU-1 strain to the KU2 strain occurred in the Anammox community. PMID:20709538

  16. Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior

    SciTech Connect

    Chen, W.; Li, F.; Mead, L.; White, H.; Walker, J.; Ingram, D.A.; Roman, A.

    2007-10-10

    One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

  17. Necessary and sufficient liveness condition of GS3PR Petri nets

    NASA Astrophysics Data System (ADS)

    Liu, GaiYun; Barkaoui, Kamel

    2015-05-01

    Structural analysis is one of the most important and efficient methods to investigate the behaviour of Petri nets. Liveness is a significant behavioural property of Petri nets. Siphons, as structural objects of a Petri net, are closely related to its liveness. Many deadlock control policies for flexible manufacturing systems (FMS) modelled by Petri nets are implemented via siphon control. Most of the existing methods design liveness-enforcing supervisors by adding control places for siphons based on their controllability conditions. To compute a liveness-enforcing supervisor with as much as permissive behaviour, it is both theoretically and practically significant to find an exact controllability condition for siphons. However, the existing conditions, max, max‧, and max″-controllability of siphons are all overly restrictive and generally sufficient only. This paper develops a new condition called max*-controllability of the siphons in generalised systems of simple sequential processes with resources (GS3PR), which are a net subclass that can model many real-world automated manufacturing systems. We show that a GS3PR is live if all its strict minimal siphons (SMS) are max*-controlled. Compared with the existing conditions, i.e., max-, max‧-, and max″-controllability of siphons, max*-controllability of the SMS is not only sufficient but also necessary. An example is used to illustrate the proposed method.

  18. Eyes only? Perceiving eye contact is neither sufficient nor necessary for attentional capture by face direction.

    PubMed

    Böckler, Anne; van der Wel, Robrecht P R D; Welsh, Timothy N

    2015-09-01

    Direct eye contact and motion onset both constitute powerful cues that capture attention. Recent research suggests that (social) gaze and (non-social) motion onset influence information processing in parallel, even when combined as sudden onset direct gaze cues (i.e., faces suddenly establishing eye contact). The present study investigated the role of eye visibility for attention capture by these sudden onset face cues. To this end, face direction was manipulated (away or towards onlooker) while faces had closed eyes (eliminating visibility of eyes, Experiment 1), wore sunglasses (eliminating visible eyes, but allowing for the expectation of eyes to be open, Experiment 2), and were inverted with visible eyes (disrupting the integration of eyes and faces, Experiment 3). Participants classified targets appearing on one of four faces. Initially, two faces were oriented towards participants and two faces were oriented away from participants. Simultaneous to target presentation, one averted face became directed and one directed face became averted. Attention capture by face direction (i.e., facilitation for faces directed towards participants) was absent when eyes were closed, but present when faces wore sunglasses. Sudden onset direct faces can, hence, induce attentional capture, even when lacking eye cues. Inverted faces, by contrast, did not elicit attentional capture. Thus, when eyes cannot be integrated into a holistic face representation they are not sufficient to capture attention. Overall, the results suggest that visibility of eyes is neither necessary nor sufficient for the sudden direct face effect. PMID:26245915

  19. Food Self-Sufficiency across scales: How local can we go?

    NASA Astrophysics Data System (ADS)

    Pradhan, Prajal; Lüdeke, Matthias K. B.; Reusser, Dominik E.; Kropp, Jürgen P.

    2013-04-01

    "Think global, act local" is a phrase often used in sustainability debates. Here, we explore the potential of regions to go for local supply in context of sustainable food consumption considering both the present state and the plausible future scenarios. We analyze data on the gridded crop calories production, the gridded livestock calories production, the gridded feed calories use and the gridded food calories consumption in 5' resolution. We derived these gridded data from various sources: Global Agro-ecological Zone (GAEZ v3.0), Gridded Livestock of the World (GLW), FAOSTAT, and Global Rural-Urban Mapping Project (GRUMP). For scenarios analysis, we considered changes in population, dietary patterns and possibility of obtaining the maximum potential yield. We investigate the food self-sufficiency multiple spatial scales. We start from the 5' resolution (i.e. around 10 km x 10 km in the equator) and look at 8 levels of aggregation ranging from the plausible lowest administrative level to the continental level. Results for the different spatial scales show that about 1.9 billion people live in the area of 5' resolution where enough calories can be produced to sustain their food consumption and the feed used. On the country level, about 4.4 billion population can be sustained without international food trade. For about 1 billion population from Asia and Africa, there is a need for cross-continental food trade. However, if we were able to achieve the maximum potential crop yield, about 2.6 billion population can be sustained within their living area of 5' resolution. Furthermore, Africa and Asia could be food self-sufficient by achieving their maximum potential crop yield and only round 630 million populations would be dependent on the international food trade. However, the food self-sufficiency status might differ under consideration of the future change in population, dietary patterns and climatic conditions. We provide an initial approach for investigating the

  20. Combustion of available fossil fuel resources sufficient to eliminate the Antarctic Ice Sheet.

    PubMed

    Winkelmann, Ricarda; Levermann, Anders; Ridgwell, Andy; Caldeira, Ken

    2015-09-01

    The Antarctic Ice Sheet stores water equivalent to 58 m in global sea-level rise. We show in simulations using the Parallel Ice Sheet Model that burning the currently attainable fossil fuel resources is sufficient to eliminate the ice sheet. With cumulative fossil fuel emissions of 10,000 gigatonnes of carbon (GtC), Antarctica is projected to become almost ice-free with an average contribution to sea-level rise exceeding 3 m per century during the first millennium. Consistent with recent observations and simulations, the West Antarctic Ice Sheet becomes unstable with 600 to 800 GtC of additional carbon emissions. Beyond this additional carbon release, the destabilization of ice basins in both West and East Antarctica results in a threshold increase in global sea level. Unabated carbon emissions thus threaten the Antarctic Ice Sheet in its entirety with associated sea-level rise that far exceeds that of all other possible sources. PMID:26601273

  1. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.

    PubMed

    Brady, Jennifer J; Chuang, Chen-Hua; Greenside, Peyton G; Rogers, Zoë N; Murray, Christopher W; Caswell, Deborah R; Hartmann, Ursula; Connolly, Andrew J; Sweet-Cordero, E Alejandro; Kundaje, Anshul; Winslow, Monte M

    2016-05-01

    The ability of cancer cells to establish lethal metastatic lesions requires the survival and expansion of single cancer cells at distant sites. The factors controlling the clonal growth ability of individual cancer cells remain poorly understood. Here, we show that high expression of the transcription factor ARNTL2 predicts poor lung adenocarcinoma patient outcome. Arntl2 is required for metastatic ability in vivo and clonal growth in cell culture. Arntl2 drives metastatic self-sufficiency by orchestrating the expression of a complex pro-metastatic secretome. We identify Clock as an Arntl2 partner and functionally validate the matricellular protein Smoc2 as a pro-metastatic secreted factor. These findings shed light on the molecular mechanisms that enable single cancer cells to form allochthonous tumors in foreign tissue environments. PMID:27150038

  2. Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements.

    PubMed

    Morley, Thomas S; Xia, Jonathan Y; Scherer, Philipp E

    2015-01-01

    Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure. Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels. These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity. Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis. PMID:26243466

  3. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-03-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

  4. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila

    NASA Technical Reports Server (NTRS)

    Nolo, R.; Abbott, L. A.; Bellen, H. J.

    2000-01-01

    The senseless (sens) gene is required for proper development of most cell types of the embryonic and adult peripheral nervous system (PNS) of Drosophila. Sens is a nuclear protein with four Zn fingers that is expressed and required in the sensory organ precursors (SOP) for proper proneural gene expression. Ectopic expression of Sens in many ectodermal cells causes induction of PNS external sensory organ formation and is able to recreate an ectopic proneural field. Hence, sens is both necessary and sufficient for PNS development. Our data indicate that proneural genes activate sens expression. Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs.

  5. Observation and manipulation of glial cell function by virtue of sufficient probe expression

    PubMed Central

    Natsubori, Akiyo; Takata, Norio; Tanaka, Kenji F.

    2015-01-01

    The development of gene-encoded indicators and actuators to observe and manipulate cellular functions is being advanced and investigated. Expressing these probe molecules in glial cells is expected to enable observation and manipulation of glial cell activity, leading to elucidate the behaviors and causal roles of glial cells. The first step toward understanding glial cell functions is to express the probes in sufficient amounts, and the Knockin-mediated ENhanced Gene Expression (KENGE)-tet system provides a strategy for achieving this. In the present article, three examples of KENGE-tet system application are reviewed: depolarization of oligodendrocytes, intracellular acidification of astrocytes, and observation of intracellular calcium levels in the fine processes of astrocytes. PMID:26005405

  6. The bag-of-frames approach: A not so sufficient model for urban soundscapes.

    PubMed

    Lagrange, Mathieu; Lafay, Grégoire; Défréville, Boris; Aucouturier, Jean-Julien

    2015-11-01

    The "bag-of-frames" (BOF) approach, which encodes audio signals as the long-term statistical distribution of short-term spectral features, is commonly regarded as an effective and sufficient way to represent environmental sound recordings (soundscapes). The present paper describes a conceptual replication of a use of the BOF approach in a seminal article using several other soundscape datasets, with results strongly questioning the adequacy of the BOF approach for the task. As demonstrated in this paper, the good accuracy originally reported with BOF likely resulted from a particularly permissive dataset with low within-class variability. Soundscape modeling, therefore, may not be the closed case it was once thought to be. PMID:26627819

  7. Combustion of available fossil-fuel resources sufficient to eliminate the Antarctic Ice Sheet

    NASA Astrophysics Data System (ADS)

    Winkelmann, R.; Levermann, A.; Ridgwell, A.; Caldeira, K.

    2015-12-01

    The Antarctic Ice Sheet stores water equivalent to 58 meters in global sea-level rise. Here we show in simulations with the Parallel Ice Sheet Model that burning the currently attainable fossil-fuel resources is sufficient to eliminate the ice sheet. With cumulative fossil-fuel emissions of 10 000 GtC, Antarctica is projected to become almost ice-free with an average contribution to sea-level rise exceeding 3 meters per century during the first millennium. Consistent with recent observations and simulations, the West Antarctic Ice Sheet becomes unstable with 600 to 800 GtC of additional carbon emissions. Beyond this additional carbon release, the destabilization of ice basins in both West- and East Antarctica results in a threshold-increase in global sea level. Unabated carbon emissions thus threaten the Antarctic Ice Sheet in its entirety with associated sea-level rise that far exceeds that of all other possible sources.

  8. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training

    PubMed Central

    Aponte, Yexica; Atasoy, Deniz; Sternson, Scott M.

    2010-01-01

    Two intermingled hypothalamic neuron populations, specified by expression of agouti-related peptide (AGRP) or pro-opiomelanocortin (POMC), positively and negatively influence feeding behavior respectively, possibly by reciprocally regulating downstream melanocortin receptors. However, the sufficiency of these neurons to control behavior, and the relationship of their activity to the magnitude and dynamics of feeding are unknown. To measure this, we used channelrhodopsin-2 for cell type-specific photostimulation. Activation of only 800 AGRP neurons in mice evoked voracious feeding within minutes. The behavioral response increased with photoexcitable neuron number, photostimulation frequency, and stimulus duration. Conversely, POMC neuron stimulation reduced food intake and body weight, which required melanocortin receptor signaling. However, AGRP neuron-mediated feeding was not dependent on suppressing this melanocortin pathway, indicating that AGRP neurons directly engage feeding circuits. Furthermore, feeding was evoked selectively over drinking without training or prior photostimulus exposure, which suggests that AGRP neurons serve a dedicated role coordinating this complex behavior. PMID:21209617

  9. Necessary and Sufficient Conditions for Attitude Estimation in Fractionated Spacecraft Systems

    NASA Technical Reports Server (NTRS)

    Blackmore, Lars; Hadaegh, Fred Y.

    2009-01-01

    This paper addresses the problem of attitude estimation in fractionated spacecraft clusters. Each module in the cluster may have either a star-tracker, a relative attitude sensor, or both. Using results in nonlinear ob- servability theory, we provide graph-theoretic sufficient conditions for the attitude of every module to be observable. In particular we show that the attitude of every module in the cluster can be observed if every module has either a star tracker with non-collinear stars, or there is a path through the sensing network from a module with a star tracker to the module without a star tracker, and each of the relative measurements along the path has either multiple non-collinear beacons or a single beacon that is not parallel to the rotation vector of the target module.

  10. Policy Capacity Is Necessary but Not Sufficient Comment on "Health Reform Requires Policy Capacity".

    PubMed

    Gen, Sheldon; Wright, Amy Conley

    2015-01-01

    Policy capacity focuses on the managerial and organizational abilities to inform policy decisions with sound research and analysis, and facilitate policy implementation with operational efficiency. It stems from a view of the policy process that is rational and positivistic, in which optimal policy choices can be identified, selected, and implemented with objectivity. By itself, however, policy capacity neglects the political aspects of policy-making that can dominate the process, even in health policies. These technical capabilities are certainly needed to advance reforms in health policies, but they are not sufficient. Instead, they must be complemented with public engagement and policy advocacy to ensure support from the public that policies are meant to serve. PMID:26673469

  11. Sufficiency of care in disasters: ventilation, ventilator triage, and the misconception of guideline-driven treatment.

    PubMed

    Trotter, Griffin

    2010-01-01

    This essay examines the management of ventilatory failure in disaster settings where clinical needs overwhelm available resources. An ethically defensible approach in such settings will adopt a "sufficiency of care" perspective that is: (1) adaptive, (2) resource-driven, and (3) responsive to the values of populations being served. Detailed, generic, antecedently written guidelines for "ventilator triage" or other management issues typically are of limited value, and may even impede ethical disaster response if they result in rescuers' clumsily interpreting events through the lens of the guideline, rather than customizing tactics to the actual context. Especially concerning is the tendency of some expert planners to mistakenly assume that medical treatment of respiratory failure: (1) always requires full-feature mechanical ventilators, (2) will always occur in hospitals, and (3) can be planned in advance without sophisticated public consultation about likely ethical dilemmas. PMID:21313863

  12. A signal sequence is sufficient for green fluorescent protein to be routed to regulated secretory granules.

    PubMed

    El Meskini, R; Jin, L; Marx, R; Bruzzaniti, A; Lee, J; Emeson, R; Mains, R

    2001-02-01

    To investigate trafficking in neuroendocrine cells, green fluorescent protein (GFP) tags were fused to various portions of the preproneuropeptide Y (NPY) precursor. Two neuroendocrine cell lines, AtT-20 corticotrope tumor cells and PC-12 pheochromocytoma cells, along with primary anterior pituitary cells, were examined. Expression of chimeric constructs did not disrupt trafficking or regulated secretion of endogenous ACTH and prohormone convertase 1 in AtT-20 cells. Western blot and immunocytochemical analyses demonstrated that the chimeric constructs remained intact, as long as the Lys-Arg cleavage site within preproNPY was deleted. GFP was stored in, and released from, regulated granules in cells expressing half of the NPY precursor fused to GFP, and also in cells in which only the signal sequence of preproNPY was fused to GFP. Thus, in neuroendocrine cells, entering the lumen of the secretory pathway is sufficient to target GFP to regulated secretory granules. PMID:11159860

  13. Combustion of available fossil fuel resources sufficient to eliminate the Antarctic Ice Sheet

    PubMed Central

    Winkelmann, Ricarda; Levermann, Anders; Ridgwell, Andy; Caldeira, Ken

    2015-01-01

    The Antarctic Ice Sheet stores water equivalent to 58 m in global sea-level rise. We show in simulations using the Parallel Ice Sheet Model that burning the currently attainable fossil fuel resources is sufficient to eliminate the ice sheet. With cumulative fossil fuel emissions of 10,000 gigatonnes of carbon (GtC), Antarctica is projected to become almost ice-free with an average contribution to sea-level rise exceeding 3 m per century during the first millennium. Consistent with recent observations and simulations, the West Antarctic Ice Sheet becomes unstable with 600 to 800 GtC of additional carbon emissions. Beyond this additional carbon release, the destabilization of ice basins in both West and East Antarctica results in a threshold increase in global sea level. Unabated carbon emissions thus threaten the Antarctic Ice Sheet in its entirety with associated sea-level rise that far exceeds that of all other possible sources. PMID:26601273

  14. The medial prefrontal cortex is both necessary and sufficient for the acquisition of conditioned defeat.

    PubMed

    Markham, Chris M; Luckett, Cloe A; Huhman, Kim L

    2012-02-01

    We have previously demonstrated that the basolateral amygdala (BLA) is a key component of a neural circuit mediating memory formation for emotionally relevant stimuli in an ethologically-based model of conditioned fear, termed conditioned defeat (CD). In this model, subjects are socially defeated by a larger, more aggressive hamster. Upon subsequent exposure to a smaller, non-aggressive intruder, the defeated animal will show high levels of submissive behaviors and fail to defend its territory. Here we examined whether the medial prefrontal cortex (mPFC), an area with extensive connections with the amygdala, is also a component of this circuit. Temporary inactivation of the mPFC using muscimol, a GABA(A) receptor agonist, significantly enhanced the acquisition but not expression of CD, while blockade of GABA(A) receptors in the mPFC using bicuculline, a GABA(A) antagonist, impaired acquisition of CD. Given these findings, we next sought to test whether plasticity related to the defeat experience occurs in the mPFC. We infused anisomycin, a protein synthesis inhibitor, in the mPFC but this treatment did not alter the acquisition of CD. In our final experiment, we demonstrated that bicuculline failed to alter the acquisition of CD. Together, these results demonstrate for the first time that while the mPFC is both necessary and sufficient for the acquisition of CD, it does not appear to mediate plasticity related to the defeat experience. In contrast, while plasticity underlying CD does appear to occur in the BLA, GABAergic receptor inhibition in the BLA is not sufficient to enhance CD. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID:22001285

  15. Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice

    PubMed Central

    Lamont, Benjamin J.; Li, Yazhou; Kwan, Edwin; Brown, Theodore J.; Gaisano, Herbert; Drucker, Daniel J.

    2011-01-01

    Glucagon-like peptide-1 (GLP-1) circulates at low levels and acts as an incretin hormone, potentiating glucose-dependent insulin secretion from islet β cells. GLP-1 also modulates gastric emptying and engages neural circuits in the portal region and CNS that contribute to GLP-1 receptor–dependent (GLP-1R–dependent) regulation of glucose homeostasis. To elucidate the importance of pancreatic GLP-1R signaling for glucose homeostasis, we generated transgenic mice that expressed the human GLP-1R in islets and pancreatic ductal cells (Pdx1-hGLP1R:Glp1r–/– mice). Transgene expression restored GLP-1R–dependent stimulation of cAMP and Akt phosphorylation in isolated islets, conferred GLP-1R–dependent stimulation of β cell proliferation, and was sufficient for restoration of GLP-1–stimulated insulin secretion in perifused islets. Systemic GLP-1R activation with the GLP-1R agonist exendin-4 had no effect on food intake, hindbrain c-fos expression, or gastric emptying but improved glucose tolerance and stimulated insulin secretion in Pdx1-hGLP1R:Glp1r–/– mice. i.c.v. GLP-1R blockade with the antagonist exendin(9–39) impaired glucose tolerance in WT mice but had no effect in Pdx1-hGLP1R:Glp1r–/– mice. Nevertheless, transgenic expression of the pancreatic GLP-1R was sufficient to normalize both oral and i.p. glucose tolerance in Glp1r–/– mice. These findings illustrate that low levels of endogenous GLP-1 secreted from gut endocrine cells are capable of augmenting glucoregulatory activity via pancreatic GLP-1Rs independent of communication with neural pathways. PMID:22182839

  16. Heterologously Expressed Staphylococcus aureus Fibronectin-Binding Proteins Are Sufficient for Invasion of Host Cells

    PubMed Central

    Sinha, Bhanu; Francois, Patrice; Que, Yok-Ai; Hussain, Muzaffar; Heilmann, Christine; Moreillon, Philippe; Lew, Daniel; Krause, Karl-Heinz; Peters, Georg; Herrmann, Mathias

    2000-01-01

    Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin α5β1 (B. Sinha et al., Cell. Microbiol. 1:101–117, 1999). However, it is unknown whether this mechanism is sufficient for S. aureus invasion. To address this question, various S. aureus adhesins (FnBPA, FnBPB, and clumping factor [ClfA]) were expressed in Staphylococcus carnosus and Lactococcus lactis subsp. cremoris. Both noninvasive gram-positive microorganisms are genetically distinct from S. aureus, lack any known S. aureus surface protein, and do not bind fibronectin. Transformants of S. carnosus and L. lactis harboring plasmids coding for various S. aureus surface proteins (FnBPA, FnBPB, and ClfA) functionally expressed adhesins (as determined by bacterial clumping in plasma, specific latex agglutination, Western ligand blotting, and binding to immobilized and soluble fibronectin). FnBPA or FnBPB but not of ClfA conferred invasiveness to S. carnosus and L. lactis. Invasion of 293 cells by transformants was comparable to that of strongly invasive S. aureus strain Cowan 1. Binding of soluble and immobilized fibronectin paralleled invasiveness, demonstrating that the amount of accessible surface FnBPs is rate limiting. Thus, S. aureus FnBPs confer invasiveness to noninvasive, apathogenic gram-positive cocci. Furthermore, FnBP-coated polystyrene beads were internalized by 293 cells, demonstrating that FnBPs are sufficient for invasion of host cells without the need for (S. aureus-specific) coreceptors. PMID:11083807

  17. Repeatability of kinematic and electromyographical measures during standing and trunk motion: how many trials are sufficient?

    PubMed

    Schinkel-Ivy, Alison; DiMonte, Stephen; Drake, Janessa D M

    2015-04-01

    Previous studies have recommended a minimum of five trials to produce repeatable kinematic and electromyography (EMG) measures during target postures or contraction levels. This study aimed to evaluate the repeatability and reliability of kinematic and EMG measures that are of primary interest in the investigation of trunk movement, and to determine the number of trials required to achieve repeatability and reliability for these measures. Thirty participants performed ten trials of upright standing and maximum trunk ranges-of-motion. Mean (upright standing) and maximum (movement tasks) kinematic and EMG measures were assessed using intraclass correlation coefficients and standard error of measurement, which were used to identify the minimum number of trials for each measure. The repeatability and reliability of the measures were generally high, with 64%, 77%, 85%, and 92% of measures producing repeatable and reliable values with two, three, four, and five trials, respectively. Ten trials were not sufficient for several upright standing angle measures and maximum twist lumbar angles. Further, several abdominal muscles during maximum flexion, as well as the left lower-thoracic erector spinae during maximum twist, required as many as five trials. These measures were typically those with very small amounts of motion, or muscles that did not act in the role of prime mover. These results suggest that as few as two trials may be sufficient for many of the kinematic and EMG measures of primary interest in the investigation of trunk movement, while the collection of four trials should produce repeatable and reliable values for over 80% of measures. These recommendations are intended to provide an acceptable trade-off between repeatable and reliable values and feasibility of the collection protocol. PMID:25661241

  18. Dexamethasone and rosiglitazone are sufficient and necessary for producing functional adipocytes from mesenchymal stem cells.

    PubMed

    Contador, David; Ezquer, Fernando; Espinosa, Maximiliano; Arango-Rodriguez, Martha; Puebla, Carlos; Sobrevia, Luis; Conget, Paulette

    2015-09-01

    The final product of adipogenesis is a functional adipocyte. This mature cell acquires the necessary machinery for lipid metabolism, loses its proliferation potential, increases its insulin sensitivity, and secretes adipokines. Multipotent mesechymal stromal cells have been recognized as a source of adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of human MSC (hMSC) has been induced up to now by using a complex stimulus which includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a classical cocktail) and evaluated according to morphological changes. The present work was aimed at demonstrating that the simultaneous activation of dexamethasone's canonical signaling pathways, through the glucocorticoid receptor and CCAAT-enhancer-binding proteins (C/EBPs) and rosiglitazone through peroxisome proliferator-activated receptor gamma (PPAR-gamma) is sufficient yet necessary for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC exposed just to dexamethasone and rosiglitazone (D&R) differentiated into cells which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2, lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase, adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose dependent on insulin stimulus and high levels of adipokines were secreted (i.e. displaying not only the morphology but also expressing mature adipocytes' specific genes and functional characteristics). This work has demonstrated that (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to induce adipogenic differentiation from hMSC, (ii) D&R producing functional adipocytes from hMSC, (iii) D&R induce adipogenic differentiation from mammalian MSC (including those which are refractory to classical adipogenic differentiation stimuli). D&R would thus seem to be a useful tool for MSC characterization, studying adipogenesis pathways and

  19. RSL genes are sufficient for rhizoid system development in early diverging land plants.

    PubMed

    Jang, Geupil; Yi, Keke; Pires, Nuno D; Menand, Benoît; Dolan, Liam

    2011-06-01

    Land plants are anchored to their substratum from which essential inorganic nutrients are taken up. These functions are carried out by a system of rhizoids in early diverging groups of land plants, such as mosses, liverworts and hornworts. Physcomitrella patens RHD SIX-LIKE1 (PpRSL1) and PpRSL2 transcription factors are necessary for rhizoid development in mosses. Similar proteins, AtRHD6 and AtRSL1, control the development of root hairs in Arabidopsis thaliana. Auxin positively regulates root hair development independently of AtRHD6 and AtRSL1 in A. thaliana but the regulatory interactions between auxin and PpRSL1 and PpRSL2 are unknown. We show here that co-expression of PpRSL1 and PpRSL2 is sufficient for the development of the rhizoid system in the moss P. patens; constitutive expression of PpRSL1 and PpRSL2 converts developing leafy shoot axes (gametophores) into rhizoids. During wild-type development, PpRSL1 and PpRSL2 are expressed in the specialized cells that develop rhizoids, indicating that cell-specific expression of PpRSL1 and PpRSL2 is sufficient to promote rhizoid differentiation during wild-type P. patens development. In contrast to A. thaliana, auxin promotes rhizoid development by positively regulating PpRSL1 and PpRSL2 activity in P. patens. This indicates that even though the same genes control the development of root hairs and rhizoids, the regulation of this transcriptional network by auxin is different in these two species. This suggests that auxin might have controlled the development of the first land plant soil anchoring systems that evolved 465 million years ago by regulating the expression of RSL genes and that this regulatory network has changed since mosses and angiosperms last shared a common ancestor. PMID:21558375

  20. Overexpression of ERβ is sufficient to inhibit hypoxia-inducible factor-1 transactivation

    SciTech Connect

    Park, Choa; Lee, YoungJoo

    2014-07-18

    Highlights: • We examined the effect of ERβ specific ligand on HIF-1 inhibition. • DPN down-regulates the ARNT protein levels in PC3 cells. • DPN did not show additional effect in ERβ transfected MCF-7 cells. • Our study shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression. - Abstract: Estrogen receptor (ER) β is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ERβ suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, we attempted to examine the effect of ERβ specific ligand on HIF-1 inhibition in ERβ positive PC3 cells and ERβ transfected MCF-7 cells. ERβ specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ERβ specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ERβ transfected MCF-7 cells. HIF-1 transcriptional activity repression by ERβ was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ERβ significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ERβ. This result shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression.

  1. Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa.

    PubMed Central

    Rayner, C F; Jackson, A D; Rutman, A; Dewar, A; Mitchell, T J; Andrew, P W; Cole, P J; Wilson, R

    1995-01-01

    Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, and pneumolysin, a hemolytic toxin, is thought to be an important virulence factor. We have studied the interaction of a pneumolysin-sufficient type II S. pneumoniae strain (PL+) and an otherwise identical pneumolysin-deficient derivative (PL-) with human respiratory mucosa in an organ culture with an air interface for up to 48 h. Ciliary beat frequency (CBF) was measured by a photometric technique, and adherence to and invasion of the epithelium were assessed by scanning and transmission electron microscopy. PL+ and PL- caused a progressive fall in CBF compared with the control which became significant (P < 0.01) at 24 h for PL+ and at 48 h for PL-. At 24 h, there was a significant increase in the percentage of the mucosa of the organ culture that was damaged for PL+ compared with the control (P < 0.01) and PL- (P < 0.02). At 48 h, there was a significant increase in mucosal damage for both PL+ (P < 0.005) and PL- (P < 0.05) compared with the control. At 24 and 48 h, PL+ and PL- adhered predominantly to mucus and damaged cells. PL+ infection alone caused separation of tight junctions between epithelial cells, and at 48 h PL+ cells were adherent to the separated edges of otherwise healthy unciliated cells. PL+ and PL- both caused damage to the epithelial cell ultrastructure. S. pneumoniae infection caused patchy damage to the respiratory mucosa and a lowered CBF. These changes were more severe and occurred earlier with the pneumolysin-sufficient variant. PMID:7822008

  2. Outflows and Bubbles in Taurus: Star-formation Feedback Sufficient to Maintain Turbulence

    NASA Astrophysics Data System (ADS)

    Li, Huixian; Li, Di; Qian, Lei; Xu, Duo; Goldsmith, Paul F.; Noriega-Crespo, Alberto; Wu, Yuefang; Song, Yuzhe; Nan, Rendong

    2015-08-01

    We have identified outflows and bubbles in the Taurus molecular cloud based on the ˜100 deg2 Five College Radio Astronomy Observatory 12CO(1-0) and 13CO(1-0) maps and the Spitzer young stellar object catalogs. In the main 44 deg2 area of Taurus, we found 55 outflows, of which 31 were previously unknown. We also found 37 bubbles in the entire 100 deg2 area of Taurus, none of which had been found previously. The total kinetic energy of the identified outflows is estimated to be ˜ 3.9× {10}45 erg, which is 1% of the cloud turbulent energy. The total kinetic energy of the detected bubbles is estimated to be ˜ 9.2× {10}46 erg, which is 29% of the turbulent energy of Taurus. The energy injection rate from the outflows is ˜ 1.3× {10}33 {erg} {{{s}}}-1, which is 0.4-2 times the dissipation rate of the cloud turbulence. The energy injection rate from bubbles is ˜ 6.4× {10}33 erg s-1, which is 2-10 times the turbulent dissipation rate of the cloud. The gravitational binding energy of the cloud is ˜ 1.5× {10}48 erg, that is, 385 and 16 times the energy of outflows and bubbles, respectively. We conclude that neither outflows nor bubbles can provide sufficient energy to balance the overall gravitational binding energy and the turbulent energy of Taurus. However, in the current epoch, stellar feedback is sufficient to maintain the observed turbulence in Taurus.

  3. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

    PubMed

    Ward, Patricia J; Jones, Laura N; Mulligan, Amanda; Goolsby, William; Wilhelm, Jennifer C; English, Arthur W

    2016-01-01

    Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons. PMID:27152611

  4. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo

    PubMed Central

    Ward, Patricia J.; Jones, Laura N.; Mulligan, Amanda; Goolsby, William; Wilhelm, Jennifer C.; English, Arthur W.

    2016-01-01

    Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons. PMID:27152611

  5. Measuring What Latent Fingerprint Examiners Consider Sufficient Information for Individualization Determinations

    PubMed Central

    Ulery, Bradford T.; Hicklin, R. Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2014-01-01

    Latent print examiners use their expertise to determine whether the information present in a comparison of two fingerprints (or palmprints) is sufficient to conclude that the prints were from the same source (individualization). When fingerprint evidence is presented in court, it is the examiner's determination—not an objective metric—that is presented. This study was designed to ascertain the factors that explain examiners' determinations of sufficiency for individualization. Volunteer latent print examiners (n = 170) were each assigned 22 pairs of latent and exemplar prints for examination, and annotated features, correspondence of features, and clarity. The 320 image pairs were selected specifically to control clarity and quantity of features. The predominant factor differentiating annotations associated with individualization and inconclusive determinations is the count of corresponding minutiae; other factors such as clarity provided minimal additional discriminative value. Examiners' counts of corresponding minutiae were strongly associated with their own determinations; however, due to substantial variation of both annotations and determinations among examiners, one examiner's annotation and determination on a given comparison is a relatively weak predictor of whether another examiner would individualize. The extensive variability in annotations also means that we must treat any individual examiner's minutia counts as interpretations of the (unknowable) information content of the prints: saying “the prints had N corresponding minutiae marked” is not the same as “the prints had N corresponding minutiae.” More consistency in annotations, which could be achieved through standardization and training, should lead to process improvements and provide greater transparency in casework. PMID:25372036

  6. Immune T lymphocyte to tumor cell adhesion. Magnesium sufficient, calcium insufficient

    PubMed Central

    1980-01-01

    The prelytic adhesion of immune cytolytic thymus-derived lymphocytes to specific antigen-bearing ascites tumor target cells has been studied. A new assay was used in which adhesions are permitted to form for 2.5 min; the cells are then dispersed to prevent further adhesion, and the predispersion adhesions are quantitated by subsequent 51Cr release from the tumor cells as a result of cytolytic activity of the adhering lymphocytes. There were the following new findings: (a) magnesium is sufficient to support optimal adhesion formation even when EGTA is added to remove contaminating traces of calcium; (b) calcium supports no adhesion formation when traces of contaminating magnesium are removed by pretreating the medium with a chelating ion exchange resin; (c) calcium synergizes with suboptimal magnesium, increasing the apparent adhesion-supporting potency of magnesium 20-fold in the presence of 50 microM calcium; (d) in the presence of optimal magnesium (2--4 mM), calcium has not effect on the properties of the adhesion by any of six criteria; and (e) manganese supports adhesion better than magnesium, and strontium is ineffective. A survey of previous literature indicates that these results are remarkably similar to the predominant pattern for nonimmunologic cell adhesion (e.g., fibroblasts) involving cells from a variety of tissues in late embryonic and adult avians and mammals. This suggests that a "magnesium sufficient, calcium insufficient" mechanism may be found among the latter types of cell adhesions when appropriately examined. Moreover, it seems that the present lymphocyte-tumor cell adhesion, although evoked by specific receptor-antigen recognition, relies predominantly on mechanisms common to nonimmunologic intercellular adhesion processes. PMID:6766945

  7. Darwin's passionate environmentalism or the dangerous fallacy of the 'All-sufficiency of natural selection' theory.

    PubMed

    Marsh, David

    2012-01-01

    Following his last edition of the Origin of Species in 1872, Darwin spent much of the rest of his life searching for possible mechanisms, such as the pangenes in the blood, which would communicate information from the environment to the genome. In each of his six editions of the 'Origin', he stated that there were two forces in evolution - natural selection and conditions of existence. Of the two, he claims that the latter is the more powerful. In so doing, he recognized that natural selection could only operate within the bounds of possibility, that is the environment. August Weismann claimed that conditions of existence had no place in evolution. His publication, the 'All-sufficiency of natural selection', was based on mutilation (cutting tails of rodents and watching the next generation grow tails), which has nothing to do with Darwin's concept of conditions of existence. Nonetheless, evolutionary biologists in general followed the line of the 'all sufficiency' theory and ignored Darwin's conditions of existence, which in other words means the environment. Natural selection has a weak predictive power as it is based on random events. However, the conditions of existence have, by contrast, strong predictive powers that can be tested. The environmental views of two of the greatest evolutionists, Lamarck and Darwin, have been consistently ignored by most evolution theorists who came after them, continuing for over 200 years. Looking at the fossil record through the eyes of Darwin's conditions of existence, not to mention the recent changes in height and shape over the last century, it is possible to draw important conclusions about the past and predictions of the future. With new knowledge of epigenetics, it is perhaps time that Darwin's conditions of existence were given a second hearing. PMID:22544777

  8. 76 FR 55407 - Announcement of Funding Awards; Public and Indian Housing Family Self-Sufficiency Program Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ...-Sufficiency Program Under the Resident Opportunity and Self-Sufficiency (ROSS) Program (PH-FSS). This announcement contains the consolidated names and addresses of the award recipients for this year under the PH... Relay Service at (800) 877-8339. SUPPLEMENTARY INFORMATION: The PH-FSS program provides grants to...

  9. The Development of University Students' Self-Sufficiency Based on Interactive Technologies by Their Immersion in the Professional Activity

    ERIC Educational Resources Information Center

    Ljubimova, Elena Mikhaelovna; Galimullina, Elvira Zufarovna; Ibatullin, Rinat Rivkatovich

    2015-01-01

    The article discusses the problems of using web technologies in the development of self-sufficiency of University students. We hypothesize that real professional situations in which he/she is obliged to work independently on the basis of web technologies contribute to the development of students' self-sufficiency. It is shown that the activity…

  10. 24 CFR 5.617 - Self-sufficiency incentives for persons with disabilities-Disallowance of increase in annual income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Self-sufficiency incentives for... Family Income § 5.617 Self-sufficiency incentives for persons with disabilities—Disallowance of increase... this section is applicable only to the following programs: HOME Investment Partnerships Program (24...

  11. Assisting Young, Unmarried Mothers to Become Self-Sufficient: The Effects of Different Types of Early Economic Support.

    ERIC Educational Resources Information Center

    Sandfort, Jodi R.; Hill, Martha S.

    1996-01-01

    Considers how different types of economic support, received soon after the birth of a first child, contribute to the later self-sufficiency of young, unmarried mothers. Findings suggest that certain economic supports assist these mothers and that life choices they make after their child's birth are important to self-sufficiency. (RJM)

  12. [Sufficiency with water-soluble vitamins and state of bone in pregnant women].

    PubMed

    Vrzhesinskaya, O A; Pereverzeva, O G; Gmoshinskaya, M V; Kodentsova, V M; Safronova, A I; Korosteleva, M M; Aleshina, I V; Fandeeva, T A

    2015-01-01

    Vitamin status and bone strength have been estimated in 91 pregnant women (29.3 ± 4.6 years old) from Moscow by non-invasive methods. Sufficiency with vitamins C, B2, B6 has been evaluated by morning urinary excretion of ascorbic acid, riboflavin and 4-piridoxic acid determined by visual titration and fluorimetric methods. The rate of bone resorption has been measured by the ratio of urinary calcium and creatinine, determined by complexometric titration and spectrophotometrically. The study of the bone strength has been conducted using an ultrasonic densitometer (the speed of the ultrasonic waves along the cortical layer). The lack of vitamin C was found in 20.4% .of the women surveyed, vitamin B2--in 27.4%. Vitamin B6 deficiency was detected most frequently (90%). Excretion of vitamins B2 and B6 in women in the third trimester of pregnancy was lower as compared with the women in the first and second trimester. In 53.3% of the women surveyed an increase in urinary excretion of calcium per creatinine has been observed. Excretion of group B vitamins (especially vitamin B6, 1.75 fold, p < 0.05) in women taking vitamin supplements was higher compared to non-taking vitamins that indicates the better sufficiency of the organism with these vitamins. Among women who took vitamin complexes, inadequate supply with water-soluble vitamins C, B2 and B6 was detected less frequently (the difference was significant for vitamin B2) than among women who did not intake vitamin complexes (in 11.9, 27.7 and 42.4% vs 16.1, 54.8 and 48.8 %). The rate of bone resorption (Ca/creatinine) in women taking vitamins was smaller (0.19 ± 0.09 vs 0.24 ± 0.14, p > 0.05). Ca/creatinine ratio was within normal range in 40% of women who intake vitamins, while in women not taking vitamins--only in 22.2%; this value exceeded the upper limit of norm in the rest. The strength of bone was broken in women in the second and third trimester of pregnancy, having worse supply of vitamins. The percentage of

  13. Sufficient conditions for the avoidance of spectral dispersion in optical prisms.

    PubMed

    Lin, Psang Dain

    2016-07-01

    Prisms are common optical elements consisting of only flat boundary surfaces. Two conditions need to be fulfilled to avoid chromatic aberration for a prism, namely, no mutual image tilt and no mutual image shift for different wavelengths. Mutual image tilt occurs when the unit directional vector of the exit ray varies as a function of the prism's refractive index, resulting in spectral dispersion. In a previous study by the present group [Appl. Opt.45, 3951 (2006)APOPAI0003-693510.1364/AO.45.003951], it was shown that when the rays enter and exit a prism perpendicularly, image reorientation is achieved without spectral dispersion. The present study derives a further sufficient condition to avoid spectral dispersion caused by refraction. The condition explains the ability of Dove prisms and solid glass corner cubes to produce the required image orientation even when the entrance and exit rays are not normal to the respective boundary surfaces. In general, the proposed condition provides a useful analytical guideline for avoiding spectral dispersion in a wide variety of optical systems. PMID:27409681

  14. Neuronal function is necessary but not sufficient for consciousness: consciousness is necessary for will.

    PubMed

    Nussbaum, David; Ibrahim, Khadija

    2012-01-01

    Behavioral neuroscience has presented philosophers with the task of clarifying the relationship between neural determinism and free will. If neural functions encode information and govern decision-making, are the constructs of will, agency and indeed morality illusions of pre-scientific ignorance? This article will argue that neuronal function is necessary for representing distinct sensory-perceptual, cognitive, motivational, emotional states, and motor functions. However, neural transmission and action potentials are simply chemical-physical representations of these informational states but are not the embodiment of consciousness itself. By some yet undiscovered mechanism, consciousness "reads" the neuronal events into conscious experience. Absent a particular specialized brain region or sufficient relevant transmitters and receptors, relevant information cannot be processed and the individual cannot be conscious of that informational state. In natural and many artificial communication systems, communications proceed bi-directionally. By an argument of symmetry, if neuronal activity can communicate with consciousness, there is no reason to preclude consciousness from communicating back and influencing neuronal function. In the intervening conscious moment, information from diverse perceptual, motivational, cognitive, and emotional sources is weighted and will results. This process then biases resultant neural processes to actualize the willed target. This approach is limited in terms of operationalization into an experimental study because at present, there is no method to measure consciousness-independent of neuronal function and subjective report. PMID:23181011

  15. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

    PubMed Central

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-01-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform. PMID:26987618

  16. Stable kinetochore–microtubule attachment is sufficient to silence the spindle assembly checkpoint in human cells

    PubMed Central

    Tauchman, Eric C.; Boehm, Frederick J.; DeLuca, Jennifer G.

    2015-01-01

    During mitosis, duplicated sister chromatids attach to microtubules emanating from opposing sides of the bipolar spindle through large protein complexes called kinetochores. In the absence of stable kinetochore–microtubule attachments, a cell surveillance mechanism known as the spindle assembly checkpoint (SAC) produces an inhibitory signal that prevents anaphase onset. Precisely how the inhibitory SAC signal is extinguished in response to microtubule attachment remains unresolved. To address this, we induced formation of hyper-stable kinetochore–microtubule attachments in human cells using a non-phosphorylatable version of the protein Hec1, a core component of the attachment machinery. We find that stable attachments are sufficient to silence the SAC in the absence of sister kinetochore bi-orientation and strikingly in the absence of detectable microtubule pulling forces or tension. Furthermore, we find that SAC satisfaction occurs despite the absence of large changes in intra-kinetochore distance, suggesting that substantial kinetochore stretching is not required for quenching the SAC signal. PMID:26620470

  17. Spirituality, hope, and self-sufficiency among low-income job seekers.

    PubMed

    2015-04-01

    Self-sufficiency (SS) is an important social welfare policy goal in the United States, yet little is known about the process that leads to SS. To address this gap in the literature, this study examined the relationship between spirituality, hope, and SS among a sample of low-income job seekers (N = 116). It was hypothesized that spirituality would be related to hope, and that hope, in turn, would be related to SS. Using survey data from two workforce development agencies, this hypothesis was confirmed-hope fully mediated the relationship between spirituality and SS. Of the two factors through which hope is commonly operationalized-agency and pathways-supplemental analysis suggested that spirituality only affects SS through the agency channel. To help foster hope in direct practice settings, it is suggested that social workers might employ spiritually modified cognitive-behavioral therapy protocols. Macrostructural interventions that block the pathway component of hope are also suggested to help reverse exclusion from labor market entry. As such, hope needs to be addressed comprehensively-intrapsychically and macrostructurally-to effect bottom-up change for SS. Engendering hope may assist clients overcome some of the many challenges they encounter on the journey to SS. PMID:25929013

  18. Is the structural diversity of tripeptides sufficient for developing functional food additives with satisfactory multiple bioactivities?

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Hui; Liu, Yong-Le; Ning, Jing-Heng; Yu, Jian; Li, Xiang-Hong; Wang, Fa-Xiang

    2013-05-01

    Multifunctional peptides have attracted increasing attention in the food science community because of their therapeutic potential, low toxicity and rapid intestinal absorption. However, previous study demonstrated that the limited structural variations make it difficult to optimize dipeptide molecules in a good balance between desirable and undesirable properties (F. Tian, P. Zhou, F. Lv, R. Song, Z. Li, J. Pept. Sci. 13 (2007) 549-566). In the present work, we attempt to answer whether the structural diversity is sufficient for a tripeptide to have satisfactory multiple bioactivities. Statistical test, structural examination and energetic analysis confirm that peptides of three amino acids long can bind tightly to human angiotensin converting enzyme (ACE) and thus exert significant antihypertensive efficacy. Further quantitative structure-activity relationship (QSAR) modeling and prediction of all 8000 possible tripeptides reveal that their ACE-inhibitory potency exhibits a good (positive) relationship to antioxidative activity, but has only a quite modest correlation with bitterness. This means that it is possible to find certain tripeptide entities possessing the optimal combination of strong ACE-inhibitory potency, high antioxidative activity and weak bitter taste, which are the promising candidates for developing multifunctional food additives with satisfactory multiple bioactivities. The marked difference between dipeptide and tripeptide can be attributed to the fact that the structural diversity of peptides increases dramatically with a slight change in sequence length.

  19. BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia.

    PubMed

    Baker-Herman, Tracy L; Fuller, David D; Bavis, Ryan W; Zabka, Andrea G; Golder, Francis J; Doperalski, Nicholas J; Johnson, Rebecca A; Watters, Jyoti J; Mitchell, Gordon S

    2004-01-01

    Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in ventral spinal segments containing the phrenic nucleus, and the magnitude of these BDNF increases correlated with pLTF magnitude. We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new therapeutic strategies for treating breathing disorders such as respiratory insufficiency after spinal injury. These experiments also illustrate the potential use of RNAi to investigate functional consequences of gene expression in the mammalian nervous system in vivo. PMID:14699417

  20. Maternal and Pediatric Health Outcomes in relation to Gestational Vitamin D Sufficiency

    PubMed Central

    Genuis, Stephen J.

    2015-01-01

    Juxtaposed with monumental improvement in maternal-fetal outcomes over the last century, there has been the recent emergence of rising rates of gestational complications including preterm birth, operative delivery, and gestational diabetes. At the same time, there has been a burgeoning problem with widespread vitamin D deficiency among populations of many developed nations. This paper provides a brief review of potential health outcomes recently linked to gestational vitamin D deficiency, including preterm birth, cesarean delivery, and gestational diabetes. Although immediate costs for obstetric complications related to gestational vitamin D insufficiency may be modest, the short- and long-term costs for pediatric healthcare resulting from such gestational complications may be enormous and present an enduring burden on healthcare systems. With increasing evidence pointing to fetal origins of some later life disease, securing vitamin D sufficiency in pregnancy appears to be a simple, safe, and cost-effective measure that can be incorporated into routine preconception and prenatal care in the offices of primary care clinicians. Education on gestational nutritional requirements should be a fundamental part of medical education and residency training, instruction that has been sorely lacking to date. PMID:26770200

  1. Construction and engineering of a thermostable self-sufficient cytochrome P450

    SciTech Connect

    Mandai, Takao; Fujiwara, Shinsuke; Imaoka, Susumu

    2009-06-19

    CYP175A1 is a thermophilic cytochrome P450 and hydroxylates {beta}-carotene. We previously identified a native electron transport system for CYP175A1. In this report, we constructed two fusion proteins consisting of CYP175A1, ferredoxin (Fdx), and ferredoxin-NADP{sup +} reductase (FNR): H{sub 2}N-CYP175A1-Fdx-FNR-COOH (175FR) and H{sub 2}N-CYP175A1-FNR-Fdx-COOH (175RF). Both 175FR and 175RF were expressed in Escherichia coli and purified. The V{sub max} value for {beta}-carotene hydroxylation was 25 times higher with 175RF than 175FR and 9 times higher with 175RF than CYP175A1 (non-fused protein), although the k{sub m} values of these enzymes were similar. 175RF retained 50% residual activity even at 80 {sup o}C. Furthermore, several mutants of the CYP175A1 domain of 175RF were prepared and one mutant (Q67G/Y68I) catalyzed the hydroxylation of an unnatural substrate, testosterone. Thus, this is the first report of a thermostable self-sufficient cytochrome P450 and the engineering of a thermophilic cytochrome P450 for the oxidation of an unnatural substrate.

  2. Bearings-only tracking in a distributed sensor network using reduced sufficient statistics

    NASA Astrophysics Data System (ADS)

    Anderson, Kraig L.; Iltis, Ronald A.

    1994-07-01

    A distributed parameter estimation algorithm is presented for a general nonlinear measurement model with additive Gaussian noise. We show that the Bayes-closed estimation algorithm developed by Kulhavy, when extended to the multisensor case leads to a linear fusion rule, regardless of the form of a local a posteriori densities. Specifically, the Kulhavy algorithm generates a set of reduced sufficient statistics representing the local sensor densities, which are simply added and subtracted at the global processor to obtain optimum fusion. We discuss various approximations to the Bayes-closed algorithm which leads to a practical parameter estimator for the nonlinear measurement model, and apply such an approximate technique to the bearings-only tracking problem. The performance of the distributed tracker is compared to an alternative algorithm based on the extended Kalman filter (EKF) implemented in modified polar coordinates. It is shown that the Bayes-closed estimator does not diverge in the sense of an ordinary EKF, and hence the Bayes-closed technique can be employed in both a unidirectional and bidirectional transmission mode.

  3. Identifying Pathways for Improving Household Food Self-Sufficiency Outcomes in the Hills of Nepal.

    PubMed

    Karki, Tika B; Sah, Shrawan K; Thapa, Resam B; McDonald, Andrew J; Davis, Adam S

    2015-01-01

    Maintaining and improving household food self-sufficiency (FSS) in mountain regions is an ongoing challenge. There are many facets to the issue, including comparatively high levels of land fragmentation, challenging terrain and transportation bottlenecks, declining labor availability due to out-migration, and low technical knowledge, among others. Using a nonparametric multivariate approach, we quantified primary associations underlying current levels of FSS in the mid-hills of Nepal. A needs assessment survey was administered to 77 households in Lungaun (Baglung District), Pang (Parbat District), and Pathlekhet (Myagdi District), with a total of 80 variables covering five performance areas; resulting data were analyzed using Classification and Regression Trees. The most parsimonious statistical model for household FSS highlighted associations with agronomic management, including yields of maize and fingermillet within a relay cropping system and adoption of improved crop cultivars. Secondary analyses of the variables retained in the first model again focused primarily on crop and livestock management. It thus appears that continued emphasis on technical agricultural improvements is warranted, independent of factors such as land holding size that, in any case, are very difficult to change through development interventions. Initiatives to increase household FSS in the mid-hills of Nepal will benefit from placing a primary focus on methods of agricultural intensification to improve crop yields and effective technology transfer to increase adoption of these methods. PMID:26047508

  4. Increased H+ efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression

    PubMed Central

    Grillo-Hill, Bree K; Choi, Changhoon; Jimenez-Vidal, Maite; Barber, Diane L

    2015-01-01

    Intracellular pH (pHi) dynamics is increasingly recognized as an important regulator of a range of normal and pathological cell behaviors. Notably, increased pHi is now acknowledged as a conserved characteristic of cancers and in cell models is confirmed to increase proliferation and migration as well as limit apoptosis. However, the significance of increased pHi for cancer in vivo remains unresolved. Using Drosophila melanogaster, we show that increased pHi is sufficient to induce dysplasia in the absence of other transforming cues and potentiates growth and invasion with oncogenic Ras. Using a genetically encoded biosensor we also confirm increased pHi in situ. Moreover, in Drosophila models and clonal human mammary cells we show that limiting H+ efflux with oncogenic Raf or Ras induces acidosis and synthetic lethality. Further, we show lethality in invasive primary tumor cell lines with inhibiting H+ efflux. Synthetic lethality with reduced H+ efflux and activated oncogene expression could be exploited therapeutically to restrain cancer progression while limiting off-target effects. DOI: http://dx.doi.org/10.7554/eLife.03270.001 PMID:25793441

  5. Loss of Desmoglein Binding Is Not Sufficient for Keratinocyte Dissociation in Pemphigus.

    PubMed

    Vielmuth, Franziska; Waschke, Jens; Spindler, Volker

    2015-12-01

    Pemphigus vulgaris (PV) is a severe autoimmune disease in which autoantibodies against the desmosomal cell adhesion molecules desmoglein (Dsg) 1 and Dsg3 cause intraepidermal blister formation. Mechanistically, the fundamental question is still unresolved whether loss of cell cohesion is a result of (1) direct inhibition of Dsg interaction by autoantibodies or (2) intracellular signaling events, which are altered in response to antibody binding and finally cause desmosome destabilization. We used atomic force microscopy (AFM) to perform Dsg3 adhesion measurements on living keratinocytes to investigate the contributions of direct inhibition and signaling to loss of cell cohesion after autoantibody treatment. Dsg3 binding was rapidly blocked following antibody exposure under conditions where no depletion of surface Dsg3 was detectable, demonstrating direct inhibition of Dsg3 interaction. Inhibition of p38MAPK, a central signaling molecule in PV pathogenesis, abrogated loss of cell cohesion, but had a minor effect on loss of Dsg3 binding. Similarly, the cholesterol-depleting agent methyl-β-cyclodextrin (β-MCD) fully blocked cell dissociation, but did not restore Dsg3 interactions or prevent the activation of p38MAPK. These results demonstrate that inhibition of Dsg3 binding is not sufficient to cause loss of cell cohesion, but rather alters signaling events which, in lipid raft-dependent manner, induce cell dissociation. PMID:26288352

  6. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy.

    PubMed

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-01-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform. PMID:26987618

  7. Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise.

    PubMed

    Mera, Paula; Laue, Kathrin; Ferron, Mathieu; Confavreux, Cyril; Wei, Jianwen; Galán-Díez, Marta; Lacampagne, Alain; Mitchell, Sarah J; Mattison, Julie A; Chen, Yun; Bacchetta, Justine; Szulc, Pawel; Kitsis, Richard N; de Cabo, Rafael; Friedman, Richard A; Torsitano, Christopher; McGraw, Timothy E; Puchowicz, Michelle; Kurland, Irwin; Karsenty, Gerard

    2016-06-14

    Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin. We further show that exogenous osteocalcin is sufficient to enhance the exercise capacity of young mice and to restore to 15-month-old mice the exercise capacity of 3-month-old mice. This study uncovers a bone-to-muscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity. PMID:27304508

  8. Identifying Pathways for Improving Household Food Self-Sufficiency Outcomes in the Hills of Nepal

    PubMed Central

    Karki, Tika B.; Sah, Shrawan K.; Thapa, Resam B.; McDonald, Andrew J.; Davis, Adam S.

    2015-01-01

    Maintaining and improving household food self-sufficiency (FSS) in mountain regions is an ongoing challenge. There are many facets to the issue, including comparatively high levels of land fragmentation, challenging terrain and transportation bottlenecks, declining labor availability due to out-migration, and low technical knowledge, among others. Using a nonparametric multivariate approach, we quantified primary associations underlying current levels of FSS in the mid-hills of Nepal. A needs assessment survey was administered to 77 households in Lungaun (Baglung District), Pang (Parbat District), and Pathlekhet (Myagdi District), with a total of 80 variables covering five performance areas; resulting data were analyzed using Classification and Regression Trees. The most parsimonious statistical model for household FSS highlighted associations with agronomic management, including yields of maize and fingermillet within a relay cropping system and adoption of improved crop cultivars. Secondary analyses of the variables retained in the first model again focused primarily on crop and livestock management. It thus appears that continued emphasis on technical agricultural improvements is warranted, independent of factors such as land holding size that, in any case, are very difficult to change through development interventions. Initiatives to increase household FSS in the mid-hills of Nepal will benefit from placing a primary focus on methods of agricultural intensification to improve crop yields and effective technology transfer to increase adoption of these methods. PMID:26047508

  9. Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation

    PubMed Central

    Huang, Jiyue; Cheng, Zhihao; Wang, Cong; Hong, Yue; Su, Hang; Wang, Jun; Copenhaver, Gregory P.; Ma, Hong; Wang, Yingxiang

    2015-01-01

    Meiosis halves diploid genomes to haploid and is essential for sexual reproduction in eukaryotes. Meiotic recombination ensures physical association of homologs and their subsequent accurate segregation and results in the redistribution of genetic variations among progeny. Most organisms have two classes of cross-overs (COs): interference-sensitive (type I) and -insensitive (type II) COs. DNA synthesis is essential for meiotic recombination, but whether DNA synthesis has a role in differentiating meiotic CO pathways is unknown. Here, we show that Arabidopsis POL2A, the homolog of the yeast DNA polymerase-ε (a leading-strand DNA polymerase), is required for plant fertility and meiosis. Mutations in POL2A cause reduced fertility and meiotic defects, including abnormal chromosome association, improper chromosome segregation, and fragmentation. Observation of prophase I cell distribution suggests that pol2a mutants likely delay progression of meiotic recombination. In addition, the residual COs in pol2a have reduced CO interference, and the double mutant of pol2a with mus81, which affects type II COs, displayed more severe defects than either single mutant, indicating that POL2A functions in the type I pathway. We hypothesize that sufficient leading-strand DNA elongation promotes formation of some type I COs. Given that meiotic recombination and DNA synthesis are conserved in divergent eukaryotes, this study and our previous study suggest a novel role for DNA synthesis in the differentiation of meiotic recombination pathways. PMID:26392549

  10. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo.

    PubMed

    Baumann, Bernd; Wagner, Martin; Aleksic, Tamara; von Wichert, Götz; Weber, Christoph K; Adler, Guido; Wirth, Thomas

    2007-06-01

    Activation of the inhibitor of NF-kappaB kinase/NF-kappaB (IKK/NF-kappaB) system and expression of proinflammatory mediators are major events in acute pancreatitis. However, the in vivo consequences of IKK activation on the onset and progression of acute pancreatitis remain unclear. Therefore, we modulated IKK activity conditionally in pancreatic acinar cells. Transgenic mice expressing the reverse tetracycline-responsive transactivator (rtTA) gene under the control of the rat elastase promoter were generated to mediate acinar cell-specific expression of IKK2 alleles. Expression of dominant-negative IKK2 ameliorated cerulein-induced pancreatitis but did not affect activation of trypsin, an initial event in experimental pancreatitis. Notably, expression of constitutively active IKK2 was sufficient to induce acute pancreatitis. This acinar cell-specific phenotype included edema, cellular infiltrates, necrosis, and elevation of serum lipase levels as well as pancreatic fibrosis. IKK2 activation caused increased expression of known NF-kappaB target genes, including mediators of the inflammatory response such as TNF-alpha and ICAM-1. Indeed, inhibition of TNF-alpha activity identified this cytokine as an important effector of IKK2-induced pancreatitis. Our data identify the IKK/NF-kappaB pathway in acinar cells as being key to the development of experimental pancreatitis and the major factor in the inflammatory response typical of this disease. PMID:17525799

  11. Sufficient Condition for Finite-Time Singularity in a High-Symmetry Euler Flow

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, A.; Ng, C. S.

    1997-11-01

    The possibility of a finite-time singularity (FTS) with a smooth initial condition is considered in a high-symmetry Euler flow (the Kida flow). It has been shown recently [C. S. Ng and A. Bhattacharjee, Phys. Rev. E 54 1530, 1996] that there must be a FTS if the fourth order pressure derivative (p_xxxx) is always positive within a finite range X on the x-axis around the origin. This sufficient condition is now extended to the case when the range X is itself time-dependent. It is shown that a FTS must still exist even when X arrow 0 if the p_xxxx value at the origin is growing faster than X-2. It is tested statistically that p_xxxx at the origin is most probably positive for a Kida flow with random Fourier amplitudes and that it is generally growing as energy cascades to Fourier modes with higher wavenumbers k. The condition that p_xxxx grows faster than X-2 is found to be satisfied when the spectral index ν of the energy spectrum E(k) ∝ k^-ν of the random flow is less than 3.

  12. Pathological tendons maintain sufficient aligned fibrillar structure on ultrasound tissue characterization (UTC).

    PubMed

    Docking, S I; Cook, J

    2016-06-01

    Structural disorganization in the tendon is associated with tendinopathy, with little research investigating whether disorganization overwhelms the overall structural integrity of the tendon. This study investigated the mean cross-sectional area (CSA) of aligned fibrillar structure as detected by ultrasound tissue characterization (UTC) in the pathological and normal Achilles and patellar tendons. Ninety-one participants had their Achilles and/or patellar tendons scanned using UTC to capture a three-dimensional image of the tendon and allow a semi-quantification of the echopattern. The mean CSA of aligned fibrillar structure (echo type I + II) and disorganized structure (echo type III + IV) was calculated based on UTC algorithms. Each tendon was classified as either pathological or normal based solely on gray-scale ultrasound. The mean CSA of aligned fibrillar structure was significantly greater (P ≤ 0.001) in the pathological tendon compared with the normal tendon, despite the pathological tendon containing greater amounts of disorganized structure (P ≤ 0.001). A significant relationship was observed between the mean CSA of disorganized structure and anteroposterior diameter of the Achilles (R(2)  = 0.587) and patellar (R(2)  = 0.559) tendons. This study is the first to show that pathological tendons have sufficient levels of aligned fibrillar structure. Pathological tendons may compensate for areas of disorganization by increasing in tendon thickness. PMID:26059532

  13. Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis.

    PubMed

    Plaks, Vicki; Brenot, Audrey; Lawson, Devon A; Linnemann, Jelena R; Van Kappel, Eline C; Wong, Karren C; de Sauvage, Frederic; Klein, Ophir D; Werb, Zena

    2013-01-31

    Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5(+)) mammary epithelial cells (MECs). We found that Lgr5(+) cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5(+) cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis. PMID:23352663

  14. Necessary and sufficient conditions for big bangs, bounces, crunches, rips, sudden singularities and extremality events

    NASA Astrophysics Data System (ADS)

    Cattoën, Céline; Visser, Matt

    2005-12-01

    Until recently, the physically relevant singularities occurring in FRW cosmologies had traditionally been thought to be limited to the 'big bang', and possibly a 'big crunch'. However, over the last few years, the zoo of cosmological singularities considered in the literature has become considerably more extensive, with 'big rips' and 'sudden singularities' added to the mix, as well as renewed interest in nonsingular cosmological events such as 'bounces' and 'turnarounds'. In this paper we present an extensive catalogue of such cosmological milestones, both at the kinematical and dynamical level. First, using generalized power series, purely kinematical definitions of these cosmological events are provided in terms of the behaviour of the scale factor a(t). The notion of a 'scale-factor singularity' is defined, and its relation to curvature singularities (polynomial and differential) is explored. Second, dynamical information is extracted by using the Friedmann equations (without assuming even the existence of any equation of state) to place constraints on whether or not the classical energy conditions are satisfied at the cosmological milestones. We use these considerations to derive necessary and sufficient conditions for the existence of cosmological milestones such as bangs, bounces, crunches, rips, sudden singularities and extremality events. Since the classification is extremely general and, modulo certain technical assumptions, is complete, the corresponding results are to a high degree model independent: in particular, we provide a characterization of the class of bangs, crunches and sudden singularities for which the dominant energy condition is satisfied.

  15. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man

    PubMed Central

    Gotter, Anthony L.; Forman, Mark S.; Harrell, Charles M.; Stevens, Joanne; Svetnik, Vladimir; Yee, Ka Lai; Li, Xiaodong; Roecker, Anthony J.; Fox, Steven V.; Tannenbaum, Pamela L.; Garson, Susan L.; Lepeleire, Inge De; Calder, Nicole; Rosen, Laura; Struyk, Arie; Coleman, Paul J.; Herring, W. Joseph; Renger, John J.; Winrow, Christopher J.

    2016-01-01

    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. PMID:27256922

  16. Retinoic Acid Is Sufficient for the In Vitro Induction of Mouse Spermatocytes.

    PubMed

    Wang, Si; Wang, Xiuxia; Ma, Longfei; Lin, Xiwen; Zhang, Daoqin; Li, Zhen; Wu, Yujian; Zheng, Chunwei; Feng, Xue; Liao, Shangying; Feng, Yanmin; Chen, Jian; Hu, Xiangjing; Wang, Min; Han, Chunsheng

    2016-07-12

    Meiosis is the key step in gametogenesis. However, the mechanism of mammalian meiosis remains poorly understood due to the lack of an in vitro model. Here, we report that retinoic acid (RA) is sufficient for inducing leptotene/zygotene spermatocytes from cultured mouse spermatogonial stem cells. Multiple genes regulated by RA were identified by RNA sequencing. RA in combination with pup Sertoli cell co-culture resulted in a higher induction efficiency of 28%. Comparisons in the transcriptomic profiles of the induced spermatogenic cells and the isolated ones revealed the progressive induction of the germ cells. Using this model, we showed that Stra8, Agpat3, Fam57a, Wdr91, and Sox30 contributed to the proliferation and meiosis initiation differentially. In conclusion, we have efficiently generated spermatocytes using an RA/pup Sertoli cell-based in vitro model and provided proof-of-concept evidence for its application in identifying genes involved in mammalian meiosis. PMID:27346680

  17. Necessary and Sufficient Standards Closure Process pilot: F- and H-Area groundwater remediation

    SciTech Connect

    Bullington, M.

    1995-09-25

    The DOE Standards Committee`s Necessary and Sufficient (N and S) Standards Closure Process was piloted at SRS on the F- and H- Area Seepage Basins Groundwater Remediation Project. For this existing Environmental Restoration project, the set of N and S standards for design and safety documentation were identified, independently confirmed and approved. Implementation of these standards on the project can lead to a $2.8 Million cost savings on the design, construction/installation, and safety documentation scope of $18 Million. These savings were primarily from site design of power distribution and piping for the water treatment units. Also contributing to the savings were a more appropriate level of safety documentation and the alternate ``commercial`` bids made by vendors in response to a request for proposals for water treatment units. The use of the N and S Process on an ER activity, details on the cost savings, lessons learned and recommendations for broader implementation of the N and S Process are described herein.

  18. Specificity and Sufficiency of EphB1 in Driving the Ipsilateral Retinal Projection

    PubMed Central

    Petros, Timothy J.; Shrestha, Brikha R.; Mason, Carol

    2009-01-01

    At the optic chiasm, retinal ganglion cell (RGC) axons make the decision to either avoid or traverse the midline, a maneuver that establishes the binocular pathways. In mice, the ipsilateral retinal projection arises from RGCs in the peripheral ventrotemporal (VT) crescent of the retina. These RGCs express the guidance receptor EphB1, which interacts with ephrin-B2 on radial glia cells at the optic chiasm to repulse VT axons away from the midline and into the ipsilateral optic tract. However, since VT RGCs express more than one EphB receptor, the sufficiency and specificity of the EphB1 receptor in directing the ipsilateral projection is unclear. In this study, we utilize in utero retinal electroporation to demonstrate that ectopic EphB1 expression can redirect RGCs with a normally crossed projection to an ipsilateral trajectory. Moreover, EphB1 is specifically required for rerouting RGC projections ipsilaterally, as introduction of the highly similar EphB2 receptor is much less efficient in redirecting RGC fibers, even when expressed at higher surface levels. Introduction of EphB1-EphB2 chimeric receptors into RGCs reveals that both extracellular and juxtamembrane domains of EphB1 are required to efficiently convert RGC projections ipsilaterally. Taken together, these data describe for the first time functional differences between two highly similar Eph receptors at a decision point in vivo, with EphB1 displaying unique properties that efficiently drives the uncrossed retinal projection. PMID:19295152

  19. Does the current fungicide risk assessment provide sufficient protection for key drivers in aquatic ecosystem functioning?

    PubMed

    Zubrod, Jochen P; Englert, Dominic; Feckler, Alexander; Koksharova, Natalia; Konschak, Marco; Bundschuh, Rebecca; Schnetzer, Nadja; Englert, Katja; Schulz, Ralf; Bundschuh, Mirco

    2015-01-20

    The level of protection provided by the present environmental risk assessment (ERA) of fungicides in the European Union for fungi is unknown. Therefore, we assessed the structural and functional implications of five fungicides with different modes of action (azoxystrobin, carbendazim, cyprodinil, quinoxyfen, and tebuconazole) individually and in mixture on communities of aquatic hyphomycetes. This is a polyphyletic group of fungi containing key drivers in the breakdown of leaf litter, governing both microbial leaf decomposition and the palatability of leaves for leaf-shredding macroinvertebrates. All fungicides impaired leaf palatability to the leaf-shredder Gammarus fossarum and caused structural changes in fungal communities. In addition, all compounds except for quinoxyfen altered microbial leaf decomposition. Our results suggest that the European Union’s first-tier ERA provides sufficient protection for the tested fungicides, with the exception of tebuconazole and the mixture, while higher-tier ERA does not provide an adequate level of protection for fungicides in general. Therefore, our results show the need to incorporate aquatic fungi as well as their functions into ERA testing schemes to safeguard the integrity of aquatic ecosystems. PMID:25517729

  20. c-Src function is necessary and sufficient for triggering microglial cell activation.

    PubMed

    Socodato, Renato; Portugal, Camila C; Domith, Ivan; Oliveira, Nádia A; Coreixas, Vivian S M; Loiola, Erick C; Martins, Tânia; Santiago, Ana Raquel; Paes-de-Carvalho, Roberto; Ambrósio, António F; Relvas, João B

    2015-03-01

    Microglial cells are the resident macrophages of the central nervous system. Their function is essential for neuronal tissue homeostasis. After inflammatory stimuli, microglial cells become activated changing from a resting and highly ramified cell shape to an amoeboid-like morphology. These morphological changes are associated with the release of proinflammatory cytokines and glutamate, as well as with high phagocytic activity. The acquisition of such phenotype has been associated with activation of cytoplasmic tyrosine kinases, including those of the Src family (SFKs). In this study, using both in vivo and in vitro inflammation models coupled to FRET-based time-lapse microscopy, lentiviruses-mediated shRNA delivery and genetic gain-of-function experiments, we demonstrate that among SFKs c-Src function is necessary and sufficient for triggering microglia proinflammatory signature, glutamate release, microglia-induced neuronal loss, and phagocytosis. c-Src inhibition in retinal neuroinflammation experimental paradigms consisting of intravitreal injection of LPS or ischemia-reperfusion injury significantly reduced microglia activation changing their morphology to a more resting phenotype and prevented neuronal apoptosis. Our data demonstrate an essential role for c-Src in microglial cell activation. PMID:25421817

  1. Self-sufficient redox biotransformation of lignin-related benzoic acids with Aspergillus flavus.

    PubMed

    Palazzolo, Martín A; Mascotti, María L; Lewkowicz, Elizabeth S; Kurina-Sanz, Marcela

    2015-12-01

    Aromatic carboxylic acids are readily obtained from lignin in biomass processing facilities. However, efficient technologies for lignin valorization are missing. In this work, a microbial screening was conducted to find versatile biocatalysts capable of transforming several benzoic acids structurally related to lignin, employing vanillic acid as model substrate. The wild-type Aspergillus flavus growing cells exhibited exquisite selectivity towards the oxidative decarboxylation product, 2-methoxybenzene-1,4-diol. Interestingly, when assaying a set of structurally related substrates, the biocatalyst displayed the oxidative removal of the carboxyl moiety or its reduction to the primary alcohol whether electron withdrawing or donating groups were present in the aromatic ring, respectively. Additionally, A. flavus proved to be highly tolerant to vanillic acid increasing concentrations (up to 8 g/L), demonstrating its potential application in chemical synthesis. A. flavus growing cells were found to be efficient biotechnological tools to perform self-sufficient, structure-dependent redox reactions. To the best of our knowledge, this is the first report of a biocatalyst exhibiting opposite redox transformations of the carboxylic acid moiety in benzoic acid derivatives, namely oxidative decarboxylation and carboxyl reduction, in a structure-dependent fashion. PMID:26445878

  2. Safety Sufficiency for NextGen: Assessment of Selected Existing Safety Methods, Tools, Processes, and Regulations

    NASA Technical Reports Server (NTRS)

    Xu, Xidong; Ulrey, Mike L.; Brown, John A.; Mast, James; Lapis, Mary B.

    2013-01-01

    NextGen is a complex socio-technical system and, in many ways, it is expected to be more complex than the current system. It is vital to assess the safety impact of the NextGen elements (technologies, systems, and procedures) in a rigorous and systematic way and to ensure that they do not compromise safety. In this study, the NextGen elements in the form of Operational Improvements (OIs), Enablers, Research Activities, Development Activities, and Policy Issues were identified. The overall hazard situation in NextGen was outlined; a high-level hazard analysis was conducted with respect to multiple elements in a representative NextGen OI known as OI-0349 (Automation Support for Separation Management); and the hazards resulting from the highly dynamic complexity involved in an OI-0349 scenario were illustrated. A selected but representative set of the existing safety methods, tools, processes, and regulations was then reviewed and analyzed regarding whether they are sufficient to assess safety in the elements of that OI and ensure that safety will not be compromised and whether they might incur intolerably high costs.

  3. The case for neuropsychoanalysis: Why a dialogue with neuroscience is necessary but not sufficient for psychoanalysis.

    PubMed

    Yovell, Yoram; Solms, Mark; Fotopoulou, Aikaterini

    2015-12-01

    Recent advances in the cognitive, affective and social neurosciences have enabled these fields to study aspects of the mind that are central to psychoanalysis. These developments raise a number of possibilities for psychoanalysis. Can it engage the neurosciences in a productive and mutually enriching dialogue without compromising its own integrity and unique perspective? While many analysts welcome interdisciplinary exchanges with the neurosciences, termed neuropsychoanalysis, some have voiced concerns about their potentially deleterious effects on psychoanalytic theory and practice. In this paper we outline the development and aims of neuropsychoanalysis, and consider its reception in psychoanalysis and in the neurosciences. We then discuss some of the concerns raised within psychoanalysis, with particular emphasis on the epistemological foundations of neuropsychoanalysis. While this paper does not attempt to fully address the clinical applications of neuropsychoanalysis, we offer and discuss a brief case illustration in order to demonstrate that neuroscientific research findings can be used to enrich our models of the mind in ways that, in turn, may influence how analysts work with their patients. We will conclude that neuropsychoanalysis is grounded in the history of psychoanalysis, that it is part of the psychoanalytic worldview, and that it is necessary, albeit not sufficient, for the future viability of psychoanalysis. PMID:26227821

  4. Improving the Rate of Sufficient Sweat Collected in Infants Referred for Sweat Testing in Michigan

    PubMed Central

    Kleyn, Mary; Langbo, Carrie; Gregoire-Bottex, Myrtha; Schuen, John; Shanmugasundaram, Krithika; Nasr, Samya Z

    2014-01-01

    Objective. Sweat collected for testing should have quantity not sufficient (QNS) rate of ≤10% in babies ≤3 months of age. Michigan (MI) cystic fibrosis (CF) centers’ QNS rates were 12% to 25% in 2009. This project was initiated to reduce sweat QNS rates in MI. Methods/Steps. (a) Each center’s sweat testing procedures were reviewed by a consultant. (b) Each center received a report with recommendations to improve QNS rates. (c) Technicians visited other participating centers to observe their procedures. Results. A total of 778 infants were identified as positive via CF newborn screening over a 2-year period. The mean age at time of sweat test was 23.2 days (SD ± 13.0 days). The overall QNS percent decreased from 14.4% to 9.5% (P = .04) during the study. Conclusion. This project and teamwork approach led to a decrease of sweat test QNS rates, opportunities to solve a common problem, and improved quality of care. PMID:27335913

  5. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.

    PubMed

    Gotter, Anthony L; Forman, Mark S; Harrell, Charles M; Stevens, Joanne; Svetnik, Vladimir; Yee, Ka Lai; Li, Xiaodong; Roecker, Anthony J; Fox, Steven V; Tannenbaum, Pamela L; Garson, Susan L; Lepeleire, Inge De; Calder, Nicole; Rosen, Laura; Struyk, Arie; Coleman, Paul J; Herring, W Joseph; Renger, John J; Winrow, Christopher J

    2016-01-01

    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. PMID:27256922

  6. Restriction of dopamine signaling to the dorsolateral striatum is sufficient for many cognitive behaviors

    PubMed Central

    Darvas, Martin; Palmiter, Richard D.

    2009-01-01

    The striatum is a vital substrate for performance, procedural memory, and learning. The ventral and medial striatum are thought to be critical for acquisition of tasks while the dorsolateral striatum is important for performance and habitual enactment of skills. Evidence based on cortical, thalamic, and amygdaloid inputs to the striatum suggests a medio-lateral zonation imposed on the classical dorso-ventral distinction. We therefore investigated the functional significance of dopaminergic signaling in cognitive tasks by studying dopamine-deficient (DD) mice and mice with dopamine signaling restored to only the dorsolateral (DL) striatum by viral rescue (vrDD-DL mice). Whereas DD mice failed in all of the tasks examined here, vrDD-DL mice displayed intact discriminatory learning, object recognition, visuospatial learning and spatial memory. Acquisition of operant behavior for food rewards was delayed in vrDD-DL mice and their motivation in a progressive ratio experiments was reduced. Therefore, dopaminergic signaling in the dorsolateral striatum is sufficient for mice to learn several different cognitive tasks although the rate of learning some of them was reduced. These results indicate that dopaminergic signaling in the ventromedial striatum is not absolutely necessary for mastery of these behaviors, but may facilitate them. PMID:19667174

  7. Morphospecies and taxonomic sufficiency of benthic megafauna in scientific bottom trawl surveys

    NASA Astrophysics Data System (ADS)

    Brind'Amour, Anik; Laffargue, Pascal; Morin, Jocelyne; Vaz, Sandrine; Foveau, Aurélie; Le Bris, Hervé

    2014-01-01

    Scientific fisheries surveys routinely identify a large diversity of commercial and non-commercial benthic megainvertebrates that could provide useful information for Marine Strategy Framework Directive (MSFD) descriptors. Species is obviously the basic taxonomic level to which most ecological studies and theories refer. Identification at this level of organization is indeed always preferred over any other taxonomic level. Nevertheless, aggregation of species to higher taxonomic levels may be unavoidable sometimes, since errors of identification are known or suspected to occur in many surveys. Using analyses of taxonomic sufficiency (identification of organisms at various taxonomic resolutions) and groups of morphospecies (taxa identified easily by non-experts on the basis of evident morphological traits), this study aims to quantify the loss of ecological information incurred by partial identification of benthic megafauna in bottom trawl surveys in order to put such data to good use. The analyses were conducted on five scientific surveys representing a large range of geographical areas (from 150 km2 to 150 000 km2) and environmental conditions. Results show that genus, family and, particularly, morphospecies are good surrogates for species identification in community analyses. We suggest that bottom trawl surveys can provide reliable megafauna data that may usefully complete those obtained by grab surveys. The use of morphospecies could lead to new strategies, combining different datasets to provide indicators for MSFD descriptors (e.g. D6).

  8. MIMO OFDM radar IRCI free range reconstruction with sufficient cyclic prefix

    NASA Astrophysics Data System (ADS)

    Xia, Xiang-gen; Zhang, Tianxian; Kong, Lingjiang

    2015-07-01

    In this paper, we propose MIMO OFDM radar with sufficient cyclic prefix (CP), where all OFDM pulses transmitted from different transmitters share the same frequency band and are orthogonal to each other for every subcarrier in the discrete frequency domain. The orthogonality is not affected by time delays from transmitters. Thus, our proposed MIMO OFDM radar has the same range resolution as single transmitter radar and achieves full spatial diversity. Orthogonal designs are used to achieve this orthogonality across the transmitters, with which it is only needed to design OFDM pulses for the first transmitter. We also propose a joint pulse compression and pulse coherent integration for range reconstruction. In order to achieve the optimal SNR for the range reconstruction, we apply the paraunitary filterbank theory to design the OFDM pulses. We then propose a modified iterative clipping and filtering (MICF) algorithm for the designs of OFDM pulses jointly, when other important factors, such as peak-to-average power ratio (PAPR) in time domain, are also considered. With our proposed MIMO OFDM radar, there is no interference for the range reconstruction not only across the transmitters but also across the range cells in a swath called inter-range-cell interference (IRCI) free that is similar to our previously proposed CP based OFDM radar for single transmitter. Simulations are presented to illustrate our proposed theory and show that the CP based MIMO OFDM radar outperforms the existing frequency-band shared MIMO radar with polyphase codes and also frequency division MIMO radar.

  9. Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists

    PubMed Central

    Güntan, İlke; Moro, Alessandro; Steinberg, Eleonora A.; Ye, Zhiwen; Zecharia, Anna Y.; Yu, Xiao; Vyssotski, Alexei L.; Brickley, Stephen G.; Yustos, Raquel; Pillidge, Zoe E.; Harding, Edward C.; Wisden, William; Franks, Nicholas P.

    2015-01-01

    Do sedatives engage natural sleep pathways? It is usually assumed that anesthetic-induced sedation and loss-of-righting-reflex (LORR) arise by influencing the same circuitry to lesser or greater extents. For the α2 adrenergic receptor agonist dexmedetomidine, we find that sedation and LORR are in fact distinct states, requiring different brain areas, the preoptic hypothalamic area and locus coeruleus (LC) respectively. Selective knockdown of α2A adrenergic receptors from the LC abolished dexmedetomidine-induced LORR, but not sedation. Instead, we found that dexmedetomidine-induced sedation resembles the deep recovery sleep that follows sleep deprivation. We used TetTag-pharmacogenetics in mice to functionally mark neurons activated in the preoptic hypothalamus during dexmedetomidine-induced sedation or recovery sleep. The neuronal ensembles could then be selectively reactivated. In both cases NREM sleep, with the accompanying drop in body temperature, was recapitulated. Thus α2 adrenergic receptor-induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states. PMID:25706476

  10. Fragile X premutation RNA is sufficient to cause primary ovarian insufficiency in mice

    PubMed Central

    Lu, Cuiling; Lin, Li; Tan, Huiping; Wu, Hao; Sherman, Stephanie L.; Gao, Fei; Jin, Peng; Chen, Dahua

    2012-01-01

    Spontaneous 46,XX primary ovarian insufficiency (POI), also known as ‘premature menopause’ or ‘premature ovarian failure’, refers to ovarian dysfunction that results in a range of abnormalities, from infertility to early menopause as the end stage. The most common known genetic cause of POI is the expansion of a CGG repeat to 55–199 copies (premutation) in the 5′ untranslated region in the X-linked fragile X mental retardation 1 (FMR1) gene. POI associated with the FMR1 premutation is referred to as fragile X-associated POI (FXPOI). Here, we characterize a mouse model carrying the human FMR1 premutation allele and show that FMR1 premutation RNA can cause a reduction in the number of growing follicles in ovaries and is sufficient to impair female fertility. Alterations in selective serum hormone levels, including FSH, LH and 17β-estradiol, are seen in this mouse model, which mimics findings in humans. In addition, we also find that LH-induced ovulation-related gene expression is specifically altered. Finally, we show that the FMR1 premutation allele can lead to reduced phosphorylation of Akt and mTOR proteins. These results together suggest that FMR1 premutation RNA could cause the POI associated with FMR1 premutation carriers, and the Akt/mTOR pathway may serve as a therapeutic target for FXPOI. PMID:22914733

  11. Mislocated FUS is sufficient for gain-of-toxic-function amyotrophic lateral sclerosis phenotypes in mice.

    PubMed

    Shiihashi, Gen; Ito, Daisuke; Yagi, Takuya; Nihei, Yoshihiro; Ebine, Taeko; Suzuki, Norihiro

    2016-09-01

    Mutations in RNA-binding proteins, including fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43, encoded by TARDBP), are associated with sporadic and familial amyotrophic lateral sclerosis. A major question is whether neuronal loss is caused by toxic gain-of-function cytoplasmic aggregates or loss of nuclear RNA-binding protein function. We generated a transgenic mouse overexpressing exogenous FUS without a nuclear localization signal (ΔNLS-FUS), which developed progressive spastic motor deficits and neuronal loss in the motor cortex. The ΔNLS-FUS protein was restricted to the cytoplasm and formed ubiquitin/p62-positive aggregates. Endogenous FUS expression, nuclear localization, and splicing activity were not altered, indicating that mislocated FUS is sufficient for proteinopathy. Crossing ΔNLS-FUS with wild-type human TDP-43 transgenic mice exacerbated pathological and behavioural phenotypes, suggesting that both proteins are involved in a common cascade. RNA-sequence analysis revealed specific transcriptome alterations, including genes regulating dynein-associated molecules and endoplasmic reticulum stress. ΔNLS-FUS mice are promising tools for understanding amyotrophic lateral sclerosis pathogenesis and testing new therapeutic approaches. PMID:27368346

  12. Non-Ligand-Induced Dimerization is Sufficient to Initiate the Signalling and Endocytosis of EGF Receptor

    PubMed Central

    Kourouniotis, George; Wang, Yi; Pennock, Steven; Chen, Xinmei; Wang, Zhixiang

    2016-01-01

    The binding of epidermal growth factor (EGF) to EGF receptor (EGFR) stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activation of intrinsic tyrosine kinase and autophosphorylation. However, in spite of intensified efforts, the results regarding the roles of these events in EGFR signalling and internalization is still very controversial. In this study, we constructed a chimeric EGFR by replacing its extracellular domain with leucine zipper (LZ) and tagged a green fluorescent protein (GFP) at its C-terminus. We showed that the chimeric LZ-EGFR-GFP was constitutively dimerized. The LZ-EGFR-GFP dimer autophosphorylated each of its five well-defined C-terminal tyrosine residues as the ligand-induced EGFR dimer does. Phosphorylated LZ-EGFR-GFP was localized to both the plasma membrane and endosomes, suggesting it is capable of endocytosis. We also showed that LZ-EGFR-GFP activated major signalling proteins including Src homology collagen-like (Shc), extracellular signal-regulated kinase (ERK) and Akt. Moreover, LZ-EGFR-GFP was able to stimulate cell proliferation. These results indicate that non-ligand induced dimerization is sufficient to activate EGFR and initiate cell signalling and EGFR endocytosis. We conclude that receptor dimerization is a critical event in EGF-induced cell signalling and EGFR endocytosis. PMID:27463710

  13. A Simple Threshold Rule Is Sufficient to Explain Sophisticated Collective Decision-Making

    PubMed Central

    Robinson, Elva J. H.; Franks, Nigel R.; Ellis, Samuel; Okuda, Saki; Marshall, James A. R.

    2011-01-01

    Decision-making animals can use slow-but-accurate strategies, such as making multiple comparisons, or opt for simpler, faster strategies to find a ‘good enough’ option. Social animals make collective decisions about many group behaviours including foraging and migration. The key to the collective choice lies with individual behaviour. We present a case study of a collective decision-making process (house-hunting ants, Temnothorax albipennis), in which a previously proposed decision strategy involved both quality-dependent hesitancy and direct comparisons of nests by scouts. An alternative possible decision strategy is that scouting ants use a very simple quality-dependent threshold rule to decide whether to recruit nest-mates to a new site or search for alternatives. We use analytical and simulation modelling to demonstrate that this simple rule is sufficient to explain empirical patterns from three studies of collective decision-making in ants, and can account parsimoniously for apparent comparison by individuals and apparent hesitancy (recruitment latency) effects, when available nests differ strongly in quality. This highlights the need to carefully design experiments to detect individual comparison. We present empirical data strongly suggesting that best-of-n comparison is not used by individual ants, although individual sequential comparisons are not ruled out. However, by using a simple threshold rule, decision-making groups are able to effectively compare options, without relying on any form of direct comparison of alternatives by individuals. This parsimonious mechanism could promote collective rationality in group decision-making. PMID:21629645

  14. Strategies for regeneration of nicotinamide coenzymes emphasizing self-sufficient closed-loop recycling systems.

    PubMed

    Hummel, Werner; Gröger, Harald

    2014-12-10

    Biocatalytic reduction reactions depending on nicotinamide coenzymes require an additional reaction to regenerate the consumed cofactor. For preparative application the preferred method is the simultaneous coupling of an in situ regeneration reaction. There are different strategically advantageous routes to achieve this goal. The standard method uses a second enzyme and a second co-substrate, for example formate and formate dehydrogenase or glucose and glucose dehydrogenase. Alternatively, a second substrate is employed which is converted by the same enzyme used for the primary reaction. For example, alcohol dehydrogenase catalyzed reactions are often coupled with excess 2-propanol which is oxidized to acetone during the regeneration of NAD(P)H. A third method utilizes a reaction-internal sequence by the direct coupling of an oxidizing and a reducing enzyme reaction. Neither an additional substrate nor a further regenerating enzyme are required for the recycling reaction. This kind of "closed-loop" or "self-sufficient" redox process for cofactor regeneration has been used rarely so far. Its most intriguing advantage is that even redox reactions with unstable precursors can be realized provided that this compound is produced in situ by an opposite redox reaction. This elegant method is applicable in special cases only but increasing numbers of examples have been published during the last years. PMID:25102236

  15. [Hospitalizations performed in patients enrolled in assistance programs for not-self-sufficient individuals].

    PubMed

    Biselli, Giuliano; Dell'amico, Maria Chiara; Vivani, Paola

    2013-04-01

    The objective of this study was to verify if the enrollement of patients aged over sixty-five (over 65), in the territorial assistance programs of a mountain area, has reduced and optimized the volume of hospitalizations. During 2009, 422 patients over 65 who were non self-sufficient, with iso-severity level (IL) from 5 to 0 (Regione Toscana, Decreto n. 1354 del 25 Marzo 2010), were enrolled in home care programs. These data were processed despite the following analytical limitations: 1) inability to provide all tax codes (entered manually in database), the corrisponding personal data; 2) necessity to make cross-comparisons among numerous archives of data from different sources; and 3) lack to identify the outcome indicators for each patient. The assisted patients are characterized by a very high hospitalization rate. Among the main diseases, the following needed at least one hospitalization: dementia, stroke, cancer, osteoarticular diseases, cerebrovascular disease and Parkinson's disease. Therefore it is necessary to re-evaluate the current procedures adopted for the management of chronic diseases in the elderly in their own homes. PMID:23748636

  16. Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective.

    PubMed

    Fisher, W; Wang, Jian; George, Nysia I; Gearhart, Jeffery M; McLanahan, Eva D

    2016-01-01

    The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150-180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately

  17. Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

    PubMed Central

    Fisher, W.; Wang, Jian; George, Nysia I.; Gearhart, Jeffery M.; McLanahan, Eva D.

    2016-01-01

    The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children’s Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150–180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately

  18. The transcension hypothesis: Sufficiently advanced civilizations invariably leave our universe, and implications for METI and SETI

    NASA Astrophysics Data System (ADS)

    Smart, John M.

    2012-09-01

    The emerging science of evolutionary developmental ("evo devo") biology can aid us in thinking about our universe as both an evolutionary system, where most processes are unpredictable and creative, and a developmental system, where a special few processes are predictable and constrained to produce far-future-specific emergent order, just as we see in the common developmental processes in two stars of an identical population type, or in two genetically identical twins in biology. The transcension hypothesis proposes that a universal process of evolutionary development guides all sufficiently advanced civilizations into what may be called "inner space," a computationally optimal domain of increasingly dense, productive, miniaturized, and efficient scales of space, time, energy, and matter, and eventually, to a black-hole-like destination. Transcension as a developmental destiny might also contribute to the solution to the Fermi paradox, the question of why we have not seen evidence of or received beacons from intelligent civilizations. A few potential evolutionary, developmental, and information theoretic reasons, mechanisms, and models for constrained transcension of advanced intelligence are briefly considered. In particular, we introduce arguments that black holes may be a developmental destiny and standard attractor for all higher intelligence, as they appear to some to be ideal computing, learning, forward time travel, energy harvesting, civilization merger, natural selection, and universe replication devices. In the transcension hypothesis, simpler civilizations that succeed in resisting transcension by staying in outer (normal) space would be developmental failures, which are statistically very rare late in the life cycle of any biological developing system. If transcension is a developmental process, we may expect brief broadcasts or subtle forms of galactic engineering to occur in small portions of a few galaxies, the handiwork of young and immature

  19. Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

    PubMed

    Dewar, Michaela; Alber, Jessica; Cowan, Nelson; Della Sala, Sergio

    2014-01-01

    People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition. PMID:25333957

  20. Smoking Lung Cancer Patients and Tobacco Cessation - Is the Current Treatment in Germany Sufficient?

    PubMed

    Vitzthum, K; Thielke, L; Deter, A; Riemer, T; Eggeling, S; Pankow, W; Mache, S

    2015-11-01

    Lung cancer is the most preventable neoplastic disease for men and women. The incidence rate per year is 14.000 in Germany. Smoking is the main risk factor for the onset of lung cancer and for a share of 90% of cases, lung cancer is associated with smoking. Recent studies have shown that the time slot of diagnosing lung cancer is a teachable moment for tobacco cessation interventions. The therapy that was rated most effective was a combination of cognitive behavioral therapy and pharmacotherapy (e. g. NRT, Bupropion, Varenicline). We examined the smoking status of all patients undergoing lung cancer surgery in 2011, 2012 and 2013 in this study. A retrospective semi structured interview via telephone was conducted regarding smoking habits and current quality of life. 131 patients (36.6% female, average age of 68.7 years) of an urban German hospital were included.Results showed a relapse rate of 22.3%, while 86.2% used to be highly addicted smokers; A multivariate analysis of covariance (MANCOVA) indicated a significant overall impact of smoking status on quality of life with a medium effect size, controlled for age, gender, living conditions, tumor stage, duration of smoking abstinence, type of cancer therapy, type of resection method, and the time period between the date of surgery and of the survey. Two thirds of all smokers did not see an association between their habit and their disease.So far motivation to quit and long term abstinence rates are not sufficiently established even among seriously sick patients in Germany; further initiatives should focus on new and more intense interventions and educational strategies. PMID:26398407

  1. Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish

    PubMed Central

    Howarth, Deanna L.; Lindtner, Claudia; Vacaru, Ana M.; Sachidanandam, Ravi; Tsedensodnom, Orkhontuya; Vasilkova, Taisa; Buettner, Christoph; Sadler, Kirsten C.

    2014-01-01

    Fatty liver disease (FLD) is characterized by lipid accumulation in hepatocytes and is accompanied by secretory pathway dysfunction, resulting in induction of the unfolded protein response (UPR). Activating transcription factor 6 (ATF6), one of three main UPR sensors, functions to both promote FLD during acute stress and reduce FLD during chronic stress. There is little mechanistic understanding of how ATF6, or any other UPR factor, regulates hepatic lipid metabolism to cause disease. We addressed this using zebrafish genetics and biochemical analyses and demonstrate that Atf6 is necessary and sufficient for FLD. atf6 transcription is significantly upregulated in the liver of zebrafish with alcoholic FLD and morpholino-mediated atf6 depletion significantly reduced steatosis incidence caused by alcohol. Moreover, overexpression of active, nuclear Atf6 (nAtf6) in hepatocytes caused FLD in the absence of stress. mRNA-Seq and qPCR analyses of livers from five day old nAtf6 transgenic larvae revealed upregulation of genes promoting glyceroneogenesis and fatty acid elongation, including fatty acid synthase (fasn), and nAtf6 overexpression in both zebrafish larvae and human hepatoma cells increased the incorporation of 14C-acetate into lipids. Srebp transcription factors are key regulators of lipogenic enzymes, but reducing Srebp activation by scap morpholino injection neither prevented FLD in nAtf6 transgenics nor synergized with atf6 knockdown to reduce alcohol-induced FLD. In contrast, fasn morpholino injection reduced FLD in nAtf6 transgenic larvae and synergistically interacted with atf6 to reduce alcoholic FLD. Thus, our data demonstrate that Atf6 is required for alcoholic FLD and epistatically interacts with fasn to cause this disease, suggesting triglyceride biogenesis as the mechanism of UPR induced FLD. PMID:24874946

  2. Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes)

    PubMed Central

    Zhou, Linyan; Charkraborty, Tapas; Zhou, Qian; Mohapatra, Sipra; Nagahama, Yoshitaka; Zhang, Yueguang

    2016-01-01

    In contrast to our understanding of testicular differentiation, ovarian differentiation is less well understood in vertebrates. In mammals, R-spondin1 (Rspo1), an activator of Wnt/β-catenin signaling pathway, is located upstream of the female sex determination pathway. However, the functions of Rspo1 in ovarian differentiation remain unclear in non-mammalian species. In order to elucidate the detailed functions of Rspo/Wnt signaling pathway in fish sex determination/differentiation, the ectopic expression of the Rspo1 gene was performed in XY medaka (Oryzias latipes). The results obtained demonstrated that the gain of Rspo1 function induced femininity in XY fish. The overexpression of Rspo1 enhanced Wnt4b and β-catenin transcription, and completely suppressed the expression of male-biased genes (Dmy, Gsdf, Sox9a2 and Dmrt1) as well as testicular differentiation. Gonadal reprograming of Rspo1-over-expressed-XY (Rspo1-OV-XY) fish, induced the production of female-biased genes (Cyp19a1a and Foxl2), estradiol-17β production and further female type secondary sexuality. Moreover, Rspo1-OV-XY females were fertile and produced successive generations. Promoter analyses showed that Rspo1 transcription was directly regulated by DM domain genes (Dmy, the sex-determining gene, and Dmrt1) and remained unresponsive to Foxl2. Taken together, our results strongly suggest that Rspo1 is sufficient to activate ovarian development and plays a decisive role in the ovarian differentiation in medaka. PMID:26782368

  3. Mouse Sperm Membrane Potential Hyperpolarization Is Necessary and Sufficient to Prepare Sperm for the Acrosome Reaction*

    PubMed Central

    De La Vega-Beltran, Jose Luis; Sánchez-Cárdenas, Claudia; Krapf, Darío; Hernandez-González, Enrique O.; Wertheimer, Eva; Treviño, Claudia L.; Visconti, Pablo E.; Darszon, Alberto

    2012-01-01

    Mammalian sperm are unable to fertilize the egg immediately after ejaculation; they acquire this capacity during migration in the female reproductive tract. This maturational process is called capacitation and in mouse sperm it involves a plasma membrane reorganization, extensive changes in the state of protein phosphorylation, increases in intracellular pH (pHi) and Ca2+ ([Ca2+]i), and the appearance of hyperactivated motility. In addition, mouse sperm capacitation is associated with the hyperpolarization of the cell membrane potential. However, the functional role of this process is not known. In this work, to dissect the role of this membrane potential change, hyperpolarization was induced in noncapacitated sperm using either the ENaC inhibitor amiloride, the CFTR agonist genistein or the K+ ionophore valinomycin. In this experimental setting, other capacitation-associated processes such as activation of a cAMP-dependent pathway and the consequent increase in protein tyrosine phosphorylation were not observed. However, hyperpolarization was sufficient to prepare sperm for the acrosome reaction induced either by depolarization with high K+ or by addition of solubilized zona pellucida (sZP). Moreover, K+ and sZP were also able to increase [Ca2+]i in non-capacitated sperm treated with these hyperpolarizing agents but not in untreated cells. On the other hand, in conditions that support capacitation-associated processes blocking hyperpolarization by adding valinomycin and increasing K+ concentrations inhibited the agonist-induced acrosome reaction as well as the increase in [Ca2+]i. Altogether, these results suggest that sperm hyperpolarization by itself is key to enabling mice sperm to undergo the acrosome reaction. PMID:23095755

  4. Necessary, but not sufficient: Raman identification of disordered carbon as a signature of ancient life.

    PubMed

    Pasteris, Jill Dill; Wopenka, Brigitte

    2003-01-01

    To identify microscopic particles as actual fossil material, it would be useful to have a means of unambiguously recognizing which carbonaceous deposits found in rocks are residues from once-living organisms (i.e., biogenic material). Those residues consist of many different, mostly aromatic (i.e., benzene ring-containing), C-O-H-dominated molecules, and typically are called kerogens. Raman microprobe spectroscopy can be applied to minute samples of ancient kerogens either isolated from their host rocks or in situ in thin section. The Raman spectra generated by monochromatic blue or green laser excitation (e.g., at 488, 514, 532 nm) typically show only generic spectral features indicative of discontinuous arrays of condensed benzene rings (i.e., structures referred to as "disordered carbonaceous material"). Thus, despite the complex chemistry of kerogens and the expected presence of H, O, and N, the Raman spectra typically do not show any evidence of functional groups, such as CH, CH(2), CH(3), CO, and CN. Moreover, the same kind of Raman spectral signature as is obtained from kerogens also is obtained from many other poorly ordered carbonaceous materials that arise through nonbiological processes, such as in situ heating of organic or inorganic compounds (whether or not they are of biological origin), metamorphic mobilization of preexisting carbon compounds, and high-temperature precipitation from hydrothermal solutions. Thus, neither a Raman spectrum, nor a Raman image derived from such spectra, definitively can identify a sample as "kerogen," but only as "disordered carbonaceous material." Clearly, the fact that small, opaque grains consist of disordered carbonaceous material is necessary, but not sufficient, to prove them to be residues of cellular material and, thus, biogenic. PMID:14987478

  5. Social Experience Is Sufficient to Modulate Sleep Need of Drosophila without Increasing Wakefulness.

    PubMed

    Lone, Shahnaz Rahman; Potdar, Sheetal; Srivastava, Manishi; Sharma, Vijay Kumar

    2016-01-01

    Organisms quickly learn about their surroundings and display synaptic plasticity which is thought to be critical for their survival. For example, fruit flies Drosophila melanogaster exposed to highly enriched social environment are found to show increased synaptic connections and a corresponding increase in sleep. Here we asked if social environment comprising a pair of same-sex individuals could enhance sleep in the participating individuals. To study this, we maintained individuals of D. melanogaster in same-sex pairs for a period of 1 to 4 days, and after separation, monitored sleep of the previously socialized and solitary individuals under similar conditions. Males maintained in pairs for 3 or more days were found to sleep significantly more during daytime and showed a tendency to fall asleep sooner as compared to solitary controls (both measures together are henceforth referred to as "sleep-enhancement"). This sleep phenotype is not strain-specific as it is observed in males from three different "wild type" strains of D. melanogaster. Previous studies on social interaction mediated sleep-enhancement presumed 'waking experience' during the interaction to be the primary underlying cause; however, we found sleep-enhancement to occur without any significant increase in wakefulness. Furthermore, while sleep-enhancement due to group-wise social interaction requires Pigment Dispersing Factor (PDF) positive neurons; PDF positive and CRYPTOCHROME (CRY) positive circadian clock neurons and the core circadian clock genes are not required for sleep-enhancement to occur when males interact in pairs. Pair-wise social interaction mediated sleep-enhancement requires dopamine and olfactory signaling, while visual and gustatory signaling systems seem to be dispensable. These results suggest that socialization alone (without any change in wakefulness) is sufficient to cause sleep-enhancement in fruit fly D. melanogaster males, and that its neuronal control is context

  6. Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone.

    PubMed

    Stires, Hillary; Saboya, Mariana; Globerman, Samantha P; Cohick, Wendie S

    2016-01-01

    A role for estrogens in breast cancer is widely accepted, however, recent evidence highlights that timing and exposure levels are important in determining whether they elicit harmful versus beneficial effects. The rat chemical carcinogen model has been widely used to study the effects of estrogens but conclusions on the levels that lead to tumor development and an absolute requirement for progesterone (P4) are lacking. A newer method of hormone administration mixes hormones with nut butter for peroral consumption allowing for a less stressful method of long-term administration with lower spikes in serum estradiol (E2) levels. The present study was designed to determine if estrogens alone at a physiological dose can drive carcinogen-induced tumors in ovariectomized (OVX) rats or if P4 is also required using this method of hormone administration. Short-term studies were conducted to determine the dose of estrogen (E) that would lead to increased uterine weight following OVX. Subsequently, rats were OVX on postnatal day (PND) 40 then treated daily with E (600 μg/kg/day), P4 (15 mg/kg/day), or the combination. On PND 50, all rats were injected with nitrosomethylurea to induce mammary tumors. Uterine weights, body weights, and serum E2 levels were measured to demonstrate the efficacy of the method for increasing E2 levels during long-term treatment. After 26 weeks, tumor incidence was similar in Sham, E, and E + P4 animals indicating that E was sufficient to induce tumorigenesis when hormone levels were normalized by this method. This study demonstrates peroral administration can be used in long-term studies to elucidate relationships between different types and levels of steroid hormones. PMID:27611094

  7. Sufficient Numbers of Early Germ Cells Are Essential for Female Sex Development in Zebrafish

    PubMed Central

    Dai, Xiangyan; Jin, Xia; Chen, Xiaowen; He, Jiangyan; Yin, Zhan

    2015-01-01

    The sex determination for zebrafish is controlled by a combination of genetic and environmental factors. The determination of sex in zebrafish has been suggested to rely on a mechanism that is affected by germ cell-derived signals. To begin our current study, a simplified and efficient germ cell-specific promoter of the dead end (dnd) gene was identified. Utilizing the metrodinazole (MTZ)/ bacterial nitroreductase (NTR) system for inducible germ cell ablation, several stable Tg (dnd:NTR-EGFP-3'UTR) and Tg (dnd:NTR-EGFP+3'UTR) zebrafish lines were then generated with the identified promoter. A thorough comparison of the expression patterns and tissue distributions of endogenous dnd and ntr-egfp transcripts in vivo revealed that the identified 2032-bp zebrafish dnd promoter can recapitulate dnd expression faithfully in stable transgenic zebrafish. The correlation between the levels of the germ cell-derived signals and requirement for maintaining the female fate has been also explored with different durations of the MTZ treatments. Our results revealed the decreasing ratios of female presented in the treated transgenic group are fairly associated with the reducing levels of the early germ cell-derived signals. After the juvenile transgenic fish treated with 5 mM MTZ for 20 days, all MTZ-treated transgenic fish exclusively developed into males with subfertilities. Taken together, our results identified here a simplified and efficient dnd promoter, and provide clear evidence indicating that it was not the presence but the sufficiency of signals derived from germ cells that is essential for female sex development in zebrafish. Our model also provides a unique system for sex control in zebrafish studies. PMID:25679390

  8. Is Compton Cooling Sufficient to Explain Evolution of Observed Quasi-periodic Oscillations in Outburst Sources?

    NASA Astrophysics Data System (ADS)

    Mondal, Santanu; Chakrabarti, Sandip K.; Debnath, Dipak

    2015-01-01

    In outburst sources, quasi-periodic oscillation (QPO) frequency is known to evolve in a certain way: in the rising phase, it monotonically goes up until a soft intermediate state is achieved. In the propagating oscillatory shock model, oscillation of the Compton cloud is thought to cause QPOs. Thus, in order to increase QPO frequency, the Compton cloud must collapse steadily in the rising phase. In decline phases, the exact opposite should be true. We investigate cause of this evolution of the Compton cloud. The same viscosity parameter that increases the Keplerian disk rate also moves the inner edge of the Keplerian component, thereby reducing the size of the Compton cloud and reducing the cooling timescale. We show that cooling of the Compton cloud by inverse Comptonization is enough for it to collapse sufficiently so as to explain the QPO evolution. In the two-component advective flow configuration of Chakrabarti-Titarchuk, centrifugal force-induced shock represents the boundary of the Compton cloud. We take the rising phase of 2010 outburst of Galactic black hole candidate H 1743-322 and find an estimation of variation of the α parameter of the sub-Keplerian flow to be monotonically rising from 0.0001 to 0.02, well within the range suggested by magnetorotational instability. We also estimate the inward velocity of the Compton cloud to be a few meters per second, which is comparable to what is found in several earlier studies of our group by empirically fitting the shock locations with the time of observations.

  9. Partial base flipping is sufficient for strand slippage near DNA duplex termini.

    PubMed

    Banavali, Nilesh K

    2013-06-01

    Strand slippage is a structural mechanism by which insertion-deletion (indel) mutations are introduced during replication by polymerases. Three-dimensional atomic-resolution structural pathways are still not known for the decades-old template slippage description. The dynamic nature of the process and the higher energy intermediates involved increase the difficulty of studying these processes experimentally. In the present study, restrained and unrestrained molecular dynamics simulations, carried out using multiple nucleic acid force fields, are used to demonstrate that partial base-flipping can be sufficient for strand slippage at DNA duplex termini. Such strand slippage can occur in either strand, i.e. near either the 3' or the 5' terminus of a DNA strand, which suggests that similar structural flipping mechanisms can cause both primer and template slippage. In the repetitive mutation hot-spot sequence studied, non-canonical base-pairing with exposed DNA groove atoms of a neighboring G:C base-pair stabilizes a partially flipped state of the cytosine. For its base-pair partner guanine, a similar partially flipped metastable intermediate was not detected, and the propensity for sustained slippage was also found to be lower. This illustrates that a relatively small metastable DNA structural distortion in polymerase active sites could allow single base insertion or deletion mutations to occur, and stringent DNA groove molecular recognition may be required to maintain intrinsic DNA polymerase fidelity. The implications of a close relationship between base-pair dissociation, base unstacking, and strand slippage are discussed in the context of sequence dependence of indel mutations. PMID:23692220

  10. School children sufficiently apply life supporting first aid: a prospective investigation

    PubMed Central

    2009-01-01

    Introduction The usefulness of CPR training in schools has been questioned because young students may not have the physical and cognitive skills needed to correctly perform such complex tasks correctly. Methods In pupils, who received six hours of CPR training from their teachers during a standard school semester at four months post training the following outcome parameters were assessed: CPR effectiveness, AED deployment, accuracy in checking vital signs, correctness of recovery position, and whether the ambulance service was effectively notified. Possible correlations of age, gender, body mass index (BMI), and outcome parameters were calculated. Results Of 147 students (mean age 13 ± 2 years), 86% performed CPR correctly. Median depth of chest compressions was 35 mm (inter quartile range (IQR) 31 to 41), and the median number of compressions per minute was 129 bpm (IQR 108 to 143). Sixty nine percent of the students tilted the mannequin head sufficiently for mouth to mouth resuscitation, and the median air volume delivered was 540 ml (IQR 0 to 750). Scores on other life supporting techniques were at least 80% or higher. Depth of chest compressions showed a correlation with BMI (r = 0.35; P < 0.0001), body weight (r = 0.38; P < 0.0001), and body height (r = 0.31; P = 0.0002) but not with age. All other outcomes were found to be unrelated to gender, age, or BMI. Conclusions Students as young as 9 years are able to successfully and effectively learn basic life support skills including AED deployment, correct recovery position and emergency calling. As in adults, physical strength may limit depth of chest compressions and ventilation volumes but skill retention is good. PMID:19646229

  11. Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes).

    PubMed

    Zhou, Linyan; Charkraborty, Tapas; Zhou, Qian; Mohapatra, Sipra; Nagahama, Yoshitaka; Zhang, Yueguang

    2016-01-01

    In contrast to our understanding of testicular differentiation, ovarian differentiation is less well understood in vertebrates. In mammals, R-spondin1 (Rspo1), an activator of Wnt/β-catenin signaling pathway, is located upstream of the female sex determination pathway. However, the functions of Rspo1 in ovarian differentiation remain unclear in non-mammalian species. In order to elucidate the detailed functions of Rspo/Wnt signaling pathway in fish sex determination/differentiation, the ectopic expression of the Rspo1 gene was performed in XY medaka (Oryzias latipes). The results obtained demonstrated that the gain of Rspo1 function induced femininity in XY fish. The overexpression of Rspo1 enhanced Wnt4b and β-catenin transcription, and completely suppressed the expression of male-biased genes (Dmy, Gsdf, Sox9a2 and Dmrt1) as well as testicular differentiation. Gonadal reprograming of Rspo1-over-expressed-XY (Rspo1-OV-XY) fish, induced the production of female-biased genes (Cyp19a1a and Foxl2), estradiol-17β production and further female type secondary sexuality. Moreover, Rspo1-OV-XY females were fertile and produced successive generations. Promoter analyses showed that Rspo1 transcription was directly regulated by DM domain genes (Dmy, the sex-determining gene, and Dmrt1) and remained unresponsive to Foxl2. Taken together, our results strongly suggest that Rspo1 is sufficient to activate ovarian development and plays a decisive role in the ovarian differentiation in medaka. PMID:26782368

  12. Disparate British Breast Reconstruction Utilization: Is Universal Coverage Sufficient to Ensure Expanded Care?

    PubMed Central

    Offodile, Anaeze C.

    2016-01-01

    Summary: Our intent is to improve the understanding of the ability of healthcare providers to deliver high-quality care as we approach an era of universal coverage. We adopted 2 unique vantage points in this article: (1) the mandated coverage for immediate breast reconstruction (IBR) surgery as a microcosmic surrogate for universal coverage overall and (2) we then scrutinized the respective IBR utilization rates in a contemporaneous system of 2 healthcare delivery models in the United Kingdom, that is, the public National Health Service trust versus private-sector hospitals. A literature review was performed for IBR rates across public trust and private-sector hospitals in the United Kingdom. The IBR rate among public trust hospitals was 17% compared with 43% in the private sector. In the trust hospital setting, the enactment of 2 government mandates, intended to increase the access to cancer care, seemed to fall short in maximizing the ability of surgical practitioners to deliver quality care to patients. Among women who did not receive IBR, 65% felt that they had received the sufficient amount of information to appropriately inform their decision. In addition, only 46% of this same cohort reported a consultation with a reconstructive surgeon preoperatively. Private-sector hospitals delivered better IBR care because of the likely presence of infrastructure and financial incentives for physicians. These results serve as a call for a better alignment between policy initiatives designed to expand care access and the perogatives of physicians to ensure an optimized delivery of the expanded care such policy mandates. PMID:27482486

  13. Conditions sufficient for nonsynaptic epileptogenesis in the CA1 region of hippocampal slices.

    PubMed

    Bikson, Marom; Baraban, Scott C; Durand, Dominique M

    2002-01-01

    Nonsynaptic mechanisms exert a powerful influence on seizure threshold. It is well-established that nonsynaptic epileptiform activity can be induced in hippocampal slices by reducing extracellular Ca(2+) concentration. We show here that nonsynaptic epileptiform activity can be readily induced in vitro in normal (2 mM) Ca(2+) levels. Those conditions sufficient for nonsynaptic epileptogenesis in the CA1 region were determined by pharmacologically mimicking the effects of Ca(2+) reduction in normal Ca(2+) levels. Increasing neuronal excitability, by removing extracellular Mg(2+) and increasing extracellular K(+) (6-15 mM), induced epileptiform activity that was suppressed by postsynaptic receptor antagonists [D-(-)-2-amino-5-phosphonopentanoic acid, picrotoxin, and 6,7-dinitroquinoxaline-2,3-dione] and was therefore synaptic in nature. Similarly, epileptiform activity induced when neuronal excitability was increased in the presence of K(Ca) antagonists (verruculogen, charybdotoxin, norepinephrine, tetraethylammonium salt, and Ba(2+)) was found to be synaptic in nature. Decreases in osmolarity also failed to induce nonsynaptic epileptiform activity in the CA1 region. However, increasing neuronal excitability (by removing extracellular Mg(2+) and increasing extracellular K(+)) in the presence of Cd(2+), a nonselective Ca(2+) channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity in vitro. Both novel models were characterized using intracellular and ion-selective electrodes. The results of this study suggest that reducing extracellular Ca(2+) facilitates bursting by increasing neuronal excitability and inhibiting Ca(2+) influx, which might, in turn, enhance a persistent sodium conductance. Furthermore, these data show that nonsynaptic mechanisms can contribute to epileptiform activity in normal Ca(2+) levels. PMID:11784730

  14. Identification of a Novel Self-Sufficient Styrene Monooxygenase from Rhodococcus opacus 1CP▿ †

    PubMed Central

    Tischler, Dirk; Eulberg, Dirk; Lakner, Silvia; Kaschabek, Stefan R.; van Berkel, Willem J. H.; Schlömann, Michael

    2009-01-01

    Sequence analysis of a 9-kb genomic fragment of the actinobacterium Rhodococcus opacus 1CP led to identification of an open reading frame encoding a novel fusion protein, StyA2B, with a putative function in styrene metabolism via styrene oxide and phenylacetic acid. Gene cluster analysis indicated that the highly related fusion proteins of Nocardia farcinica IFM10152 and Arthrobacter aurescens TC1 are involved in a similar physiological process. Whereas 413 amino acids of the N terminus of StyA2B are highly similar to those of the oxygenases of two-component styrene monooxygenases (SMOs) from pseudomonads, the residual 160 amino acids of the C terminus show significant homology to the flavin reductases of these systems. Cloning and functional expression of His10-StyA2B revealed for the first time that the fusion protein does in fact catalyze two separate reactions. Strictly NADH-dependent reduction of flavins and highly enantioselective oxygenation of styrene to (S)-styrene oxide were shown. Inhibition studies and photometric analysis of recombinant StyA2B indicated the absence of tightly bound heme and flavin cofactors in this self-sufficient monooxygenase. StyA2B oxygenates a spectrum of aromatic compounds similar to those of two-component SMOs. However, the specific activities of the flavin-reducing and styrene-oxidizing functions of StyA2B are one to two orders of magnitude lower than those of StyA/StyB from Pseudomonas sp. strain VLB120. PMID:19482928

  15. IS COMPTON COOLING SUFFICIENT TO EXPLAIN EVOLUTION OF OBSERVED QUASI-PERIODIC OSCILLATIONS IN OUTBURST SOURCES?

    SciTech Connect

    Mondal, Santanu; Chakrabarti, Sandip K.; Debnath, Dipak E-mail: chakraba@bose.res.in

    2015-01-01

    In outburst sources, quasi-periodic oscillation (QPO) frequency is known to evolve in a certain way: in the rising phase, it monotonically goes up until a soft intermediate state is achieved. In the propagating oscillatory shock model, oscillation of the Compton cloud is thought to cause QPOs. Thus, in order to increase QPO frequency, the Compton cloud must collapse steadily in the rising phase. In decline phases, the exact opposite should be true. We investigate cause of this evolution of the Compton cloud. The same viscosity parameter that increases the Keplerian disk rate also moves the inner edge of the Keplerian component, thereby reducing the size of the Compton cloud and reducing the cooling timescale. We show that cooling of the Compton cloud by inverse Comptonization is enough for it to collapse sufficiently so as to explain the QPO evolution. In the two-component advective flow configuration of Chakrabarti-Titarchuk, centrifugal force-induced shock represents the boundary of the Compton cloud. We take the rising phase of 2010 outburst of Galactic black hole candidate H 1743-322 and find an estimation of variation of the α parameter of the sub-Keplerian flow to be monotonically rising from 0.0001 to 0.02, well within the range suggested by magnetorotational instability. We also estimate the inward velocity of the Compton cloud to be a few meters per second, which is comparable to what is found in several earlier studies of our group by empirically fitting the shock locations with the time of observations.

  16. Inactivation of p53 Is Sufficient to Induce Development of Pulmonary Hypertension in Rats

    PubMed Central

    Jacquin, S.; Rincheval, V.; Mignotte, B.; Richard, S.; Humbert, M.; Mercier, O.; Londoño-Vallejo, A.; Fadel, E.; Eddahibi, S.

    2015-01-01

    Objective Pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterial hypertension (PAH) show similarities to cancer cells. Due to the growth-suppressive and pro-apoptotic effects of p53 and its inactivation in cancer, we hypothesized that the p53 pathway could be altered in PAH. We therefore explored the involvement of p53 in the monocrotaline (MCT) rat model of pulmonary hypertension (PH) and the pathophysiological consequences of p53 inactivation in response to animal treatment with pifithrin-α (PFT, an inhibitor of p53 activity). Methods and Results PH development was assessed by pulmonary arterial pressure, right ventricular hypertrophy and arterial wall thickness. The effect of MCT and PFT on lung p53 pathway expression was evaluated by western blot. Fourteen days of daily PFT treatment (2.2 mg/kg/day), similar to a single injection of MCT (60 mg/kg), induced PH and aggravated MCT-induced PH. In the first week after MCT administration and prior to PH development, p53, p21 and MDM2 protein levels were significantly reduced; whereas PFT administration effectively altered the protein level of p53 targets. Anti-apoptotic and pro-proliferative effects of PFT were revealed by TUNEL and MTT assays on cultured human PA-SMCs treated with 50 μM PFT. Conclusions Pharmacological inactivation of p53 is sufficient to induce PH with a chronic treatment by PFT, an effect related to its anti-apoptotic and pro-proliferative properties. The p53 pathway was down-regulated during the first week in the rat MCT model. These in vivo experiments implicate the p53 pathway at the initiation stages of PH pathogenesis. PMID:26121334

  17. Social Experience Is Sufficient to Modulate Sleep Need of Drosophila without Increasing Wakefulness

    PubMed Central

    Lone, Shahnaz Rahman; Potdar, Sheetal; Srivastava, Manishi; Sharma, Vijay Kumar

    2016-01-01

    Organisms quickly learn about their surroundings and display synaptic plasticity which is thought to be critical for their survival. For example, fruit flies Drosophila melanogaster exposed to highly enriched social environment are found to show increased synaptic connections and a corresponding increase in sleep. Here we asked if social environment comprising a pair of same-sex individuals could enhance sleep in the participating individuals. To study this, we maintained individuals of D. melanogaster in same-sex pairs for a period of 1 to 4 days, and after separation, monitored sleep of the previously socialized and solitary individuals under similar conditions. Males maintained in pairs for 3 or more days were found to sleep significantly more during daytime and showed a tendency to fall asleep sooner as compared to solitary controls (both measures together are henceforth referred to as “sleep-enhancement”). This sleep phenotype is not strain-specific as it is observed in males from three different “wild type” strains of D. melanogaster. Previous studies on social interaction mediated sleep-enhancement presumed ‘waking experience’ during the interaction to be the primary underlying cause; however, we found sleep-enhancement to occur without any significant increase in wakefulness. Furthermore, while sleep-enhancement due to group-wise social interaction requires Pigment Dispersing Factor (PDF) positive neurons; PDF positive and CRYPTOCHROME (CRY) positive circadian clock neurons and the core circadian clock genes are not required for sleep-enhancement to occur when males interact in pairs. Pair-wise social interaction mediated sleep-enhancement requires dopamine and olfactory signaling, while visual and gustatory signaling systems seem to be dispensable. These results suggest that socialization alone (without any change in wakefulness) is sufficient to cause sleep-enhancement in fruit fly D. melanogaster males, and that its neuronal control is

  18. Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin

    PubMed Central

    López Sastre, José B; Pérez Solís, David; Roqués Serradilla, Vicente; Fernández Colomer, Belén; Coto Cotallo, Gil D; Krauel Vidal, Xavier; Narbona López, Eduardo; García del Río, Manuel; Sánchez Luna, Manuel; Belaustegui Cueto, Antonio; Moro Serrano, Manuel; Urbón Artero, Alfonso; Álvaro Iglesias, Emilio; Cotero Lavín, Ángel; Martínez Vilalta, Eduardo; Jiménez Cobos, Bartolomé

    2006-01-01

    Background It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be

  19. Are single odorous components of a predator sufficient to elicit defensive behaviors in prey species?

    PubMed Central

    Apfelbach, Raimund; Parsons, Michael H.; Soini, Helena A.; Novotny, Milos V.

    2015-01-01

    When exposed to the odor of a sympatric predator, prey animals typically display escape or defensive responses. These phenomena have been well-documented, especially in rodents, when exposed to the odor of a cat, ferret, or fox. As a result of these experiments new discussions center on the following questions: (1) is a single volatile compound such as a major or a minor mixture constituent in urine or feces, emitted by the predator sufficient to cause defensive reactions in a potential prey species or (2) is a whole array of odors required to elicit a response and (3) will the relative size or escapability of the prey as compared to the predator influence responsiveness. Most predator-prey studies on this topic have been performed in the laboratory or under semi-natural conditions. Field studies could help to find answers to these questions. Australian mammals are completely naïve toward the introduced placental carnivores. That offers ideal opportunities to analyze in the field the responses of potential prey species to unknown predator odors. During the last decades researchers have accumulated an enormous amount of data exploring the effects of eutherian predator odors on native marsupial mammals. In this review, we will give a survey about the development of olfactory research, chemical signals and their influence on the behavior and—in some cases—physiology of prey species. In addition, we report on the effects of predator odor experiments performed under natural conditions in Australia. When studying all these literature we learned that data gained under controlled laboratory conditions elucidate the role of individual odors on brain structures and ultimately on a comparatively narrow range behaviors. In contrast to single odors odor arrays mimic much more the situation prey animals are confronted to in nature. Therefore, a broad range of methodology—from chemistry to ecology including anatomy, physiology, and behavior—is needed to understand all

  20. Reliability-based structural optimization using response surface approximations and probabilistic sufficiency factor

    NASA Astrophysics Data System (ADS)

    Qu, Xueyong

    Uncertainties exist practically everywhere from structural design to manufacturing, product lifetime service, and maintenance. Uncertainties can be introduced by errors in modeling and simulation; by manufacturing imperfections (such as variability in material properties and structural geometric dimensions); and by variability in loading. Structural design by safety factors using nominal values without considering uncertainties may lead to designs that are either unsafe, or too conservative and thus not efficient. The focus of this dissertation is reliability-based design optimization (RBDO) of composite structures. Uncertainties are modeled by the probabilistic distributions of random variables. Structural reliability is evaluated in term of the probability of failure. RBDO minimizes cost such as structural weight subject to reliability constraints. Since engineering structures usually have multiple failure modes, Monte Carlo simulation (MCS) was used employed to calculate the system probability of failure. Response surface (RS) approximation techniques were used to solve the difficulties associated with MCS. The high computational cost of a large number of MCS samples was alleviated by analysis RS, and numerical noise in the results of MCS was filtered out by design RS. RBDO of composite laminates is investigated for use in hydrogen tanks in cryogenic environments. The major challenge is to reduce the large residual strains developed due to thermal mismatch between matrix and fibers while maintaining the load carrying capacity. RBDO is performed to provide laminate designs, quantify the effects of uncertainties on the optimum weight, and identify those parameters that have the largest influence on optimum design. Studies of weight and reliability tradeoffs indicate that the most cost-effective measure for reducing weight and increasing reliability is quality control. A probabilistic sufficiency factor (PSF) approach was developed to improve the computational

  1. Genotypic Variation for N2-FIXATION in Voandzou (vigna Subterranea) Under P Deficiency and P Sufficiency

    NASA Astrophysics Data System (ADS)

    Andry, A.; Mahamadou, M.; Lilia, R.; Laurie, A.; Hélène, V.; Dominique, M.; Christian, M.; Jean-Jacques, D.

    2011-12-01

    Genetic variation associated with N2 fixation exists in numerous legume species (Graham, 2004). High symbiotic N2 fixation under P deficiency is related closely to nodulation which was used in legume selection for N2 fixation (Herridge and Rose, 2000). Until now, study of genetic potential of neglected crops like Vigna subterranea (bambara groundnut or voandzou) is often limited while its agronomic properties is interesting for the farmers of Africa. In order to assess the genotypic variation of voandzou for tolerance to phosphorus deficiency, a physiological approach of cultivar selection was performed with 54 cultivars from Madagascar, Niger and Mali in hydroponic culture under P deficiency and P sufficiency and inoculated with the reference strain of Bradyrhizobium sp. Vigna CB756. The results of nodulation and plant biomass, which are closely related, showed a large dispersion between cultivars (0.05-0.43 g nodule dry weight per plant and 0.50-5.51 g shoot dry weight per plant). The cultivars which presented the maximum growth during the experiment presented a high efficiency in use of the rhizobial symbiosis calculated as the slope of plant biomass regression as a function of nodulation. A large increase in nodulated-root O2 consumption under P deficiency was observed for the two most tolerant cultivars. The microscopic analysis with in situ RT-PCR of the nodule sections showed an increase of a phytase gene expression with tolerance of cultivars to P deficiency. From two most contrasting cultivars, an isotopic exchange method 32P was carried out on rhizosphere soil in rhizotron culture in order to assess the direct effect induced by the roots in terms of phosphorus mobilization. The rhizospheric effect was observed under P deficiency marked by a strong re-supplying capacity of soil solution in the diffusive phosphate ion between solid phase and soil solution leading to great phosphorus nutrition. These results highlight the genotypic variability among voandzou

  2. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.

    PubMed

    Pusic, Iskra; Jiang, Shi Yuan; Landua, Scott; Uy, Geoffrey L; Rettig, Michael P; Cashen, Amanda F; Westervelt, Peter; Vij, Ravi; Abboud, Camille N; Stockerl-Goldstein, Keith E; Sempek, Diane S; Smith, Angela L; DiPersio, John F

    2008-09-01

    The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those

  3. Unwanted scour holes in morphodynamic experiments: seeking necessary and sufficient conditions

    NASA Astrophysics Data System (ADS)

    Kleinhans, Maarten; Marra, Wouter; Leuven, Jasper; Braat, Lisanne; Baar, Anne; Nabi, Mohamed

    2015-04-01

    Morphodynamic landscape experiments of river reaches, deltas and estuaries often feature unrealistically large scour holes, which are on average 2 cm deep and 5 cm long. Such scours occur under similar conditions as current ripples (as opposed to other bedforms such as dunes. It has long been suspected that they form on hydraulically smooth boundaries, which occur at low boundary Reynolds numbers, typically induced in fine sand and under relatively low sediment mobility. Until now three strategies exist to prevent the unwanted scour holes. The first is to use use coarser sand to disrupt the laminar sublayer, but this means low or no mobility. The second is to use fine but poorly sorted sand where the coarser material disrupts the laminar sublayer and the small caliber causes higher mobility, and the third is to use coarse granular material which has a low-density that increases mobility. However, we lack systematic study to determine causes of the scour holes, on which to base experimental design and material choice. Here we present experiments in which we systematically varied sediment types and used various methods to provoke scour holes or removal thereof. We also conducted model runs of Computational Fluid Dynamics and sediment transport in which bedforms automatically emerge. All model runs and most experiments confirm that ripples and scour holes both form in hydraulic smooth conditions induced by low boundary Reynolds numbers. On the other hand, they are absent in coarser sediment and poorly sorted sediment. The experiments also show that scours can be provoked by perturbations even below generalised sediment motion. However, granular material of intermediate density and poor sorting deviated in behaviour: this formed scours despite the addition of coarser fractions that were sufficient to prevent scours in the case of sand. We observed this unexplained behaviour also in channelisation experiments, where peculiar, sharp bends with unrealistically deep outer

  4. The transcension hypothesis: Sufficiently advanced civilizations invariably leave our universe, and implications for METI and SETI

    NASA Astrophysics Data System (ADS)

    Smart, John M.

    2012-09-01

    The emerging science of evolutionary developmental ("evo devo") biology can aid us in thinking about our universe as both an evolutionary system, where most processes are unpredictable and creative, and a developmental system, where a special few processes are predictable and constrained to produce far-future-specific emergent order, just as we see in the common developmental processes in two stars of an identical population type, or in two genetically identical twins in biology. The transcension hypothesis proposes that a universal process of evolutionary development guides all sufficiently advanced civilizations into what may be called "inner space," a computationally optimal domain of increasingly dense, productive, miniaturized, and efficient scales of space, time, energy, and matter, and eventually, to a black-hole-like destination. Transcension as a developmental destiny might also contribute to the solution to the Fermi paradox, the question of why we have not seen evidence of or received beacons from intelligent civilizations. A few potential evolutionary, developmental, and information theoretic reasons, mechanisms, and models for constrained transcension of advanced intelligence are briefly considered. In particular, we introduce arguments that black holes may be a developmental destiny and standard attractor for all higher intelligence, as they appear to some to be ideal computing, learning, forward time travel, energy harvesting, civilization merger, natural selection, and universe replication devices. In the transcension hypothesis, simpler civilizations that succeed in resisting transcension by staying in outer (normal) space would be developmental failures, which are statistically very rare late in the life cycle of any biological developing system. If transcension is a developmental process, we may expect brief broadcasts or subtle forms of galactic engineering to occur in small portions of a few galaxies, the handiwork of young and immature

  5. The buoyancy of large siliceous magma chambers is sufficient to initiate supereruptions

    NASA Astrophysics Data System (ADS)

    Malfait, W.; Sanchez-Valle, C.; Seifert, R.; Petitgirard, S.; Perrillat, J.; Ota, T.; Nakamura, E.; Lerch, P.; Mezouar, M.

    2012-12-01

    The geological record shows abundant evidence for rare, but extremely large caldera-forming eruptions of siliceous magmas that dwarf all historical volcanic episodes in erupted volume [1] and environmental impact [2, 3]. Because of the large size of the magma chambers that feed these eruptions, the overpressure generated by magma recharge is insufficient to fracture the cap rock and trigger an eruption [4]. For these thick magma chambers, the buoyancy of the magma potentially creates a sufficient overpressure capable of fracturing the cap rock, but the lack of data on the density of rhyolite melts precludes the appropriate estimation of the overpressure and the role of buoyancy in initiating supervolcano eruptions. The density of rhyolite melts has not been determined at super-liquidus temperatures or elevated pressures because traditional techniques, including Archimedean methods, sink/float experiments and acoustic measurements, are limited by the high melt viscosity. Here, we measured the density of rhyolitic/granitic melts with 0, 4.5 and 7.7 wt% of dissolved water at geologically relevant conditions: 0.9 to 3.6 GPa, 1270 to 1950 K. High pressure and temperature conditions were generated in a Paris-Edinburgh large volume press. Before and after each density measurement, the molten state of the sample was verified by X-ray diffraction. The density of the melt (ρPT) was determined from the X-ray attenuation coefficient of the sample, determined in situ (μPT) and at room conditions (μ0), and the density at room conditions (ρ0): ρPT=ρ0.(μPT/μ0). The acquired data were combined with available ambient pressure data on super-cooled liquids [5, 6] to derive a third order Birch-Murnaghan equation of state that accurately predicts the density of rhyolite melts as a function of pressure, temperature and water content, and the partial molar volume of dissolved water. Application of the melt equation of state to calculate the overpressure at the roof of supervolcano

  6. Self-formed Dynamic Meandering Rivers and Floodplains in the Laboratory: Necessary and Sufficient Conditions

    NASA Astrophysics Data System (ADS)

    Kleinhans, M. G.; van Dijk, W. M.; van de Lageweg, W. I.; Markies, H.; van der Gon-Netscher, T.; van de Meer, H.; van Maarseveen, M.; Postma, G.

    2010-12-01

    the cut-off location rises, so modest levees and crevasse splays are built and former channels are flooded, though usually not reactivated. After applying floods laden with silica flour to build the floodplain; the river evolved to, on average, a much less mobile single channel with infrequent chute cut-offs. The lateral channel migration rate decreases with increased floodplain building in agreement with natural systems (Lavooi et al., this conference). Ongoing work quantifies the effect of migration rate and amplitude of the inflow position on the morphodynamics and channel pattern. We conclude that necessary and sufficient conditions for a self-formed, dynamically meandering channel in the laboratory are the presence of floods and floodplain-building sediment and a dynamic boundary condition simulating meander migration. In smaller-scale pilot experiments we use different vegetation species and controlled conditions allow adjustable growth rate, bank strength and hydraulic resistance (van Breemen et al., this conference). We will apply this in the large-scale experiment next year to be able to use less silica flour yet inhance floodplain formation.

  7. Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa

    PubMed Central

    Williams, Hannah L.; Mansell, Steven; Alasmari, Wardah; Brown, Sean G.; Wilson, Stuart M.; Sutton, Keith A.; Miller, Melissa R.; Lishko, Polina V.; Barratt, Christopher L.R.; Publicover, Steven J.; Martins da Silva, Sarah

    2015-01-01

    STUDY QUESTION Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? SUMMARY ANSWER Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. WHAT IS KNOWN ALREADY In human spermatozoa, Ca2+ influx induced by progesterone is mediated by CatSper, a sperm-specific Ca2+ channel. A suboptimal Ca2+ influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca2+]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. STUDY DESIGN, SIZE, DURATION Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were primarily screened using the Ca2+ influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca2+ response to progesterone was defined using the 99

  8. Sufficient condition for a finite-time singularity in a high-symmetry Euler flow: Analysis and statistics

    NASA Astrophysics Data System (ADS)

    Ng, C. S.; Bhattacharjee, A.

    1996-08-01

    A sufficient condition is obtained for the development of a finite-time singularity in a highly symmetric Euler flow, first proposed by Kida [J. Phys. Soc. Jpn. 54, 2132 (1995)] and recently simulated by Boratav and Pelz [Phys. Fluids 6, 2757 (1994)]. It is shown that if the second-order spatial derivative of the pressure (pxx) is positive following a Lagrangian element (on the x axis), then a finite-time singularity must occur. Under some assumptions, this Lagrangian sufficient condition can be reduced to an Eulerian sufficient condition which requires that the fourth-order spatial derivative of the pressure (pxxxx) at the origin be positive for all times leading up to the singularity. Analytical as well as direct numerical evaluation over a large ensemble of initial conditions demonstrate that for fixed total energy, pxxxx is predominantly positive with the average value growing with the numbers of modes.

  9. Necessary and sufficient conditions on n-qudit state for perfect teleportation of an arbitrary single qudit state

    NASA Astrophysics Data System (ADS)

    Shang-Guan, Li-Ying; Sun, Hong-Xiang; Wen, Qiao-Yan; Zhu, Fu-Chen

    2009-12-01

    Firstly, we investigate the necessary and sufficient conditions that an entangled channel of n-qubits should satisfy to carry out perfect teleportation of an arbitrary single qubit state and dense coding. It is shown that the sender can transmit two classical bits of information by sending one qubit. Further, the case of high-dimension quantum state is also considered. Utilizing n-qudit state as quantum channel, it is proposed that the necessary and sufficient conditions are {(d+2)(d-1)}/{2} in all to teleport an arbitrary single qudit state. The sender can transmit 2log2d classical bits of information to the receiver conditioned on the constraints.

  10. Tritium self-sufficiency time and inventory evolution for solid-type breeding blanket materials for DEMO

    NASA Astrophysics Data System (ADS)

    Packer, L. W.; Pampin, R.; Zheng, S.

    2011-10-01

    One of the primary functions of a fusion blanket is to generate enough tritium to make a fusion power plant (FPP) self-sufficient. To ensure that there is satisfactory tritium production in a real plant the tritium breeding ratio (TBR) in the blanket must be greater than 1 + M, where M is the breeding margin. For solid-type blanket designs, the initial TBR must be significantly higher than 1 + M, since the blanket TBR will be reduced over time as the lithium fuel is consumed. The rate of TBR reduction will impact on the overall blanket self-sufficiency time, the time in which the net tritium inventory of the system is positive. DEMO relevant blanket materials, Li 4SiO 4 and Li 2TiO 3, are investigated by computational simulation using radiation transport tools coupled with time-dependent inventory calculations. The results include tritium inventory assessments and depletion of breeding materials over time, which enable self-sufficiency times and maximum surplus tritium inventories to be evaluated, which are essential quantities to determine to allow one to design a credible FPP using solid-type breeding material concepts. The blanket concepts investigated show self-sufficiency times of several years in some cases and maximum surplus inventories of up to a few tens of kg.

  11. The Development of Economic Self-Sufficiency among Former Welfare Recipients: Lessons Learned from Wisconsin's Welfare to Work Program

    ERIC Educational Resources Information Center

    Alfred, Mary V.; Martin, Larry G.

    2007-01-01

    In 1996, the US Congress passed the Personal Responsibility and Work Opportunity Reconciliation Act, changing the culture of welfare from a system of dependency to one of personal responsibility and economic self-sufficiency through workplace participation. Through the expert views of case managers and area employers of Wisconsin, this research…

  12. 78 FR 9935 - Notice of Submission of Proposed Information Collection to OMB; Family Self-Sufficiency Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB; Family Self... is an evaluation of the Family Self-Sufficiency Program operated at Public Housing Agencies (PHAs... is essentially case management plus an escrow account. FSS case managers create a plan with...

  13. Empirical evaluation of sufficient similarity in dose-response for environmental risk assessment of a mixture of 11 pyrethroids.

    EPA Science Inventory

    Chemical mixtures in the environment are often the result of a dynamic process. When dose-response data are available on random samples throughout the process, equivalence testing can be used to determine whether the mixtures are sufficiently similar based on a pre-specified biol...

  14. An empirical approach to sufficient similarity in dose-responsiveness: Utilization of statistical distance as a similarity measure.

    EPA Science Inventory

    Using statistical equivalence testing logic and mixed model theory an approach has been developed, that extends the work of Stork et al (JABES,2008), to define sufficient similarity in dose-response for chemical mixtures containing the same chemicals with different ratios ...

  15. The Adequacy of the Information that Students Utilize when Choosing a College: An Attribute Importance and Information Sufficiency Approach

    ERIC Educational Resources Information Center

    Dolinsky, Arthur L.

    2010-01-01

    This study employed a college student sample to retrospectively assess the adequacy of the college-related attribute information they received when deciding to attend college. The assessment separately considered males and females in the study's information sufficiency-importance framework with resulting strategies. The results suggest that when…

  16. 37 CFR 1.424 - Assignee, obligated assignee, or person having sufficient proprietary interest as applicant in an...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... under an obligation to assign the invention may be an applicant in an international application which designates the United States of America. A person who otherwise shows sufficient proprietary interest in the matter may be an applicant in an international application which designates the United States of...

  17. 37 CFR 1.424 - Assignee, obligated assignee, or person having sufficient proprietary interest as applicant in an...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... under an obligation to assign the invention may be an applicant in an international application which designates the United States of America. A person who otherwise shows sufficient proprietary interest in the matter may be an applicant in an international application which designates the United States of...

  18. Programs To Enhance the Self-Sufficiency of Welfare Families: Working towards a Model of Effects on Young Children.

    ERIC Educational Resources Information Center

    Zaslow, Martha; Moore, Kristin; Coiro, Mary Jo; Morrison, Donna Ruane

    Although it has been assumed that increasing maternal education or family income will improve children's well-being, considering the impact on child care arrangements and home environment raises the possibility of negative effects. This paper reviews experimental evaluations of seven programs designed to enhance welfare families' self-sufficiency,…

  19. The State of the Science of Employment and Economic Self-Sufficiency for People with Intellectual and Developmental Disabilities

    ERIC Educational Resources Information Center

    Nord, Derek; Luecking, Richard; Mank, David; Kiernan, William; Wray, Christina

    2013-01-01

    Employment, career advancement, and financial independence are highly valued in the United States. As expectations, they are often instilled at a young age and incentivized throughout adulthood. Despite their importance, employment and economic sufficiency continue to be out of reach for most people with intellectual and developmental disabilities…

  20. [Roundtables of SFTS Congress 2013: Needs, indications and safety of blood products; self-sufficiency in blood products].

    PubMed

    Hermine, O; Lassale, B; Morel, P; Samama, C M; Folléa, G; Monsellier, M; Noël, S; Tissot, J-D; Lefrère, J-J

    2014-06-01

    The current issues debate brings together experts around the themes of self-sufficiency (in its national and European aspects) and of needs in cellular blood products. The point of view of the manufacturer and prescribers of blood products are confronted. PMID:24906893

  1. 75 FR 31805 - Announcement of Funding Awards for the Resident Opportunity and Self-Sufficiency (ROSS)-Service...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... 36602. Jonesboro Urban Renewal & Housing 330 Union, Jonesboro, AR 152,630 Authority. 72401. Little Rock... URBAN DEVELOPMENT Announcement of Funding Awards for the Resident Opportunity and Self-Sufficiency (ROSS... and Urban Development Reform Act of 1989, this announcement notifies the public of funding...

  2. Self-Sufficiency in Northern Justice Issues. Proceedings of the Northern Justice Society Meeting (5th, Sitka, Alaska, April 1991).

    ERIC Educational Resources Information Center

    Griffiths, Curt Taylor, Ed.

    As indigenous peoples in the Arctic move closer to sovereignty, self-sufficiency in the realm of criminal justice assumes paramount importance. This book outlines initiatives and strategies to improve the delivery of justice services to aboriginal peoples in Canada, Alaska, and Greenland. Topics include: social and spiritual causes of alcoholism…

  3. The Impact of Population Density on the Likelihood of Aid to Dependent Children (ADC) Clients Becoming Economically Self-Sufficient.

    ERIC Educational Resources Information Center

    Bendixen-Noe, Mary K.; And Others

    The impact of population density on the likelihood of Aid to Dependent Children (ADC) clients becoming economically self-sufficient was examined through a study of 2,647 ADC recipients referred to a total of 8 comprehensive vocational assessment centers (CVACs) for ADC clients that were established in Ohio in 1992. Of the CVACs, two were from each…

  4. Mitochondrial DNA evidence for admixed origins of central Siberian populations.

    PubMed

    Pakendorf, Brigitte; Wiebe, Victor; Tarskaia, Larissa A; Spitsyn, Victor A; Soodyall, Himla; Rodewald, Alexander; Stoneking, Mark

    2003-03-01

    The Yakuts of northeastern Siberia are a Turkic-speaking population of horse- and cattle-breeders surrounded by Tungusic-speaking reindeer-herders and hunter-gatherers. Archaeological and ethnohistorical data suggest that Yakuts stem from a common ancestral population with the Buryats living near Lake Baikal. To address this hypothesis, we obtained sequences of the first hypervariable segment (HV1) of the mitochondrial DNA control region from Yakuts and Buryats and compared these with sequences from other Eurasian populations. The mtDNA results show that the Buryats have close affinities with both Central Asian Turkic groups and Mongols, while the Yakuts have close affinities with northeastern Siberian, Tungusic-speaking Evenks and south Siberian, Turkic-speaking Tuvans. This different ancestry of the Yakuts and the Tuvans (compared with other Turkic-speaking groups) most likely reflects extensive admixture that occurred between Turkic-speaking steppe groups and Evenks as the former migrated into Siberia. Moreover, the Yakuts are unique among Siberian populations in having a high number of haplotypes shared exclusively with Europeans, suggesting, contrary to the historical record, that occasionally Yakut men took Russian women as wives. PMID:12567375

  5. 49 CFR 40.265 - What happens when an employee is unable to provide a sufficient amount of breath for an alcohol...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... a sufficient amount of breath for an alcohol test? 40.265 Section 40.265 Transportation Office of... sufficient amount of breath for an alcohol test? (a) If an employee does not provide a sufficient amount of breath to permit a valid breath test, you must take the steps listed in this section. (b) As the BAT...

  6. 49 CFR 40.265 - What happens when an employee is unable to provide a sufficient amount of breath for an alcohol...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... a sufficient amount of breath for an alcohol test? 40.265 Section 40.265 Transportation Office of... sufficient amount of breath for an alcohol test? (a) If an employee does not provide a sufficient amount of breath to permit a valid breath test, you must take the steps listed in this section. (b) As the BAT...

  7. 49 CFR 40.265 - What happens when an employee is unable to provide a sufficient amount of breath for an alcohol...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... a sufficient amount of breath for an alcohol test? 40.265 Section 40.265 Transportation Office of... sufficient amount of breath for an alcohol test? (a) If an employee does not provide a sufficient amount of breath to permit a valid breath test, you must take the steps listed in this section. (b) As the BAT...

  8. 49 CFR 40.265 - What happens when an employee is unable to provide a sufficient amount of breath for an alcohol...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... a sufficient amount of breath for an alcohol test? 40.265 Section 40.265 Transportation Office of... sufficient amount of breath for an alcohol test? (a) If an employee does not provide a sufficient amount of breath to permit a valid breath test, you must take the steps listed in this section. (b) As the BAT...

  9. 49 CFR 40.265 - What happens when an employee is unable to provide a sufficient amount of breath for an alcohol...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... a sufficient amount of breath for an alcohol test? 40.265 Section 40.265 Transportation Office of... sufficient amount of breath for an alcohol test? (a) If an employee does not provide a sufficient amount of breath to permit a valid breath test, you must take the steps listed in this section. (b) As the BAT...

  10. 49 CFR 40.263 - What happens when an employee is unable to provide a sufficient amount of saliva for an alcohol...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... a sufficient amount of saliva for an alcohol screening test? 40.263 Section 40.263 Transportation... sufficient amount of saliva for an alcohol screening test? (a) As the STT, you must take the following steps if an employee is unable to provide sufficient saliva to complete a test on a saliva screening...

  11. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

    PubMed Central

    Nguyen, Liem H.; Robinton, Daisy A.; Seligson, Marc; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha; Yang, Erin; Powers, John T.; Shinoda, Gen; Shah, Samar; Hammer, Robert; Daley, George Q.; Zhu, Hao

    2014-01-01

    SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID:25117712

  12. Using Paraffin PCM to Make Optical Communication Type of Payloads Thermally Self-Sufficient for Operation in Orion Crew Module

    NASA Technical Reports Server (NTRS)

    Choi, Michael K.

    2016-01-01

    An innovative concept of using paraffin phase change material with a melting point of 28 C to make Optical Communication type of payload thermally self-sufficient for operation in the Orion Crew Module is presented. It stores the waste heat of the payload and permits it to operate for about one hour by maintaining its temperature within the maximum operating limit. It overcomes the problem of relying on the availability of cold plate heat sink in the Orion Crew Module.

  13. Are elevated serum amyloid A levels and amyloid-enhancing factor sufficient to induce inflammation-associated amyloid deposition?

    PubMed

    Kisilevsky, R; Tan, R; Subrahmanyan, L; Snow, A

    1984-01-01

    During inflammation-associated amyloidosis two coincident factors, serum amyloid A (SAA) and amyloid-enhancing factor (AEF) are apparently necessary for amyloid A (AA) deposition. It is shown by passive transfer of cytokines, which stimulate SAA production, and AEF that these are not sufficient. A further factor(s) is necessary, which stems from the acute inflammatory response. Potential candidates are serum or tissue glycosaminoglycans. PMID:6400464

  14. A combined system of microbial fuel cell and intermittently aerated biological filter for energy self-sufficient wastewater treatment.

    PubMed

    Dong, Yue; Feng, Yujie; Qu, Youpeng; Du, Yue; Zhou, Xiangtong; Liu, Jia

    2015-01-01

    Energy self-sufficiency is a highly desirable goal of sustainable wastewater treatment. Herein, a combined system of a microbial fuel cell and an intermittently aerated biological filter (MFC-IABF) was designed and operated in an energy self-sufficient manner. The system was fed with synthetic wastewater (COD = 1000 mg L(-1)) in continuous mode for more than 3 months at room temperature (~25 °C). Voltage output was increased to 5 ± 0.4 V using a capacitor-based circuit. The MFC produced electricity to power the pumping and aeration systems in IABF, concomitantly removing COD. The IABF operating under an intermittent aeration mode (aeration rate 1000 ± 80 mL h(-1)) removed the residual nutrients and improved the water quality at HRT = 7.2 h. This two-stage combined system obtained 93.9% SCOD removal and 91.7% TCOD removal (effluent SCOD = 61 mg L(-1), TCOD = 82.8 mg L(-1)). Energy analysis indicated that the MFC unit produced sufficient energy (0.27 kWh m(-3)) to support the pumping system (0.014 kWh m(-3)) and aeration system (0.22 kWh m(-3)). These results demonstrated that the combined MFC-IABF system could be operated in an energy self-sufficient manner, resulting to high-quality effluent. PMID:26666392

  15. Retrocausal Effects As A Consequence of Orthodox Quantum Mechanics Refined To Accommodate The Principle Of Sufficient Reason

    NASA Astrophysics Data System (ADS)

    Stapp, Henry P.

    2011-11-01

    The principle of sufficient reason asserts that anything that happens does so for a reason: no definite state of affairs can come into being unless there is a sufficient reason why that particular thing should happen. This principle is usually attributed to Leibniz, although the first recorded Western philosopher to use it was Anaximander of Miletus. The demand that nature be rational, in the sense that it be compatible with the principle of sufficient reason, conflicts with a basic feature of contemporary orthodox physical theory, namely the notion that nature's response to the probing action of an observer is determined by pure chance, and hence on the basis of absolutely no reason at all. This appeal to pure chance can be deemed to have no rational fundamental place in reason-based Western science. It is argued here, on the basis of the other basic principles of quantum physics, that in a world that conforms to the principle of sufficient reason, the usual quantum statistical rules will naturally emerge at the pragmatic level, in cases where the reason behind nature's choice of response is unknown, but that the usual statistics can become biased in an empirically manifest way when the reason for the choice is empirically identifiable. It is shown here that if the statistical laws of quantum mechanics were to be biased in this way then the basically forward-in-time unfolding of empirical reality described by orthodox quantum mechanics would generate the appearances of backward-time-effects of the kind that have been reported in the scientific literature.

  16. A combined system of microbial fuel cell and intermittently aerated biological filter for energy self-sufficient wastewater treatment

    PubMed Central

    Dong, Yue; Feng, Yujie; Qu, Youpeng; Du, Yue; Zhou, Xiangtong; Liu, Jia

    2015-01-01

    Energy self-sufficiency is a highly desirable goal of sustainable wastewater treatment. Herein, a combined system of a microbial fuel cell and an intermittently aerated biological filter (MFC-IABF) was designed and operated in an energy self-sufficient manner. The system was fed with synthetic wastewater (COD = 1000 mg L−1) in continuous mode for more than 3 months at room temperature (~25 °C). Voltage output was increased to 5 ± 0.4 V using a capacitor-based circuit. The MFC produced electricity to power the pumping and aeration systems in IABF, concomitantly removing COD. The IABF operating under an intermittent aeration mode (aeration rate 1000 ± 80 mL h−1) removed the residual nutrients and improved the water quality at HRT = 7.2 h. This two-stage combined system obtained 93.9% SCOD removal and 91.7% TCOD removal (effluent SCOD = 61 mg L−1, TCOD = 82.8 mg L−1). Energy analysis indicated that the MFC unit produced sufficient energy (0.27 kWh m−3) to support the pumping system (0.014 kWh m−3) and aeration system (0.22 kWh m−3). These results demonstrated that the combined MFC-IABF system could be operated in an energy self-sufficient manner, resulting to high-quality effluent. PMID:26666392

  17. Identification of Molecular Pathologies Sufficient to Cause Neuropathic Excitability in Primary Somatosensory Afferents Using Dynamical Systems Theory

    PubMed Central

    Rho, Young-Ah; Prescott, Steven A.

    2012-01-01

    Pain caused by nerve injury (i.e. neuropathic pain) is associated with development of neuronal hyperexcitability at several points along the pain pathway. Within primary afferents, numerous injury-induced changes have been identified but it remains unclear which molecular changes are necessary and sufficient to explain cellular hyperexcitability. To investigate this, we built computational models that reproduce the switch from a normal spiking pattern characterized by a single spike at the onset of depolarization to a neuropathic one characterized by repetitive spiking throughout depolarization. Parameter changes that were sufficient to switch the spiking pattern also enabled membrane potential oscillations and bursting, suggesting that all three pathological changes are mechanistically linked. Dynamical analysis confirmed this prediction by showing that excitability changes co-develop when the nonlinear mechanism responsible for spike initiation switches from a quasi-separatrix-crossing to a subcritical Hopf bifurcation. This switch stems from biophysical changes that bias competition between oppositely directed fast- and slow-activating conductances operating at subthreshold potentials. Competition between activation and inactivation of a single conductance can be similarly biased with equivalent consequences for excitability. “Bias” can arise from a multitude of molecular changes occurring alone or in combination; in the latter case, changes can add or offset one another. Thus, our results identify pathological change in the nonlinear interaction between processes affecting spike initiation as the critical determinant of how simple injury-induced changes at the molecular level manifest complex excitability changes at the cellular level. We demonstrate that multiple distinct molecular changes are sufficient to produce neuropathic changes in excitability; however, given that nerve injury elicits numerous molecular changes that may be individually sufficient to

  18. Sampling sufficiency for analyzing taxonomic relatedness of periphytic ciliate communities using an artificial substratum in coastal waters

    NASA Astrophysics Data System (ADS)

    Xu, Henglong; Zhang, Wei; Jiang, Yong; Zhu, Mingzhuang; Al-Rasheid, Khaled A. S.

    2012-08-01

    Taxonomic relatedness measures of ciliated protozoan communities have successively been used as useful indicators for assessing water quality in marine ecosystems with a number of desirable properties. Sampling sufficiency for analyzing taxonomic relatedness indices of periphytic ciliate communities was studied in coastal waters of the Yellow Sea, northern China, from May to June, 2010. Samples were collected at two depths of 1 m and 3 m using an artificial substratum (glass slides), and were analyzed based on different sampling strategies (slide replicates). For achieving a dissimilarity of < 10%, more slide replicates were required with shortening community ages: 3-10 slide replicates were sufficient for the young (1-7 days) communities while 2-4 slide replicates were for the mature (10-28 days). The standard errors of four taxonomic relatedness indices due to the sample sizes were increased only in the young communities with shortening colonization times. For achieving a standard error of < 10%, 1 slide replicate was generally sufficient for the mature communities, whereas 4-10 were required for the young. These findings suggested that low slide replicates were required for measuring taxonomic relatedness indices compared to analyzing the community patterns, and that these indices were more sensitive to the sample sizes of a young community than a mature one of periphytic ciliates in marine ecosystems.

  19. Microbial fuel cells for energy self-sufficient domestic wastewater treatment-a review and discussion from energetic consideration.

    PubMed

    Lefebvre, Olivier; Uzabiaga, Arnaud; Chang, In Seop; Kim, Byung-Hong; Ng, How Yong

    2011-01-01

    As the microbial fuel cell (MFC) technology is getting nearer to practical applications such as wastewater treatment, it is crucial to consider the different aspects that will make this technology viable in the future. In this paper, we provide information about the specifications of an energy self-sufficient MFC system as a basis to extrapolate on the potential benefits and limits of a future MFC-based wastewater treatment plant. We particularly emphasize on the importance of two crucial parameters that characterize an MFC: its electromotive force (E (emf)) and its internal resistance (R (int)). A numerical projection using state-of-art values (E (emf) = 0.8 V and R (int) = 5 Ω) emphasized on the difficulty at this moment to reach self-sufficiency using a reasonable number of MFCs at the laboratory scale. We found that a realistic number of MFCs to provide enough voltage (=5 V) at a sufficient current (=0.8 A) to power a pump requiring 4 W would be of 13 MFCs in series and 10 stacks of MFCs in parallel, resulting in a total number of 130 MFCs. That would result in a treatment capacity of 144 L of domestic wastewater (0.5 g-COD L(-1)) per day. The total MFC system would be characterized by an internal resistance of 6.5 Ω. PMID:20931187

  20. Self sufficient world

    ERIC Educational Resources Information Center

    George, Lynn

    1974-01-01

    Described the efforts of Sietze Leeflang, a Dutch scientific journalist, and his group of young scientists to take a practical stand on environmental pollution by working their small farm in innovative fashion. (RK)

  1. Necessary but Not Sufficient...

    PubMed Central

    Harvey, Gill; Kitson, Alison

    2015-01-01

    The challenge of mobilizing knowledge to improve patient care, population health and ensure effective use of resources is an enduring one in healthcare systems across the world. This commentary reflects on an earlier paper by Ferlie and colleagues that proposes the resource-based view (RBV) of the firm as a useful theoretical lens through which to study knowledge mobilization in healthcare. Specifically, the commentary considers 3 areas that need to be addressed in relation to the proposed application of RBV: the definition of competitive advantage in healthcare; the contribution of macro level theory to understanding knowledge mobilization in healthcare; and the need to embrace and align multiple theories at the micro, meso, and macro levels of implementation. PMID:26673476

  2. Some sufficient conditions for persistency and permanency of two stages DNA splicing languages via Yusof-Goode approach

    NASA Astrophysics Data System (ADS)

    Mudaber, Mohammad Hassan; Yusof, Yuhani; Mohamad, Mohd Sham

    2014-07-01

    Splicing system that was first introduced by Head makes a connection between field of formal language theory and molecular biology. This system modeled the biological process of splitting and ligating on double stranded deoxyribonucleic acid (DNA) molecules under effect of restriction enzymes and appropriate ligase. In this paper, the concept of two stages DNA splicing languages is introduced. Some sufficient conditions for persistency and permanency of the above DNA splicing languages focusing on two rules and two initial strings will be investigated by usingYusof-Good (Y-G) approach.

  3. An outboard shield design for TIBER-II with potential for tritium self-sufficiency: Appendix A-1

    SciTech Connect

    Sawan, M.E.; Sviatoslavsky, I.N.

    1987-01-01

    The outboard breeding shield design for TIBER-II is described. The design allows for tritium self-sufficiency without compromising magnet protection, design simplicity, and the testing mission of the device. The shield consists of a beryllium pebble front zone backed by a steel pebble zone. The shield is cooled by an aqueous solution containing 16 g LiNO/sub 3/ per 100 cm/sup 3/. A double first wall is used to insure uniform cooling and minimize pressure. The design pressure for the outboard shield is 0.19 MPa and the coolant temperature is less than 75/sup 0/C. 6 refs., 5 figs., 3 tabs.

  4. Giving Economically Disadvantaged, Minority Food Pantry Patrons' a Voice: Implications for Equitable Access to Sufficient, Nutritious Food.

    PubMed

    Greer, Anna E; Cross-Denny, Bronwyn; McCabe, Michelle; Castrogivanni, Brianna

    2016-01-01

    This study provides economically disadvantaged, minority food pantry patrons (hereafter, patrons) a meaning-ful voice by examining their experiences trying to obtain sufficient, nutritious food. Five focus groups were conducted using a semistructured discussion guide. Atlast.ti software was used to manage and analyze the data. Patrons reported that pantry staff who preserved their dignity by showing compassion were highly valued. Stigma and shame associated with pantry use were major concerns. Patrons suggested environmental and policy changes to improve their food acquisition experiences. These findings suggest that multilevel interventions addressing food access, food distribution policies, and patron-staff interactions are warranted. PMID:27214675

  5. Play It, Learn It, Make It Last: Developing an Online Game to Create Self-Sufficient Library Information Users.

    PubMed

    Boyce, Lindsay M

    2016-01-01

    Library orientation at an academic health sciences library consisted of a five-minute overview within new student orientation. Past experience indicated this brief presentation was insufficient for students to learn about library resources. In 2014, an effort was made to supplement orientation by developing an online game aimed at enabling students to become self-sufficient through hands-on learning. A gaming model was chosen with expectations that competition and rewards would motivate students. Although the pilots suffered from low participation rates, the experience merits further research into the potential of a broader model of online library instruction in the health sciences environment. PMID:27391178

  6. Evidence that a single monolayer tubulin-GTP cap is both necessary and sufficient to stabilize microtubules.

    PubMed Central

    Caplow, M; Shanks, J

    1996-01-01

    Evidence that 13 or 14 contiguous tubulin-GTP subunits are sufficient to cap and stabilize a microtubule end and that loss of only one of these subunits results in the transition to rapid disassembly(catastrophe) was obtained using the slowly hydrolyzable GTP analogue guanylyl-(a,b)-methylene-diphosphonate (GMPCPP). The minus end of microtubules assembled with GTP was transiently stabilized against dilution-induced disassembly by reaction with tubulin-GMPCPP subunits for a time sufficient to cap the end with an average 40 subunits. The minimum size of a tubulin-GMPCPP cap sufficient to prevent disassembly was estimated from an observed 25- to 2000-s lifetime of the GMPCPP-stabilized microtubules following dilution with buffer and from the time required for loss of a single tubulin-GMPCPP subunit from the microtubule end (found to be 15 s). Rather than assuming that the 25- to 2000-s dispersion in cap lifetime results from an unlikely 80-fold range in the number of tubulin-GMPCpP subunits added in the 25-s incubation, it is proposed that this results because the minimum stable cap contains 13 to 14 tubulin-GMPCPP subunits. As a consequence, a microtubule capped with 13-14 tubulin-GMPCPP subunits switches to disassembly after only one dissociation event (in about 15 s), whereas the time required for catastrophe of a microtubule with only six times as many subunits (84 subunits) corresponds to 71 dissociation events (84-13). The minimum size of a tubulin-GMPCPP cap sufficient to prevent disassembly was also estimated with microtubules in which a GMPCPP-cap was formed by allowing chance to result in the accumulation of multiple contiguous tubulin-GMPCPP subunits at the end, during the disassembly of microtubules containing both GDP and GMPCPP. Our observation that the disassembly rate was inhibited in proportion to the 13-14th power of the fraction of subunits containing GMPCPP again suggests that a minimum cap contains 13-14 tubulin-GMPCPP subunits. A remeasurement of

  7. Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

    PubMed Central

    Ashhad, Sufyan; Johnston, Daniel

    2014-01-01

    The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if InsP3R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of d-myo-InsP3 in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP3 concentration, emphasizing the graded dependence of such plasticity on InsP3R activation. Mechanistically, we found that this InsP3-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP3Rs, the influx of calcium through N-methyl-d-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP3Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis. PMID:25552640

  8. Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate

    PubMed Central

    Wu, Fuguo; Kaczynski, Tadeusz J.; Sethuramanujam, Santhosh; Li, Renzhong; Jain, Varsha; Slaughter, Malcolm; Mu, Xiuqian

    2015-01-01

    As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors—atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)—occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear. Here we report that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate. The RGCs thus formed are largely normal in gene expression, survive to postnatal stages, and are physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for the RGC fate. We further conclude that during development a core group of limited transcription factors, including Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and initiate RGC differentiation. PMID:25775587

  9. Circulating C3 is necessary and sufficient for induction of autoantibody-mediated arthritis in a mouse model

    PubMed Central

    Monach, Paul A; Verschoor, Admar; Jacobs, Jonathan P; Carroll, Michael C; Wagers, Amy J; Benoist, Christophe; Mathis, Diane

    2007-01-01

    Objective For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation. Methods Radiation bone marrow chimeras between normal and C3−/− mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3−/− mice to irradiated wild-type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice. Results In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum-transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3. Conclusion In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction. PMID:17763447

  10. Linear and ponderal growth trajectories in well-nourished, iron-sufficient infants are unimpaired by iron supplementation.

    PubMed

    Gahagan, Sheila; Yu, Sunkyung; Kaciroti, Niko; Castillo, Marcela; Lozoff, Betsy

    2009-11-01

    Iron deficiency remains the most common nutritional deficiency worldwide and supplementation is recommended during periods of high risk, including infancy. However, questions have been raised about possible adverse effects of iron on growth in iron-sufficient (IS) infants and the advisability of across-the-board iron supplementation. This study examined whether short- or long-term growth was impaired in IS infants who received iron supplementation. From a longitudinal study of healthy, breast-fed, low- to middle-income Chilean infants randomly assigned to iron supplementation or usual nutrition at 6 or 12 mo, we retrospectively identified infants meeting criteria for iron sufficiency at the time of random assignment (n = 273). Using multilevel analysis, ponderal and linear growth were modeled before, during, and after iron supplementation up to 10 y in 3 comparisons: 1) iron supplementation compared with usual nutrition from 6 to 12 mo; 2) iron supplementation compared with usual nutrition from 12 to 18 mo; and 3) 15 mg/d of iron as drops compared with iron-fortified formula (12 mg/L). Growth trajectories did not differ during or after supplementation indicating no adverse effect of iron in any comparison. These results suggest that, at least in some environments, iron does not impair growth in IS infants. PMID:19776186

  11. Engineering of daidzein 3’-hydroxylase P450 enzyme into catalytically self-sufficient cytochrome P450

    PubMed Central

    2012-01-01

    A cytochrome P450 (CYP) enzyme, 3’-daidzein hydroxylase, CYP105D7 (3’-DH), responsible for daidzein hydroxylation at the 3’-position, was recently reported. CYP105D7 (3’-DH) is a class I type of CYP that requires electrons provided through electron transfer proteins such as ferredoxin and ferredoxin reductase. Presently, we constructed an artificial CYP in order to develop a reaction host for the production of a hydroxylated product. Fusion-mediated construction with the reductase domain from self-sufficient CYP102D1 was done to increase electron transfer efficiency and coupling with the oxidative process. An artificial self-sufficient daidzein hydroxylase (3’-ASDH) displayed distinct spectral properties of both flavoprotein and CYP. The fusion enzyme catalyzed hydroxylation of daidzein more efficiently, with a kcat/Km value of 16.8 μM-1 min-1, which was about 24-fold higher than that of the 3’-DH-camA/B reconstituted enzyme. Finally, a recombinant Streptomyces avermitilis host for the expression of 3’-ASDH and production of the hydroxylated product was developed. The conversion that was attained (34.6%) was 5.2-fold higher than that of the wild-type. PMID:22697884

  12. Do street food vendors sell a sufficient variety of foods for a healthful diet? The case of Nairobi.

    PubMed

    Mwangi, Alice Mboganie; den Hartog, Adel P; Mwadime, Robert K N; van Staveren, Wija A; Foeken, Dick W J

    2002-03-01

    This study examined whether street food vendors sell a sufficient variety of foods for a healthful diet. It was hypothesized that vendors sold only low-cost food groups to enable the buyer to afford the food while the vendor also made a profit. A structured questionnaire was administered to 580 vendors in three selected locations. Data included product names, ingredients, methods of preparation, and the sex of the vendor. A little more than half of the vendors (53%) sold food of only one group; 44% sold cereals. Overall, 36% of vendors, mostly men, sold only carbohydrate products. The percentage of vendors selling foods of more than one group was higher in the working area (53%) than in the slum area (43%, p < .05), and it was higher in both of these areas taken together than in the lower-middle income area (21%, p < .001). Micronutrient and mixed-nutrient products were associated with female vendors. Although a slight majority of all street vendors sell foods of only one group, women vendors are capable of supplying a sufficient variety of food groups that consumers can afford. It appears that consumer purchasing power dictates the food groups provided by vendors, especially cereal-based-foods. A policy on micronutrient fortification of cereal flours and fats used in popular street food preparation needs to be considered. This could be coupled with consumer and vendor education programs focusing on the importance of healthful diets. PMID:11975369

  13. 49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must...

  14. 49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must...

  15. 49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must...

  16. 49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must...

  17. IS PROTOSTELLAR HEATING SUFFICIENT TO HALT FRAGMENTATION? A CASE STUDY OF THE MASSIVE PROTOCLUSTER G8.68-0.37

    SciTech Connect

    Longmore, S. N.; Pillai, T.; Keto, E.; Zhang, Q.; Qiu, K.

    2011-01-10

    If star formation proceeds by thermal fragmentation and the subsequent gravitational collapse of the individual fragments, how is it possible to form fragments massive enough for O and B stars in a typical star-forming molecular cloud where the Jeans mass is about 1 M{sub sun} at the typical densities (10{sup 4} cm{sup -3}) and temperatures (10 K)? We test the hypothesis that a first generation of low-mass stars may heat the gas enough that subsequent thermal fragmentation results in fragments {>=}10 M{sub sun}, sufficient to form B stars. We combine ATCA and Submillimeter Array observations of the massive star-forming region G8.68-0.37 with radiative transfer modeling to derive the present-day conditions in the region and use this to infer the conditions in the past, at the time of core formation. Assuming that the current mass/separation of the observed cores equals the fragmentation Jeans mass/length and the region's average density has not changed requires the gas temperature to have been 100 K at the time of fragmentation. The postulated first generation of low-mass stars would still be around today, but the number required to heat the cloud exceeds the limits imposed by the observations. Several lines of evidence suggest the observed cores in the region should eventually form O stars yet none have sufficient raw material. Even if feedback may have suppressed fragmentation, it was not sufficient to halt it to this extent. To develop into O stars, the cores must obtain additional mass from outside their observationally defined boundaries. The observations suggest that they are currently fed via infall from the very massive reservoir ({approx}1500 M{sub sun}) of gas in the larger parsec scale cloud around the star-forming cores. This suggests that massive stars do not form in the collapse of individual massive fragments, but rather in smaller fragments that themselves continue to gain mass by accretion from larger scales.

  18. Secretory phospholipase A{sub 2} mediates progression of acute liver injury in the absence of sufficient cyclooxygenase-2

    SciTech Connect

    Bhave, Vishakha S.; Donthamsetty, Shashikiran; Latendresse, John R.; Muskhelishvili, Levan; Mehendale, Harihara M.

    2008-04-15

    Previous studies have shown that injury initiated by toxicants progresses even after most of the toxicant is eliminated from the body. One mechanism of progression of injury is the extracellular appearance of hydrolytic enzymes following leakage or upon cell lyses. Under normal conditions, after exposure to low to moderate doses of toxicants, secretory phospholipase A{sub 2} (sPLA{sub 2}) and other hydrolytic enzymes are known to appear in the extracellular spaces in order to cleanup the post-necrotic debris in tissues. We tested the hypothesis that sPLA{sub 2} contributes to progression of toxicant-initiated liver injury because of hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas in the absence of sufficient cyclooxygenase-2 (COX-2). Male Sprague-Dawley rats were administered either a moderately hepatotoxic dose (MD, 2 ml CCl{sub 4}/kg, ip) or a highly hepatotoxic dose (HD, 3 ml CCl{sub 4}/kg, ip) of CCl{sub 4}. After MD, liver sPLA{sub 2} and COX-2 were co-localized in the necrotic and perinecrotic areas and their activities in plasma and liver increased before decreasing in tandem with liver injury (ALT and histopathology) leading to 100% survival. In contrast, after the HD, high extracellular and hepatic sPLA{sub 2} activities were accompanied by minimal COX-2 activity and localization in the liver throughout the time course. This led to progression of liver injury and 70% mortality. These data suggested a destructive role of sPLA{sub 2} in the absence of sufficient COX-2. Time- and dose-dependent destruction of hepatocytes by sPLA{sub 2} in isolated hepatocyte incubations confirmed the destructive ability of sPLA{sub 2} when present extracellularly, suggesting its ability to spread injury in vivo. These findings suggest that sPLA{sub 2}, secreted for cleanup of necrotic debris upon initiation of hepatic necrosis, requires the co-presence of sufficiently induced COX-2 activity to prevent the run-away destructive action of sPLA{sub 2

  19. The Effect of Herbal Tea Containing Fenugreek Seed on the Signs of Breast Milk Sufficiency in Iranian Girl Infants

    PubMed Central

    Ghasemi, Vida; Kheirkhah, Masoomeh; Vahedi, Mohsen

    2015-01-01

    Background: One of the important reasons behind termination of breast-feeding in the first six months after childbirth is insufficient production of breast milk. Objectives: The aim of this study was to determine the effect of herbal tea containing fenugreek seed on the signs of breast milk sufficiency in Iranian girl infants aged 0 - 4 months, at the medical health centers of Tehran university of medical sciences. Patients and Methods: This study was a clinical trial with a control group. Seventy-eight girl infants, 0 - 4 months old that were exclusively breastfed by their mothers, were randomly assigned to the intervention group (received herbal tea containing 7.5 g fenugreek seed powder in addition to 3 g of black tea, three times a day) and the control group (received herbal tea containing 3 g of black tea powder, three times a day). Before and during the four weeks of study, the signs of breast milk sufficiency were evaluated through measurement of growth parameters and use of follow-up forms for measuring the number of wet diapers in one day, frequency of defecation and infant breast-feeding times in a day. Results: Before the intervention there was no significant difference between weight, height, head circumference, the number of wet diapers and frequency of defecation between the two groups (P > 0.05), yet the number of breast feeding times of the control group was more than the Fenugreek group. At the end of the fourth week in proportion to the pre-intervention conditions, the weight of the infants in the fenugreek group increased significantly from 5282.0513 ± 1021.51121 to 6383.0769 ± 952.06190, while head circumference increased from 38.3103 ± 1.62736 to 39.9256 ± 1.50660, number of wet diapers from 5.2821 ± 0.93044 to 8.1648 ± 1.20620, frequency of defecation from 1.8846 ± 1.08495 to 2.7326 ± 0.94771 and the number of breast feeding times from 9.1795 ± 1.39778 to 15.9597 ± 1.45056 (P < 0.001). However, there was no significant effect on

  20. The Intracellular Concentration of Acetyl Phosphate in Escherichia coli Is Sufficient for Direct Phosphorylation of Two-Component Response Regulators▿

    PubMed Central

    Klein, Adam H.; Shulla, Ana; Reimann, Sylvia A.; Keating, David H.; Wolfe, Alan J.

    2007-01-01

    Acetyl phosphate, the intermediate of the AckA-Pta pathway, acts as a global signal in Escherichia coli. Although acetyl phosphate clearly signals through two-component response regulators, it remains unclear whether acetyl phosphate acts as a direct phospho donor or functions through an indirect mechanism. We used two-dimensional thin-layer chromatography to measure the relative concentrations of acetyl phosphate, acetyl coenzyme A, ATP, and GTP over the course of the entire growth curve. We estimated that the intracellular concentration of acetyl phosphate in wild-type cells reaches at least 3 mM, a concentration sufficient to activate two-component response regulators via direct phosphoryl transfer. PMID:17545286

  1. Membrane disordering is not sufficient for membrane permeabilization by islet amyloid polypeptide: studies of IAPP(20-29) fragments.

    PubMed

    Brender, Jeffrey R; Heyl, Deborah L; Samisetti, Shyamprasad; Kotler, Samuel A; Osborne, Joshua M; Pesaru, Ranadheer R; Ramamoorthy, Ayyalusamy

    2013-06-21

    A key factor in the development of type II diabetes is the loss of insulin-producing beta-cells. Human islet amyloid polypeptide protein (human-IAPP) is believed to play a crucial role in this process by forming small aggregates that exhibit toxicity by disrupting the cell membrane. The actual mechanism of membrane disruption is complex and appears to involve an early component before fiber formation and a later component associated with fiber formation on the membrane. By comparing the peptide-lipid interactions derived from solid-state NMR experiments of two IAPP fragments that cause membrane disordering to IAPP derived peptides known to cause significant early membrane permeabilization, we show here that membrane disordering is not likely to be sufficient by itself to cause the early membrane permeabilization observed by IAPP, and may play a lesser role in IAPP membrane disruption than expected. PMID:23493863

  2. Membrane Disordering is not Sufficient for Membrane Permeabilization by Islet Amyloidogenic Polypeptide: Studies of IAPP(20-29) Fragments

    PubMed Central

    Brender, Jeffrey R.; Heyl, Deborah L.; Samisetti, Shyamprasad; Kotler, Samuel A.; Osborne, Joshua M.; Pesaru, Ranadheer R.; Ramamoorthy, Ayyalusamy

    2013-01-01

    A key factor in the development of type II diabetes is the loss of insulin-producing beta-cells. Human islet amyloid polypeptide protein (human-IAPP) is believed to play a crucial role in this process by forming small aggregates that exhibit toxicity by disrupting the cell membrane. The actual mechanism of membrane disruption is complex and appears to involve an early component before fiber formation and later component associated with fiber formation on the membrane. By comparing the peptide-lipid interactions derived from solid-state NMR experiments of two IAPP fragments that bind the membrane and cause membrane disordering to IAPP derived peptides known to cause significant early membrane permeabilization, we show here that membrane disordering is not likely to be sufficient by itself to cause the early membrane permeabilization observed by IAPP, and may play a lesser role in IAPP membrane disruption than expected. PMID:23493863

  3. The N-X-S/T consensus sequence is required but not sufficient for bacterial N-linked protein glycosylation.

    PubMed

    Nita-Lazar, Mihai; Wacker, Michael; Schegg, Belinda; Amber, Saba; Aebi, Markus

    2005-04-01

    In the Gram-negative bacterium Campylobacter jejuni there is a pgl (protein glycosylation) locus-dependent general N-glycosylation system of proteins. One of the proteins encoded by pgl locus, PglB, a homolog of the eukaryotic oligosaccharyltransferase component Stt3p, is proposed to function as an oligosaccharyltransferase in this prokaryotic system. The sequence requirements of the acceptor polypeptide for N-glycosylation were analyzed by reverse genetics using the reconstituted glycosylation of the model protein AcrA in Escherichia coli. As in eukaryotes, the N-X-S/T sequon is an essential but not a sufficient determinant for N-linked protein glycosylation. This conclusion was supported by the analysis of a novel C. jejuni glycoprotein, HisJ. Export of the polypeptide to the periplasm was required for glycosylation. Our data support the hypothesis that eukaryotic and bacterial N-linked protein glycosylation are homologous processes. PMID:15574802

  4. MMP-14 is necessary but not sufficient for invasion of three-dimensional collagen by human muscle satellite cells

    PubMed Central

    Lund, Dane K.; Mouly, Vincent

    2014-01-01

    The twenty-five known matrix metalloproteases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteases (TIMPs), mediate cell invasion through the extracellular matrix (ECM). In a comparative three-dimensional assay, we analyzed human and mouse satellite cells' competence to invade an artificial ECM (collagen I). We identified a single MMP that 1) is expressed by human muscle satellite cells; 2) is induced at the mRNA/protein level by adhesion to collagen I; and 3) is necessary for invasion into a collagen I matrix. Interestingly, murine satellite cells neither express this MMP, nor invade the collagen matrix. However, exogenous human MMP-14 is not sufficient to induce invasion of a collagen matrix by murine cells, emphasizing species differences. PMID:24898588

  5. MMP-14 is necessary but not sufficient for invasion of three-dimensional collagen by human muscle satellite cells.

    PubMed

    Lund, Dane K; Mouly, Vincent; Cornelison, D D W

    2014-07-15

    The twenty-five known matrix metalloproteases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteases (TIMPs), mediate cell invasion through the extracellular matrix (ECM). In a comparative three-dimensional assay, we analyzed human and mouse satellite cells' competence to invade an artificial ECM (collagen I). We identified a single MMP that 1) is expressed by human muscle satellite cells; 2) is induced at the mRNA/protein level by adhesion to collagen I; and 3) is necessary for invasion into a collagen I matrix. Interestingly, murine satellite cells neither express this MMP, nor invade the collagen matrix. However, exogenous human MMP-14 is not sufficient to induce invasion of a collagen matrix by murine cells, emphasizing species differences. PMID:24898588

  6. TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

    NASA Technical Reports Server (NTRS)

    Zhang, D.; Gaussin, V.; Taffet, G. E.; Belaguli, N. S.; Yamada, M.; Schwartz, R. J.; Michael, L. H.; Overbeek, P. A.; Schneider, M. D.

    2000-01-01

    The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

  7. Necessary and sufficient condition for steerability of two-qubit states by the geometry of steering outcomes

    NASA Astrophysics Data System (ADS)

    Chau Nguyen, H.; Vu, Thanh

    2016-07-01

    Fully characterizing the steerability of a quantum state of a bipartite system has remained an open problem ever since the concept of steerability was first defined. In this paper, using our recent geometrical approach to steerability, we suggest a necessary and sufficient condition for a two-qubit state to be steerable with respect to projective measurements. To this end, we define the critical radius of local models and show that a state of two qubits is steerable with respect to projective measurements from Alice's side if and only if her critical radius of local models is less than 1. As an example, we calculate the critical radius of local models for the so-called T-states by proving the optimality of a recently suggested local hidden state model.

  8. Life cycle assessment of energy self-sufficiency systems based on agricultural residues for organic arable farms.

    PubMed

    Kimming, M; Sundberg, C; Nordberg, A; Baky, A; Bernesson, S; Norén, O; Hansson, P-A

    2011-01-01

    The agricultural industry today consumes large amounts of fossil fuels. This study used consequential life cycle assessment (LCA) to analyse two potential energy self-sufficient systems for organic arable farms, based on agricultural residues. The analysis focused on energy balance, resource use and greenhouse gas (GHG) emissions. A scenario based on straw was found to require straw harvest from 25% of the farm area; 45% of the total energy produced from the straw was required for energy carrier production and GHG emissions were reduced by 9% compared with a fossil fuel-based reference scenario. In a scenario based on anaerobic digestion of ley, the corresponding figures were 13%, 24% and 35%. The final result was sensitive to assumptions regarding, e.g., soil carbon content and handling of by-products. PMID:20970998

  9. How close is close: 16S rRNA sequence identity may not be sufficient to guarantee species identity

    NASA Technical Reports Server (NTRS)

    Fox, G. E.; Wisotzkey, J. D.; Jurtshuk, P. Jr

    1992-01-01

    16S rRNA (genes coding for rRNA) sequence comparisons were conducted with the following three psychrophilic strains: Bacillus globisporus W25T (T = type strain) and Bacillus psychrophilus W16AT, and W5. These strains exhibited more than 99.5% sequence identity and within experimental uncertainty could be regarded as identical. Their close taxonomic relationship was further documented by phenotypic similarities. In contrast, previously published DNA-DNA hybridization results have convincingly established that these strains do not belong to the same species if current standards are used. These results emphasize the important point that effective identity of 16S rRNA sequences is not necessarily a sufficient criterion to guarantee species identity. Thus, although 16S rRNA sequences can be used routinely to distinguish and establish relationships between genera and well-resolved species, very recently diverged species may not be recognizable.

  10. Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts.

    PubMed

    Li, Jun; Wu, Chuanchuan; Wang, Hui; Liu, Huanyuan; Vuitton, Dominique A; Wen, Hao; Zhang, Wenbao

    2014-01-01

    Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis. PMID:25456565

  11. Necessary and sufficient conditions for the boundedness of rough B-fractional integral operators in the Lorentz spaces

    NASA Astrophysics Data System (ADS)

    Guliyev, Vagif S.; Serbetci, Ayhan; Ekincioglu, Ismail

    2007-12-01

    In this paper, the necessary and sufficient conditions are found for the boundedness of the rough B-fractional integral operators from the Lorentz spaces Lp,s,[gamma] to Lq,r,[gamma], 1

  12. Low level expression of glycine receptor beta subunit transgene is sufficient for phenotype correction in spastic mice.

    PubMed Central

    Hartenstein, B; Schenkel, J; Kuhse, J; Besenbeck, B; Kling, C; Becker, C M; Betz, H; Weiher, H

    1996-01-01

    Mutations in inhibitory glycine receptor (GlyR) subunit genes are associated with neuromotor diseases in man and mouse. To use the potential of the mouse mutants as animal models of human disease, we altered GlyR levels in mutant mice and studied their phenotype. A transgene coding for the beta subunit of the rat GlyR was introduced into the genetic background of the spa mutation, which is characterized by low endogenous expression levels of the beta subunit and a dramatic neuromotor phenotype. The resulting transgenic mice expressed the beta subunit mRNA at intermediate levels, and their phenotype was rescued. This provides formal proof for the casual relationship between GlyR beta gene mutation and motor disease, and indicates that a low level of beta gene expression (25% of normal) is sufficient for proper functioning of glycinergic synapses. Images PMID:8635460

  13. Use of non-petroleum fuels to reduce military energy vulnerabilities: self-sufficient bases and new weapon propulsion systems

    SciTech Connect

    Freiwald, D.A.

    1980-01-01

    The US fossil synfuels program may not have significant impact on domestic fuel supplies until near the year 2000, resulting in a continuing mobility fuels vulnerability for the US military until then. But there are other mobility fuel options for both propulsion systems and stationary base-energy sources, for which the base technology is commercially available or at least demonstrated. For example, for surface propulsion systems, hydrogen-fuel-cell/battery-electric hybrids may be considered; for weapons systems these may offer some new flexibilities, standardization possibilities, and multiple military-controlled fuel-supply options. Hydrogen-fueled aircraft may provide interesting longer-term possibilities in terms of military energy self-sufficiency and multiple supply options, as well as performance specifications. These scenarios will be discussed, along with possibilities for demonstrations in the MX-system ground vehicles.

  14. Low levels of glutathione are sufficient for survival of keratinocytes after UV irradiation and for healing of mouse skin wounds.

    PubMed

    Telorack, Michèle; Abplanalp, Jeannette; Werner, Sabine

    2016-08-01

    Reduced levels of the cellular antioxidant glutathione are associated with premature skin aging, cancer and impaired wound healing, but the in vivo functions of glutathione in the skin remain largely unknown. Therefore, we analyzed mice lacking the modifier subunit of the glutamate cysteine ligase (Gclm), the enzyme that catalyzes the rate-limiting step of glutathione biosynthesis. Glutathione levels in the skin of these mice were reduced by 70 %. However, neither skin development and homeostasis, nor UVA- or UVB-induced apoptosis in the epidermis were affected. Histomorphometric analysis of excisional wounds did not reveal wound healing abnormalities in young Gclm-deficient mice, while the area of hyperproliferative epithelium as well as keratinocyte proliferation were affected in aged mice. These findings suggest that low levels of glutathione are sufficient for wound repair in young mice, but become rate-limiting upon aging. PMID:27262586

  15. A simple negative interaction in the positive transcriptional feedback of a single gene is sufficient to produce reliable oscillations.

    PubMed

    Miró-Bueno, Jesús M; Rodríguez-Patón, Alfonso

    2011-01-01

    Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. PMID:22205920

  16. A Simple Negative Interaction in the Positive Transcriptional Feedback of a Single Gene Is Sufficient to Produce Reliable Oscillations

    PubMed Central

    Miró-Bueno, Jesús M.; Rodríguez-Patón, Alfonso

    2011-01-01

    Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. PMID:22205920

  17. Synaptic vesicle exocytosis and increased cytosolic calcium are both necessary but not sufficient for activity-dependent bulk endocytosis.

    PubMed

    Morton, Andrew; Marland, Jamie R K; Cousin, Michael A

    2015-08-01

    Activity-dependent bulk endocytosis (ADBE) is the dominant synaptic vesicle (SV) endocytosis mode in central nerve terminals during intense neuronal activity. By definition this mode is triggered by neuronal activity; however, key questions regarding its mechanism of activation remain unaddressed. To determine the basic requirements for ADBE triggering in central nerve terminals, we decoupled SV fusion events from activity-dependent calcium influx using either clostridial neurotoxins or buffering of intracellular calcium. ADBE was monitored both optically and morphologically by observing uptake of the fluid phase markers tetramethylrhodamine-dextran and horse radish peroxidase respectively. Ablation of SV fusion with tetanus toxin resulted in the arrest of ADBE, but had no effect on other calcium-dependent events such as activity-dependent dynamin I dephosphorylation, indicating that SV exocytosis is necessary for triggering. Furthermore, the calcium chelator EGTA abolished ADBE while leaving SV exocytosis intact, demonstrating that ADBE is triggered by intracellular free calcium increases outside the active zone. Activity-dependent dynamin I dephosphorylation was also arrested in EGTA-treated neurons, consistent with its proposed role in triggering ADBE. Thus, SV fusion and increased cytoplasmic free calcium are both necessary but not sufficient individually to trigger ADBE. Activity-dependent bulk endocytosis (ADBE) is the dominant synaptic vesicle (SV) endocytosis mode in central nerve terminals during intense neuronal activity. To determine the minimal requirements for ADBE triggering, we decoupled SV fusion events from activity-dependent calcium influx using either clostridial neurotoxins or buffering of intracellular calcium. We found that SV fusion and increased cytoplasmic free calcium are both necessary but not sufficient to trigger ADBE. PMID:25913068

  18. Internalin of Listeria monocytogenes with an intact leucine-rich repeat region is sufficient to promote internalization.

    PubMed Central

    Lecuit, M; Ohayon, H; Braun, L; Mengaud, J; Cossart, P

    1997-01-01

    Listeria monocytogenes can use two different surface proteins, internalin (InlA) and InlB, to invade mammalian cells. The exact role of these invasiveness factors in vivo remains to be determined. In cultured cells, InlA is necessary to promote Listeria entry into human epithelial cells, such as Caco-2 cells, whereas InlB is necessary to promote Listeria internalization in several other cell types, including hepatocytes, fibroblasts, and epithelioid cells, such as Vero, HeLa, CHO, or Hep-2 cells. We have recently reported that the InlA receptor on Caco-2 cells is the cell adhesion molecule E-cadherin and demonstrated that nonpermissive fibroblasts become permissive for internalin-mediated entry when transfected with the gene coding for LCAM, the chicken homolog of the human E-cadherin gene. In this study, we demonstrate for the first time that the internalin protein alone is sufficient to promote internalization into cells expressing its receptor. Indeed, internalin confers invasiveness to both Enterococcus faecalis and internalin-coated latex beads. As shown by transmission electron microscopy, these beads were phagocytosed via a "zipper" mechanism similar to that observed during the internalin-E-cadherin-mediated entry of Listeria. Moreover, a functional analysis of internalin demonstrates that its amino-terminal region, encompassing the leucine-rich repeat (LRR) region and the inter-repeat (IR) region, is necessary and sufficient to promote bacterial entry into cells expressing its receptor. Several lines of evidence suggest that the LRR region would interact directly with E-cadherin, whereas the IR region would be required for a proper folding of the LRR region. PMID:9393831

  19. A Small Conserved Domain in the Yeast Spa2p Is Necessary and Sufficient for Its Polarized Localization

    PubMed Central

    Arkowitz, Robert A.; Lowe, Nick

    1997-01-01

    SPA2 encodes a yeast protein that is one of the first proteins to localize to sites of polarized growth, such as the shmoo tip and the incipient bud. The dynamics and requirements for Spa2p localization in living cells are examined using Spa2p green fluorescent protein fusions. Spa2p localizes to one edge of unbudded cells and subsequently is observable in the bud tip. Finally, during cytokinesis Spa2p is present as a ring at the mother–daughter bud neck. The bud emergence mutants bem1 and bem2 and mutants defective in the septins do not affect Spa2p localization to the bud tip. Strikingly, a small domain of Spa2p comprised of 150 amino acids is necessary and sufficient for localization to sites of polarized growth. This localization domain and the amino terminus of Spa2p are essential for its function in mating. Searching the yeast genome database revealed a previously uncharacterized protein which we name, Sph1p (Spa2p homolog), with significant homology to the localization domain and amino terminus of Spa2p. This protein also localizes to sites of polarized growth in budding and mating cells. SPH1, which is similar to SPA2, is required for bipolar budding and plays a role in shmoo formation. Overexpression of either Spa2p or Sph1p can block the localization of either protein fused to green fluorescent protein, suggesting that both Spa2p and Sph1p bind to and are localized by the same component. The identification of a 150–amino acid domain necessary and sufficient for localization of Spa2p to sites of polarized growth and the existence of this domain in another yeast protein Sph1p suggest that the early localization of these proteins may be mediated by a receptor that recognizes this small domain. PMID:9214378

  20. Forebrain-specific CRF overproduction during development is sufficient to induce enduring anxiety and startle abnormalities in adult mice.

    PubMed

    Toth, Mate; Gresack, Jodi E; Bangasser, Debra A; Plona, Zach; Valentino, Rita J; Flandreau, Elizabeth I; Mansuy, Isabelle M; Merlo-Pich, Emilio; Geyer, Mark A; Risbrough, Victoria B

    2014-05-01

    Corticotropin releasing factor (CRF) regulates physiological and behavioral responses to stress. Trauma in early life or adulthood is associated with increased CRF in the cerebrospinal fluid and heightened anxiety. Genetic variance in CRF receptors is linked to altered risk for stress disorders. Thus, both heritable differences and environmentally induced changes in CRF neurotransmission across the lifespan may modulate anxiety traits. To test the hypothesis that CRF hypersignaling is sufficient to modify anxiety-related phenotypes (avoidance, startle, and conditioned fear), we induced transient forebrain-specific overexpression of CRF (CRFOE) in mice (1) during development to model early-life stress, (2) in adulthood to model adult-onset stress, or (3) across the entire postnatal lifespan to model heritable increases in CRF signaling. The consequences of these manipulations on CRF peptide levels and behavioral responses were examined in adulthood. We found that transient CRFOE during development decreased startle habituation and prepulse inhibition, and increased avoidance (particularly in females) recapitulating the behavioral effects of lifetime CRFOE despite lower CRF peptide levels at testing. In contrast, CRFOE limited to adulthood reduced contextual fear learning in females and increased startle reactivity in males but did not change avoidance or startle plasticity. These findings suggest that forebrain CRFOE limited to development is sufficient to induce enduring alterations in startle plasticity and anxiety, while forebrain CRFOE during adulthood results in a different phenotype profile. These findings suggest that startle circuits are particularly sensitive to forebrain CRFOE, and that the impact of CRFOE may be dependent on the time of exposure. PMID:24326400

  1. Orbital apocenter is not a sufficient condition for HST/STIS detection of Europa's water vapor aurora.

    PubMed

    Roth, Lorenz; Retherford, Kurt D; Saur, Joachim; Strobel, Darrell F; Feldman, Paul D; McGrath, Melissa A; Nimmo, Francis

    2014-12-01

    We report far-ultraviolet observations of Jupiter's moon Europa taken by Space Telescope Imaging Spectrograph (STIS) of the Hubble Space Telescope (HST) in January and February 2014 to test the hypothesis that the discovery of a water vapor aurora in December 2012 by local hydrogen (H) and oxygen (O) emissions with the STIS originated from plume activity possibly correlated with Europa's distance from Jupiter through tidal stress variations. The 2014 observations were scheduled with Europa near the apocenter similar to the orbital position of its previous detection. Tensile stresses on south polar fractures are expected to be highest in this orbital phase, potentially maximizing the probability for plume activity. No local H and O emissions were detected in the new STIS images. In the south polar region where the emission surpluses were observed in 2012, the brightnesses are sufficiently low in the 2014 images to be consistent with any H2O abundance from (0-5)×10(15) cm(-2). Large high-latitude plumes should have been detectable by the STIS, independent of the observing conditions and geometry. Because electron excitation of water vapor remains the only viable explanation for the 2012 detection, the new observations indicate that although the same orbital position of Europa for plume activity may be a necessary condition, it is not a sufficient condition. However, the December 2012 detection of coincident HI Lyman-α and OI 1304-Å emission surpluses in an ∼200-km high region well separated above Europa's limb is a firm result and not invalidated by our 2014 STIS observations. PMID:25404343

  2. SU-E-J-245: Is Off-Line Adaptive Radiotherapy Sufficient for Head and Neck Cancer with IGRT?

    SciTech Connect

    Li, Z; Shang, Q; Liu, H; Greskovich, J; Koyfman, S; Xia, P

    2014-06-01

    Purpose: Radiation doses delivered to patients with head and neck cancer (HN) may deviate from the planned doses because of variations in patient setup and anatomy. This study was to evaluate whether off-line Adaptive Radiotherapy (ART) is sufficient. Methods: Ten HN patients, who received IMRT under daily imaging guidance using CT-on-rail/KV-CBCT, were randomly selected for this study. For each patient, the daily treatment setup was corrected with translational only directions. Sixty weekly verification CTs were retrospectively analyzed. On these weekly verification CTs, the tumor volumes and OAR contours were manually delineated by a physician. With the treatment iso-center placed on the verification CTs, according to the recorded clinical shifts, the treatment beams from the original IMRT plans were then applied to these CTs to calculate the delivered doses. The electron density of the planning CTs and weekly CTs were overridden to 1 g/cm3. Results: Among 60 fractions, D99 of the CTVs in 4 fractions decreased more than 5% of the planned doses. The maximum dose of the spinal cord exceeded 10% of the planned values in 2 fractions. A close examination indicated that the dose discrepancy in these 6 fractions was due to patient rotations, especially shoulder rotations. After registering these 6 CTs with the planning CT allowing six degree of freedoms, the maximum rotations around 3 axes were > 1.5° for these fractions. With rotation setup errors removed, 4 out of 10 patients still required off-line ART to accommodate anatomical changes. Conclusion: A significant shoulder rotations were observed in 10% fractions, requiring patient re-setup. Off-line ART alone is not sufficient to correct for random variations of patient position, although ART is effective to adapt to patients' gradual anatomic changes. Re-setup or on-line ART may be considered for patients with large deviations detected early by daily IGRT images. The study is supported in part by Siemens Medical

  3. Orbital apocenter is not a sufficient condition for HST/STIS detection of Europa’s water vapor aurora

    PubMed Central

    Retherford, Kurt D.; Saur, Joachim; Strobel, Darrell F.; Feldman, Paul D.; McGrath, Melissa A.; Nimmo, Francis

    2014-01-01

    We report far-ultraviolet observations of Jupiter’s moon Europa taken by Space Telescope Imaging Spectrograph (STIS) of the Hubble Space Telescope (HST) in January and February 2014 to test the hypothesis that the discovery of a water vapor aurora in December 2012 by local hydrogen (H) and oxygen (O) emissions with the STIS originated from plume activity possibly correlated with Europa’s distance from Jupiter through tidal stress variations. The 2014 observations were scheduled with Europa near the apocenter similar to the orbital position of its previous detection. Tensile stresses on south polar fractures are expected to be highest in this orbital phase, potentially maximizing the probability for plume activity. No local H and O emissions were detected in the new STIS images. In the south polar region where the emission surpluses were observed in 2012, the brightnesses are sufficiently low in the 2014 images to be consistent with any H2O abundance from (0–5)×1015 cm−2. Large high-latitude plumes should have been detectable by the STIS, independent of the observing conditions and geometry. Because electron excitation of water vapor remains the only viable explanation for the 2012 detection, the new observations indicate that although the same orbital position of Europa for plume activity may be a necessary condition, it is not a sufficient condition. However, the December 2012 detection of coincident HI Lyman-α and OI 1304-Å emission surpluses in an ∼200-km high region well separated above Europa’s limb is a firm result and not invalidated by our 2014 STIS observations. PMID:25404343

  4. A model for determining when an analysis contains sufficient detail to provide adequate NEPA coverage for a proposed action

    SciTech Connect

    Eccleston, C.H.

    1994-11-01

    Neither the National Environmental Policy Act (NEPA) nor its subsequent regulations provide substantive guidance for determining the Level of detail, discussion, and analysis that is sufficient to adequately cover a proposed action. Yet, decisionmakers are routinely confronted with the problem of making such determinations. Experience has shown that no two decisionmakers are Likely to completely agree on the amount of discussion that is sufficient to adequately cover a proposed action. one decisionmaker may determine that a certain Level of analysis is adequate, while another may conclude the exact opposite. Achieving a consensus within the agency and among the public can be problematic. Lacking definitive guidance, decisionmakers and critics alike may point to a universe of potential factors as the basis for defending their claim that an action is or is not adequately covered. Experience indicates that assertions are often based on ambiguous opinions that can be neither proved nor disproved. Lack of definitive guidance slows the decisionmaking process and can result in project delays. Furthermore, it can also Lead to inconsistencies in decisionmaking, inappropriate Levels of NEPA documentation, and increased risk of a project being challenged for inadequate coverage. A more systematic and less subjective approach for making such determinations is obviously needed. A paradigm for reducing the degree of subjectivity inherent in such decisions is presented in the following paper. The model is specifically designed to expedite the decisionmaking process by providing a systematic approach for making these determination. In many cases, agencies may find that using this model can reduce the analysis and size of NEPA documents.

  5. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    PubMed Central

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-01-01

    Objective Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the long-latency stretch reflex leading to hypertonia. Approach We modelled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable Very-Large-Scale-Integrated-circuit (VLSI) hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32ms delay and a long-latency pathway with 64ms loop-delay representing transcortical/supra-spinal connections. Main results When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the long-latency stretch reflex is by itself sufficient to cause many of the features of hypertonic dystonia. PMID:25946372

  6. Forebrain-Specific CRF Overproduction During Development is Sufficient to Induce Enduring Anxiety and Startle Abnormalities in Adult Mice

    PubMed Central

    Toth, Mate; Gresack, Jodi E; Bangasser, Debra A; Plona, Zach; Valentino, Rita J; Flandreau, Elizabeth I; Mansuy, Isabelle M; Merlo-Pich, Emilio; Geyer, Mark A; Risbrough, Victoria B

    2014-01-01

    Corticotropin releasing factor (CRF) regulates physiological and behavioral responses to stress. Trauma in early life or adulthood is associated with increased CRF in the cerebrospinal fluid and heightened anxiety. Genetic variance in CRF receptors is linked to altered risk for stress disorders. Thus, both heritable differences and environmentally induced changes in CRF neurotransmission across the lifespan may modulate anxiety traits. To test the hypothesis that CRF hypersignaling is sufficient to modify anxiety-related phenotypes (avoidance, startle, and conditioned fear), we induced transient forebrain-specific overexpression of CRF (CRFOE) in mice (1) during development to model early-life stress, (2) in adulthood to model adult-onset stress, or (3) across the entire postnatal lifespan to model heritable increases in CRF signaling. The consequences of these manipulations on CRF peptide levels and behavioral responses were examined in adulthood. We found that transient CRFOE during development decreased startle habituation and prepulse inhibition, and increased avoidance (particularly in females) recapitulating the behavioral effects of lifetime CRFOE despite lower CRF peptide levels at testing. In contrast, CRFOE limited to adulthood reduced contextual fear learning in females and increased startle reactivity in males but did not change avoidance or startle plasticity. These findings suggest that forebrain CRFOE limited to development is sufficient to induce enduring alterations in startle plasticity and anxiety, while forebrain CRFOE during adulthood results in a different phenotype profile. These findings suggest that startle circuits are particularly sensitive to forebrain CRFOE, and that the impact of CRFOE may be dependent on the time of exposure. PMID:24326400

  7. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    NASA Astrophysics Data System (ADS)

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-06-01

    Objective. Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the LLSR leading to hypertonia. Approach. We modeled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable very-large-scale-integrated-circuit hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a long-latency pathway with 64 ms loop-delay representing transcortical/supra-spinal connections. Main results. When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance. Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the LLSR is by itself sufficient to cause many of the features of hypertonic dystonia.

  8. The Relationship of Social Support and Economic Self-Sufficiency to Substance Abuse Outcomes in a Long-Term Recovery Program for Women.

    ERIC Educational Resources Information Center

    Gregoire, Thomas K.; Snively, Carol

    2001-01-01

    Explores outcomes for 59 women who attended long term substance abuse treatment in a women's facility that emphasized employment and economic self sufficiency. Results revealed that reductions in substance abuse were associated with an increase in economic self sufficiency. Additionally, women living in drug free social environments had high rates…

  9. From Support to Self-Sufficiency: How Successful Are Programs in Advancing the Financial Independence and Well-Being of Welfare Recipients?

    ERIC Educational Resources Information Center

    Long, D. A.

    2001-01-01

    Reviews recent evaluation research findings about welfare recipients from a perspective of support-to-self-sufficiency rather than the welfare-to-work viewpoint that denominates the evaluation literature. Recent research suggests that many families have moved from welfare to work, but few of these families have achieved financial self-sufficiency.…

  10. 49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to... 49 Transportation 1 2010-10-01 2010-10-01 false What is the effect of procedural problems that are not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the...

  11. A simple, sufficient, and consistent method to score the status of threats and demography of imperiled species

    PubMed Central

    Webber, Whitney M.; Li, Ya-Wei

    2016-01-01

    Managers of large, complex wildlife conservation programs need information on the conservation status of each of many species to help strategically allocate limited resources. Oversimplifying status data, however, runs the risk of missing information essential to strategic allocation. Conservation status consists of two components, the status of threats a species faces and the species’ demographic status. Neither component alone is sufficient to characterize conservation status. Here we present a simple key for scoring threat and demographic changes for species using detailed information provided in free-form textual descriptions of conservation status. This key is easy to use (simple), captures the two components of conservation status without the cost of more detailed measures (sufficient), and can be applied by different personnel to any taxon (consistent). To evaluate the key’s utility, we performed two analyses. First, we scored the threat and demographic status of 37 species recently recommended for reclassification under the Endangered Species Act (ESA) and 15 control species, then compared our scores to two metrics used for decision-making and reports to Congress. Second, we scored the threat and demographic status of all non-plant ESA-listed species from Florida (54 spp.), and evaluated scoring repeatability for a subset of those. While the metrics reported by the U.S. Fish and Wildlife Service (FWS) are often consistent with our scores in the first analysis, the results highlight two problems with the oversimplified metrics. First, we show that both metrics can mask underlying demographic declines or threat increases; for example, ∼40% of species not recommended for reclassification had changes in threats or demography. Second, we show that neither metric is consistent with either threats or demography alone, but conflates the two. The second analysis illustrates how the scoring key can be applied to a substantial set of species to understand

  12. A simple, sufficient, and consistent method to score the status of threats and demography of imperiled species.

    PubMed

    Malcom, Jacob W; Webber, Whitney M; Li, Ya-Wei

    2016-01-01

    Managers of large, complex wildlife conservation programs need information on the conservation status of each of many species to help strategically allocate limited resources. Oversimplifying status data, however, runs the risk of missing information essential to strategic allocation. Conservation status consists of two components, the status of threats a species faces and the species' demographic status. Neither component alone is sufficient to characterize conservation status. Here we present a simple key for scoring threat and demographic changes for species using detailed information provided in free-form textual descriptions of conservation status. This key is easy to use (simple), captures the two components of conservation status without the cost of more detailed measures (sufficient), and can be applied by different personnel to any taxon (consistent). To evaluate the key's utility, we performed two analyses. First, we scored the threat and demographic status of 37 species recently recommended for reclassification under the Endangered Species Act (ESA) and 15 control species, then compared our scores to two metrics used for decision-making and reports to Congress. Second, we scored the threat and demographic status of all non-plant ESA-listed species from Florida (54 spp.), and evaluated scoring repeatability for a subset of those. While the metrics reported by the U.S. Fish and Wildlife Service (FWS) are often consistent with our scores in the first analysis, the results highlight two problems with the oversimplified metrics. First, we show that both metrics can mask underlying demographic declines or threat increases; for example, ∼40% of species not recommended for reclassification had changes in threats or demography. Second, we show that neither metric is consistent with either threats or demography alone, but conflates the two. The second analysis illustrates how the scoring key can be applied to a substantial set of species to understand overall

  13. The C-terminal domain of NifL is sufficient to inhibit NifA activity.

    PubMed Central

    Narberhaus, F; Lee, H S; Schmitz, R A; He, L; Kustu, S

    1995-01-01

    In Klebsiella pneumoniae, transcription of all nif (nitrogen fixation) operons except the regulatory nifLA operon itself is regulated by the proteins NifA and NifL. NifA, an enhancer-binding protein, activates transcription by RNA polymerase containing the alternative sigma factor sigma 54. The central catalytic domain of NifA is sufficient for transcriptional activation, which can occur from solution. In vivo, NifL antagonizes the action of NifA in the presence of molecular oxygen or combined nitrogen. Inhibition has also been shown in vitro, but it was not responsive to environmental signals. Assuming a two-domain structure of NifL, we localized inhibition by NifL to its carboxy (C)-terminal domain, which is more soluble than the intact protein. The first line of evidence for this is that internal deletions of NifL containing an intact C-terminal domain were able to inhibit transcriptional activation by NifA in a coupled transcription-translation system. The second line of evidence is that the isolated C-terminal domain of NifL (assayed as a fusion to the soluble maltose-binding protein [MBP]) was sufficient to inhibit transcriptional activation by the central domain of NifA in a purified transcription system. The final line of evidence is that an MBP fusion to the C-terminal domain of NifL inhibited transcriptional activation by NifA in vivo. On the basis of these data, we postulate that the inhibitory function of NifL lies in its C-terminal domain and hence infer that this domain is responsible for interaction with NifA. Gel filtration experiments with MBP-NifL fusion derivatives lacking portions of the N- or C-terminal domain of the protein revealed that the C-terminal domain is the most soluble part of NifL. Up to 50% of two MBP-NifL truncations containing only the C-terminal domain appeared to be in a defined dimeric state. PMID:7665487

  14. Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements

    PubMed Central

    Erokhin, Maksim; Elizar’ev, Pavel; Parshikov, Aleksander; Schedl, Paul; Georgiev, Pavel; Chetverina, Darya

    2015-01-01

    In Drosophila, Polycomb (PcG) and Trithorax (TrxG) group proteins are assembled on Polycomb response elements (PREs) to maintain tissue and stage-specific patterns of gene expression. Critical to coordinating gene expression with the process of differentiation, the activity of PREs can be switched “on” and “off.” When on, the PRE imposes a silenced state on the genes in the same domain that is stably inherited through multiple rounds of cell division. When the PRE is switched off, the domain is in a state permissive for gene expression that can be stably inherited. Previous studies have suggested that a burst of transcription through a PRE sequence displaces PcG proteins and provides a universal mechanism for inducing a heritable switch in PRE activity from on to off; however, the evidence favoring this model is indirect. Here, we have directly tested the transcriptional read-through mechanism. Contrary to previous suggestions, we show that transcription through the PRE is not sufficient for inducing an epigenetic switch in PRE activity. In fact, even high levels of continuous transcription through a PRE fails to dislodge the PcG proteins, nor does it remove repressive histone marks. Our results indicate that other mechanisms involving adjacent DNA regulatory elements must be implicated in heritable switch of PRE activity. PMID:26504232

  15. Development of a sufficiently reactive thioalkylester involving the side-chain thiol of cysteine applicable for kinetically controlled ligation.

    PubMed

    Tsuda, Shugo; Mochizuki, Masayoshi; Nishio, Hideki; Yoshiya, Taku; Nishiuchi, Yuji

    2016-11-01

    N(α) -Trifluoroacetyl-Cys-Leu-NH2 (TfaC-Leu-NH2 ) was incorporated into thioesters through its side-chain thiol group to develop a more reactive peptide-thioester than the commonly used peptide-3-mercaptopropionic acid (MPA)-thioester. The TfaC-thioester could be readily synthesized by solid-phase peptide synthesis (SPPS) with Boc chemistry using in situ neutralization protocols in sufficient yield without any side reaction associated with the use of TfaC. This thioester proved to display a much higher reactivity in the thiol-free native chemical ligation (NCL) reaction than the MPA-thioester and to be comparable to the thioarylester, such as the 4-mercaptophenylacetic acid (MPAA)-thioester, in terms of the ligation rate. We were able to demonstrate the usefulness of the TfaC-thioester by using it to synthesize neuromedin S via a one-pot sequential NCL approach followed by desulfurization. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 503-511, 2016. PMID:26583564

  16. An artificial self-sufficient cytochrome P450 directly nitrates fluorinated tryptophan analogs with a different regio-selectivity.

    PubMed

    Zuo, Ran; Zhang, Yi; Huguet-Tapia, Jose C; Mehta, Mishal; Dedic, Evelina; Bruner, Steven D; Loria, Rosemary; Ding, Yousong

    2016-05-01

    Aromatic nitration is an immensely important industrial process to produce chemicals for a variety of applications, but it often suffers from multiple unsolved challenges. Enzymes as biocatalysts have been increasingly used for organic chemistry synthesis due to their high selectivity and environmental friendliness, but nitration has benefited minimally from the development of biocatalysis. In this work, we aimed to develop TxtE as practical biocatalysts for aromatic nitration. TxtE is a unique class I cytochrome P450 enzyme that nitrates the indole of l-tryptophan. To develop cost-efficient nitration processes, we fused TxtE with the reductase domains of CYP102A1 (P450BM3) and of P450RhF to create class III self-sufficient biocatalysts. The best engineered fusion protein was comparable with wild type TxtE in terms of nitration performance and other key biochemical properties. To demonstrate the application potential of the fusion enzyme, we nitrated 4-F-dl-tryptophan and 5-F-l-tryptophan in large scale enzymatic reactions. Tandem MS/MS and NMR analyses of isolated products revealed altered nitration sites. To our knowledge, these studies represent the first practice in developing biological nitration approaches and lay a solid basis to the use of TxtE-based biocatalysts for the production of valuable nitroaromatics. PMID:26743860

  17. Necessary, but not sufficient: links between neurocognition, social cognition, and metacognition in schizophrenia are moderated by disorganized symptoms.

    PubMed

    Minor, Kyle S; Lysaker, Paul H

    2014-10-01

    Intact neurocognition has been posited as a necessary, but not sufficient prerequisite for efficient social cognition and metacognition in schizophrenia. Disorganized symptoms likely play a prominent role in these cognitive processes, given the detrimental effects of disorganization on one's ability to synthesize discrete information into an organized whole. However, the relationship between disorganized symptoms and cognitive processes remains unclear. In this study, we examined whether disorganized symptoms: 1) exhibited stronger inverse relationships with cognitive processes than other symptoms, and 2) moderated links between neurocognition and a) social cognition, and b) metacognition. Trained raters assessed psychotic symptoms, neurocognition, social cognition, and metacognition in patients with schizophrenia from a Midwestern VA Medical Center (n=68) using validated, clinician-rated instruments. We observed significantly greater inverse associations with cognitive processes for disorganized compared to reality distortion symptoms; inverse associations with neurocognition and social cognition were significantly greater for disorganized than negative symptoms. Our hypotheses that disorganized symptoms would moderate relationships between neurocognition and a) social cognition, and b) metacognition were also supported. These findings highlight the importance of disorganized symptoms in elucidating links between neurocognition and social cognitive and metacognitive abilities. Future work should assess whether similar findings occur across the schizophrenia-spectrum, and investigate if targeting disorganization can ameliorate social cognitive and metacognitive impairments in schizophrenia. PMID:25192756

  18. The Arabidopsis homeotic genes APETALA3 and PISTILLATA are sufficient to provide the B class organ identity function.

    PubMed

    Krizek, B A; Meyerowitz, E M

    1996-01-01

    The class B organ identity genes, APETALA3 and PISTILLATA, are required to specify petal and stamen identity in the Arabidopsis flower. We show here that the activities of these two genes are sufficient to specify petals and stamens in flowers, in combination with the class A and C genes, respectively. Flowers of plants constitutively expressing both PISTILLATA and APETALA3 under the control of the 35S promoter from cauliflower mosaic virus consist of two outer whorls of petals and inner whorls of stamens. These plants also exhibit vegetative phenotypes that are not present in either of the singly (APETALA3 or PISTILLATA) overexpressing lines. These phenotypes include leaf curling and the partial conversion of later-arising cauline leaves to petals. The presence of additional floral whorls in flowers ectopically expressing APETALA3 and PISTILLATA and the rescue of missing organs in class A mutants by ectopic B function suggest that APETALA3 and PISTILLATA play an additional role in proliferation of the floral meristem. PMID:8565821

  19. 13C-MFA delineates the photomixotrophic metabolism of Synechocystis sp. PCC 6803 under light- and carbon-sufficient conditions.

    PubMed

    You, Le; Berla, Bert; He, Lian; Pakrasi, Himadri B; Tang, Yinjie J

    2014-05-01

    The central carbon metabolism of cyanobacteria is under debate. For over 50 years, the lack of α-ketoglutarate dehydrogenase has led to the belief that cyanobacteria have an incomplete TCA cycle. Recent in vitro enzymatic experiments suggest that this cycle may in fact be closed. The current study employed (13) C isotopomers to delineate pathways in the cyanobacterium Synechocystis sp. PCC 6803. By tracing the incorporation of supplemented glutamate into the downstream metabolites in the TCA cycle, we observed a direct in vivo transformation of α-ketoglutarate to succinate. Additionally, isotopic tracing of glyoxylate did not show a functional glyoxylate shunt and glyoxylate was used for glycine synthesis. The photomixotrophic carbon metabolism was then profiled with (13) C-MFA under light and carbon-sufficient conditions. We observed that: (i) the in vivo flux through the TCA cycle reactions (α-ketoglutarate → succinate) was minimal (<2%); (ii) the flux ratio of CO2 fixation was six times higher than that of glucose utilization; (iii) the relative flux through the oxidative pentose phosphate pathway was low (<2%); (iv) high flux through malic enzyme served as a main route for pyruvate synthesis. Our results improve the understanding of the versatile metabolism in cyanobacteria and shed light on their application for photo-biorefineries. PMID:24659531

  20. HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore

    PubMed Central

    Barnhart, Meghan C.; Kuich, P. Henning J. L.; Stellfox, Madison E.; Ward, Jared A.; Bassett, Emily A.; Black, Ben E.

    2011-01-01

    Centromeres of higher eukaryotes are epigenetically marked by the centromere-specific CENP-A nucleosome. New CENP-A recruitment requires the CENP-A histone chaperone HJURP. In this paper, we show that a LacI (Lac repressor) fusion of HJURP drove the stable recruitment of CENP-A to a LacO (Lac operon) array at a noncentromeric locus. Ectopically targeted CENP-A chromatin at the LacO array was sufficient to direct the assembly of a functional centromere as indicated by the recruitment of the constitutive centromere-associated network proteins, the microtubule-binding protein NDC80, and the formation of stable kinetochore–microtubule attachments. An amino-terminal fragment of HJURP was able to assemble CENP-A nucleosomes in vitro, demonstrating that HJURP is a chromatin assembly factor. Furthermore, HJURP recruitment to endogenous centromeres required the Mis18 complex. Together, these data suggest that the role of the Mis18 complex in CENP-A deposition is to recruit HJURP and that the CENP-A nucleosome assembly activity of HJURP is responsible for centromeric chromatin assembly to maintain the epigenetic mark. PMID:21768289

  1. HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore.

    PubMed

    Barnhart, Meghan C; Kuich, P Henning J L; Stellfox, Madison E; Ward, Jared A; Bassett, Emily A; Black, Ben E; Foltz, Daniel R

    2011-07-25

    Centromeres of higher eukaryotes are epigenetically marked by the centromere-specific CENP-A nucleosome. New CENP-A recruitment requires the CENP-A histone chaperone HJURP. In this paper, we show that a LacI (Lac repressor) fusion of HJURP drove the stable recruitment of CENP-A to a LacO (Lac operon) array at a noncentromeric locus. Ectopically targeted CENP-A chromatin at the LacO array was sufficient to direct the assembly of a functional centromere as indicated by the recruitment of the constitutive centromere-associated network proteins, the microtubule-binding protein NDC80, and the formation of stable kinetochore-microtubule attachments. An amino-terminal fragment of HJURP was able to assemble CENP-A nucleosomes in vitro, demonstrating that HJURP is a chromatin assembly factor. Furthermore, HJURP recruitment to endogenous centromeres required the Mis18 complex. Together, these data suggest that the role of the Mis18 complex in CENP-A deposition is to recruit HJURP and that the CENP-A nucleosome assembly activity of HJURP is responsible for centromeric chromatin assembly to maintain the epigenetic mark. PMID:21768289

  2. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

    PubMed Central

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-way; Wang, Ting-Fang; Chang, Chun-che; Lin, Ming-Der

    2015-01-01

    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation. PMID:26419889

  3. The Signal Peptide of a Vacuolar Protein Is Necessary and Sufficient for the Efficient Secretion of a Cytosolic Protein 1

    PubMed Central

    Hunt, Dale C.; Chrispeels, Maarten J.

    1991-01-01

    A cytosolic pea (Pisum sativum) seed albumin (ALB) and a chimeric protein (PHALB) consisting of the signal peptide and first three amino acids of phytohemagglutinin (PHA) and the amino acid sequence of ALB were expressed in parallel suspension cultures of tobacco (Nicotiana tabacum) cells and their intracellular fates examined. PHALB was efficiently secreted by the cells whereas ALB remained intracellular. These experiments show that the information contained in the signal peptide of a vacuolar protein is both necessary and sufficient for efficient secretion, and define secretion as a default or bulk-flow pathway. Entry into the secretory pathway was accompanied by glycosylation and the efficient conversion of the high mannose glycans into complex glycans indicating that transported glycoproteins do not need specific recognition domains for the modifying enzymes in the Golgi. Tunicamycin depressed the accumulation of the unglycosylated polypeptide in the culture medium much less than the accumulation of other glycoproteins. We interpret this as evidence that glycans on proteins that are not normally glycosylated do not have the same function of stabilizing and protecting the polypeptide as on natural glycoproteins. ImagesFigure 2Figure 3Figure 5Figure 6Figure 7Figure 8 PMID:16668149

  4. Wholesale electricity market design with increasing levels of renewable generation: Revenue sufficiency and long-term reliability

    DOE PAGESBeta

    Milligan, Michael; Frew, Bethany A.; Bloom, Aaron; Ela, Erik; Botterud, Audun; Townsend, Aaron; Levin, Todd

    2016-03-22

    This paper discusses challenges that relate to assessing and properly incentivizing the resources necessary to ensure a reliable electricity system with growing penetrations of variable generation (VG). The output of VG (primarily wind and solar generation) varies over time and cannot be predicted precisely. Therefore, the energy from VG is not always guaranteed to be available at times when it is most needed. This means that its contribution towards resource adequacy can be significantly less than the contribution from traditional resources. Variable renewable resources also have near-zero variable costs, and with production-based subsidies they may even have negative offer costs.more » Because variable costs drive the spot price of energy, this can lead to reduced prices, sales, and therefore revenue for all resources within the energy market. The characteristics of VG can also result in increased price volatility as well as the need for more flexibility in the resource fleet in order to maintain system reliability. Furthermore, we explore both traditional and evolving electricity market designs in the United States that aim to ensure resource adequacy and sufficient revenues to recover costs when those resources are needed for long-term reliability. We also investigate how reliability needs may be evolving and discuss how VG may affect future electricity market designs.« less

  5. Four hours of daily contact with sexually active males is sufficient to induce fertile ovulation in anestrous goats.

    PubMed

    Bedos, M; Flores, J A; Fitz-Rodríguez, G; Keller, M; Malpaux, B; Poindron, P; Delgadillo, J A

    2010-08-01

    The study was conducted on two consecutive years to determine whether ovulatory activity can be induced in anovulatory goats by exposing them to sexually active bucks for 4, 8, 12 or 16 h per day during 15 consecutive days. In experiment 1, females remained continuously in the experimental pens where they were in contact with males. One group remained isolated from males (controls) and four other groups were exposed to sexually active males for 4, 8, 12 or 16 h per day. In experiment 2, females were taken away to "resting" pens free of male odours between the periods of contact with bucks. They were allocated to 5 groups as in experiment 1. Ovulations were determined by progesterone plasma levels and transrectal ultrasonography. Pregnancy was determined by abdominal ultrasonography. In both experiments, more than 90% of females exposed to the bucks had at least one ovulation during the whole experiment whereas only 11 or 0% (experiments 1 and 2, respectively) did so in the control group (P<0.001). Furthermore, the proportion of females ovulating did not differ among groups depending on duration of contact with bucks (P>0.05). In both experiments, pregnancy rates were not affected by the daily duration of contact with males (P>0.05). To conclude, 4h of daily contact with sexually active males is sufficient to stimulate ovulatory activity in anovulatory goats and this effect is not due to the presence of olfactory cues from the males remaining in the pens. PMID:20457159

  6. Serotonin-1A autoreceptors are necessary and sufficient for the normal formation of circuits underlying innate anxiety

    PubMed Central

    Richardson-Jones, Jesse W; Craige, Caryne P; Nguyen, Thanh H; Kung, Hank F; Gardier, Alain M; Dranovsky, Alex; David, Denis J; Guiard, Bruno P; Beck, Sheryl G; Hen, René; Leonardo, E David

    2011-01-01

    Identifying factors contributing to the etiology of anxiety and depression is critical for the development of more efficacious therapies. Serotonin (5-HT) is intimately linked to both disorders. The inhibitory serotonin-1A (5-HT1A) receptor exists in two separate populations with distinct effects on serotonergic signaling: 1) an autoreceptor that limits 5-HT release throughout the brain, and 2) a heteroreceptor that mediates inhibitory responses to released 5-HT. Traditional pharmacologic and transgenic strategies have not addressed the distinct roles of these two receptor populations. Here we use a recently developed genetic mouse system to independently manipulate 5-HT1A auto and heteroreceptor receptor populations. We show that 5-HT1A autoreceptors act to affect anxiety-like behavior. In contrast, 5-HT1A heteroreceptors affect responses to forced swim stress, without effects on anxiety-like behavior. Together with our previously reported work, these results establish distinct roles for the two receptor populations, providing evidence that signaling through endogenous 5-HT1A autoreceptors is necessary and sufficient for the establishment of normal anxiety-like behavior. PMID:21508226

  7. Delta frequency optogenetic stimulation of a thalamic nucleus reuniens is sufficient to produce working memory deficits; relevance to schizophrenia

    PubMed Central

    Duan, Aranda R.; Varela, Carmen; Zhang, Yuchun; Shen, Yinghua; Xiong, Lealia; Wilson, Matthew; Lisman, John

    2015-01-01

    Background Low-frequency (delta/theta) oscillations in the thalamocortical system are elevated in schizophrenia during wakefulness and are also induced in the NMDAR hypofunction rat model. To determine whether abnormal delta oscillations might produce functional deficits, we used optogenetic methods in awake rats. We illuminated channelrhodopsin-2 in the thalamic nucleus reuniens (RE) at delta frequency and measured the effect on working memory performance (the RE is involved in working memory (WM), a process affected in schizophrenia (SZ)). Methods We injected RE with a virus (AAV) to transduce cells with channelrhodopsin-2. An optical fiber was implanted just dorsal to the hippocampus in order to illuminate RE axon terminals. Results During optogenetic delta frequency stimulation, rats displayed a strong WM deficit. On the following day, performance was normal if illumination was omitted. Conclusions The optogenetic experiments showed that delta frequency stimulation of a thalamic nucleus is sufficient to produce deficits in WM. This result supports the hypothesis that delta frequency bursting in particular thalamic nuclei has a causal role producing WM deficits in this SZ. The action potentials in these bursts may jam communication through the thalamus, thereby interfering with behaviors dependent on WM. Studies in thalamic slices using the NMDAR hypofunction model show that delta frequency bursting is dependent on T-type Ca2+ channels, a result that we confirmed here in vivo. These channels, which are strongly implicated in SZ by GWAS studies, may thus be a therapeutic target for treatment of SZ. PMID:25891221

  8. PKD1 Mono-Allelic Knockout Is Sufficient to Trigger Renal Cystogenesis in a Mini-Pig Model

    PubMed Central

    He, Jin; Li, Qiuyan; Fang, Suyun; Guo, Ying; Liu, Tongxin; Ye, Jianhua; Yu, Zhengquan; Zhang, Ran; Zhao, Yaofeng; Hu, Xiaoxiang; Bai, Xueyuan; Chen, Xiangmei; Li, Ning

    2015-01-01

    PKD1 and PKD2 mutations could lead to autosomal dominant polycystic kidney disease (ADPKD), which afflicts millions of people worldwide. Due to the marked differences in the lifespan, size, anatomy, and physiology from humans, rodent ADPKD models cannot fully mimic the disease. To obtain a large animal model that recapitulates the disease, we constructed a mini-pig model by mono-allelic knockout (KO) of PKD1 using zinc finger nuclease. The mono-allelic KO pigs had lower PKD1 expression than their wild-type littermates at both the transcriptional and translational levels. After approximately six months, renal cysts appeared and grew progressively in the KO pigs. Histological analysis showed that renal cysts were scatteredly distributed in the mutant pig kidneys and were lined by either cuboidal or flattened epithelial cells. Contrast-enhanced computed tomography confirmed that all of the mutant pigs had renal and hepatic cysts, when they were 11-month-old. Immunohistochemical analysis revealed that most of the cysts were derived from the proximal tubules and collecting ducts. Therefore, the PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis, and this pig model may provide a platform for future study of renal cyst formation. PMID:25798056

  9. Lmo4 and Other LIM domain only factors are necessary and sufficient for multiple retinal cell type development.

    PubMed

    Jin, Kangxin; Xiao, Dongchang; Andersen, Bogi; Xiang, Mengqing

    2016-08-01

    Understanding the molecular basis by which distinct cell types are specified is a central issue in retinogenesis and retinal disease development. Here we examined the role of LIM domain only 4 (Lmo4) in retinal development using both gain-of-function and loss-of-function approaches. By immunostaining, Lmo4 was found to be expressed in mouse retina from E10.5 to mature stages. Retroviral delivery of Lmo4 into retinal progenitor cells could promote the amacrine, bipolar and Müller cell fates at the expense of photoreceptors. It also inhibited the fate of early-born retinal ganglion cells. Using a dominant-negative form of Lmo4 which suppresses transcriptional activities of all LIM domain only factors, we demonstrated that LIM domain only factors are both necessary and sufficient for promoting amacrine and bipolar cell development, but not for the differentiation of ganglion, horizontal, Müller, or photoreceptor cells. Taken together, our study uncovers multiple roles of Lmo4 during retinal development and demonstrates the importance of LIM domain only factors in ensuring proper retinal cell specification and differentiation. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 900-915, 2016. PMID:26579872

  10. Preserved striate cortex is not sufficient to support the McCollough effect: evidence from two patients with cerebral achromatopsia.

    PubMed

    Mullin, Caitlin R; Démonet, Jean François; Kentridge, Robert W; Heywood, Charles A; Goodale, Melvyn A; Steeves, Jennifer K E

    2009-01-01

    The McCollough effect (ME) is a colour aftereffect contingent on pattern orientation. This effect is generally thought to be mediated by primary visual cortex (V1) although this has remained the subject of some debate. To determine whether V1 is in fact sufficient to subserve the ME, we compared McCollough adaptation in controls to adaptation in two patients with damage to ventrotemporal cortex, resulting in achromatopsia, but who have spared V1. Each of these patients has some residual colour abilities of which he is unaware. Participants performed a 2AFC orientation-discrimination task for pairs of oblique and vertical/horizontal gratings both before and after adaptation to red/green oblique induction gratings. Successful ME induction would manifest itself as an improvement in oblique-orientation discrimination owing to the additional colour cue after adaptation. Indeed, in controls oblique grating discrimination improved post-adaptation. Further, a subdivision of our control group demonstrated successful ME induction despite a lack of conscious awareness of the added colour cue, indicating that conscious colour awareness is not required for ME induction. The patients, however, did not show improvement in oblique-orientation discrimination, indicating a lack of ME induction. This suggests that V1 must be connected to higher cortical colour areas to drive ME induction. PMID:20192125

  11. The use of Jatropha curcas to achieve a self sufficient water distribution system: A case study in rural Senegal

    NASA Astrophysics Data System (ADS)

    Archer, Alexandra

    The use of Jatropha curcas as a source of oil for fueling water pumps holds promise for rural communities struggling to achieve water security in arid climates. The potential for use in developing communities as an affordable, sustainable fuel source has been highly recommended for many reasons: it is easily propagated, drought resistant, grows rapidly, and has high-oil-content seeds, as well as medicinal and economic potential. This study uses a rural community in Senegal, West Africa, and calculates at what level of Jatropha curcas production the village is able to be self-sufficient in fueling their water system to meet drinking, sanitation and irrigation requirements. The current water distribution system was modelled to represent irrigation requirements for nine different Jatropha curcas cultivation and processing schemes. It was found that a combination of using recycled greywater for irrigation and a mechanical press to maximize oil recovered from the seeds of mature Jatropha curcas trees, would be able to operate the water system with no diesel required.

  12. Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage.

    PubMed

    Pikovskaya, Olga; Chaix, Julie; Rothman, Nyanza J; Collins, Amélie; Chen, Yen-Hua; Scipioni, Anna M; Vivier, Eric; Reiner, Steven L

    2016-02-15

    Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK cells (cNKs). All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNKs additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK development. Formation of the entire lymphoid and nonlymphoid type 1 ILC compartment appears to require the semiredundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes induces cNK-like properties across the lymphoid and nonlymphoid type 1 ILC compartments. Subsequent to their divergent lineage specification, hILC1s and cNKs thus possess substantial developmental plasticity. PMID:26792802

  13. Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

    PubMed Central

    Spurrier, Ryan Gregory; Speer, Allison L.; Hou, Xiaogang; El-Nachef, Wael N.

    2015-01-01

    Purpose: Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Materials and Methods: Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immune-deficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. Results: TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. Conclusions: TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies. PMID:25298083

  14. Preventing the Degradation of Mps1 at Centrosomes Is Sufficient to Cause Centrosome Reduplication in Human Cells

    PubMed Central

    Kasbek, Christopher; Yang, Ching-Hui; Yusof, Adlina Mohd; Chapman, Heather M.; Winey, Mark

    2007-01-01

    Supernumerary centrosomes promote the assembly of abnormal mitotic spindles in many human tumors. In human cells, overexpression of the cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication. Cdk2 activity protects the Mps1 protein kinase from proteasome-mediated degradation, and we demonstrate here that Mps1 mediates cyclin A-dependent centrosome reduplication. Overexpression of cyclin A or a brief proteasome inhibition increases the centrosomal levels of Mps1, whereas depletion of Cdk2 leads to the proteasome-dependent loss of Mps1 from centrosomes only. When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. In contrast, phosphomimetic mutations at T468 or deletion of the region surrounding T468 prevent the proteasome-dependent removal of Mps1 from centrosomes in the absence of Cdk2 activity. Moreover, cyclin A-dependent centrosome reduplication requires Mps1, and these stabilizing Mps1 mutations cause centrosome reduplication, bypassing cyclin A. Together, our data demonstrate that the region surrounding T468 contains a motif that regulates the accumulation of Mps1 at centrosomes. We suggest that phosphorylation of T468 attenuates the degradation of Mps1 at centrosomes and that preventing this degradation is necessary and sufficient to cause centrosome reduplication in human cells. PMID:17804818

  15. Nucleocytoplasmic human O-GlcNAc transferase is sufficient for O-GlcNAcylation of mitochondrial proteins

    PubMed Central

    Trapannone, Riccardo; Mariappa, Daniel; Ferenbach, Andrew T.; vanAalten, Daan M.F.

    2016-01-01

    O-linked N-acetylglucosamine modification (O-GlcNAcylation) is a nutrient-dependent protein post-translational modification (PTM), dynamically and reversibly driven by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyse the addition and the removal of the O-GlcNAc moieties to/from serine and threonine residues of target proteins respectively. Increasing evidence suggests involvement of O-GlcNAcylation in many biological processes, including transcription, signalling, neuronal development and mitochondrial function. The presence of a mitochondrial O-GlcNAc proteome and a mitochondrial OGT (mOGT) isoform has been reported. We explored the presence of mOGT in human cell lines and mouse tissues. Surprisingly, analysis of genomic sequences indicates that this isoform cannot be expressed in most of the species analysed, except some primates. In addition, we were not able to detect endogenous mOGT in a range of human cell lines. Knockdown experiments and Western blot analysis of all the predicted OGT isoforms suggested the expression of only a single OGT isoform. In agreement with this, we demonstrate that overexpression of the nucleocytoplasmic OGT (ncOGT) isoform leads to increased O-GlcNAcylation of mitochondrial proteins, suggesting that ncOGT is necessary and sufficient for the generation of the O-GlcNAc mitochondrial proteome. PMID:27048592

  16. DNA-histone interactions are sufficient to position a single nucleosome juxtaposing Drosophila Adh adult enhancer and distal promoter.

    PubMed Central

    Jackson, J R; Benyajati, C

    1993-01-01

    The alcohol dehydrogenase gene (Adh) of Drosophila melanogaster is transcribed from two tandem promoters in distinct developmental and tissue-specific patterns. Both promoters are regulated by separate upstream enhancer regions. In its wild-type context the adult enhancer specifically stimulates only the distal promoter, approximately 400 bp downstream, and not the proximal promoter, which is approximately 700 bp further downstream. Genomic footprinting and micrococcal nuclease analyses have revealed a specifically positioned nucleosome between the distal promoter and adult enhancer. In vitro reconstitution of this nucleosome demonstrated that DNA-core histone interactions alone are sufficient to position the nucleosome. Based on this observation and sequence periodicities in the underlying DNA, the mechanism of positioning appears to involve specific DNA structural features (ie flexibility or curvature). We have observed this nucleosome positioned early during development, before tissue differentiation, and before non-histone protein-DNA interactions are established at the distal promoter or adult enhancer. This nucleosome positioning element in the Adh regulatory region could be involved in establishing a specific tertiary nucleoprotein structure that facilitates specific cis-element accessibility and/or distal promoter-adult enhancer interactions. Images PMID:8451195

  17. Mutant HSPB1 overexpression in neurons is sufficient to cause age-related motor neuronopathy in mice

    PubMed Central

    Srivastava, Amit K.; Renusch, Samantha R.; Naiman, Nicole E.; Gu, Shuping; Sneh, Amita; Arnold, W. David; Sahenk, Zarife; Kolb, Stephen J.

    2012-01-01

    The small heat shock protein HSPB1 is a multifunctional, α-crystallin-based protein that has been shown to be neuroprotective in animal models of motor neuron disease and peripheral nerve injury. Missense mutations in HSPB1 result in axonal Charcot-Marie-Tooth disease with minimal sensory involvement (CMT2F) and distal hereditary motor neuropathy type 2 (dHMN-II). These disorders are characterized by a selective loss of motor axons in peripheral nerve resulting in distal muscle weakness and often severe disability. To investigate the pathogenic mechanisms of HSPB1 mutations in motor neurons in vivo, we have developed and characterized transgenic PrP-HSPB1 and PrP-HSPB1(R136W) mice. These mice express the human HSPB1 protein throughout the nervous system including in axons of peripheral nerve. Although both mouse strains lacked obvious motor deficits, the PrP-HSPB1(R136W) mice developed an age-dependent motor axonopathy. Mutant mice showed axonal pathology in spinal cord and peripheral nerve with evidence of impaired neurofilament cytoskeleton, associated with organelle accumulation. Accompanying these findings, increases in the number of Schmidt-Lanterman incisures, as evidence of impaired axon-Schwann cell interactions, were present. These observations suggest that overexpression of HSPB1(R136W) in neurons is sufficient to cause pathological and electrophysiological changes in mice that are seen in patients with hereditary motor neuropathy. PMID:22521462

  18. Nucleocytoplasmic human O-GlcNAc transferase is sufficient for O-GlcNAcylation of mitochondrial proteins.

    PubMed

    Trapannone, Riccardo; Mariappa, Daniel; Ferenbach, Andrew T; van Aalten, Daan M F

    2016-06-15

    O-linked N-acetylglucosamine modification (O-GlcNAcylation) is a nutrient-dependent protein post-translational modification (PTM), dynamically and reversibly driven by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyse the addition and the removal of the O-GlcNAc moieties to/from serine and threonine residues of target proteins respectively. Increasing evidence suggests involvement of O-GlcNAcylation in many biological processes, including transcription, signalling, neuronal development and mitochondrial function. The presence of a mitochondrial O-GlcNAc proteome and a mitochondrial OGT (mOGT) isoform has been reported. We explored the presence of mOGT in human cell lines and mouse tissues. Surprisingly, analysis of genomic sequences indicates that this isoform cannot be expressed in most of the species analysed, except some primates. In addition, we were not able to detect endogenous mOGT in a range of human cell lines. Knockdown experiments and Western blot analysis of all the predicted OGT isoforms suggested the expression of only a single OGT isoform. In agreement with this, we demonstrate that overexpression of the nucleocytoplasmic OGT (ncOGT) isoform leads to increased O-GlcNAcylation of mitochondrial proteins, suggesting that ncOGT is necessary and sufficient for the generation of the O-GlcNAc mitochondrial proteome. PMID:27048592

  19. Artificial ubiquitylation is sufficient for sorting of a plasma membrane ATPase to the vacuolar lumen of Arabidopsis cells.

    PubMed

    Herberth, Stefanie; Shahriari, Mojgan; Bruderek, Michael; Hessner, Florian; Müller, Britta; Hülskamp, Martin; Schellmann, Swen

    2012-07-01

    Sorting of transmembrane proteins into the inner vesicles of multivesicular bodies for subsequent delivery to the vacuole/lysosome can be induced by attachment of a single ubiquitin or K63-linked ubiquitin chains to the cytosolic portion of the cargo in yeast and mammals. In plants, large efforts have been undertaken to elucidate the mechanisms of vacuolar trafficking of soluble proteins. Sorting of transmembrane proteins, by contrast, is still largely unexplored. As a proof of principle, that ubiquitin is involved in vacuolar sorting in plants we show that a translational fusion of a single ubiquitin to the Arabidopsis plasma membrane ATPase PMA-EGFP is sufficient to induce its endocytosis and sorting into the vacuolar lumen. Sorting of the artificial reporter is not dependent on ubiquitin chain formation, but involves ubiquitin's hydrophobic patch and can be inhibited by coexpression of a dominant-negative version of the ESCRT (endosomal sorting complex required for transport) related protein AtSKD1 (SUPPRESSOR OF K+ TRANSPORT GROWTH DEFECT1). Our results suggest that ubiquitin can in principle act as vacuolar sorting signal in plants. PMID:22258747

  20. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

    PubMed

    Yano, S; Shinohara, H; Herbst, R S; Kuniyasu, H; Bucana, C D; Ellis, L M; Davis, D W; McConkey, D J; Fidler, I J

    2000-09-01

    We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target. PMID:10987313

  1. Sequence-directed nucleosome-depletion is sufficient to activate transcription from a yeast core promoter in vivo.

    PubMed

    Ichikawa, Yuichi; Morohashi, Nobuyuki; Tomita, Nobuyuki; Mitchell, Aaron P; Kurumizaka, Hitoshi; Shimizu, Mitsuhiro

    2016-07-22

    Nucleosome-depleted regions (NDRs) (also called nucleosome-free regions or NFRs) are often found in the promoter regions of many yeast genes, and are formed by multiple mechanisms, including the binding of activators and enhancers, the actions of chromatin remodeling complexes, and the specific DNA sequences themselves. However, it remains unclear whether NDR formation per se is essential for transcriptional activation. Here, we examined the relationship between nucleosome organization and gene expression using a defined yeast reporter system, consisting of the CYC1 minimal core promoter and the lacZ gene. We introduced simple repeated sequences that should be either incorporated in nucleosomes or excluded from nucleosomes in the site upstream of the TATA boxes. The (CTG)12, (GAA)12 and (TGTAGG)6 inserts were incorporated into a positioned nucleosome in the core promoter region, and did not affect the reporter gene expression. In contrast, the insertion of (CGG)12, (TTAGGG)6, (A)34 or (CG)8 induced lacZ expression by 10-20 fold. Nucleosome mapping analyses revealed that the inserts that induced the reporter gene expression prevented nucleosome formation, and created an NDR upstream of the TATA boxes. Thus, our results demonstrated that NDR formation dictated by DNA sequences is sufficient for transcriptional activation from the core promoter in vivo. PMID:27208777

  2. Pancreatic SEC23B deficiency is sufficient to explain the perinatal lethality of germline SEC23B deficiency in mice.

    PubMed

    Khoriaty, Rami; Everett, Lesley; Chase, Jennifer; Zhu, Guojing; Hoenerhoff, Mark; McKnight, Brooke; Vasievich, Matthew P; Zhang, Bin; Tomberg, Kärt; Williams, John; Maillard, Ivan; Ginsburg, David

    2016-01-01

    In humans, loss of function mutations in SEC23B result in Congenital Dyserythropoietic Anemia type II (CDAII), a disease limited to defective erythroid development. Patients with two nonsense SEC23B mutations have not been reported, suggesting that complete SEC23B deficiency might be lethal. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration and that mice with hematopoietic SEC23B deficiency do not exhibit CDAII. We now show that SEC23B deficiency restricted to the pancreas is sufficient to explain the lethality observed in mice with global SEC23B-deficiency. Immunohistochemical stains demonstrate an acinar cell defect but normal islet cells. Mammalian genomes contain two Sec23 paralogs, Sec23A and Sec23B. The encoded proteins share ~85% amino acid sequence identity. We generate mice with pancreatic SEC23A deficiency and demonstrate that these mice survive normally, exhibiting normal pancreatic weights and histology. Taken together, these data demonstrate that SEC23B but not SEC23A is essential for murine pancreatic development. We also demonstrate that two BAC transgenes spanning Sec23b rescue the lethality of mice homozygous for a Sec23b gene trap allele, excluding a passenger gene mutation as the cause of the pancreatic lethality, and indicating that the regulatory elements critical for Sec23b pancreatic function reside within the BAC transgenes. PMID:27297878

  3. Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

    PubMed Central

    Schweizer, Nadine; Pupe, Stéfano; Arvidsson, Emma; Nordenankar, Karin; Smith-Anttila, Casey J. A.; Mahmoudi, Souha; Andrén, Anna; Dumas, Sylvie; Rajagopalan, Aparna; Lévesque, Daniel; Leão, Richardson N.; Wallén-Mackenzie, Åsa

    2014-01-01

    The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knockout mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects. PMID:24821804

  4. Feasibility studies towards future self-sufficient supply of the 99Mo-99mTc isotopes with Japanese accelerators

    PubMed Central

    NAKAI, Kozi; TAKAHASHI, Naruto; HATAZAWA, Jun; SHINOHARA, Atsushi; HAYASHI, Yoshihiko; IKEDA, Hayato; KANAI, Yasukazu; WATABE, Tadashi; FUKUDA, Mitsuhiro; HATANAKA, Kichiji

    2014-01-01

    In order to establish a self-sufficient supply of 99mTc, we studied feasibilities to produce its parent nucleus, 99Mo, using Japanese accelerators. The daughter nucleus, 99mTc, is indispensable for medical diagnosis. 99Mo has so far been imported from abroad, which is separated from fission products generated in nuclear reactors using enriched 235U fuel. We investigated 99mTc production possibilities based on the following three scenarios: (1) 99Mo production by the (n, 2n) reaction by spallation neutrons at the J-PARC injector, LINAC; (2) 99Mo production by the (p, pn) reaction at Ep = 50–80 MeV proton at the RCNP cyclotron; (3) 99mTc direct production with a 20 MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for a scheme on a global scale, scenario (2) works in a local area, and both cases take a long time for negotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for 99mTc production. We here consider both the advantages and disadvantages among the three scenarios by taking account of the Japanese accelerator situation. PMID:25504230

  5. An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity.

    PubMed Central

    Graves, M C; Lim, J J; Heimer, E P; Kramer, R A

    1988-01-01

    In order to define the protease domain of human immunodeficiency virus 1, various regions of the pol open reading frame were cloned and expressed in Escherichia coli. Antiserum directed against the conserved retroviral protease active site was used to identify pol precursor and processed species containing the presumed protease domain. The smallest product that accumulates is about 11 kDa as measured by NaDodSO4/PAGE. This size agrees with that predicted from the presence in this region of two Phe-Pro sequences, which is one of the cleavage sites recognized by HIV protease. DNA encoding only the predicted 11-kDa protein was cloned, bypassing the need for autoprocessing, and the protein was expressed to a high level in E. coli. This form is active as demonstrated by its ability to specifically cleave protease-deficient pol protein in vivo in E. coli. Extracts of E. coli containing the 11-kDa protease also process human immunodeficiency virus gag substrates in vitro. These results demonstrate that the 11-kDa protease is sufficient for enzymatic activity and are consistent with a major role for this form in virus maturation. Images PMID:3282230

  6. A 90-liter stackable baffled microbial fuel cell for brewery wastewater treatment based on energy self-sufficient mode.

    PubMed

    Dong, Yue; Qu, Youpeng; He, Weihua; Du, Yue; Liu, Jia; Han, Xiaoyu; Feng, Yujie

    2015-11-01

    A 90-liter stackable pilot microbial fuel cell was designed and proved to be capable for brewery wastewater treatment and simultaneous electricity harvested. The system was stacked by 5 easily-stackable modules, and operated in an energy self-sufficient manner for more than 6 months. Tests were conducted under two different influent strengths (diluted wastewater, stage 1; raw wastewater, stage 2). The COD, SS removal efficiencies were 84.7% and 81.7% at stage 1, 87.6% and 86.3% at stage 2. The system produced enough energy (0.056 kWh/m(3) at stage 1, 0.097 kWh/m(3) at stage 2) to power the pumping system (0.027 kWh/m(3) at both stages), net electrical energy of 0.021 kWh/m(3) and 0.034 kWh/m(3) were harvested. These results show that this pilot-scale system could be used to effectively treat real wastewater with zero energy input. PMID:26096580

  7. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction.

    PubMed

    Watson, Carole S; Bialek, Peter; Anzo, Makoto; Khosravi, Javad; Yee, Siu-Pok; Han, Victor K M

    2006-03-01

    IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs. Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal growth restriction (FGR). To establish a causal relationship between high circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP-1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474 +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g compared with 1.62 +/- 0.04 g for wild type (WT); P < 0.05], and they did not demonstrate any postnatal catch-up growth. The placentas of the AFP-BP1 mice were larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT at E16.5; P < 0.05). Thus, this model of FGR is associated with a larger placenta, but without postnatal catch-up growth. Overall, these data clearly demonstrate that high concentrations of circulating IGFBP-1 are sufficient to cause FGR. PMID:16293667

  8. Podocyte-Specific Overexpression of Wild Type or Mutant Trpc6 in Mice Is Sufficient to Cause Glomerular Disease

    PubMed Central

    Kairath, Pamela; Carmona-Mora, Paulina; Molina, Jessica; Carpio, J. Daniel; Ruiz, Phillip; Mezzano, Sergio A.; Li, Jing; Wei, Changli; Reiser, Jochen; Young, Juan I.; Walz, Katherina

    2010-01-01

    Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2–3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease. PMID:20877463

  9. Beta-manganese dioxide nanorods for sufficient high-temperature electromagnetic interference shielding in X-band

    NASA Astrophysics Data System (ADS)

    Song, Wei-Li; Cao, Mao-Sheng; Hou, Zhi-Ling; Lu, Ming-Ming; Wang, Chan-Yuan; Yuan, Jie; Fan, Li-Zhen

    2014-09-01

    As the development of electronic and communication technology, electromagnetic interference (EMI) shielding and attenuation is an effective strategy to ensure the operation of the electronic devices. Among the materials for high-performance shielding in aerospace industry and related high-temperature working environment, the thermally stable metal oxide semiconductors with narrow band gap are promising candidates. In this work, beta-manganese dioxide ( β-MnO2) nanorods were synthesized by a hydrothermal method. The bulk materials of the β-MnO2 were fabricated to evaluate the EMI shielding performance in the temperature range of 20-500 °C between 8.2 and 12.4 GHz (X-band). To understand the mechanisms of high-temperature EMI shielding, the contribution of reflection and absorption to EMI shielding was discussed based on temperature-dependent electrical properties and complex permittivity. Highly sufficient shielding effectiveness greater than 20 dB was observed over all the investigated range, suggesting β-MnO2 nanorods as promising candidates for high-temperature EMI shielding. The results have also established a platform to develop high-temperature EMI shielding materials based on nanoscale semiconductors.

  10. Sufficient condition for the mode mismatch of single photons for scalability of the boson-sampling computer

    NASA Astrophysics Data System (ADS)

    Shchesnovich, V. S.

    2014-02-01

    The boson sampler proposed by Aaronson and Arkhipov is a nonuniversal quantum computer, which can serve as evidence against the extended Church-Turing thesis. It samples the probability distribution at the output of a linear unitary optical network with indistinguishable single photons at the input. Four experimental groups have already tested their small-scale prototypes with up to four photons. A boson sampler with a few dozens of single photons is believed to be hard to simulate on a classical computer. For scalability of a realistic boson sampler with current technology it is necessary to know the effect of the photon mode mismatch on its operation. Here a nondeterministic model of the boson sampler is analyzed, which employs partially indistinguishable single photons emitted by identical sources. A sufficient condition on the average mutual fidelity of the single photons is found, which guarantees that the realistic boson sampler outperforms the classical computer. Moreover, the boson-sampler computer with partially indistinguishable single photons is scalable and has more power than classical computers when the single-photon mode mismatch 1- scales as O (N-3/2) with the total number of photons N.

  11. Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

    SciTech Connect

    Craft, Willie Warren; Dutch, Rebecca Ellis . E-mail: rdutc2@uky.edu

    2005-10-10

    The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F{sub 0}, and proteolytically cleaved into the mature F{sub 1} and F{sub 2} heterodimer, following an HDLVDGVK{sub 109} motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK{sub 109} motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK{sub 109} motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein.

  12. Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

    PubMed Central

    Hein, A.M.; Stutzman, D.L.; Bland, S.T.; Barrientos, R.M.; Watkins, L.R.; Rudy, J.W.; Maier, S.F.

    2008-01-01

    The intra-hippocampal administration of interleukin-1β (IL-1β) as well as the induction of elevated but physiological levels of IL-1β within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1β is involved in impairments in working and spatial memory following IL-1β. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1β injection into the dorsal hippocampus. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1β and COX inhibition alone also disrupted contextual memory, suggesting an inverted U-shaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1β mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs. PMID:18035502

  13. Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness.

    PubMed

    Jobe, Njainday Pulo; Rösel, Daniel; Dvořánková, Barbora; Kodet, Ondřej; Lacina, Lukáš; Mateu, Rosana; Smetana, Karel; Brábek, Jan

    2016-08-01

    Tumour microenvironment plays a critical role in cell invasion and metastasis. To investigate the role of cancer-associated fibroblasts (CAFs) in melanoma cell invasiveness, we used 3D spheroid invasion assay. The effect of conditioned media from normal fibroblasts and CAFs cultivated alone or co-cultivated with melanoma cells on BLM or A2058 melanoma spheroid invasion was analysed. We found that conditioned media from CAFs and CAFs co-cultured with melanoma cells, especially, promote invasion and migration, without significant effect on melanoma cell proliferation. We further analysed the expression of pro-invasive cytokines IL-8 and IL-6 in media and found that melanoma cells are dominant producers of IL-8 and fibroblasts are dominant producers of IL-6 in 2D monocultures, while co-cultivation of CAFs with melanoma cells induces production/secretion of IL-6 and IL-8 into the media. The analyses of IL-6 levels in 3D cultures and human melanoma samples, however, revealed that at least in some cases IL-6 is also produced directly by melanoma cells. Analysis of the role of IL-6 and IL-8 in CAF-induced melanoma invasion, using neutralising antibodies, revealed that simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. In summary, these experiments indicate the important role of CAFs and IL-8 and IL-6 cytokines in melanoma cell invasiveness. PMID:27102177

  14. Seven N-terminal Residues of a Thermophilic Xylanase Are Sufficient to Confer Hyperthermostability on Its Mesophilic Counterpart

    PubMed Central

    Zhang, Shan; He, Yongzhi; Yu, Haiying; Dong, Zhiyang

    2014-01-01

    Xylanases, and especially thermostable xylanases, are increasingly of interest for the deconstruction of lignocellulosic biomass. In this paper, the termini of a pair of xylanases, mesophilic SoxB and thermophilic TfxA, were studied. Two regions in the N-terminus of TfxA were discovered to be potentially important for the thermostability. By focusing on Region 4, it was demonstrated that only two mutations, N32G and S33P cooperated to improve the thermostability of mesophilic SoxB. By introducing two potential regions into SoxB in combination, the most thermostable mutant, M2-N32G-S33P, was obtained. The M2-N32G-S33P had a melting temperature (Tm) that was 25.6°C higher than the Tm of SoxB. Moreover, M2-N32G-S33P was even three-fold more stable than TfxA and had a Tm value that was 9°C higher than the Tm of TfxA. Thus, for the first time, the mesophilic SoxB “pupil” outperformed its thermophilic TfxA “master” and acquired hyperthermostability simply by introducing seven thermostabilizing residues from the extreme N-terminus of TfxA. This work suggested that mutations in the extreme N-terminus were sufficient for the mesophilic xylanase SoxB to acquire hyperthermostability. PMID:24498158

  15. Visual cues given by humans are not sufficient for Asian elephants (Elephas maximus) to find hidden food.

    PubMed

    Plotnik, Joshua M; Pokorny, Jennifer J; Keratimanochaya, Titiporn; Webb, Christine; Beronja, Hana F; Hennessy, Alice; Hill, James; Hill, Virginia J; Kiss, Rebecca; Maguire, Caitlin; Melville, Beckett L; Morrison, Violet M B; Seecoomar, Dannah; Singer, Benjamin; Ukehaxhaj, Jehona; Vlahakis, Sophia K; Ylli, Dora; Clayton, Nicola S; Roberts, John; Fure, Emilie L; Duchatelier, Alicia P; Getz, David

    2013-01-01

    Recent research suggests that domesticated species--due to artificial selection by humans for specific, preferred behavioral traits--are better than wild animals at responding to visual cues given by humans about the location of hidden food. \\Although this seems to be supported by studies on a range of domesticated (including dogs, goats and horses) and wild (including wolves and chimpanzees) animals, there is also evidence that exposure to humans positively influences the ability of both wild and domesticated animals to follow these same cues. Here, we test the performance of Asian elephants (Elephas maximus) on an object choice task that provides them with visual-only cues given by humans about the location of hidden food. Captive elephants are interesting candidates for investigating how both domestication and human exposure may impact cue-following as they represent a non-domesticated species with almost constant human interaction. As a group, the elephants (n = 7) in our study were unable to follow pointing, body orientation or a combination of both as honest signals of food location. They were, however, able to follow vocal commands with which they were already familiar in a novel context, suggesting the elephants are able to follow cues if they are sufficiently salient. Although the elephants' inability to follow the visual cues provides partial support for the domestication hypothesis, an alternative explanation is that elephants may rely more heavily on other sensory modalities, specifically olfaction and audition. Further research will be needed to rule out this alternative explanation. PMID:23613804

  16. Correlation between International Normalized Ratio values and sufficiency of two different local hemostatic measures in anticoagulated patients

    PubMed Central

    Amer, Mohamed Zaghlool; Mourad, Samah I.; Salem, Ahmed S.; Abdelfadil, Ehab

    2014-01-01

    Objectives: The management of patients receiving oral anticoagulant therapy (OAT) undergoing minor oral surgeries is controversial. This study was designed to evaluate the correlation between International Normalized Ratio (INR) values and the sufficiency of two different local hemostatic measures in controlling postextraction bleeding in anticoagulated patients. Materials and Methods: One hundred and sixty patients receiving Warfarin OAT were included in this study. Patients were selected so that 80 patients have INR values of ≤2, whereas the remaining patients have the INR values ranging from 2 to 3. Forty patients were then randomly selected from each category to form two equal groups. Forty-five patients who had never been on OAT were selected as a negative control group (group 1). Failure to achieve hemostasis using a pressure pack was managed using either tranexamic acid (group 2) or Ankaferd Blood Stopper (ABS) (group 3). Results: The INR values of patients included in group 2 and 3 ranged from 1.5 to 3, with a mean of 2.2. No significant difference was recorded between the use of either tranexamic acid or ABS in achieving hemostasis in anticoagulated patients with INR values ranging between 2 and 3 (P = 0.93). Conclusion: Based on our findings, ABS is a hemostatic agent of good efficacy. The effect of ABS in controlling post-extraction bleeding in anticoagulated patients with INR values ≤3 is comparable to tranexamic acid with no evidence to support the superiority of tranexamic acid over ABS. PMID:25512727

  17. Sufficient utilization of natural fluctuating light intensity is an effective approach of promoting lipid productivity in oleaginous microalgal cultivation outdoors.

    PubMed

    He, Qiaoning; Yang, Haijian; Xu, Liangliang; Xia, Ling; Hu, Chunxiang

    2015-03-01

    The effects of fluctuating intensity of solar radiation on biomass and lipid in oleaginous microalgae are important. However, this topic has not been the subject of studies for a long time. In this study, four oleaginous microalgae from semi-arid areas were screened and cultivated outdoors under different fluctuating intensities. Results showed that the highest lipid productivities and neutral lipid (NL) contents occurred under high fluctuating intensity (HFI), in which 13-20% of the increased NL came from glycolipid transformation without phospholipid conversion. Chlorella sp. L1 and Monoraphidium dybowskii Y2 obtained from biological soil crusts in desert had the largest biomass (137.13, 106.61mgL(-1)d(-1)) and lipid yields (35.06, 32.45mgL(-1)d(-1)) under HFI. The highest areal lipid productivities of 9.06 and 8.95gm(-2)d(-1) and better biodiesel quality were observed under HFI. Accordingly, sufficiently adopting fluctuating light intensity outdoors to culture microalgae was an economic and effective approach. PMID:25590422

  18. Pancreatic SEC23B deficiency is sufficient to explain the perinatal lethality of germline SEC23B deficiency in mice

    PubMed Central

    Khoriaty, Rami; Everett, Lesley; Chase, Jennifer; Zhu, Guojing; Hoenerhoff, Mark; McKnight, Brooke; Vasievich, Matthew P.; Zhang, Bin; Tomberg, Kärt; Williams, John; Maillard, Ivan; Ginsburg, David

    2016-01-01

    In humans, loss of function mutations in SEC23B result in Congenital Dyserythropoietic Anemia type II (CDAII), a disease limited to defective erythroid development. Patients with two nonsense SEC23B mutations have not been reported, suggesting that complete SEC23B deficiency might be lethal. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration and that mice with hematopoietic SEC23B deficiency do not exhibit CDAII. We now show that SEC23B deficiency restricted to the pancreas is sufficient to explain the lethality observed in mice with global SEC23B-deficiency. Immunohistochemical stains demonstrate an acinar cell defect but normal islet cells. Mammalian genomes contain two Sec23 paralogs, Sec23A and Sec23B. The encoded proteins share ~85% amino acid sequence identity. We generate mice with pancreatic SEC23A deficiency and demonstrate that these mice survive normally, exhibiting normal pancreatic weights and histology. Taken together, these data demonstrate that SEC23B but not SEC23A is essential for murine pancreatic development. We also demonstrate that two BAC transgenes spanning Sec23b rescue the lethality of mice homozygous for a Sec23b gene trap allele, excluding a passenger gene mutation as the cause of the pancreatic lethality, and indicating that the regulatory elements critical for Sec23b pancreatic function reside within the BAC transgenes. PMID:27297878

  19. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

    NASA Astrophysics Data System (ADS)

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

    2015-09-01

    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

  20. Is floral divergence sufficient to maintain species boundaries upon secondary contact in Mediterranean food-deceptive orchids?

    PubMed Central

    Zitari, A; Scopece, G; Helal, A N; Widmer, A; Cozzolino, S

    2012-01-01

    Analyzing the processes that determine whether species boundaries are maintained on secondary contact may shed light on the early phase of speciation. In Anacamptis morio and Anacamptis longicornu, two Mediterranean orchid sister-species, we used molecular and morphological analyses, together with estimates of pollination success and experimental crosses, to assess whether floral isolation can shelter the species' genomes from genetic admixture on secondary contact. We found substantial genetic and morphological homogenization in sympatric populations in combination with an apparent lack of postmating isolation. We further detected asymmetric introgression in the sympatric populations and an imbalance in cytotype representation, which may be due either to a difference in flowering phenology or else be a consequence of cytonuclear incompatibilities. Estimates of genetic clines for markers across sympatric zones revealed markers that significantly deviated from neutral expectations. We observed a significant correlation between spur length and reproductive success in sympatric populations, which may suggest that directional selection is the main cause of morphological differentiation in this species pair. Our results suggest that allopatric divergence has not led to the evolution of sufficient reproductive isolation to prevent genomic admixture on secondary contact in this orchid species pair. PMID:21792224

  1. Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy.

    PubMed

    Kechele, Daniel O; Dunworth, William P; Trincot, Claire E; Wetzel-Strong, Sarah E; Li, Manyu; Ma, Hong; Liu, Jiandong; Caron, Kathleen M

    2016-09-01

    RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2(-/-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases. PMID:27402918

  2. Increased Classical Endoplasmic Reticulum Stress Is Sufficient to Reduce Chondrocyte Proliferation Rate in the Growth Plate and Decrease Bone Growth

    PubMed Central

    Kung, Louise H. W.; Rajpar, M. Helen; Preziosi, Richard; Briggs, Michael D.; Boot-Handford, Raymond P.

    2015-01-01

    Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole. PMID:25693198

  3. Sufficient oxygen can be transported to resting skeletal muscle via arterialization of the vein: theoretical considerations in a rat model.

    PubMed

    Koyama, Tomiyasu; Koyama, Tomiyasu; Sasajima, Tadahiro

    2011-01-01

    The blood supply to the lower limbs is often interrupted in patients suffering from arteriosclerosis obliterans (AO). In this condition, it is necessary to establish an oxygen supply via an alternative route. In the present theoretical study on rats, the possibility that adequate oxygen could be supplied through the venous system has been considered using simple calculations. The study was undertaken in the light of a report of a successful surgical approach in which the capillary bed is bypassed [1].The total lengths of the collecting venules and of the arcade venules per mm3 are reported to be 2.32 and 2.11 mm, respectively [2]. If these vessels were stretched out and connected to form a single, narrow venular tube, the total density would be 4.43 mm/mm(3). From the reciprocal of this value, the tissue cylinder surrounding the venule would have a radius of 268 µm. Taking an oxygen consumption rate for resting skeletal muscle of 0.16 ml/100g/min, and pO2 value of 40 mmHg, the one-dimensional diffusion equation gives a maximal diffusion distance of 328 µm. This is larger than the radius of the tissue cylinder surrounding the venular tube. A calculation for Krogh's tissue cylinder gives an oxygen partial pressure gradient of 54 mmHg between the inflow and the outflow terminals. These calculations suggest the oxygen content of the venous blood is adequate to supply sufficient oxygen to resting skeletal muscle. This is consistent with the successful outcome in patients with direct A-V anastomoses and implies that the capillary network is not essential for oxygen transport to resting skeletal muscle. PMID:21445806

  4. Knowledge of Native Protein-Protein Interfaces Is Sufficient To Construct Predictive Models for the Selection of Binding Candidates.

    PubMed

    Popov, Petr; Grudinin, Sergei

    2015-10-26

    Selection of putative binding poses is a challenging part of virtual screening for protein-protein interactions. Predictive models to filter out binding candidates with the highest binding affinities comprise scoring functions that assign a score to each binding pose. Existing scoring functions are typically deduced by collecting statistical information about interfaces of native conformations of protein complexes along with interfaces of a large generated set of non-native conformations. However, the obtained scoring functions become biased toward the method used to generate the non-native conformations, i.e., they may not recognize near-native interfaces generated with a different method. The present study demonstrates that knowledge of only native protein-protein interfaces is sufficient to construct well-discriminative predictive models for the selection of binding candidates. Here we introduce a new scoring method that comprises a knowledge-based potential called KSENIA deduced from structural information about the native interfaces of 844 crystallographic protein-protein complexes. We derive KSENIA using convex optimization with a training set composed of native protein complexes and their near-native conformations obtained using deformations along the low-frequency normal modes. As a result, our knowledge-based potential has only marginal bias toward a method used to generate putative binding poses. Furthermore, KSENIA is smooth by construction, which allows it to be used along with rigid-body optimization to refine the binding poses. Using several test benchmarks, we demonstrate that our method discriminates well native and near-native conformations of protein complexes from non-native ones. Our methodology can be easily adapted to the recognition of other types of molecular interactions, such as protein-ligand, protein-RNA, etc. KSENIA will be made publicly available as a part of the SAMSON software platform at https://team.inria.fr/nano-d/software . PMID

  5. Organic Fertilization and Sufficient Nutrient Status in Prehistoric Agriculture? – Indications from Multi-Proxy Analyses of Archaeological Topsoil Relicts

    PubMed Central

    Lauer, Franziska; Prost, Katharina; Gerlach, Renate; Pätzold, Stefan; Wolf, Mareike; Urmersbach, Sarah; Lehndorff, Eva; Eckmeier, Eileen; Amelung, Wulf

    2014-01-01

    Neolithic and Bronze Age topsoil relicts revealed enhanced extractable phosphorus (P) and plant available inorganic P fractions, thus raising the question whether there was targeted soil amelioration in prehistoric times. This study aimed (i) at assessing the overall nutrient status and the soil organic matter content of these arable topsoil relicts, and (ii) at tracing ancient soil fertilizing practices by respective stable isotope and biomarker analyses. Prehistoric arable topsoils were preserved in archaeological pit fillings, whereas adjacent subsoils served as controls. One Early Weichselian humic zone represented the soil status before the introduction of agriculture. Recent topsoils served as an additional reference. The applied multi-proxy approach comprised total P and micronutrient contents, stable N isotope ratios, amino acid, steroid, and black carbon analyses as well as soil color measurements. Total contents of P and selected micronutrients (I, Cu, Mn, Mo, Se, Zn) of the arable soil relicts were above the limits for which nutrient deficiencies could be assumed. All pit fillings exhibited elevated δ15N values close to those of recent topsoils (δ15N>6 to 7‰), giving first hints for prehistoric organic N-input. Ancient legume cultivation as a potential source for N input could not be verified by means of amino acid analysis. In contrast, bile acids as markers for faecal input exhibited larger concentrations in the pit fillings compared with the reference and control soils indicating faeces (i.e. manure) input to Neolithic arable topsoils. Also black carbon contents were elevated, amounting up to 38% of soil organic carbon, therewith explaining the dark soil color in the pit fillings and pointing to inputs of burned biomass. The combination of different geochemical analyses revealed a sufficient nutrient status of prehistoric arable soils, as well as signs of amelioration (inputs of organic material like charcoal and faeces-containing manure). PMID

  6. The DNA binding and activation domains of Gal4p are sufficient for conveying its regulatory signals.

    PubMed Central

    Ding, W V; Johnston, S A

    1997-01-01

    The transcriptional activation function of the Saccharomyces cerevisiae activator Gal4p is known to rely on a DNA binding activity at its amino terminus and an activation domain at its carboxy terminus. Although both domains are required for activation, truncated forms of Gal4p containing only these domains activate poorly in vivo. Also, mutations in an internal conserved region of Gal4p inactivate the protein, suggesting that this internal region has some function critical to the activity of Gal4p. We have addressed the question of what is the minimal form of Gal4 protein that can perform all of its known functions. A form with an internal deletion of the internal conserved domain of Gal4p is transcriptionally inactive, allowing selection for suppressors. All suppressors isolated were intragenic alterations that had further amino acid deletions (miniGAL4s). Characterization of the most active miniGal4 proteins demonstrated that they possess all of the known functions of full-length Gal4p, including glucose repression, galactose induction, response to deletions of gal11 or gal6, and interactions with other proteins such as Ga180p, Sug1p, and TATA binding protein. Analysis of the transcriptional activities, protein levels, and DNA binding abilities of these miniGal4ps and a series of defined internal mutants compared to those of the full-length Gal4p indicates that the DNA binding and activation domains are necessary and sufficient qualitatively for all of these known functions of Gal4p. Our observations imply that the internal region of Gal4 protein may serve as a spacer to augment transcription and/or may be involved in intramolecular or Gal4p-Gal4p interactions. PMID:9111323

  7. The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor.

    PubMed

    Bouhouche-Chatelier, L; Chadli, A; Catelli, M G

    2001-10-01

    To understand how the molecular chaperone Hsp90 participates in conformational maturation of the estrogen receptor (ER), we analyzed the interaction of immobilized purified avian Hsp90 with mammalian cytosolic ER. Hsp90 was either immunoadsorbed to BF4 antibody-Sepharose or GST-Hsp90 fusion protein (GST.90) was adsorbed to glutathione-Sepharose. GST.90 was able to retain specifically ER, similarly to immunoadsorbed Hsp90. When cells were treated with estradiol and the hormone treatment was maintained during cell homogenization, binding, and washing steps, GST.90 still interacted efficiently with ER, suggesting that ER may form complexes with Hsp90 even after its activation by hormone and salt extraction from nuclei. The GST.90-ER interaction was consistently reduced in the presence of increasing concentrations of potassium chloride or when cytosolic ER-Hsp90 complexes were previously stabilized by molybdate, indicating that GST.90-ER complexes behave like cytosolic Hsp90-ER complexes. A purified thioredoxin-ER fusion protein was also able to form complexes with GST.90, suggesting that the presence of other chaperones is not required. ER was retained only by GST.90 deletion mutants bearing an intact Hsp90 N-terminal region (1-224), the interaction being more efficient when the charged region A was present in the mutant (1-334). The N-terminal fragment 1-334, devoid of the dimeric GST moiety, was also able to interact with ER, pointing to the monomeric N-terminal adenosine triphosphate binding region of Hsp90 (1-224) as the region necessary and sufficient for interaction. These results contribute to understand the Hsp90-dependent process responsible for conformational competence of ER. PMID:11795466

  8. Metabolic hormone FGF21 is induced in ground squirrels during hibernation but its overexpression is not sufficient to cause torpor.

    PubMed

    Nelson, Bethany T; Ding, Xunshan; Boney-Montoya, Jamie; Gerard, Robert D; Kliewer, Steven A; Andrews, Matthew T

    2013-01-01

    Hibernation is a natural adaptation that allows certain mammals to survive physiological extremes that are lethal to humans. Near freezing body temperatures, heart rates of 3-10 beats per minute, absence of food consumption, and depressed metabolism are characteristic of hibernation torpor bouts that are periodically interrupted by brief interbout arousals (IBAs). The molecular basis of torpor induction is unknown, however starved mice overexpressing the metabolic hormone fibroblast growth factor 21 (FGF21) promote fat utilization, reduce body temperature, and readily enter torpor-all hallmarks of mammalian hibernation. In this study we cloned FGF21 from the naturally hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and found that levels of FGF21 mRNA in liver and FGF21 protein in serum are elevated during hibernation torpor bouts and significantly elevated during IBAs compared to summer active animals. The effects of artificially elevating circulating FGF21 concentrations 50 to 100-fold via adenoviral-mediated overexpression were examined at three different times of the year. This is the first time that a transgenic approach has been used in a natural hibernator to examine mechanistic aspects of hibernation. Surgically implanted transmitters measured various metrics of the hibernation phenotype over a 7-day period including changes in motor activity, heart rate and core body temperature. In April fed-state animals, FGF21 overexpression decreased blood insulin and free fatty acid concentrations, effects similar to those seen in obese mice. However, elevated FGF21 concentrations did not cause torpor in these fed-state animals nor did they cause torpor or affect metabolic parameters in fasted-state animals in March/April, August or October. We conclude that FGF21 is strongly regulated during torpor and IBA but that its overexpression is not sufficient to cause torpor in naturally hibernating ground squirrels. PMID:23301087

  9. H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration.

    PubMed

    Adams, Dany S; Masi, Alessio; Levin, Michael

    2007-04-01

    In many systems, ion flows and long-term endogenous voltage gradients regulate patterning events, but molecular details remain mysterious. To establish a mechanistic link between biophysical events and regeneration, we investigated the role of ion transport during Xenopus tail regeneration. We show that activity of the V-ATPase H(+) pump is required for regeneration but not wound healing or tail development. The V-ATPase is specifically upregulated in existing wound cells by 6 hours post-amputation. Pharmacological or molecular genetic loss of V-ATPase function and the consequent strong depolarization abrogates regeneration without inducing apoptosis. Uncut tails are normally mostly polarized, with discrete populations of depolarized cells throughout. After amputation, the normal regeneration bud is depolarized, but by 24 hours post-amputation becomes rapidly repolarized by the activity of the V-ATPase, and an island of depolarized cells appears just anterior to the regeneration bud. Tail buds in a non-regenerative ;refractory' state instead remain highly depolarized relative to uncut or regenerating tails. Depolarization caused by V-ATPase loss-of-function results in a drastic reduction of cell proliferation in the bud, a profound mispatterning of neural components, and a failure to regenerate. Crucially, induction of H(+) flux is sufficient to rescue axonal patterning and tail outgrowth in otherwise non-regenerative conditions. These data provide the first detailed mechanistic synthesis of bioelectrical, molecular and cell-biological events underlying the regeneration of a complex vertebrate structure that includes spinal cord, and suggest a model of the biophysical and molecular steps underlying tail regeneration. Control of H(+) flows represents a very important new modality that, together with traditional biochemical approaches, may eventually allow augmentation of regeneration for therapeutic applications. PMID:17329365

  10. How Fast Is Your Body Motion? Determining a Sufficient Frame Rate for an Optical Motion Tracking System Using Passive Markers.

    PubMed

    Song, Min-Ho; Godøy, Rolf Inge

    2016-01-01

    This paper addresses how to determine a sufficient frame (sampling) rate for an optical motion tracking system using passive reflective markers. When using passive markers for the optical motion tracking, avoiding identity confusion between the markers becomes a problem as the speed of motion increases, necessitating a higher frame rate to avoid a failure of the motion tracking caused by marker confusions and/or dropouts. Initially, one might believe that the Nyquist-Shannon sampling rate estimated from the assumed maximal temporal variation of a motion (i.e. a sampling rate at least twice that of the maximum motion frequency) could be the complete solution to the problem. However, this paper shows that also the spatial distance between the markers should be taken into account in determining the suitable frame rate of an optical motion tracking with passive markers. In this paper, a frame rate criterion for the optical tracking using passive markers is theoretically derived and also experimentally verified using a high-quality optical motion tracking system. Both the theoretical and the experimental results showed that the minimum frame rate is proportional to the ratio between the maximum speed of the motion and the minimum spacing between markers, and may also be predicted precisely if the proportional constant is known in advance. The inverse of the proportional constant is here defined as the tracking efficiency constant and it can be easily determined with some test measurements. Moreover, this newly defined constant can provide a new way of evaluating the tracking algorithm performance of an optical tracking system. PMID:26967900

  11. β-Subunit Binding Is Sufficient for Ligands to Open the Integrin αIIbβ3 Headpiece.

    PubMed

    Lin, Fu-Yang; Zhu, Jianghai; Eng, Edward T; Hudson, Nathan E; Springer, Timothy A

    2016-02-26

    The platelet integrin αIIbβ3 binds to a KQAGDV motif at the fibrinogen γ-chain C terminus and to RGD motifs present in loops in many extracellular matrix proteins. These ligands bind in a groove between the integrin α and β-subunits; the basic Lys or Arg side chain hydrogen bonds to the αIIb-subunit, and the acidic Asp side chain coordinates to a metal ion held by the β3-subunit. Ligand binding induces headpiece opening, with conformational change in the β-subunit. During this opening, RGD slides in the ligand-binding pocket toward αIIb, with movement of the βI-domain β1-α1 loop toward αIIb, enabling formation of direct, charged hydrogen bonds between the Arg side chain and αIIb. Here we test whether ligand interactions with β3 suffice for stable ligand binding and headpiece opening. We find that the AGDV tetrapeptide from KQAGDV binds to the αIIbβ3 headpiece with affinity comparable with the RGDSP peptide from fibronectin. AGDV induced complete headpiece opening in solution as shown by increase in hydrodynamic radius. Soaking of AGDV into closed αIIbβ3 headpiece crystals induced intermediate states similarly to RGDSP. AGDV has very little contact with the α-subunit. Furthermore, as measured by epitope exposure, AGDV, like the fibrinogen γ C-terminal peptide and RGD, caused integrin extension on the cell surface. Thus, pushing by the β3-subunit on Asp is sufficient for headpiece opening and ligand sliding, and no pulling by the αIIb subunit on Arg is required. PMID:26631735

  12. Evidence that cytosolic calcium increases are not sufficient to stimulate phospholipid scrambling in human T-lymphocytes.

    PubMed Central

    Wurth, Georjeana A; Zweifach, Adam

    2002-01-01

    Phospholipid scrambling, the disruption of normal plasma-membrane asymmetry, occurs during apoptotic and necrotic cell death and during the activation of platelets and neutrophils. It is currently believed that phospholipid scrambling is triggered simply by increases in bulk cytosolic [Ca(2+)]. We have presented evidence previously that the styryl dye FM1-43 is sensitive to phospholipid scrambling in Jurkat human leukaemic T-lymphocytes. Here we have used FM1-43, in combination with fura 2 and the Ca(2+)-elevating agents ionomycin and thapsigargin, in imaging experiments to test the idea that increases in bulk cytosolic [Ca(2+)] stimulate scrambling. Intracellular Ca(2+) increases of approximately 2 microM accompanied ionomycin-stimulated scrambling in approximately 50% of cells, and scrambling occurred in >99% of cells in which intracellular Ca(2+) rose to 4 microM. Chelating intracellular Ca(2+) with bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid or EGTA suppressed both ionomycin-stimulated intra cellular Ca(2+) increases and scrambling, demonstrating that intracellular Ca(2+) increases are necessary for ionomycin-stimulated scrambling. However, elevating intracellular Ca(2+) to 2-4 microM with thapsigargin, a drug that depletes intracellular Ca(2+) stores and triggers Ca(2+) entry via Ca(2+)-release-activated Ca(2+) channels, did not trigger scrambling, as assessed with either FM1-43 or FITC-labelled annexin V. These results suggest that increases in intracellular [Ca(2+)] are necessary but not sufficient to stimulate scrambling in lymphoyctes, and indicate that ionomycin has an additional effect that is required to stimulate scrambling. PMID:11879198

  13. Metabolic Hormone FGF21 Is Induced in Ground Squirrels during Hibernation but Its Overexpression Is Not Sufficient to Cause Torpor

    PubMed Central

    Nelson, Bethany T.; Ding, Xunshan; Boney-Montoya, Jamie; Gerard, Robert D.; Kliewer, Steven A.; Andrews, Matthew T.

    2013-01-01

    Hibernation is a natural adaptation that allows certain mammals to survive physiological extremes that are lethal to humans. Near freezing body temperatures, heart rates of 3–10 beats per minute, absence of food consumption, and depressed metabolism are characteristic of hibernation torpor bouts that are periodically interrupted by brief interbout arousals (IBAs). The molecular basis of torpor induction is unknown, however starved mice overexpressing the metabolic hormone fibroblast growth factor 21 (FGF21) promote fat utilization, reduce body temperature, and readily enter torpor–all hallmarks of mammalian hibernation. In this study we cloned FGF21 from the naturally hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and found that levels of FGF21 mRNA in liver and FGF21 protein in serum are elevated during hibernation torpor bouts and significantly elevated during IBAs compared to summer active animals. The effects of artificially elevating circulating FGF21 concentrations 50 to 100-fold via adenoviral-mediated overexpression were examined at three different times of the year. This is the first time that a transgenic approach has been used in a natural hibernator to examine mechanistic aspects of hibernation. Surgically implanted transmitters measured various metrics of the hibernation phenotype over a 7-day period including changes in motor activity, heart rate and core body temperature. In April fed-state animals, FGF21 overexpression decreased blood insulin and free fatty acid concentrations, effects similar to those seen in obese mice. However, elevated FGF21 concentrations did not cause torpor in these fed-state animals nor did they cause torpor or affect metabolic parameters in fasted-state animals in March/April, August or October. We conclude that FGF21 is strongly regulated during torpor and IBA but that its overexpression is not sufficient to cause torpor in naturally hibernating ground squirrels. PMID:23301087

  14. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles

    PubMed Central

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-01-01

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity. PMID:22531556

  15. Retinoic Acid Activity in Undifferentiated Neural Progenitors Is Sufficient to Fulfill Its Role in Restricting Fgf8 Expression for Somitogenesis

    PubMed Central

    Cunningham, Thomas J.; Brade, Thomas; Sandell, Lisa L.; Lewandoski, Mark; Trainor, Paul A.; Colas, Alexandre; Mercola, Mark; Duester, Gregg

    2015-01-01

    Bipotent axial stem cells residing in the caudal epiblast during late gastrulation generate neuroectodermal and presomitic mesodermal progeny that coordinate somitogenesis with neural tube formation, but the mechanism that controls these two fates is not fully understood. Retinoic acid (RA) restricts the anterior extent of caudal fibroblast growth factor 8 (Fgf8) expression in both mesoderm and neural plate to control somitogenesis and neurogenesis, however it remains unclear where RA acts to control the spatial expression of caudal Fgf8. Here, we found that mouse Raldh2-/- embryos, lacking RA synthesis and displaying a consistent small somite defect, exhibited abnormal expression of key markers of axial stem cell progeny, with decreased Sox2+ and Sox1+ neuroectodermal progeny and increased Tbx6+ presomitic mesodermal progeny. The Raldh2-/- small somite defect was rescued by treatment with an FGF receptor antagonist. Rdh10 mutants, with a less severe RA synthesis defect, were found to exhibit a small somite defect and anterior expansion of caudal Fgf8 expression only for somites 1–6, with normal somite size and Fgf8 expression thereafter. Rdh10 mutants were found to lack RA activity during the early phase when somites are small, but at the 6-somite stage RA activity was detected in neural plate although not in presomitic mesoderm. Expression of a dominant-negative RA receptor in mesoderm eliminated RA activity in presomitic mesoderm but did not affect somitogenesis. Thus, RA activity in the neural plate is sufficient to prevent anterior expansion of caudal Fgf8 expression associated with a small somite defect. Our studies provide evidence that RA restriction of Fgf8 expression in undifferentiated neural progenitors stimulates neurogenesis while also restricting the anterior extent of the mesodermal Fgf8 mRNA gradient that controls somite size, providing new insight into the mechanism that coordinates somitogenesis with neurogenesis. PMID:26368825

  16. Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake

    PubMed Central

    Coble, Jeffrey P.; Cassell, Martin D.; Davis, Deborah R.; Grobe, Justin L.

    2014-01-01

    Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. Renin and angiotensinogen are coexpressed within the same cells of the subfornical organ, and the production and action of ANG II through the ANG II type 1 receptor in the subfornical organ (SFO) are necessary for fluid intake due to increased activity of the brain renin-angiotensin system. We generated an inducible model of ANG II production by breeding transgenic mice expressing human renin in neurons controlled by the synapsin promoter with transgenic mice containing a Cre-recombinase-inducible human angiotensinogen construct. Adenoviral delivery of Cre-recombinase causes SFO-selective induction of human angiotensinogen expression. Selective production of ANG II in the SFO results in increased water intake but did not change blood pressure or resting metabolic rate. The increase in water intake was ANG II type 1 receptor-dependent. When given a choice between water and 0.15 M NaCl, these mice increased total fluid and sodium, but not water, because of an increased preference for NaCl. When provided a choice between water and 0.3 M NaCl, the mice exhibited increased fluid, water, and sodium intake, but no change in preference for NaCl. The increase in fluid intake was blocked by an inhibitor of PKC, but not ERK, and was correlated with increased phosphorylated cyclic AMP response element binding protein in the subfornical organ. Thus, increased production and action of ANG II specifically in the subfornical organ are sufficient on their own to mediate an increase in drinking through PKC. PMID:24965793

  17. Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

    PubMed Central

    2012-01-01

    Background The first meningococcal serogroup C (MenC) conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed. PMID:22316426

  18. Mechanical properties of collagen membranes modified with pores--are they still sufficient for orbital floor reconstruction?

    PubMed

    Birkenfeld, F; Flörke, C; Behrens, E; Rohnen, M; Kern, M; Gassling, V; Wiltfang, J

    2015-12-01

    Adequate mechanical strength is essential for materials used to reconstruct the orbital floor, and collagen membranes have recently been suggested for the repair of isolated fractures of the orbital floor. However, their mechanical properties after modification with pores for increased drainage of blood into the sinus have not been sufficiently investigated. We have tested the mechanical resistance of polydioxanone foils (PDS) to distortion and compared it with that of 3 resorbable collagen membranes (Smartbrane(®), Bio-Gide(®), and Creos(®)) in mint condition and when artificially aged (3 weeks, 6 weeks, and 8 weeks) after modification with pores (diameter 2mm) in a standard configuration (n=12 in each group). PDS and Creos(®) had comparable initial values for mechanical resistance of about 2.3N/mm(2), and Bio-Gide(®) and Smartbrane(®) had about 20% and 80% lower initial mechanical resistance, respectively. All materials tested had lower values after artificial ageing. After eight weeks of ageing, PDS lost about 99% of its initial mechanical resistance, Creos(®) about 66%, Bio-Gide(®) about 30%, and Smartbrane(®) about 95%. After 3 weeks the mechanical resistance in all groups was significantly less than the initial values (p=0.05), but there was no difference between samples aged artificially for 6 compared with 8 weeks. The mechanical resistance of the tested materials was not influenced by the presence of pores in a standard configuration and was in the appropriate range for moderate fractures of the orbital floor. We recommend further clinical investigations of collagen membranes modified with pores. PMID:26255542

  19. Internal carbonic anhydrase activity in the tissue of scleractinian corals is sufficient to support proposed roles in photosynthesis and calcification.

    PubMed

    Hopkinson, Brian M; Tansik, Anna L; Fitt, William K

    2015-07-01

    Reef-building corals import inorganic carbon (Ci) to build their calcium carbonate skeletons and to support photosynthesis by the symbiotic algae that reside in their tissue. The internal pathways that deliver Ci for both photosynthesis and calcification are known to involve the enzyme carbonic anhydrase (CA), which interconverts CO2 and HCO3 (-). We have developed a method for absolute quantification of internal CA (iCA) activity in coral tissue based on the rate of (18)O-removal from labeled Ci. The method was applied to three Caribbean corals (Orbicella faveolata, Porites astreoides and Siderastrea radians) and showed that these species have similar iCA activities per unit surface area, but that S. radians has ∼10-fold higher iCA activity per unit tissue volume. A model of coral Ci processing shows that the measured iCA activity is sufficient to support the proposed roles for iCA in Ci transport for photosynthesis and calcification. This is the case even when iCA activity is homogeneously distributed throughout the coral, but the model indicates that it would be advantageous to concentrate iCA in the spaces where calcification (the calcifying fluid) and photosynthesis (the oral endoderm) take place. We argue that because the rates of photosynthesis and calcification per unit surface area are similar among the corals studied here, the areal iCA activity used to deliver Ci for these reactions should also be similar. The elevated iCA activity per unit volume of S. radians compared with that of the other species is probably due to the thinner effective tissue thickness in this species. PMID:25908060

  20. Buying Years to Extinction: Is Compensatory Mitigation for Marine Bycatch a Sufficient Conservation Measure for Long-Lived Seabirds?

    PubMed Central

    Forero, Manuela G.; Oro, Daniel

    2009-01-01

    Along the lines of the ‘polluter pays principle’, it has recently been proposed that the local long-line fishing industry should fund eradication of terrestrial predators at seabird breeding colonies, as a compensatory measure for the bycatch caused by the fishing activity. The measure is economically sound, but a quantitative and reliable test of its biological efficacy has never been conducted. Here, we investigated the demographic consequences of predator eradication for Cory's shearwater Calonectris diomedea, breeding in the Mediterranean, using a population model that integrates demographic rates estimated from individual life-history information with experimental measures of predation and habitat structure. We found that similar values of population growth rate can be obtained by different combinations of habitat characteristics, predator abundance and adult mortality, which explains the persistence of shearwater colonies in islands with introduced predators. Even so, given the empirically obtained values of survival, all combinations of predator abundance and habitat characteristics projected a decline in shearwater numbers. Perturbation analyses indicated that the value and the sensitivity of shearwater population growth rates were affected by all covariates considered and their interactions. A decrease in rat abundance delivered only a small increase in the population growth rate, whereas a change in adult survival (a parameter independent of rat abundance) had the strongest impact on population dynamics. When adult survival is low, rat eradication would allow us to “buy” years before extinction but does not reverse the process. Rat eradication can therefore be seen as an emergency measure if threats on adult survival are eliminated in the medium-term period. For species with low fecundity and long life expectancy, our results suggest that rat control campaigns are not a sufficient, self-standing measure to compensate the biological toll of long

  1. Membrane anchoring domain of herpes simplex virus glycoprotein gB is sufficient for nuclear envelope localization.

    PubMed Central

    Gilbert, R; Ghosh, K; Rasile, L; Ghosh, H P

    1994-01-01

    We have used the glycoprotein gB of herpes simplex virus type 1 (gB-1), which buds from the inner nuclear membrane, as a model protein to study localization of membrane proteins in the nuclear envelope. To determine whether specific domains of gB-1 glycoprotein are involved in localization in the nuclear envelope, we have used deletion mutants of gB-1 protein as well as chimeric proteins constructed by replacing the domains of the cell surface glycoprotein G of vesicular stomatitis virus with the corresponding domains of gB. Mutant and chimeric proteins expressed in COS cells were localized by immunoelectron microscopy. A chimeric protein (gB-G) containing the ectodomain of gB and the transmembrane and cytoplasmic domains of G did not localize in the nuclear envelope. When the ectodomain of G was fused to the transmembrane and cytoplasmic domains of gB, however, the resulting chimeric protein (G-gB) was localized in the nuclear envelope. Substitution of the transmembrane domain of G with the 69 hydrophobic amino acids containing the membrane anchoring domain of gB allowed the hybrid protein (G-tmgB) to be localized in the nuclear envelope, suggesting that residues 721 to 795 of gB can promote retention of proteins in the nuclear envelope. Deletion mutations in the hydrophobic region further showed that a transmembrane segment of 21 hydrophobic amino acids, residues 774 to 795 of gB, was sufficient for localization in the nuclear envelope. Since wild-type gB and the mutant and chimeric proteins that were localized in the nuclear envelope were also retained in the endoplasmic reticulum, the membrane spanning segment of gB could also influence retention in the endoplasmic reticulum. Images PMID:8139012

  2. Oxidation of nanoscale zero-valent iron under sufficient and limited dissolved oxygen: Influences on aggregation behaviors.

    PubMed

    Jiang, Danlie; Hu, Xialin; Wang, Rui; Yin, Daqiang

    2015-03-01

    Oxidations of nanoscale zero-valent iron (nZVI) under aerobic (dissolved oxygen≈8mgL(-1)) and anaerobic (dissolved oxygen <3mgL(-1)) conditions were simulated, and their influences on aggregation behaviors of nZVI were investigated. The two oxidation products were noted as HO-nZVI (nZVI oxidized in highly oxygenated water) and LO-nZVI (nZVI oxidized in lowly oxygenated water) respectively. The metallic iron of the oxidized nZVI was almost exhausted (Fe(0)≈8±5%), thus magnetization mainly depended on magnetite content. Since sufficient dissolved oxygen led to the much less magnetite (∼15%) in HO-nZVI than that in LO-nZVI (>90%), HO-nZVI was far less magnetic (Ms=88kAm(-1)) than LO-nZVI (Ms=365kAm(-1)). Consequently, HO-nZVI formed small agglomerates (228±10nm), while LO-nZVI tended to form chain-like aggregations (>1μm) which precipitated rapidly. Based on the EDLVO theory, we suggested that dissolved oxygen level determined aggregation morphologies by controlling the degree of oxidation and the magnitude of magnetization. Then the chain-like alignment of LO-nZVI would promote further aggregation, but the agglomerate morphology of HO-nZVI would eliminate magnetic forces and inhibit the aggregation while HO-nZVI remained magnetic. Our results indicated the fine colloidal stability of HO-nZVI, which might lead to the great mobility in the environment. PMID:25441925

  3. A three-nucleotide helix I is sufficient for full activity of a hammerhead ribozyme: advantages of an asymmetric design.

    PubMed Central

    Tabler, M; Homann, M; Tzortzakaki, S; Sczakiel, G

    1994-01-01

    Trans-cleaving hammerhead ribozymes with long target-specific antisense sequences flanking the catalytic domain share some features with conventional antisense RNA and are therefore termed 'catalytic antisense RNAs'. Sequences 5' to the catalytic domain form helix I and sequences 3' to it form helix III when complexed with the target RNA. A catalytic antisense RNA of more than 400 nucleotides, and specific for the human immunodeficiency virus type 1 (HIV-1), was systematically truncated within the arm that constituted originally a helix I of 128 base pairs. The resulting ribozymes formed helices I of 13, 8, 5, 3, 2, 1 and 0 nucleotides, respectively, and a helix III of about 280 nucleotides. When their in vitro cleavage activity was compared with the original catalytic antisense RNA, it was found that a helix I of as little as three nucleotides was sufficient for full endonucleolytic activity. The catalytically active constructs inhibited HIV-1 replication about four-fold more effectively than the inactive ones when tested in human cells. A conventional hammerhead ribozyme having helices of just 8 nucleotides on either side failed to cleave the target RNA in vitro when tested under the conditions for catalytic antisense RNA. Cleavage activity could only be detected after heat-treatment of the ribozyme substrate mixture which indicates that hammerhead ribozymes with short arms do not associate as efficiently to the target RNA as catalytic antisense RNA. The requirement of just a three-nucleotide helix I allows simple PCR-based generation strategies for asymmetric hammerhead ribozymes. Advantages of an asymmetric design will be discussed. Images PMID:7937118

  4. Damage to the pyramidal tracts is necessary and sufficient for the production of the pyramidal syndrome in man.

    PubMed

    de Oliveira-Souza, Ricardo

    2015-07-01

    The causal role played by damage to the pyramidal tracts in the production of spastic hemiplegia in man has been hotly debated over the past hundred years. Two broad streams of thought have emerged from this dispute. The first, which is grounded on the clinicopathological schools of Jean-Martin Charcot (1825-1893) and Paul Flechsig (1847-1929), claimed that the four cardinal signs of hemiplegia, namely (i) paralysis, (ii) spasticity, (iii) hyperactive phasic muscle reflexes ("tendon jerks") and (iv) the sign of Babinski, are caused by injury or dysfunction of the pyramidal tracts. The second school, championed by John Farquhar Fulton (1899-1960) and Derek Denny-Brown (1901-1981), reflects the increasing influence of experimental neurology on clinicopathological concepts after World War II. According to this school, most elements of the pyramidal syndrome are caused by the added release or injury of extrapyramidal structures at different levels of the forebrain and brainstem. Most symptoms of spastic hemiplegia were thus interpreted as signs of extrapyramidal (e.g., reticulospinal) release or damage. However, consensus on which symptoms of spastic hemiplegia were due to pyramidal or extrapyramidal changes was never reached. To add to this uncertainty, a number of clinicopathological cases that supported the old view were sporadically published over the same period. The purpose of the present essay is to provide clinicoanatomic perspective to the neurological literature in support of the hypothesis that damage to the pyramidal tracts is a necessary and sufficient condition for the production of the complete pyramidal syndrome in man. PMID:25959865

  5. The Sca2 Autotransporter Protein from Rickettsia conorii Is Sufficient To Mediate Adherence to and Invasion of Cultured Mammalian Cells▿

    PubMed Central

    Cardwell, Marissa M.; Martinez, Juan J.

    2009-01-01

    Obligate intracellular bacteria of the genus Rickettsia must adhere to and invade the host endothelium in order to establish an infection. These processes require the interaction of rickettsial surface proteins with mammalian host cell receptors. A previous bioinformatic analysis of sequenced rickettsial species identified a family of at least 17 predicted “surface cell antigen” (sca) genes whose products resemble autotransporter proteins. Two members of this family, rOmpA and rOmpB of spotted fever group (SFG) rickettsiae have been identified as adhesion and invasion factors, respectively; however, little is known about the putative functions of the other sca gene products. An intact sca2 gene is found in the majority of pathogenic SFG rickettsiae and, due to its sequence conservation among these species, we predict that Sca2 may play an important function at the rickettsial surface. Here we have shown that sca2 is transcribed and expressed in Rickettsia conorii and have used a heterologous gain-of-function assay in E. coli to determine the putative role of Sca2. Using this system, we have demonstrated that expression of Sca2 at the outer membrane of nonadherent, noninvasive E. coli is sufficient to mediate adherence to and invasion of a panel of mammalian cells, including endothelial cells. Furthermore, soluble Sca2 protein is capable of diminishing R. conorii invasion of cultured mammalian cells. This is the first evidence that Sca2 participates in the interaction between SFG rickettsiae and host cells and suggests that in addition to other surface proteins, Sca2 may play a critical role in rickettsial pathogenesis. PMID:19805531

  6. Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

    PubMed Central

    Barrio, Gregorio; Brugal, M. Teresa; de la Fuente, Luis; Ballesta, Rosario; Bravo, María J.; Silva, Teresa C.; Rodríguez-Martos, Alicia

    2006-01-01

    To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 street-recruited current heroin users aged 18–30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and pre-coded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed. PMID:16739049

  7. β-Subunit Binding Is Sufficient for Ligands to Open the Integrin αIIbβ3 Headpiece*

    PubMed Central

    Lin, Fu-Yang; Zhu, Jianghai; Eng, Edward T.; Hudson, Nathan E.; Springer, Timothy A.

    2016-01-01

    The platelet integrin αIIbβ3 binds to a KQAGDV motif at the fibrinogen γ-chain C terminus and to RGD motifs present in loops in many extracellular matrix proteins. These ligands bind in a groove between the integrin α and β-subunits; the basic Lys or Arg side chain hydrogen bonds to the αIIb-subunit, and the acidic Asp side chain coordinates to a metal ion held by the β3-subunit. Ligand binding induces headpiece opening, with conformational change in the β-subunit. During this opening, RGD slides in the ligand-binding pocket toward αIIb, with movement of the βI-domain β1-α1 loop toward αIIb, enabling formation of direct, charged hydrogen bonds between the Arg side chain and αIIb. Here we test whether ligand interactions with β3 suffice for stable ligand binding and headpiece opening. We find that the AGDV tetrapeptide from KQAGDV binds to the αIIbβ3 headpiece with affinity comparable with the RGDSP peptide from fibronectin. AGDV induced complete headpiece opening in solution as shown by increase in hydrodynamic radius. Soaking of AGDV into closed αIIbβ3 headpiece crystals induced intermediate states similarly to RGDSP. AGDV has very little contact with the α-subunit. Furthermore, as measured by epitope exposure, AGDV, like the fibrinogen γ C-terminal peptide and RGD, caused integrin extension on the cell surface. Thus, pushing by the β3-subunit on Asp is sufficient for headpiece opening and ligand sliding, and no pulling by the αIIb subunit on Arg is required. PMID:26631735

  8. Buying years to extinction: is compensatory mitigation for marine bycatch a sufficient conservation measure for long-lived seabirds?

    PubMed

    Igual, José Manuel; Tavecchia, Giacomo; Jenouvrier, Stephanie; Forero, Manuela G; Oro, Daniel

    2009-01-01

    Along the lines of the 'polluter pays principle', it has recently been proposed that the local long-line fishing industry should fund eradication of terrestrial predators at seabird breeding colonies, as a compensatory measure for the bycatch caused by the fishing activity. The measure is economically sound, but a quantitative and reliable test of its biological efficacy has never been conducted. Here, we investigated the demographic consequences of predator eradication for Cory's shearwater Calonectris diomedea, breeding in the Mediterranean, using a population model that integrates demographic rates estimated from individual life-history information with experimental measures of predation and habitat structure. We found that similar values of population growth rate can be obtained by different combinations of habitat characteristics, predator abundance and adult mortality, which explains the persistence of shearwater colonies in islands with introduced predators. Even so, given the empirically obtained values of survival, all combinations of predator abundance and habitat characteristics projected a decline in shearwater numbers. Perturbation analyses indicated that the value and the sensitivity of shearwater population growth rates were affected by all covariates considered and their interactions. A decrease in rat abundance delivered only a small increase in the population growth rate, whereas a change in adult survival (a parameter independent of rat abundance) had the strongest impact on population dynamics. When adult survival is low, rat eradication would allow us to "buy" years before extinction but does not reverse the process. Rat eradication can therefore be seen as an emergency measure if threats on adult survival are eliminated in the medium-term period. For species with low fecundity and long life expectancy, our results suggest that rat control campaigns are not a sufficient, self-standing measure to compensate the biological toll of long

  9. Translational Compensation of a Frameshift Mutation Affecting Herpes Simplex Virus Thymidine Kinase Is Sufficient To Permit Reactivation from Latency

    PubMed Central

    Griffiths, Anthony; Chen, Shun-Hua; Horsburgh, Brian C.; Coen, Donald M.

    2003-01-01

    Herpes simplex virus thymidine kinase is important for reactivation of virus from its latent state and is a target for the antiviral drug acyclovir. Most acyclovir-resistant isolates have mutations in the thymidine kinase gene; however, how these mutations confer clinically relevant resistance is unclear. Reactivation from explanted mouse ganglia was previously observed with a patient-derived drug-resistant isolate carrying a single guanine insertion within a run of guanines in the thymidine kinase gene. Despite this mutation, low levels of active enzyme were synthesized following an unusual ribosomal frameshift. Here we report that a virus, generated from a pretherapy isolate from the same patient, engineered to lack thymidine kinase activity, was competent for reactivation. This suggested that the clinical isolate contains alleles of other genes that permit reactivation in the absence of thymidine kinase. Therefore, to establish whether thymidine kinase synthesized via a ribosomal frameshift was sufficient for reactivation under conditions where reactivation requires this enzyme, we introduced the mutation into the well-characterized strain KOS. This mutant virus reactivated from latency, albeit less efficiently than KOS. Plaque autoradiography revealed three phenotypes of reactivating viruses: uniformly low thymidine kinase activity, mixed high and low activity, and uniformly high activity. We generated a recombinant thymidine kinase-null virus from a reactivating virus expressing uniformly low activity. This virus did not reactivate, confirming that mutations in other genes that would influence reactivation had not arisen. Therefore, in strains that require thymidine kinase for reactivation from latency, low levels of enzyme synthesized via a ribosomal frameshift can suffice. PMID:12663777

  10. Limited physical contact through a mesh barrier is sufficient for social reward-conditioned place preference in adolescent male rats

    PubMed Central

    Peartree, Natalie A.; Hood, Lauren E.; Thiel, Kenneth J.; Sanabria, Federico; Pentkowski, Nathan S.; Chandler, Kayla N.; Neisewander, Janet L.

    2012-01-01

    Adolescence is a period of enhanced sensitivity to social influences and vulnerability to drug abuse. Social reward in adolescent rats has been demonstrated with the conditioned place preference (CPP) model, but it is not clear whether limited contact with another rat without play is sufficient to produce reward. We investigated this issue using an apparatus containing two main compartments each with a wire mesh barrier that allowed rats placed on either side of the barrier to have limited physical contact. Adolescent male rats were given two conditioning sessions/day for 2 or 8 days following baseline preference tests. Rats were placed into their preferred side alone for one daily 10-min session and into their initially non-preferred side (i.e., CS) for the other session during which they either had restricted or unrestricted physical access to another rat (Rat/Mesh or Rat/Phys, respectively) or to a tennis ball (Ball/Mesh or Ball/Phys, respectively) unconditioned stimulus (US). Only the Rat/Phys group exhibited CPP after 2 CS-US pairings; however, after 8 CS-US pairings, the Rat/Mesh and Ball/Phys groups also exhibited CPP. During conditioning, the rat US elicited more robust approach and contact behavior compared to the ball, regardless of physical or restricted access. The incidence of contact and/or approach increased as the number of exposures increased. The results suggest that the rank order of US reward efficacy was physical contact with a rat > limited contact with a rat > physical contact with a ball, and that rough-and-tumble play is not necessary to establish social reward-CPP. The findings have important implications for emerging drug self-administration models in which two rats self-administering drug intravenously have limited physical contact via a mesh barrier shared between their respective operant conditioning chambers. PMID:22008744

  11. Limited physical contact through a mesh barrier is sufficient for social reward-conditioned place preference in adolescent male rats.

    PubMed

    Peartree, Natalie A; Hood, Lauren E; Thiel, Kenneth J; Sanabria, Federico; Pentkowski, Nathan S; Chandler, Kayla N; Neisewander, Janet L

    2012-02-01

    Adolescence is a period of enhanced sensitivity to social influences and vulnerability to drug abuse. Social reward in adolescent rats has been demonstrated with the conditioned place preference (CPP) model, but it is not clear whether limited contact with another rat without play is sufficient to produce reward. We investigated this issue using an apparatus containing two main compartment, each with a wire mesh barrier that allowed rats placed on either side of the barrier to have limited physical contact. Adolescent male rats were given two conditioning sessions/day for 2 or 8 days following baseline preference tests. Rats were placed into their preferred side alone for one daily 10-min session and into their initially non-preferred side (i.e., CS) for the other session during which they either had restricted or unrestricted physical access to another rat (Rat/Mesh or Rat/Phys, respectively) or to a tennis ball (Ball/Mesh or Ball/Phys, respectively) unconditioned stimulus (US). Only the Rat/Phys group exhibited CPP after 2 CS-US pairings; however, after 8 CS-US pairings, the Rat/Mesh and Ball/Phys groups also exhibited CPP. During conditioning, the rat US elicited more robust approach and contact behavior compared to the ball, regardless of physical or restricted access. The incidence of contact and/or approach increased as the number of exposures increased. The results suggest that the rank order of US reward efficacy was physical contact with a rat>limited contact with a rat>physical contact with a ball, and that rough-and-tumble play is not necessary to establish social reward-CPP. The findings have important implications for emerging drug self-administration models in which two rats self-administering drug intravenously have limited physical contact via a mesh barrier shared between their respective operant conditioning chambers. PMID:22008744

  12. The final follow-up plain radiograph is sufficient for clinical evaluation of polyethylene wear in total hip arthroplasty

    PubMed Central

    2010-01-01

    Background and purpose Radiostereometric analysis (RSA) is a highly accurate tool for assessment of polyethylene (PE) wear in total hip arthroplasty (THA); however, PE wear measurements in clinical studies are often limited to plain radiographs. We evaluated the agreement between PE wear measured with PolyWare software, which uses plain radiographs, and by model-based RSA, which uses stereo radiographs. Methods Measurements of PE wear postoperatively and at final follow-up (after mean 6 years) on plain radiographs of 12 patients after cementless THA were evaluated with PolyWare software and the results were compared with those from RSA as the gold standard (Model-based RSA using elementary geometrical shape models; EGS-RSA). With PolyWare, we either used the final radiographic follow-up (PW1) only or both the postoperative follow-up and the final follow-up (PW2). Results The 2D mean wear measured (in mm) was 0.80, 1.07, and 0.60 for the PW2, PW1, and RSA method. 2D intra-method repeatability was similar for PW1 and RSA with limits of agreement (LOAs, in mm) of ± 0.22, and ± 0.23, respectively. 2D inter-method concurrent validity was best between PW1 and EGS-RSA with LOAs of ± 0.55. For 2D linear wear measurements, the PW1 method had a clinical repeatability similar to that of RSA. Interpretation PW1 is sufficient for retrospective determination of 2D wear from medium-term wear measurements above 0.5 mm, It alleviates the need for baseline plain radiographs, has a clinical precision similar to that of RSA, and is easy and inexpensive to use. PMID:20860443

  13. Organic fertilization and sufficient nutrient status in prehistoric agriculture?--Indications from multi-proxy analyses of archaeological topsoil relicts.

    PubMed

    Lauer, Franziska; Prost, Katharina; Gerlach, Renate; Pätzold, Stefan; Wolf, Mareike; Urmersbach, Sarah; Lehndorff, Eva; Eckmeier, Eileen; Amelung, Wulf

    2014-01-01

    Neolithic and Bronze Age topsoil relicts revealed enhanced extractable phosphorus (P) and plant available inorganic P fractions, thus raising the question whether there was targeted soil amelioration in prehistoric times. This study aimed (i) at assessing the overall nutrient status and the soil organic matter content of these arable topsoil relicts, and (ii) at tracing ancient soil fertilizing practices by respective stable isotope and biomarker analyses. Prehistoric arable topsoils were preserved in archaeological pit fillings, whereas adjacent subsoils served as controls. One Early Weichselian humic zone represented the soil status before the introduction of agriculture. Recent topsoils served as an additional reference. The applied multi-proxy approach comprised total P and micronutrient contents, stable N isotope ratios, amino acid, steroid, and black carbon analyses as well as soil color measurements. Total contents of P and selected micronutrients (I, Cu, Mn, Mo, Se, Zn) of the arable soil relicts were above the limits for which nutrient deficiencies could be assumed. All pit fillings exhibited elevated δ15N values close to those of recent topsoils (δ15N>6 to 7‰), giving first hints for prehistoric organic N-input. Ancient legume cultivation as a potential source for N input could not be verified by means of amino acid analysis. In contrast, bile acids as markers for faecal input exhibited larger concentrations in the pit fillings compared with the reference and control soils indicating faeces (i.e. manure) input to Neolithic arable topsoils. Also black carbon contents were elevated, amounting up to 38% of soil organic carbon, therewith explaining the dark soil color in the pit fillings and pointing to inputs of burned biomass. The combination of different geochemical analyses revealed a sufficient nutrient status of prehistoric arable soils, as well as signs of amelioration (inputs of organic material like charcoal and faeces-containing manure). PMID

  14. How Fast Is Your Body Motion? Determining a Sufficient Frame Rate for an Optical Motion Tracking System Using Passive Markers

    PubMed Central

    Song, Min-Ho; Godøy, Rolf Inge

    2016-01-01

    This paper addresses how to determine a sufficient frame (sampling) rate for an optical motion tracking system using passive reflective markers. When using passive markers for the optical motion tracking, avoiding identity confusion between the markers becomes a problem as the speed of motion increases, necessitating a higher frame rate to avoid a failure of the motion tracking caused by marker confusions and/or dropouts. Initially, one might believe that the Nyquist-Shannon sampling rate estimated from the assumed maximal temporal variation of a motion (i.e. a sampling rate at least twice that of the maximum motion frequency) could be the complete solution to the problem. However, this paper shows that also the spatial distance between the markers should be taken into account in determining the suitable frame rate of an optical motion tracking with passive markers. In this paper, a frame rate criterion for the optical tracking using passive markers is theoretically derived and also experimentally verified using a high-quality optical motion tracking system. Both the theoretical and the experimental results showed that the minimum frame rate is proportional to the ratio between the maximum speed of the motion and the minimum spacing between markers, and may also be predicted precisely if the proportional constant is known in advance. The inverse of the proportional constant is here defined as the tracking efficiency constant and it can be easily determined with some test measurements. Moreover, this newly defined constant can provide a new way of evaluating the tracking algorithm performance of an optical tracking system. PMID:26967900

  15. 49 CFR 40.195 - What happens when an individual is unable to provide a sufficient amount of urine for a pre...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... provide a sufficient amount of urine for a pre-employment follow-up or return-to-duty test because of a...-employment follow-up or return-to-duty test because of a permanent or long-term medical condition? (a) This... providing a sufficient specimen for a pre-employment follow-up or return-to-duty test and the...

  16. 49 CFR 40.195 - What happens when an individual is unable to provide a sufficient amount of urine for a pre...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... provide a sufficient amount of urine for a pre-employment follow-up or return-to-duty test because of a...-employment follow-up or return-to-duty test because of a permanent or long-term medical condition? (a) This... providing a sufficient specimen for a pre-employment follow-up or return-to-duty test and the...

  17. 49 CFR 40.195 - What happens when an individual is unable to provide a sufficient amount of urine for a pre...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... provide a sufficient amount of urine for a pre-employment follow-up or return-to-duty test because of a...-employment follow-up or return-to-duty test because of a permanent or long-term medical condition? (a) This... providing a sufficient specimen for a pre-employment follow-up or return-to-duty test and the...

  18. 49 CFR 40.195 - What happens when an individual is unable to provide a sufficient amount of urine for a pre...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... provide a sufficient amount of urine for a pre-employment follow-up or return-to-duty test because of a...-employment follow-up or return-to-duty test because of a permanent or long-term medical condition? (a) This... providing a sufficient specimen for a pre-employment follow-up or return-to-duty test and the...

  19. FGF Signaling Is Necessary for Neurogenesis in Young Mice and Sufficient to Reverse Its Decline in Old Mice

    PubMed Central

    Kang, Wenfei

    2015-01-01

    maintains and expands subsets of neural precursor cells. Moreover, in older mice, increasing FGF signaling is sufficient to reverse the decline in neuron production to levels found in young adults, providing a potential means of reversing age-related hippocampal deficits. PMID:26180198

  20. Environmental sustainability of an energy self-sufficient sewage treatment plant: improvements through DEMON and co-digestion.

    PubMed

    Schaubroeck, Thomas; De Clippeleir, Haydée; Weissenbacher, Norbert; Dewulf, Jo; Boeckx, Pascal; Vlaeminck, Siegfried E; Wett, Bernhard

    2015-05-01

    It is still not proven that treatment of sewage in a wastewater treatment plant (WWTP) is (in every case) environmentally friendly. To address this matter, we have applied a state-of-the-art life cycle assessment (LCA) to an energy self-sufficient WWTP in Strass (Austria), its supply chain and the valorization of its 'products': produced electricity out of biogas from sludge digestion and the associated stabilized digestate, applied as agricultural fertilizer. Prominent aspects of our study are: a holistic environmental impact assessment, measurement of greenhouse gas emissions (including N2O), and accounting for infrastructure, replacement of conventional fertilizers and toxicity of metals present in the stabilized digestate. Additionally, the environmental sustainability improvement by implementing one-stage partial nitritation/anammox (e.g. DEMON(®)) and co-digestion was also assessed. DEMON on the digesters reject water leads to a considerable saving of natural resources compared to nitritiation/denitritation (about 33% of the life cycle resource input), this through the lowering of sludge consumption for N-removal, and thus increasing electricity production via a higher sludge excess. However, its N2O emission could be restrained through further optimization as it represents a large share (30-66%) of the plants' damaging effect on human health, this through climate change. The co-substrate addition to the digester resulted in no significant improvement of the digestion process but induced net electricity generation. If respective amounts of conventional fertilizers are replaced, the land application of the stabilized digestate is environmentally friendly through prevention of natural resource consumption and diversity loss, but possibly not regarding human health impact due the presence of toxic heavy metals, mainly Zn, in the digestate. The outcomes show that the complete life cycle results in a prevention of resource extraction from nature and a potential