DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

Science.gov (United States)

Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

2015-10-01

The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

Energy Technology Data Exchange (ETDEWEB)

Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

2008-02-10

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

Science.gov (United States)

Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

2014-07-24

Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

Survey of French spine surgeons reveals significant variability in spine trauma practices in 2013.

Science.gov (United States)

Lonjon, G; Grelat, M; Dhenin, A; Dauzac, C; Lonjon, N; Kepler, C K; Vaccaro, A R

2015-02-01

In France, attempts to define common ground during spine surgery meetings have revealed significant variability in clinical practices across different schools of surgery and the two specialities involved in spine surgery, namely, neurosurgery and orthopaedic surgery. To objectively characterise this variability by performing a survey based on a fictitious spine trauma case. Our working hypothesis was that significant variability existed in trauma practices and that this variability was related to a lack of strong scientific evidence in spine trauma care. We performed a cross-sectional survey based on a clinical vignette describing a 31-year-old male with an L1 burst fracture and neurologic symptoms (numbness). Surgeons received the vignette and a 14-item questionnaire on the management of this patient. For each question, surgeons had to choose among five possible answers. Differences in answers across surgeons were assessed using the Index of Qualitative Variability (IQV), in which 0 indicates no variability and 1 maximal variability. Surgeons also received a questionnaire about their demographics and surgical experience. Of 405 invited spine surgeons, 200 responded to the survey. Five questions had an IQV greater than 0.9, seven an IQV between 0.5 and 0.9, and two an IQV lower than 0.5. Variability was greatest about the need for MRI (IQV=0.93), degree of urgency (IQV=0.93), need for fusion (IQV=0.92), need for post-operative bracing (IQV=0.91), and routine removal of instrumentation (IQV=0.94). Variability was lowest for questions about the need for surgery (IQV=0.42) and use of the posterior approach (IQV=0.36). Answers were influenced by surgeon specialty, age, experience level, and type of centre. Clinical practice regarding spine trauma varies widely in France. Little published evidence is available on which to base recommendations that would diminish this variability. Copyright © 2015. Published by Elsevier Masson SAS.

Teaching physical activities to students with significant disabilities using video modeling.

Science.gov (United States)

Cannella-Malone, Helen I; Mizrachi, Sharona V; Sabielny, Linsey M; Jimenez, Eliseo D

2013-06-01

The objective of this study was to examine the effectiveness of video modeling on teaching physical activities to three adolescents with significant disabilities. The study implemented a multiple baseline across six physical activities (three per student): jumping rope, scooter board with cones, ladder drill (i.e., feet going in and out), ladder design (i.e., multiple steps), shuttle run, and disc ride. Additional prompt procedures (i.e., verbal, gestural, visual cues, and modeling) were implemented within the study. After the students mastered the physical activities, we tested to see if they would link the skills together (i.e., complete an obstacle course). All three students made progress learning the physical activities, but only one learned them with video modeling alone (i.e., without error correction). Video modeling can be an effective tool for teaching students with significant disabilities various physical activities, though additional prompting procedures may be needed.

Targeted Gene-Silencing Reveals the Functional Significance of Myocardin Signaling in the Failing Heart

Science.gov (United States)

Torrado, Mario; Iglesias, Raquel; Centeno, Alberto; López, Eduardo; Mikhailov, Alexander T.

2011-01-01

Background Myocardin (MYOCD), a potent transcriptional coactivator of smooth muscle (SM) and cardiac genes, is upregulated in failing myocardium in animal models and human end-stage heart failure (HF). However, the molecular and functional consequences of myocd upregulation in HF are still unclear. Methodology/Principal Findings The goal of the present study was to investigate if targeted inhibition of upregulated expression of myocd could influence failing heart gene expression and function. To this end, we used the doxorubicin (Dox)-induced diastolic HF (DHF) model in neonatal piglets, in which, as we show, not only myocd but also myocd-dependent SM-marker genes are highly activated in failing left ventricular (LV) myocardium. In this model, intra-myocardial delivery of short-hairpin RNAs, designed to target myocd variants expressed in porcine heart, leads on day 2 post-delivery to: (1) a decrease in the activated expression of myocd and myocd-dependent SM-marker genes in failing myocardium to levels seen in healthy control animals, (2) amelioration of impaired diastolic dysfunction, and (3) higher survival rates of DHF piglets. The posterior restoration of elevated myocd expression (on day 7 post-delivery) led to overexpression of myocd-dependent SM-marker genes in failing LV-myocardium that was associated with a return to altered diastolic function. Conclusions/Significance These data provide the first evidence that a moderate inhibition (e.g., normalization) of the activated MYOCD signaling in the diseased heart may be promising from a therapeutic point of view. PMID:22028870

Targeted gene-silencing reveals the functional significance of myocardin signaling in the failing heart.

Directory of Open Access Journals (Sweden)

Mario Torrado

Full Text Available BACKGROUND: Myocardin (MYOCD, a potent transcriptional coactivator of smooth muscle (SM and cardiac genes, is upregulated in failing myocardium in animal models and human end-stage heart failure (HF. However, the molecular and functional consequences of myocd upregulation in HF are still unclear. METHODOLOGY/PRINCIPAL FINDINGS: The goal of the present study was to investigate if targeted inhibition of upregulated expression of myocd could influence failing heart gene expression and function. To this end, we used the doxorubicin (Dox-induced diastolic HF (DHF model in neonatal piglets, in which, as we show, not only myocd but also myocd-dependent SM-marker genes are highly activated in failing left ventricular (LV myocardium. In this model, intra-myocardial delivery of short-hairpin RNAs, designed to target myocd variants expressed in porcine heart, leads on day 2 post-delivery to: (1 a decrease in the activated expression of myocd and myocd-dependent SM-marker genes in failing myocardium to levels seen in healthy control animals, (2 amelioration of impaired diastolic dysfunction, and (3 higher survival rates of DHF piglets. The posterior restoration of elevated myocd expression (on day 7 post-delivery led to overexpression of myocd-dependent SM-marker genes in failing LV-myocardium that was associated with a return to altered diastolic function. CONCLUSIONS/SIGNIFICANCE: These data provide the first evidence that a moderate inhibition (e.g., normalization of the activated MYOCD signaling in the diseased heart may be promising from a therapeutic point of view.

Significant uncertainty in global scale hydrological modeling from precipitation data erros

NARCIS (Netherlands)

Sperna Weiland, F.; Vrugt, J.A.; Beek, van P.H.; Weerts, A.H.; Bierkens, M.F.P.

2015-01-01

In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we

Significant uncertainty in global scale hydrological modeling from precipitation data errors

NARCIS (Netherlands)

Weiland, Frederiek C. Sperna; Vrugt, Jasper A.; van Beek, Rens (L. ) P. H.; Weerts, Albrecht H.; Bierkens, Marc F. P.

2015-01-01

In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we

Integrative modelling reveals mechanisms linking productivity and plant species richness.

Science.gov (United States)

Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

2016-01-21

How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

Science.gov (United States)

Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

2016-12-01

The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

How Often Is the Misfit of Item Response Theory Models Practically Significant?

Science.gov (United States)

Sinharay, Sandip; Haberman, Shelby J.

2014-01-01

Standard 3.9 of the Standards for Educational and Psychological Testing ([, 1999]) demands evidence of model fit when item response theory (IRT) models are employed to data from tests. Hambleton and Han ([Hambleton, R. K., 2005]) and Sinharay ([Sinharay, S., 2005]) recommended the assessment of practical significance of misfit of IRT models, but…

Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

DEFF Research Database (Denmark)

Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

2013-01-01

Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

Choice experiments versus revealed choice models : a before-after study of consumer spatial shopping behavior

NARCIS (Netherlands)

Timmermans, H.J.P.; Borgers, A.W.J.; Waerden, van der P.J.H.J.

1992-01-01

The purpose of this article is to compare a set of multinomial logit models derived from revealed choice data and a decompositional choice model derived from experimental data in terms of predictive success in the context of consumer spatial shopping behavior. Data on consumer shopping choice

77 FR 34121 - Culturally Significant Objects Imported for Exhibition Determinations: “Revealing the African...

Science.gov (United States)

2012-06-08

... exhibition ``Revealing the African Presence in Renaissance Europe'' imported from abroad for temporary... exhibit objects at The Walters Art Museum, Baltimore, MD, from on or about October 14, 2012, until on or about January 21, 2013; at the Princeton University Art Museum, Princeton, NJ, from on or about February...

Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders

Directory of Open Access Journals (Sweden)

Shuji Mizumoto

2017-03-01

Full Text Available The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.

Asymmetric biotic interactions and abiotic niche differences revealed by a dynamic joint species distribution model.

Science.gov (United States)

Lany, Nina K; Zarnetske, Phoebe L; Schliep, Erin M; Schaeffer, Robert N; Orians, Colin M; Orwig, David A; Preisser, Evan L

2018-05-01

A species' distribution and abundance are determined by abiotic conditions and biotic interactions with other species in the community. Most species distribution models correlate the occurrence of a single species with environmental variables only, and leave out biotic interactions. To test the importance of biotic interactions on occurrence and abundance, we compared a multivariate spatiotemporal model of the joint abundance of two invasive insects that share a host plant, hemlock woolly adelgid (HWA; Adelges tsugae) and elongate hemlock scale (EHS; Fiorina externa), to independent models that do not account for dependence among co-occurring species. The joint model revealed that HWA responded more strongly to abiotic conditions than EHS. Additionally, HWA appeared to predispose stands to subsequent increase of EHS, but HWA abundance was not strongly dependent on EHS abundance. This study demonstrates how incorporating spatial and temporal dependence into a species distribution model can reveal the dependence of a species' abundance on other species in the community. Accounting for dependence among co-occurring species with a joint distribution model can also improve estimation of the abiotic niche for species affected by interspecific interactions. © 2018 by the Ecological Society of America.

Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication.

Science.gov (United States)

Sison-Young, Rowena L C; Mitsa, Dimitra; Jenkins, Rosalind E; Mottram, David; Alexandre, Eliane; Richert, Lysiane; Aerts, Hélène; Weaver, Richard J; Jones, Robert P; Johann, Esther; Hewitt, Philip G; Ingelman-Sundberg, Magnus; Goldring, Christopher E P; Kitteringham, Neil R; Park, B Kevin

2015-10-01

In vitro preclinical models for the assessment of drug-induced liver injury (DILI) are usually based on cryopreserved primary human hepatocytes (cPHH) or human hepatic tumor-derived cell lines; however, it is unclear how well such cell models reflect the normal function of liver cells. The physiological, pharmacological, and toxicological phenotyping of available cell-based systems is necessary in order to decide the testing purpose for which they are fit. We have therefore undertaken a global proteomic analysis of 3 human-derived hepatic cell lines (HepG2, Upcyte, and HepaRG) in comparison with cPHH with a focus on drug metabolizing enzymes and transport proteins (DMETs), as well as Nrf2-regulated proteins. In total, 4946 proteins were identified, of which 2722 proteins were common across all cell models, including 128 DMETs. Approximately 90% reduction in expression of cytochromes P450 was observed in HepG2 and Upcyte cells, and approximately 60% in HepaRG cells relative to cPHH. Drug transporter expression was also lower compared with cPHH with the exception of MRP3 and P-gp (MDR1) which appeared to be significantly expressed in HepaRG cells. In contrast, a high proportion of Nrf2-regulated proteins were more highly expressed in the cell lines compared with cPHH. The proteomic database derived here will provide a rational basis for the context-specific selection of the most appropriate 'hepatocyte-like' cell for the evaluation of particular cellular functions associated with DILI and, at the same time, assist in the construction of a testing paradigm which takes into account the in vivo disposition of a new drug. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

Science.gov (United States)

Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

2014-01-01

Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

Identification of sequence motifs significantly associated with antisense activity

Directory of Open Access Journals (Sweden)

Peek Andrew S

2007-06-01

Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

ARMA modeling of stochastic processes in nuclear reactor with significant detection noise

International Nuclear Information System (INIS)

Zavaljevski, N.

1992-01-01

The theoretical basis of ARMA modelling of stochastic processes in nuclear reactor was presented in a previous paper, neglecting observational noise. The identification of real reactor data indicated that in some experiments the detection noise is significant. Thus a more rigorous theoretical modelling of stochastic processes in nuclear reactor is performed. Starting from the fundamental stochastic differential equations of the Langevin type for the interaction of the detector with neutron field, a new theoretical ARMA model is developed. preliminary identification results confirm the theoretical expectations. (author)

The quest for significance model of radicalization: implications for the management of terrorist detainees.

Science.gov (United States)

Dugas, Michelle; Kruglanski, Arie W

2014-01-01

Radicalization and its culmination in terrorism represent a grave threat to the security and stability of the world. A related challenge is effective management of extremists who are detained in prison facilities. The major aim of this article is to review the significance quest model of radicalization and its implications for management of terrorist detainees. First, we review the significance quest model, which elaborates on the roles of motivation, ideology, and social processes in radicalization. Secondly, we explore the implications of the model in relation to the risks of prison radicalization. Finally, we analyze the model's implications for deradicalization strategies and review preliminary evidence for the effectiveness of a rehabilitation program targeting components of the significance quest. Based on this evidence, we argue that the psychology of radicalization provides compelling reason for the inclusion of deradicalization efforts as an essential component of the management of terrorist detainees. Copyright © 2014 John Wiley & Sons, Ltd.

Different continuous cropping spans significantly affect microbial community membership and structure in a vanilla-grown soil as revealed by deep pyrosequencing.

Science.gov (United States)

Xiong, Wu; Zhao, Qingyun; Zhao, Jun; Xun, Weibing; Li, Rong; Zhang, Ruifu; Wu, Huasong; Shen, Qirong

2015-07-01

In the present study, soil bacterial and fungal communities across vanilla continuous cropping time-series fields were assessed through deep pyrosequencing of 16S ribosomal RNA (rRNA) genes and internal transcribed spacer (ITS) regions. The results demonstrated that the long-term monoculture of vanilla significantly altered soil microbial communities. Soil fungal diversity index increased with consecutive cropping years, whereas soil bacterial diversity was relatively stable. Bray-Curtis dissimilarity cluster and UniFrac-weighted principal coordinate analysis (PCoA) revealed that monoculture time was the major determinant for fungal community structure, but not for bacterial community structure. The relative abundances (RAs) of the Firmicutes, Actinobacteria, Bacteroidetes, and Basidiomycota phyla were depleted along the years of vanilla monoculture. Pearson correlations at the phyla level demonstrated that Actinobacteria, Armatimonadetes, Bacteroidetes, Verrucomicrobia, and Firmicutes had significant negative correlations with vanilla disease index (DI), while no significant correlation for fungal phyla was observed. In addition, the amount of the pathogen Fusarium oxysporum accumulated with increasing years and was significantly positively correlated with vanilla DI. By contrast, the abundance of beneficial bacteria, including Bradyrhizobium and Bacillus, significantly decreased over time. In sum, soil weakness and vanilla stem wilt disease after long-term continuous cropping can be attributed to the alteration of the soil microbial community membership and structure, i.e., the reduction of the beneficial microbes and the accumulation of the fungal pathogen.

78 FR 55772 - Culturally Significant Object Imported for Exhibition Determinations: “Beauty Revealed: Images of...

Science.gov (United States)

2013-09-11

..., 1965 (79 Stat. 985; 22 U.S.C. 2459), Executive Order 12047 of March 27, 1978, the Foreign Affairs...). The mailing address is U.S. Department of State, SA-5, L/PD, Fifth Floor (Suite 5H03), Washington, DC... Determinations: ``Beauty Revealed: Images of Women in Qing Dynasty Chinese Painting'' SUMMARY: Notice is hereby...

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

Directory of Open Access Journals (Sweden)

Irakli Dzneladze

Full Text Available Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID, a tool which examines the relationship between a continuous variable (e.g. gene expression, and a test parameter (e.g. CoxPH or Fisher's exact P values. In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

Science.gov (United States)

Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

2018-01-01

Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

Science.gov (United States)

Roopin, Modi; Levy, Oren

2012-01-01

Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

Mapping the Most Significant Computer Hacking Events to a Temporal Computer Attack Model

OpenAIRE

Heerden , Renier ,; Pieterse , Heloise; Irwin , Barry

2012-01-01

Part 4: Section 3: ICT for Peace and War; International audience; This paper presents eight of the most significant computer hacking events (also known as computer attacks). These events were selected because of their unique impact, methodology, or other properties. A temporal computer attack model is presented that can be used to model computer based attacks. This model consists of the following stages: Target Identification, Reconnaissance, Attack, and Post-Attack Reconnaissance stages. The...

Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

Science.gov (United States)

Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

1997-09-01

We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

Australasian disasters of national significance: an epidemiological analysis, 1900-2012.

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Bradt, David A; Bartley, Bruce; Hibble, Belinda A; Varshney, Kavita

2015-04-01

A regional epidemiological analysis of Australasian disasters in the 20th century to present was undertaken to examine trends in disaster epidemiology; to characterise the impacts on civil society through disaster policy, practice and legislation; and to consider future potential limitations in national disaster resilience. A surveillance definition of disaster was developed conforming to the Centre for Research on the Epidemiology of Disasters (CRED) criteria (≥10 deaths, ≥100 affected, or declaration of state emergency or appeal for international assistance). The authors then applied economic and legislative inclusion criteria to identify additional disasters of national significance. The surveillance definition yielded 165 disasters in the period, from which 65 emerged as disasters of national significance. There were 38 natural disasters, 22 technological disasters, three offshore terrorist attacks and two domestic mass shootings. Geographic analysis revealed that states with major population centres experienced the vast majority of disasters of national significance. Timeline analysis revealed an increasing incidence of disasters since the 1980s, which peaked in the period 2005-2009. Recent seasonal bushfires and floods have incurred the highest death toll and economic losses in Australasian history. Reactive hazard-specific legislation emerged after all terrorist acts and after most disasters of national significance. Timeline analysis reveals an increasing incidence in natural disasters over the past 15 years, with the most lethal and costly disasters occurring in the past 3 years. Vulnerability to disaster in Australasia appears to be increasing. Reactive legislation is a recurrent feature of Australasian disaster response that suggests legislative shortsightedness and a need for comprehensive all-hazards model legislation in the future. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

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Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

2011-06-01

Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

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Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

2016-03-29

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

Azimuth cut-off model for significant wave height investigation along coastal water of Kuala Terengganu, Malaysia

Science.gov (United States)

Marghany, Maged; Ibrahim, Zelina; Van Genderen, Johan

2002-11-01

The present work is used to operationalize the azimuth cut-off concept in the study of significant wave height. Three ERS-1 images have been used along the coastal waters of Terengganu, Malaysia. The quasi-linear transform was applied to map the SAR wave spectra into real ocean wave spectra. The azimuth cut-off was then used to model the significant wave height. The results show that azimuth cut-off varied with the different period of the ERS-1 images. This is because of the fact that the azimuth cut-off is a function of wind speed and significant wave height. It is of interest to find that the significant wave height modeled from azimuth cut-off is in good relation with ground wave conditions. It can be concluded that ERS-1 can be used as a monitoring tool in detecting the significant wave height variation. The azimuth cut-off can be used to model the significant wave height. This means that the quasi-linear transform could be a good application to significant wave height variation during different seasons.

Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions.

Science.gov (United States)

Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen; Plósz, Benedek Gy

2014-10-15

Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D) SST model structures and parameters. We identify the critical sources of uncertainty in WWTP models through global sensitivity analysis (GSA) using the Benchmark simulation model No. 1 in combination with first- and second-order 1-D SST models. The results obtained illustrate that the contribution of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets for WWTP model calibration, and propose optimal choice of 1-D SST models under different flow and settling boundary conditions. Additionally, the hydraulic parameters in the second-order SST model are found significant under dynamic wet-weather flow conditions. These results highlight the importance of developing a more mechanistic based flow-dependent hydraulic sub-model in second-order 1-D SST models in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

Science.gov (United States)

Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

2015-01-01

The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

DEFF Research Database (Denmark)

Huang, Sijia; Chong, Nicole; Lewis, Nathan

2016-01-01

diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...... metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease...

The history of nursing in the home: revealing the significance of place in the expression of moral agency.

Science.gov (United States)

Peter, Elizabeth

2002-06-01

The history of nursing in the home: revealing the significance of place in the expression of moral agency The relationship between place and moral agency in home care nursing is explored in this paper. The notion of place is argued to have relevance to moral agency beyond moral context. This argument is theoretically located in feminist ethics and human geography and is supported through an examination of historical documents (1900-33) that describe the experiences and insights of American home care/private duty nurses or that are related to nursing ethics. Specifically, the role of place in inhibiting and enhancing care, justice, good relationships, and power in the practice of private duty nurses is explored. Several implications for current nursing ethics come out of this analysis. (i) The moral agency of nurses is highly nuanced. It is not only structured by nurses' relationships to patients and health professionals, i.e. moral context, it is also structured by the place of nursing care. (ii) Place has the potential to limit and enhance the power of nurses. (iii) Some aspects of nursing's conception of the good, such as what constitutes a good nurse-patient relationship, are historically and geographically relative.

Modeling carbon dioxide sequestration in saline aquifers: Significance of elevated pressures and salinities

International Nuclear Information System (INIS)

Allen, D.E.; Strazisar, B.R.; Soong, Y.; Hedges, S.W.

2005-01-01

The ultimate capacity of saline formations to sequester carbon dioxide by solubility and mineral trapping must be determined by simulating sequestration with geochemical models. These models, however, are only as reliable as the data and reaction scheme on which they are based. Several models have been used to make estimates of carbon dioxide solubility and mineral formation as a function of pressure and fluid composition. Intercomparison of modeling results indicates that failure to adjust all equilibrium constants to account for elevated carbon dioxide pressures results in significant errors in both solubility and mineral formation estimates. Absence of experimental data at high carbon dioxide pressures and high salinities make verification of model results difficult. Results indicate standalone solubility models that do not take mineral reactions into account will underestimate the total capacity of aquifers to sequester carbon dioxide in the long term through enhanced solubility and mineral trapping mechanisms. Overall, it is difficult to confidently predict the ultimate sequestration capacity of deep saline aquifers using geochemical models. (author)

Meta-Analysis Reveals Significant Association of the 3'-UTR VNTR in SLC6A3 with Alcohol Dependence.

Science.gov (United States)

Ma, Yunlong; Fan, Rongli; Li, Ming D

2016-07-01

Although many studies have analyzed the association of 3'-untranslated region variable-number tandem repeat (VNTR) polymorphism in SLC6A3 with alcohol dependence (AD), the results remain controversial. This study aimed to determine whether this variant indeed has any genetic effect on AD by integrating 17 reported studies with 5,929 participants included. The A9-dominant genetic model that considers A9-repeat and non-A9 repeat as 2 genotypes and compared their frequencies in alcoholics with that in controls was adopted. Considering the potential influence of ethnicity, differences in diagnostic criteria of AD, and alcoholic subgroups, stratified meta-analyses were conducted. There existed no evidence for the presence of heterogeneity among the studied samples, indicating the results under the fixed-effects model are acceptable. We found a significant association of VNTR A9 genotypes with AD in all ethnic populations (pooled odds ratio [OR] 1.12; 95% confidence interval [CI] 1.00, 1.25; p = 0.045) and the Caucasian population (pooled OR 1.15; 95% CI 1.01, 1.31; p = 0.036). We also found VNTR A9 genotypes to be significantly associated with alcoholism as defined by the DSM-IV criteria (pooled OR 1.18; 95% CI 1.03, 1.36; p = 0.02). Further, we found a significant association between VNTR A9 genotypes and alcoholism associated with alcohol withdrawal seizure or delirium tremens (pooled OR 1.55; 95% CI 1.24, 1.92; p = 1.0 × 10(-4) ). In all these meta-analyses, no evidence of publication bias was detected. We concluded that the VNTR polymorphism has an important role in the etiology of AD, and individuals with at least 1 A9 allele are more likely to be dependent on alcohol than persons carrying the non-A9 allele. Copyright © 2016 by the Research Society on Alcoholism.

Significant uncertainty in global scale hydrological modeling from precipitation data errors

Science.gov (United States)

Sperna Weiland, Frederiek C.; Vrugt, Jasper A.; van Beek, Rens (L.) P. H.; Weerts, Albrecht H.; Bierkens, Marc F. P.

2015-10-01

In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we focus on large-scale hydrologic modeling and analyze the effect of parameter and rainfall data uncertainty on simulated discharge dynamics with the global hydrologic model PCR-GLOBWB. We use three rainfall data products; the CFSR reanalysis, the ERA-Interim reanalysis, and a combined ERA-40 reanalysis and CRU dataset. Parameter uncertainty is derived from Latin Hypercube Sampling (LHS) using monthly discharge data from five of the largest river systems in the world. Our results demonstrate that the default parameterization of PCR-GLOBWB, derived from global datasets, can be improved by calibrating the model against monthly discharge observations. Yet, it is difficult to find a single parameterization of PCR-GLOBWB that works well for all of the five river basins considered herein and shows consistent performance during both the calibration and evaluation period. Still there may be possibilities for regionalization based on catchment similarities. Our simulations illustrate that parameter uncertainty constitutes only a minor part of predictive uncertainty. Thus, the apparent dichotomy between simulations of global-scale hydrologic behavior and actual data cannot be resolved by simply increasing the model complexity of PCR-GLOBWB and resolving sub-grid processes. Instead, it would be more productive to improve the characterization of global rainfall amounts at spatial resolutions of 0.5° and smaller.

Automatic sleep classification using a data-driven topic model reveals latent sleep states

DEFF Research Database (Denmark)

Koch, Henriette; Christensen, Julie Anja Engelhard; Frandsen, Rune

2014-01-01

Latent Dirichlet Allocation. Model application was tested on control subjects and patients with periodic leg movements (PLM) representing a non-neurodegenerative group, and patients with idiopathic REM sleep behavior disorder (iRBD) and Parkinson's Disease (PD) representing a neurodegenerative group......Background: The golden standard for sleep classification uses manual scoring of polysomnography despite points of criticism such as oversimplification, low inter-rater reliability and the standard being designed on young and healthy subjects. New method: To meet the criticism and reveal the latent...... sleep states, this study developed a general and automatic sleep classifier using a data-driven approach. Spectral EEG and EOG measures and eye correlation in 1 s windows were calculated and each sleep epoch was expressed as a mixture of probabilities of latent sleep states by using the topic model...

Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

Science.gov (United States)

He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

2014-12-01

Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae.

Science.gov (United States)

Wang, Xiaoming; Zhou, Guofa; Zhong, Daibin; Wang, Xiaoling; Wang, Ying; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

2016-06-06

Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes.

The geography of demography: long-term demographic studies and species distribution models reveal a species border limited by adaptation.

Science.gov (United States)

Eckhart, V M; Geber, M A; Morris, W F; Fabio, E S; Tiffin, P; Moeller, D A

2011-10-01

Potential causes of species' geographic distribution limits fall into two broad classes: (1) limited adaptation across spatially variable environments and (2) limited opportunities to colonize unoccupied areas. Combining demographic studies, analyses of demographic responses to environmental variation, and species distribution models, we investigated the causes of range limits in a model system, the eastern border of the California annual plant Clarkia xantiana ssp. xantiana. Vital rates of 20 populations varied with growing season temperature and precipitation: fruit number and overwinter survival of 1-year-old seeds declined steeply, while current-year seed germination increased modestly along west-to-east gradients in decreasing temperature, decreasing mean precipitation, and increasing variation in precipitation. Long-term stochastic finite rate of increase, λ(s), exhibited a fourfold range and varied among geologic surface materials as well as with temperature and precipitation. Growth rate declined significantly toward the eastern border, falling below 1 in three of the five easternmost populations. Distribution models employing demographically important environmental variables predicted low habitat favorability beyond the eastern border. Models that filtered or weighted population presences by λ(s) predicted steeper eastward declines in favorability and assigned greater roles in setting the distribution to among-year variation in precipitation and to geologic surface material. These analyses reveal a species border likely set by limited adaptation to declining environmental quality.

Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

Directory of Open Access Journals (Sweden)

Anne L Baldock

Full Text Available Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532 from gross total resection over subtotal/biopsy, while those with nodular (less diffuse tumors showed a significant benefit (P = 0.00142 with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors.These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

A keyword spotting model using perceptually significant energy features

Science.gov (United States)

Umakanthan, Padmalochini

The task of a keyword recognition system is to detect the presence of certain words in a conversation based on the linguistic information present in human speech. Such keyword spotting systems have applications in homeland security, telephone surveillance and human-computer interfacing. General procedure of a keyword spotting system involves feature generation and matching. In this work, new set of features that are based on the psycho-acoustic masking nature of human speech are proposed. After developing these features a time aligned pattern matching process was implemented to locate the words in a set of unknown words. A word boundary detection technique based on frame classification using the nonlinear characteristics of speech is also addressed in this work. Validation of this keyword spotting model was done using widely acclaimed Cepstral features. The experimental results indicate the viability of using these perceptually significant features as an augmented feature set in keyword spotting.

EXPLORATORY DATA ANALYSIS AND MULTIVARIATE STRATEGIES FOR REVEALING MULTIVARIATE STRUCTURES IN CLIMATE DATA

Directory of Open Access Journals (Sweden)

2016-12-01

Full Text Available This paper is on data analysis strategy in a complex, multidimensional, and dynamic domain. The focus is on the use of data mining techniques to explore the importance of multivariate structures; using climate variables which influences climate change. Techniques involved in data mining exercise vary according to the data structures. The multivariate analysis strategy considered here involved choosing an appropriate tool to analyze a process. Factor analysis is introduced into data mining technique in order to reveal the influencing impacts of factors involved as well as solving for multicolinearity effect among the variables. The temporal nature and multidimensionality of the target variables is revealed in the model using multidimensional regression estimates. The strategy of integrating the method of several statistical techniques, using climate variables in Nigeria was employed. R2 of 0.518 was obtained from the ordinary least square regression analysis carried out and the test was not significant at 5% level of significance. However, factor analysis regression strategy gave a good fit with R2 of 0.811 and the test was significant at 5% level of significance. Based on this study, model building should go beyond the usual confirmatory data analysis (CDA, rather it should be complemented with exploratory data analysis (EDA in order to achieve a desired result.

A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

Directory of Open Access Journals (Sweden)

Guillem Casanovas

2014-01-01

Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

Significance of categorization and the modeling of age related factors for radiation protection

International Nuclear Information System (INIS)

Matsuoka, Osamu

1987-01-01

It is proposed that the categorization and modelling are necessary with regard to age related factors of radionuclide metabolism for the radiation protection of the public. In order to utilize the age related information as a model for life time risk estimate of public, it is necessary to generalize and simplify it according to the categorized model patterns. Since the patterns of age related changes in various parameters of radionuclide metabolism seem to be rather simple, it is possible to categorize them into eleven types of model patterns. Among these models, five are selected as positively significant models to be considered. Examples are shown as to the fitting of representative parameters of both physiological and metabolic parameter of radionuclides into the proposed model. The range of deviation from adult standard value is also analyzed for each model. The fitting of each parameter to categorized models, and its comparative consideration provide the effective information as to the physiological basis of radionuclide metabolism. Discussions are made on the problems encountered in the application of available age related information to radiation protection of the public, i.e. distribution of categorized parameter, period of life covered, range of deviation from adult value, implication to other dosimetric and pathological models and to the final estimation. 5 refs.; 3 figs.; 4 tabs

Computation of spatial significance of mountain objects extracted from multiscale digital elevation models

International Nuclear Information System (INIS)

Sathyamoorthy, Dinesh

2014-01-01

The derivation of spatial significance is an important aspect of geospatial analysis and hence, various methods have been proposed to compute the spatial significance of entities based on spatial distances with other entities within the cluster. This paper is aimed at studying the spatial significance of mountain objects extracted from multiscale digital elevation models (DEMs). At each scale, the value of spatial significance index SSI of a mountain object is the minimum number of morphological dilation iterations required to occupy all the other mountain objects in the terrain. The mountain object with the lowest value of SSI is the spatially most significant mountain object, indicating that it has the shortest distance to the other mountain objects. It is observed that as the area of the mountain objects reduce with increasing scale, the distances between the mountain objects increase, resulting in increasing values of SSI. The results obtained indicate that the strategic location of a mountain object at the centre of the terrain is more important than its size in determining its reach to other mountain objects and thus, its spatial significance

Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

Science.gov (United States)

Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

2016-08-01

Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

Science.gov (United States)

Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

2017-01-01

Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88�

Puerto Rico Revealed Preference Survey Data 2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

Intriguing model significantly reduces boarding of psychiatric patients, need for inpatient hospitalization.

Science.gov (United States)

2015-01-01

As new approaches to the care of psychiatric emergencies emerge, one solution is gaining particular traction. Under the Alameda model, which has been put into practice in Alameda County, CA, patients who are brought to regional EDs with emergency psychiatric issues are quickly transferred to a designated emergency psychiatric facility as soon as they are medically stabilized. This alleviates boarding problems in area EDs while also quickly connecting patients with specialized care. With data in hand on the model's effectiveness, developers believe the approach could alleviate boarding problems in other communities as well. The model is funded by through a billing code established by California's Medicaid program for crisis stabilization services. Currently, only 22% of the patients brought to the emergency psychiatric facility ultimately need to be hospitalized; the other 78% are able to go home or to an alternative situation. In a 30-day study of the model, involving five community hospitals in Alameda County, CA, researchers found that ED boarding times were as much as 80% lower than comparable ED averages, and that patients were stabilized at least 75% of the time, significantly reducing the need for inpatient hospitalization.

Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

Directory of Open Access Journals (Sweden)

Marianna Caterino

2018-03-01

Full Text Available Background:/Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS, however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1 disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2 urinary markers of renal dysfunction. Methods: Fourteen individuals (7 males and 7 females with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR in a mean follow-up period of 4 years (3-7. Results: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN (r2=0.28; p<0.05, CD44 antigen (r2 =0.35; p<0.03 and lysosomal alfa glucosidase ( r20.27; p<0.05 abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05 was significantly correlated with ΔeGFR. Conclusion: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis.

Independent component analysis reveals new and biologically significant structures in micro array data

Directory of Open Access Journals (Sweden)

Veerla Srinivas

2006-06-01

Full Text Available Abstract Background An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. Results We applied independent component analysis (ICA to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. Conclusion Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.

Significance of the S100A4 protein in psoriasis

DEFF Research Database (Denmark)

Zibert, John R; Skov, Lone; Thyssen, Jacob P

2010-01-01

the expression and significance of S100A4 in psoriasis. We found significant upregulation of S100A4 in the dermis of psoriatic skin compared with normal skin. This pattern of S100A4 expression differs considerably from that of other S100 proteins, S100A7 and S100A8/9, with predominant expression in the epidermis...... of psoriasis. Furthermore, we revealed a massive release of the biologically active forms of S100A4 from psoriatic skin. Interestingly, we found stabilization (increase) of p53 in the basal layer of epidermis in close proximity to cells expressing S100A4. To examine the possible implication of S100A4...... in the pathogenesis of psoriasis, we analyzed the effect of S100A4 blocking antibodies in a human psoriasis xenograft SCID mouse model and observed a significant reduction of the epidermal thickness and impairment in cell proliferation and dermal vascularization. In conclusion, we showed strong upregulation...

Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.

Science.gov (United States)

Sikirzhytski, Vitali; Topilina, Natalya I; Takor, Gaius A; Higashiya, Seiichiro; Welch, John T; Uversky, Vladimir N; Lednev, Igor K

2012-05-14

Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.

In what root-zone N concentration does nitrate start to leach significantly? A reasonable answer from modeling Mediterranean field data and closed root-zone experiments

Science.gov (United States)

Kurtzman, D.; Kanner, B.; Levy, Y.; Shapira, R. H.; Bar-Tal, A.

2017-12-01

Closed-root-zone experiments (e.g. pots, lyzimeters) reveal in many cases a mineral-nitrogen (N) concentration from which the root-N-uptake efficiency reduces significantly and nitrate leaching below the root-zone increases dramatically. A les-direct way to reveal this threshold concentration in agricultural fields is to calibrate N-transport models of the unsaturated zone to nitrate data of the deep samples (under the root-zone) by fitting the threshold concentration of the nitrate-uptake function. Independent research efforts of these two types in light soils where nitrate problems in underlying aquifers are common reviled: 1) that the threshold exists for most crops (filed, vegetables and orchards); 2) nice agreement on the threshold value between the two very different research methodologies; and 3) the threshold lies within 20-50 mg-N/L. Focusing on being below the threshold is a relatively simple aim in the way to maintain intensive agriculture with limited effects on the nitrate concentration in the underlying water resource. Our experience show that in some crops this threshold coincides with the end-of-rise of the N-yield curve (e.g. corn); in this case, it is relatively easy to convince farmers to fertilize below threshold. In other crops, although significant N is lost to leaching the crop can still use higher N concentration to increase yield (e.g. potato).

Laboratory simulation reveals significant impacts of ocean acidification on microbial community composition and host-pathogen interactions between the blood clam and Vibrio harveyi.

Science.gov (United States)

Zha, Shanjie; Liu, Saixi; Su, Wenhao; Shi, Wei; Xiao, Guoqiang; Yan, Maocang; Liu, Guangxu

2017-12-01

It has been suggested that climate change may promote the outbreaks of diseases in the sea through altering the host susceptibility, the pathogen virulence, and the host-pathogen interaction. However, the impacts of ocean acidification (OA) on the pathogen components of bacterial community and the host-pathogen interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA high-throughput sequencing and host-pathogen interaction analysis between blood clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study to gain a better understanding of the ecological impacts of ocean acidification. The results obtained revealed a significant impact of ocean acidification on the composition of microbial community at laboratory scale. Notably, the abundance of Vibrio, a major group of pathogens to many marine organisms, was significantly increased under ocean acidification condition. In addition, the survival rate and haemolytic activity of V. harveyi were significantly higher in the presence of haemolymph of OA treated T. granosa, indicating a compromised immunity of the clam and enhanced virulence of V. harveyi under future ocean acidification scenarios. Conclusively, the results obtained in this study suggest that future ocean acidification may increase the risk of Vibrio pathogen infection for marine bivalve species, such as blood clams. Copyright © 2017 Elsevier Ltd. All rights reserved.

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

Science.gov (United States)

van Leeuwen, Pim J; Hayen, Andrew; Thompson, James E; Moses, Daniel; Shnier, Ron; Böhm, Maret; Abuodha, Magdaline; Haynes, Anne-Maree; Ting, Francis; Barentsz, Jelle; Roobol, Monique; Vass, Justin; Rasiah, Krishan; Delprado, Warick; Stricker, Phillip D

2017-12-01

To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P prostate cancer. Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Assessing Asset Pricing Models Using Revealed Preference

OpenAIRE

Jonathan B. Berk; Jules H. van Binsbergen

2014-01-01

We propose a new method of testing asset pricing models that relies on using quantities rather than prices or returns. We use the capital flows into and out of mutual funds to infer which risk model investors use. We derive a simple test statistic that allows us to infer, from a set of candidate models, the model that is closest to the model that investors use in making their capital allocation decisions. Using this methodology, we find that of the models most commonly used in the literature,...

Probabilistic Inference: Task Dependency and Individual Differences of Probability Weighting Revealed by Hierarchical Bayesian Modeling.

Science.gov (United States)

Boos, Moritz; Seer, Caroline; Lange, Florian; Kopp, Bruno

2016-01-01

Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modeling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities) by two (likelihoods) design. Five computational models of cognitive processes were compared with the observed behavior. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted) S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model's success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modeling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modeling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

Energy Technology Data Exchange (ETDEWEB)

Brenner, David J.

2009-07-22

Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

Dynamical significance of tides over the Bay of Bengal

Science.gov (United States)

Bhagawati, Chirantan; Pandey, Suchita; Dandapat, Sumit; Chakraborty, Arun

2018-06-01

Tides play a significant role in the ocean surface circulations and vertical mixing thereby influencing the Sea Surface Temperatures (SST) as well. This, in turn, plays an important role in the global circulation when used as a lower boundary condition in a global atmospheric general circulation model. Therefore in the present study, the dynamics of tides over the Bay of Bengal (BoB) is investigated through numerical simulations using a high resolution (1/12°) Regional Ocean Modeling System (ROMS). Based on statistical analysis it is observed that incorporation of explicit tidal forcing improves the model performance in simulating the basin averaged monthly surface circulation features by 64% compared to the simulation without tides. The model simulates also Mixed Layer Depth (MLD) and SST realistically. The energy exchange between tidal oscillations and eddies leads to redistribution of surface kinetic energy density with a net decrease of 0.012 J m-3 in the western Bay and a net increase of 0.007 J m-3 in the eastern Bay. The tidal forcing also affects the potential energy anomaly and vertical mixing thereby leading to a fall in monthly MLD over the BoB. The mixing due to tides leads to a subsequent reduction in monthly SST and a corresponding reduction in surface heat exchange. These results from the numerical simulation using ROMS reveal that tides have a significant influence over the air-sea heat exchange which is the most important parameter for prediction of Tropical Cyclone frequency and its future variability over the BoB.

Modeling of environmentally significant interfaces: Two case studies

International Nuclear Information System (INIS)

Williford, R.E.

2006-01-01

When some parameters cannot be easily measured experimentally, mathematical models can often be used to deconvolute or interpret data collected on complex systems, such as those characteristic of many environmental problems. These models can help quantify the contributions of various physical or chemical phenomena that contribute to the overall behavior, thereby enabling the scientist to control and manipulate these phenomena, and thus to optimize the performance of the material or device. In the first case study presented here, a model is used to test the hypothesis that oxygen interactions with hydrogen on the catalyst particles of solid oxide fuel cell anodes can sometimes occur a finite distance away from the triple phase boundary (TPB), so that such reactions are not restricted to the TPB as normally assumed. The model may help explain a discrepancy between the observed structure of SOFCs and their performance. The second case study develops a simple physical model that allows engineers to design and control the sizes and shapes of mesopores in silica thin films. Such pore design can be useful for enhancing the selectivity and reactivity of environmental sensors and catalysts. This paper demonstrates the mutually beneficial interactions between experiment and modeling in the solution of a wide range of problems

Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key Msn2 control mechanism.

Science.gov (United States)

Sunnåker, Mikael; Zamora-Sillero, Elias; Dechant, Reinhard; Ludwig, Christina; Busetto, Alberto Giovanni; Wagner, Andreas; Stelling, Joerg

2013-05-28

Predictive dynamical models are critical for the analysis of complex biological systems. However, methods to systematically develop and discriminate among systems biology models are still lacking. We describe a computational method that incorporates all hypothetical mechanisms about the architecture of a biological system into a single model and automatically generates a set of simpler models compatible with observational data. As a proof of principle, we analyzed the dynamic control of the transcription factor Msn2 in Saccharomyces cerevisiae, specifically the short-term mechanisms mediating the cells' recovery after release from starvation stress. Our method determined that 12 of 192 possible models were compatible with available Msn2 localization data. Iterations between model predictions and rationally designed phosphoproteomics and imaging experiments identified a single-circuit topology with a relative probability of 99% among the 192 models. Model analysis revealed that the coupling of dynamic phenomena in Msn2 phosphorylation and transport could lead to efficient stress response signaling by establishing a rate-of-change sensor. Similar principles could apply to mammalian stress response pathways. Systematic construction of dynamic models may yield detailed insight into nonobvious molecular mechanisms.

Multilayer Stochastic Block Models Reveal the Multilayer Structure of Complex Networks

Directory of Open Access Journals (Sweden)

Toni Vallès-Català

2016-03-01

Full Text Available In complex systems, the network of interactions we observe between systems components is the aggregate of the interactions that occur through different mechanisms or layers. Recent studies reveal that the existence of multiple interaction layers can have a dramatic impact in the dynamical processes occurring on these systems. However, these studies assume that the interactions between systems components in each one of the layers are known, while typically for real-world systems we do not have that information. Here, we address the issue of uncovering the different interaction layers from aggregate data by introducing multilayer stochastic block models (SBMs, a generalization of single-layer SBMs that considers different mechanisms of layer aggregation. First, we find the complete probabilistic solution to the problem of finding the optimal multilayer SBM for a given aggregate-observed network. Because this solution is computationally intractable, we propose an approximation that enables us to verify that multilayer SBMs are more predictive of network structure in real-world complex systems.

Divergent Significance of Bone Mineral Density Changes in Aging Depending on Sites and Sex Revealed through Separate Analyses of Bone Mineral Content and Area

Directory of Open Access Journals (Sweden)

Yasumoto Matsui

2012-01-01

Full Text Available Bone mineral density (aBMD is equivalent to bone mineral content (BMC divided by area. We rechecked the significance of aBMD changes in aging by examining BMC and area separately. Subjects were 1167 community-dwelling Japanese men and women, aged 40–79 years. ABMDs of femoral neck and lumbar spine were assessed by DXA twice, at 6-year intervals. The change rates of BMC and area, as well as aBMD, were calculated and described separately by the age stratum and by sex. In the femoral neck region, aBMDs were significantly decreased in all age strata by an increase in area as well as BMC loss in the same pattern in both sexes. In the lumbar spine region, aBMDs decreased until the age of 60 in women, caused by the significant BMC decrease accompanying the small area change. Very differently in men, aBMDs increased after their 50s due to BMC increase, accompanied by an area increase. Separate analyses of BMC and area change revealed that the significance of aBMD changes in aging was very divergent among sites and between sexes. This may explain in part the dissociation of aBMD change and bone strength, suggesting that we should be more cautious when interpreting the meaning of aBMD change.

Probabilistic inference: Task dependency and individual differences of probability weighting revealed by hierarchical Bayesian modelling

Directory of Open Access Journals (Sweden)

Moritz eBoos

2016-05-01

Full Text Available Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modelling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities by two (likelihoods design. Five computational models of cognitive processes were compared with the observed behaviour. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model’s success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modelling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modelling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

Strategies for Testing Statistical and Practical Significance in Detecting DIF with Logistic Regression Models

Science.gov (United States)

Fidalgo, Angel M.; Alavi, Seyed Mohammad; Amirian, Seyed Mohammad Reza

2014-01-01

This study examines three controversial aspects in differential item functioning (DIF) detection by logistic regression (LR) models: first, the relative effectiveness of different analytical strategies for detecting DIF; second, the suitability of the Wald statistic for determining the statistical significance of the parameters of interest; and…

A systematic experimental investigation of significant parameters affecting model tire hydroplaning

Science.gov (United States)

Wray, G. A.; Ehrlich, I. R.

1973-01-01

The results of a comprehensive parametric study of model and small pneumatic tires operating on a wet surface are presented. Hydroplaning inception (spin down) and rolling restoration (spin up) are discussed. Conclusions indicate that hydroplaning inception occurs at a speed significantly higher than the rolling restoration speed. Hydroplaning speed increases considerably with tread depth, surface roughness and tire inflation pressure of footprint pressure, and only moderately with increased load. Water film thickness affects spin down speed only slightly. Spin down speed varies inversely as approximately the one-sixth power of film thickness. Empirical equations relating tire inflation pressure, normal load, tire diameter and water film thickness have been generated for various tire tread and surface configurations.

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

Science.gov (United States)

Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki

2018-01-01

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

Directory of Open Access Journals (Sweden)

Kosuke Okuda

Full Text Available Mutations in the Cyclin-dependent kinase-like 5 (CDKL5 gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be

Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

Science.gov (United States)

Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi

2018-01-01

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

Chain networking revealed by molecular dynamics simulation

Science.gov (United States)

Zheng, Yexin; Tsige, Mesfin; Wang, Shi-Qing

Based on Kremer-Grest model for entangled polymer melts, we demonstrate how the response of a polymer glass depends critically on the chain length. After quenching two melts of very different chain lengths (350 beads per chain and 30 beads per chain) into deeply glassy states, we subject them to uniaxial extension. Our MD simulations show that the glass of long chains undergoes stable necking after yielding whereas the system of short chains is unable to neck and breaks up after strain localization. During ductile extension of the polymer glass made of long chain significant chain tension builds up in the load-bearing strands (LBSs). Further analysis is expected to reveal evidence of activation of the primary structure during post-yield extension. These results lend support to the recent molecular model 1 and are the simulations to demonstrate the role of chain networking. This work is supported, in part, by a NSF Grant (DMR-EAGER-1444859)

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

Science.gov (United States)

Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

2016-08-18

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Field significance of performance measures in the context of regional climate model evaluation. Part 2: precipitation

Science.gov (United States)

Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

2018-04-01

A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as `field' or `global' significance. The block length for the local resampling tests is precisely determined to adequately account for the time series structure. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Daily precipitation climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. While the downscaled precipitation distributions are statistically indistinguishable from the observed ones in most regions in summer, the biases of some distribution characteristics are significant over large areas in winter. WRF-NOAH generates appropriate stationary fine-scale climate features in the daily precipitation field over regions of complex topography in both seasons and appropriate transient fine-scale features almost everywhere in summer. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the clear additional value of dynamical downscaling over global climate simulations. The evaluation methodology has a broad spectrum of applicability as it is

Modelling vocal anatomy's significant effect on speech

NARCIS (Netherlands)

de Boer, B.

2010-01-01

This paper investigates the effect of larynx position on the articulatory abilities of a humanlike vocal tract. Previous work has investigated models that were built to resemble the anatomy of existing species or fossil ancestors. This has led to conflicting conclusions about the relation between

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

Science.gov (United States)

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

2016-01-01

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

Science.gov (United States)

Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

2017-09-01

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

Directory of Open Access Journals (Sweden)

Tommasino Massimo

2011-06-01

Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

Discovering the Significance of Scientific Design Practice

DEFF Research Database (Denmark)

Pries-Heje, Jan; Baskerville, Richard

2016-01-01

This paper discusses and defines the achievement of significance in design science research. We review the values and processes of old-science and how this mode of science attacks the complexity of scientific knowledge production through analysis. We then explain how new-science attacks...... the complexity of scientific knowledge production through synthesis. The work argues that significance of the new-science contribution in design science can be obfuscated when wrapped in old-science. This understanding helps reveal how new-science, such as design science research, constitutes its significance...

Revealed preference with limited consideration

NARCIS (Netherlands)

Demuynck, T.; Seel, C.

2014-01-01

We derive revealed preference tests for models where individuals use consideration sets to simplify their consumption problem. Our basic test provides necessary and sufficient conditions for consistency of observed choices with the existence of consideration set restrictions. The same conditions can

Integrative demographic modeling reveals population level impacts of PCB toxicity to juvenile snapping turtles

International Nuclear Information System (INIS)

Salice, Christopher J.; Rowe, Christopher L.; Eisenreich, Karen M.

2014-01-01

A significant challenge in ecotoxicology and risk assessment lies in placing observed contaminant effects in a meaningful ecological context. Polychlorinated biphenyls (PCBs) have been shown to affect juvenile snapping turtle survival and growth but the ecological significance of these effects is difficult to discern without a formal, population-level assessment. We used a demographic matrix model to explore the potential population-level effects of PCBs on turtles. Our model showed that effects of PCBs on juvenile survival, growth and size at hatching could translate to negative effects at the population level despite the fact that these life cycle components do not typically contribute strongly to population level processes. This research points to the utility of using integrative demographic modeling approaches to better understand contaminant effects in wildlife. The results indicate that population-level effects are only evident after several years, suggesting that for long-lived species, detecting adverse contaminant effects could prove challenging. -- Highlights: • Previous studies have shown the PCBs can impact juvenile snapping turtles. • We used a demographic model of turtles to evaluate population-level PCB effects. • PCB effects on turtles may translate to negative population responses. • Long-term monitoring is needed to detect contaminant effects on natural turtle populations. • Demographic models can improve our understanding contaminant ecotoxicity. -- A demographic model was used to show that PCB induced effects on young snapping turtles can result in adverse effects at the population level

Significance of Bias Correction in Drought Frequency and Scenario Analysis Based on Climate Models

Science.gov (United States)

Aryal, Y.; Zhu, J.

2015-12-01

Assessment of future drought characteristics is difficult as climate models usually have bias in simulating precipitation frequency and intensity. To overcome this limitation, output from climate models need to be bias corrected based on the specific purpose of applications. In this study, we examine the significance of bias correction in the context of drought frequency and scenario analysis using output from climate models. In particular, we investigate the performance of three widely used bias correction techniques: (1) monthly bias correction (MBC), (2) nested bias correction (NBC), and (3) equidistance quantile mapping (EQM) The effect of bias correction in future scenario of drought frequency is also analyzed. The characteristics of drought are investigated in terms of frequency and severity in nine representative locations in different climatic regions across the United States using regional climate model (RCM) output from the North American Regional Climate Change Assessment Program (NARCCAP). The Standardized Precipitation Index (SPI) is used as the means to compare and forecast drought characteristics at different timescales. Systematic biases in the RCM precipitation output are corrected against the National Centers for Environmental Prediction (NCEP) North American Regional Reanalysis (NARR) data. The results demonstrate that bias correction significantly decreases the RCM errors in reproducing drought frequency derived from the NARR data. Preserving mean and standard deviation is essential for climate models in drought frequency analysis. RCM biases both have regional and timescale dependence. Different timescale of input precipitation in the bias corrections show similar results. Drought frequency obtained from the RCM future (2040-2070) scenarios is compared with that from the historical simulations. The changes in drought characteristics occur in all climatic regions. The relative changes in drought frequency in future scenario in relation to

Revealing topographic lineaments through IHS enhancement of DEM data. [Digital Elevation Model

Science.gov (United States)

Murdock, Gary

1990-01-01

Intensity-hue-saturation (IHS) processing of slope (dip), aspect (dip direction), and elevation to reveal subtle topographic lineaments which may not be obvious in the unprocessed data are used to enhance digital elevation model (DEM) data from northwestern Nevada. This IHS method of lineament identification was applied to a mosiac of 12 square degrees using a Cray Y-MP8/864. Square arrays from 3 x 3 to 31 x 31 points were tested as well as several different slope enhancements. When relatively few points are used to fit the plane, lineaments of various lengths are observed and a mechanism for lineament classification is described. An area encompassing the gold deposits of the Carlin trend and including the Rain in the southeast to Midas in the northwest is investigated in greater detail. The orientation and density of lineaments may be determined on the gently sloping pediment surface as well as in the more steeply sloping ranges.

miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

DEFF Research Database (Denmark)

Gravgaard, Karina Hedelund; Terp, Mikkel G; Lund, Rikke R

2015-01-01

To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered...... proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4......,000 proteins were identified, of which 92 were consistently differentially expressed. Network analysis revealed that the altered proteins were associated with cellular functions such as movement, growth and survival as well as cell-to-cell signaling and interaction. Downregulation of the three metastasis...

Constrained parameterisation of photosynthetic capacity causes significant increase of modelled tropical vegetation surface temperature

Science.gov (United States)

Kattge, J.; Knorr, W.; Raddatz, T.; Wirth, C.

2009-04-01

Photosynthetic capacity is one of the most sensitive parameters of terrestrial biosphere models whose representation in global scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Due to its coupling to stomatal conductance changes in the parameterisation of photosynthetic capacity may potentially influence transpiration rates and vegetation surface temperature. Here, we provide a constrained parameterisation of photosynthetic capacity for different plant functional types in the context of the photosynthesis model proposed by Farquhar et al. (1980), based on a comprehensive compilation of leaf photosynthesis rates and leaf nitrogen content. Mean values of photosynthetic capacity were implemented into the coupled climate-vegetation model ECHAM5/JSBACH and modelled gross primary production (GPP) is compared to a compilation of independent observations on stand scale. Compared to the current standard parameterisation the root-mean-squared difference between modelled and observed GPP is substantially reduced for almost all PFTs by the new parameterisation of photosynthetic capacity. We find a systematic depression of NUE (photosynthetic capacity divided by leaf nitrogen content) on certain tropical soils that are known to be deficient in phosphorus. Photosynthetic capacity of tropical trees derived by this study is substantially lower than standard estimates currently used in terrestrial biosphere models. This causes a decrease of modelled GPP while it significantly increases modelled tropical vegetation surface temperatures, up to 0.8°C. These results emphasise the importance of a constrained parameterisation of photosynthetic capacity not only for the carbon cycle, but also for the climate system.

Field significance of performance measures in the context of regional climate model evaluation. Part 1: temperature

Science.gov (United States)

Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

2018-04-01

A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as "field" or "global" significance. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Monthly temperature climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. In winter and in most regions in summer, the downscaled distributions are statistically indistinguishable from the observed ones. A systematic cold summer bias occurs in deep river valleys due to overestimated elevations, in coastal areas due probably to enhanced sea breeze circulation, and over large lakes due to the interpolation of water temperatures. Urban areas in concave topography forms have a warm summer bias due to the strong heat islands, not reflected in the observations. WRF-NOAH generates appropriate fine-scale features in the monthly temperature field over regions of complex topography, but over spatially homogeneous areas even small biases can lead to significant deteriorations relative to the driving reanalysis. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the

Floodplain forest succession reveals fluvial processes: A hydrogeomorphic model for temperate riparian woodlands.

Science.gov (United States)

Egger, Gregory; Politti, Emilio; Lautsch, Erwin; Benjankar, Rohan; Gill, Karen M; Rood, Stewart B

2015-09-15

River valley floodplains are physically-dynamic environments where fluvial processes determine habitat gradients for riparian vegetation. These zones support trees and shrubs whose life stages are adapted to specific habitat types and consequently forest composition and successional stage reflect the underlying hydrogeomorphic processes and history. In this study we investigated woodland vegetation composition, successional stage and habitat properties, and compared these with physically-based indicators of hydraulic processes. We thus sought to develop a hydrogeomorphic model to evaluate riparian woodland condition based on the spatial mosaic of successional phases of the floodplain forest. The study investigated free-flowing and dam-impacted reaches of the Kootenai and Flathead Rivers, in Idaho and Montana, USA and British Columbia, Canada. The analyses revealed strong correspondence between vegetation assessments and metrics of fluvial processes indicating morphodynamics (erosion and shear stress), inundation and depth to groundwater. The results indicated that common successional stages generally occupied similar hydraulic environments along the different river segments. Comparison of the spatial patterns between the free-flowing and regulated reaches revealed greater deviation from the natural condition for the braided channel segment than for the meandering segment. This demonstrates the utility of the hydrogeomorphic approach and suggests that riparian woodlands along braided channels could have lower resilience than those along meandering channels and might be more vulnerable to influences such as from river damming or climate change. Copyright © 2015 Elsevier Ltd. All rights reserved.

A critical review of predictive models for the onset of significant void in forced-convection subcooled boiling

International Nuclear Information System (INIS)

Dorra, H.; Lee, S.C.; Bankoff, S.G.

1993-06-01

This predictive models for the onset of significant void (OSV) in forced-convection subcooled boiling are reviewed and compared with extensive data. Three analytical models and seven empirical correlations are considered in this review. These models and correlations are put onto a common basis and are compared, again on a common basis, with a variety of data. The evaluation of their range of validity and applicability under various operating conditions are discussed. The results show that the correlations of Saha-Zuber seems to be the best model to predict OSV in vertical subcooled boiling flow

On the significance of the noise model for the performance of a linear MPC in closed-loop operation

DEFF Research Database (Denmark)

Hagdrup, Morten; Boiroux, Dimitri; Mahmoudi, Zeinab

2016-01-01

This paper discusses the significance of the noise model for the performance of a Model Predictive Controller when operating in closed-loop. The process model is parametrized as a continuous-time (CT) model and the relevant sampled-data filtering and control algorithms are developed. Using CT...... models typically means less parameters to identify. Systematic tuning of such controllers is discussed. Simulation studies are conducted for linear time-invariant systems showing that choosing a noise model of low order is beneficial for closed-loop performance. (C) 2016, IFAC (International Federation...

Phasic firing in vasopressin cells: understanding its functional significance through computational models.

Directory of Open Access Journals (Sweden)

Duncan J MacGregor

Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

Diurnal sampling reveals significant variation in CO2 emission from a tropical productive lake.

Science.gov (United States)

Reis, P C J; Barbosa, F A R

2014-08-01

It is well accepted in the literature that lakes are generally net heterotrophic and supersaturated with CO2 because they receive allochthonous carbon inputs. However, autotrophy and CO2 undersaturation may happen for at least part of the time, especially in productive lakes. Since diurnal scale is particularly important to tropical lakes dynamics, we evaluated diurnal changes in pCO2 and CO2 flux across the air-water interface in a tropical productive lake in southeastern Brazil (Lake Carioca) over two consecutive days. Both pCO2 and CO2 flux were significantly different between day (9:00 to 17:00) and night (21:00 to 5:00) confirming the importance of this scale for CO2 dynamics in tropical lakes. Net heterotrophy and CO2 outgassing from the lake were registered only at night, while significant CO2 emission did not happen during the day. Dissolved oxygen concentration and temperature trends over the diurnal cycle indicated the dependence of CO2 dynamics on lake metabolism (respiration and photosynthesis). This study indicates the importance of considering the diurnal scale when examining CO2 emissions from tropical lakes.

The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

Science.gov (United States)

Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

2017-09-01

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Revealing Business Opportunities in the Norwegian Power Industry: How the implementation of AMR facilitates new business models

OpenAIRE

Platou, Rikke Stoud; Sleire, Maren

2011-01-01

This thesis aims to map out the current state of the Norwegian power industry and reveal opportunities that can serve as a fundament for the formation of new business models in the industry post AMR implementation.Demand side management (DSM) arouse to include end customers and give them incentives for having a power consumption pattern which also benefits the power system. Market structure; lack of ICT infrastructure and understanding of the solutions; costs and competitiveness, as well as t...

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

Science.gov (United States)

Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

2016-05-01

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist communities of potential significance in biofouling.

Science.gov (United States)

Liébana, Raquel; Arregui, Lucía; Belda, Ignacio; Gamella, Luis; Santos, Antonio; Marquina, Domingo; Serrano, Susana

2015-01-01

The yeast community was studied in a municipal full-scale membrane bioreactor wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts indicated that the activated sludge formed a suitable environment for them to proliferate, with cellular concentrations of 2.2 ± 0.8 × 10(3) CFU ml(-1). Sixteen species of seven genera were present in the biological reactor, with Ascomycetes being the most prevalent group (93%). Most isolates were able to grow in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop biofilms of variable complexity. The relationship between yeast populations and the protists in the MBR-WWTP was also studied, revealing that some protist species preyed on and ingested yeasts. These results suggest that yeast populations may play a role in the food web of a WWTP and, to some extent, contribute to membrane biofouling in MBR systems.

The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.

Science.gov (United States)

Gustorff, Burkhard; Sycha, Thomas; Lieba-Samal, Doris; Rolke, Roman; Treede, Rolf-Detlef; Magerl, Walter

2013-04-01

The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (Psunburn was surrounded by large areas of pinprick hyperalgesia (mean±SEM, 218±32 cm(2)) and a small rim of dynamic mechanical allodynia but no other sensory changes. Although of smaller magnitude, secondary hyperalgesia and dynamic mechanical allodynia adjacent to the UVB-irradiated area were statistically highly significant. Primary and secondary hyperalgesia developed in parallel within hours, peaked after 24-32 h, and lasted for more than 96 h. These data reveal that the UVB sunburn model activates a broad spectrum of peripheral and central sensitization mechanisms and hence is a useful human surrogate model to be used as a screening tool for target engagement in phases 1 and 2a of drug development. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Scoping review identifies significant number of knowledge translation theories, models and frameworks with limited use.

Science.gov (United States)

Strifler, Lisa; Cardoso, Roberta; McGowan, Jessie; Cogo, Elise; Nincic, Vera; Khan, Paul A; Scott, Alistair; Ghassemi, Marco; MacDonald, Heather; Lai, Yonda; Treister, Victoria; Tricco, Andrea C; Straus, Sharon E

2018-04-13

To conduct a scoping review of knowledge translation (KT) theories, models and frameworks that have been used to guide dissemination or implementation of evidence-based interventions targeted to prevention and/or management of cancer or other chronic diseases. We used a comprehensive multistage search process from 2000-2016, which included traditional bibliographic database searching, searching using names of theories, models and frameworks, and cited reference searching. Two reviewers independently screened the literature and abstracted data. We found 596 studies reporting on the use of 159 KT theories, models or frameworks. A majority (87%) of the identified theories, models or frameworks were used in five or fewer studies, with 60% used once. The theories, models and frameworks were most commonly used to inform planning/design, implementation and evaluation activities, and least commonly used to inform dissemination and sustainability/scalability activities. Twenty-six were used across the full implementation spectrum (from planning/design to sustainability/scalability) either within or across studies. All were used for at least individual-level behavior change, while 48% were used for organization-level, 33% for community-level and 17% for system-level change. We found a significant number of KT theories, models and frameworks with a limited evidence base describing their use. Copyright © 2018. Published by Elsevier Inc.

Pubertal status, interaction with significant others, and self-esteem of adolescent girls.

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Lacković-Grgin, K; Dekovíc, M; Opacić, G

1994-01-01

The aim of this study was to examine the relationship between pubertal status, the quality of interactions with significant others, and the self-esteem of adolescent girls. The model which was tested, hypothesized that pubertal status affects self-esteem through girls' interactions with their parents and friends. Pubertal status was operationalized as the number of months between occurrence of the first menstrual periods and time of the investigation. The measure of self-esteem was the shortened form of the Coopersmith Self-Esteem Inventory. Analyses revealed that girls who begun menstruating six months before the investigation obtained higher scores on the measure of self-esteem than did girls who had been menstruating 13 months or more. The best predictor of self-esteem, however, was the quality of interaction with their mothers. The results support the theoretical view that stresses the importance of interaction with significant others for the development of self-esteem.

A new model using routinely available clinical parameters to predict significant liver fibrosis in chronic hepatitis B.

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Wai-Kay Seto

Full Text Available OBJECTIVE: We developed a predictive model for significant fibrosis in chronic hepatitis B (CHB based on routinely available clinical parameters. METHODS: 237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108 and validation group (n = 129. Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed. RESULTS: Based on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP, a model to predict significant liver fibrosis (Ishak fibrosis score ≥3 was derived using the five best parameters (age, ALP, AST, AFP and platelet. Using the formula log(index+1 = 0.025+0.0031(age+0.1483 log(ALP+0.004 log(AST+0.0908 log(AFP+1-0.028 log(platelet, the PAPAS (Platelet/Age/Phosphatase/AFP/AST index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA index, AST/platelet ratio index (APRI, and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively. Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided. CONCLUSION: The PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients.

Comparative genomic sequence analysis of strawberry and other rosids reveals significant microsynteny

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Abbott Albert

2010-06-01

Full Text Available Abstract Background Fragaria belongs to the Rosaceae, an economically important family that includes a number of important fruit producing genera such as Malus and Prunus. Using genomic sequences from 50 Fragaria fosmids, we have examined the microsynteny between Fragaria and other plant models. Results In more than half of the strawberry fosmids, we found syntenic regions that are conserved in Populus, Vitis, Medicago and/or Arabidopsis with Populus containing the greatest number of syntenic regions with Fragaria. The longest syntenic region was between LG VIII of the poplar genome and the strawberry fosmid 72E18, where seven out of twelve predicted genes were collinear. We also observed an unexpectedly high level of conserved synteny between Fragaria (rosid I and Vitis (basal rosid. One of the strawberry fosmids, 34E24, contained a cluster of R gene analogs (RGAs with NBS and LRR domains. We detected clusters of RGAs with high sequence similarity to those in 34E24 in all the genomes compared. In the phylogenetic tree we have generated, all the NBS-LRR genes grouped together with Arabidopsis CNL-A type NBS-LRR genes. The Fragaria RGA grouped together with those of Vitis and Populus in the phylogenetic tree. Conclusions Our analysis shows considerable microsynteny between Fragaria and other plant genomes such as Populus, Medicago, Vitis, and Arabidopsis to a lesser degree. We also detected a cluster of NBS-LRR type genes that are conserved in all the genomes compared.

Significance evaluation in factor graphs

DEFF Research Database (Denmark)

Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

2017-01-01

in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions

DEFF Research Database (Denmark)

Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

2014-01-01

Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks...... (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D...... of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets...

Clinical Significance of Resistin Expression in Osteoarthritis: A Meta-Analysis

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Xiao-Chuan Li

2014-01-01

Full Text Available Background. The objective of this study was to conduct a systematic review of literature evaluating human resistin expression as a diagnostic factor in osteoarthritis development and to quantify the overall diagnostic effect. Method. Relevant studies were identified and evaluated for quality through multiple search strategies. Studies analyzing resistin expression in the development of OA were eligible for inclusion. Data from eligible studies were extracted and included into the meta-analysis using a random-effects model. Results. Four case-control studies consisting of a total of 375 OA patients and 214 controls as well as three sex-stratified analyses composed of 53 males and 104 females were incorporated into our meta-analysis. Our results revealed that resistin levels were significantly higher in male OA subjects and OA patients overall. Country-stratified analysis yielded significantly different estimates in resistin levels between male OA subjects and female OA subjects in the Canadian subgroup but not among the French and USA subgroups. Based on the resistin levels in OA cases and controls, resistin levels were heightened in OA patients in the Dutch population. Conclusion. These results support the hypothesis that high expression of resistin represents a significant and reproducible marker of poor progression in OA patients, especially in males.

Correction of the significance level when attempting multiple transformations of an explanatory variable in generalized linear models

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2013-01-01

Background In statistical modeling, finding the most favorable coding for an exploratory quantitative variable involves many tests. This process involves multiple testing problems and requires the correction of the significance level. Methods For each coding, a test on the nullity of the coefficient associated with the new coded variable is computed. The selected coding corresponds to that associated with the largest statistical test (or equivalently the smallest pvalue). In the context of the Generalized Linear Model, Liquet and Commenges (Stat Probability Lett,71:33–38,2005) proposed an asymptotic correction of the significance level. This procedure, based on the score test, has been developed for dichotomous and Box-Cox transformations. In this paper, we suggest the use of resampling methods to estimate the significance level for categorical transformations with more than two levels and, by definition those that involve more than one parameter in the model. The categorical transformation is a more flexible way to explore the unknown shape of the effect between an explanatory and a dependent variable. Results The simulations we ran in this study showed good performances of the proposed methods. These methods were illustrated using the data from a study of the relationship between cholesterol and dementia. Conclusion The algorithms were implemented using R, and the associated CPMCGLM R package is available on the CRAN. PMID:23758852

Landscape effects on demersal fish revealed by field observations and predictive seabed modelling.

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Elliott, Sophie A M; Sabatino, Alessandro D; Heath, Michael R; Turrell, William R; Bailey, David M

2017-01-01

Nature conservation and fisheries management often focus on particular seabed features that are considered vulnerable or important to commercial species. As a result, individual seabed types are protected in isolation, without any understanding of what effect the mixture of seabed types within the landscape has on ecosystem functions. Here we undertook predictive seabed modelling within a coastal marine protected area using observations from underwater stereo-video camera deployments and environmental information (depth, wave fetch, maximum tidal speeds, distance from coast and underlying geology). The effect of the predicted substratum type, extent and heterogeneity or the diversity of substrata, within a radius of 1500 m around each camera deployment of juvenile gadoid relative abundance was analysed. The predicted substratum model performed well with wave fetch and depth being the most influential predictor variables. Gadus morhua (Atlantic cod) were associated with relatively more rugose substrata (Algal-gravel-pebble and seagrass) and heterogeneous landscapes, than Melanogrammus aeglefinus (haddock) or Merlangius merlangus (whiting) (sand and mud). An increase in M. merlangus relative abundance was observed with increasing substratum extent. These results reveal that landscape effects should be considered when protecting the seabed for fish and not just individual seabed types. The landscape approach used in this study therefore has important implications for marine protected area, fisheries management and monitoring advice concerning demersal fish populations.

Revealing driving factors of China's PM2.5 pollution

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Zheng, Y.; Zhao, H.; Zhang, Q.; Geng, G.; Tong, D.; Peng, L.; He, K.

2017-12-01

China's rapid economic development and intensive energy consumption are deteriorating the air quality significantly. Understanding the key driving factors behind China's growing emissions of air pollutants and the accompanying PM2.5 pollution is critical for the development of China's clean air policies and also provides insight into how other emerging economies may develop a clear sky future. Here we reveal the socioeconomic drivers of the variations of China's PM2.5 concentrations during 2002-2012 by using an interdisciplinary framework that integrates an emission inventory model, an index decomposition analysis model, and a regional air quality model. The decomposition results demostrate that the improvements in emission efficiency and energy efficiency failed to offset the increased emissions of both primary PM2.5 and gaseous PM2.5 precursors (including SO2 NOx, and volatile organic compounds) triggered by the surging economic growth during 2002-2012. During the same time, the effects of energy structure, production structure and population growth were relatively less significant to all pollutants, which indicates the potential of large emission abatements through energy structure and production structure adjustment. Sensitivity simulations by the air quality model based on the provincial decomposition results also show that the economic growth have outpaced efficiency improvements in the increments of PM2.5 concentrations during the study years. As China continues to develop rapidly, future policies should promote further improvements in efficiency and accelerate the adjustments toward clean energy and production structures, which are critical for reducing China's emissions and alleviating the severe PM2.5 pollution.

A Reformulation of the Dual Career Conceptual Model for Analysis in an Organizational Scope: Revealing new Aspects

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Heliani Berlato

2017-01-01

Full Text Available Couples who live a dual career, in general, are characterized by their continuing professional engagement and their desire for personal growth together. It is a synergy between career aspirations and family sphere, so that they co-exist; reflecting nowadays, a challenge for people who seek to live this duality. Not exempt from it, it is possible to understand the need for management models of people who are in harmony with the desires of dual career couples who are part of organizations. If in the 1980s the existence of dual career couples was not so common in Brazil, nowadays organizations increasingly receive these couples, which impacts the need for people management models to keep up with these social changes. Therefore, the model recognizes that the personal dimension (impacts on the organizational context cannot be avoided, and also that other factors affect both spheres (personal and organizational when referring to the normative roles that permeate these areas. The main intention of this essay is to construct a theoretical model of dual career to consider the factor - organization, as vital to understand (and accept the need to consider other dimensions on the dual career analytical perspective. The first evidences of dual career studies in Brazil revealed that the look at this movement only from the individual's margin is limited. This way, to consider the existence of other dimensions and consequently the influences they may cause, favors an expansion of the perspective, and also brings a detailing about the external factors (organization, society and culture that influence the dual career couple. To consider that this couple, as well as having personal challenges in the relationship between work and family, is subject to the culture that regulates their roles (men and women and that directly influences how organizations will handle that topic reveals the merit of this study. This, in turn, draws attention to the organizational sphere

Genome-wide investigation reveals high evolutionary rates in annual model plants.

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Yue, Jia-Xing; Li, Jinpeng; Wang, Dan; Araki, Hitoshi; Tian, Dacheng; Yang, Sihai

2010-11-09

Rates of molecular evolution vary widely among species. While significant deviations from molecular clock have been found in many taxa, effects of life histories on molecular evolution are not fully understood. In plants, annual/perennial life history traits have long been suspected to influence the evolutionary rates at the molecular level. To date, however, the number of genes investigated on this subject is limited and the conclusions are mixed. To evaluate the possible heterogeneity in evolutionary rates between annual and perennial plants at the genomic level, we investigated 85 nuclear housekeeping genes, 10 non-housekeeping families, and 34 chloroplast genes using the genomic data from model plants including Arabidopsis thaliana and Medicago truncatula for annuals and grape (Vitis vinifera) and popular (Populus trichocarpa) for perennials. According to the cross-comparisons among the four species, 74-82% of the nuclear genes and 71-97% of the chloroplast genes suggested higher rates of molecular evolution in the two annuals than those in the two perennials. The significant heterogeneity in evolutionary rate between annuals and perennials was consistently found both in nonsynonymous sites and synonymous sites. While a linear correlation of evolutionary rates in orthologous genes between species was observed in nonsynonymous sites, the correlation was weak or invisible in synonymous sites. This tendency was clearer in nuclear genes than in chloroplast genes, in which the overall evolutionary rate was small. The slope of the regression line was consistently lower than unity, further confirming the higher evolutionary rate in annuals at the genomic level. The higher evolutionary rate in annuals than in perennials appears to be a universal phenomenon both in nuclear and chloroplast genomes in the four dicot model plants we investigated. Therefore, such heterogeneity in evolutionary rate should result from factors that have genome-wide influence, most likely those

Significance tests to determine the direction of effects in linear regression models.

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Wiedermann, Wolfgang; Hagmann, Michael; von Eye, Alexander

2015-02-01

Previous studies have discussed asymmetric interpretations of the Pearson correlation coefficient and have shown that higher moments can be used to decide on the direction of dependence in the bivariate linear regression setting. The current study extends this approach by illustrating that the third moment of regression residuals may also be used to derive conclusions concerning the direction of effects. Assuming non-normally distributed variables, it is shown that the distribution of residuals of the correctly specified regression model (e.g., Y is regressed on X) is more symmetric than the distribution of residuals of the competing model (i.e., X is regressed on Y). Based on this result, 4 one-sample tests are discussed which can be used to decide which variable is more likely to be the response and which one is more likely to be the explanatory variable. A fifth significance test is proposed based on the differences of skewness estimates, which leads to a more direct test of a hypothesis that is compatible with direction of dependence. A Monte Carlo simulation study was performed to examine the behaviour of the procedures under various degrees of associations, sample sizes, and distributional properties of the underlying population. An empirical example is given which illustrates the application of the tests in practice. © 2014 The British Psychological Society.

Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

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Ekaterini Blaveri

2010-09-01

Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration

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Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

2017-01-01

Abstract The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer’s disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer’s disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions’ experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular

Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling

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Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang

2015-01-01

Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

The elastic network model reveals a consistent picture on intrinsic functional dynamics of type II restriction endonucleases

International Nuclear Information System (INIS)

Uyar, A; Kurkcuoglu, O; Doruker, P; Nilsson, L

2011-01-01

The vibrational dynamics of various type II restriction endonucleases, in complex with cognate/non-cognate DNA and in the apo form, are investigated with the elastic network model in order to reveal common functional mechanisms in this enzyme family. Scissor-like and tong-like motions observed in the slowest modes of all enzymes and their complexes point to common DNA recognition and cleavage mechanisms. Normal mode analysis further points out that the scissor-like motion has an important role in differentiating between cognate and non-cognate sequences at the recognition site, thus implying its catalytic relevance. Flexible regions observed around the DNA-binding site of the enzyme usually concentrate on the highly conserved β-strands, especially after DNA binding. These β-strands may have a structurally stabilizing role in functional dynamics for target site recognition and cleavage. In addition, hot spot residues based on high-frequency modes reveal possible communication pathways between the two distant cleavage sites in the enzyme family. Some of these hot spots also exist on the shortest path between the catalytic sites and are highly conserved

Development of uncertainty-based work injury model using Bayesian structural equation modelling.

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Chatterjee, Snehamoy

2014-01-01

This paper proposed a Bayesian method-based structural equation model (SEM) of miners' work injury for an underground coal mine in India. The environmental and behavioural variables for work injury were identified and causal relationships were developed. For Bayesian modelling, prior distributions of SEM parameters are necessary to develop the model. In this paper, two approaches were adopted to obtain prior distribution for factor loading parameters and structural parameters of SEM. In the first approach, the prior distributions were considered as a fixed distribution function with specific parameter values, whereas, in the second approach, prior distributions of the parameters were generated from experts' opinions. The posterior distributions of these parameters were obtained by applying Bayesian rule. The Markov Chain Monte Carlo sampling in the form Gibbs sampling was applied for sampling from the posterior distribution. The results revealed that all coefficients of structural and measurement model parameters are statistically significant in experts' opinion-based priors, whereas, two coefficients are not statistically significant when fixed prior-based distributions are applied. The error statistics reveals that Bayesian structural model provides reasonably good fit of work injury with high coefficient of determination (0.91) and less mean squared error as compared to traditional SEM.

Empowering Yoruba Women in Nigeria to Prevent HIV/AIDS: The Relative Significance of Behavioural and Social Determinant Models

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Oluwatosin Ige Alo

2013-10-01

Full Text Available This article uncovers the relevance to practice of behavioural and social determinant models of HIV prevention among Yoruba women in Nigeria. Exploring what factors influence health behaviour in heterosexual relationships, the key question raised was whether the women’s experiences support the assumptions and prescriptions for action of these two dominant public health models. Eight focus group discussions and 39 in-depth interviews were conducted, which involved 121 women and men who were chosen purposefully and through self-nomination technique. This study revealed that the women were very much constrained by social environments in negotiating safe sex, despite having at least a basic knowledge of HIV prevention. Limiting factors included the fear of relationship breakup, economic dependence, violence, and the difficulties in justifying why they feel the need to insist on condom use, especially since initiating condom use is antithetical to trust. Furthermore, evidence suggested that improved access to income and education might be vital but it does not automatically constitute a direct means of empowering women to prevent HIV infection. The limitations of both behavioural and social determinants perspectives thus suggests the need for a combination prevention model, which focuses on how social, behavioural and biomedical factors overlap in shaping health outcomes.

Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

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Fabyano Fonseca e Silva

Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

Predicting significant torso trauma.

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Nirula, Ram; Talmor, Daniel; Brasel, Karen

2005-07-01

Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

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Hai-Yan Xu

2014-05-01

Full Text Available Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM was used to evaluate and compare the impact of weekly Absolute Humidity (AH and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing

Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

Science.gov (United States)

Xu, Hai-Yan; Fu, Xiuju; Lee, Lionel Kim Hock; Ma, Stefan; Goh, Kee Tai; Wong, Jiancheng; Habibullah, Mohamed Salahuddin; Lee, Gary Kee Khoon; Lim, Tian Kuay; Tambyah, Paul Anantharajah; Lim, Chin Leong; Ng, Lee Ching

2014-05-01

Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into

Model training across multiple breeding cycles significantly improves genomic prediction accuracy in rye (Secale cereale L.).

Science.gov (United States)

Auinger, Hans-Jürgen; Schönleben, Manfred; Lehermeier, Christina; Schmidt, Malthe; Korzun, Viktor; Geiger, Hartwig H; Piepho, Hans-Peter; Gordillo, Andres; Wilde, Peer; Bauer, Eva; Schön, Chris-Carolin

2016-11-01

Genomic prediction accuracy can be significantly increased by model calibration across multiple breeding cycles as long as selection cycles are connected by common ancestors. In hybrid rye breeding, application of genome-based prediction is expected to increase selection gain because of long selection cycles in population improvement and development of hybrid components. Essentially two prediction scenarios arise: (1) prediction of the genetic value of lines from the same breeding cycle in which model training is performed and (2) prediction of lines from subsequent cycles. It is the latter from which a reduction in cycle length and consequently the strongest impact on selection gain is expected. We empirically investigated genome-based prediction of grain yield, plant height and thousand kernel weight within and across four selection cycles of a hybrid rye breeding program. Prediction performance was assessed using genomic and pedigree-based best linear unbiased prediction (GBLUP and PBLUP). A total of 1040 S 2 lines were genotyped with 16 k SNPs and each year testcrosses of 260 S 2 lines were phenotyped in seven or eight locations. The performance gap between GBLUP and PBLUP increased significantly for all traits when model calibration was performed on aggregated data from several cycles. Prediction accuracies obtained from cross-validation were in the order of 0.70 for all traits when data from all cycles (N CS  = 832) were used for model training and exceeded within-cycle accuracies in all cases. As long as selection cycles are connected by a sufficient number of common ancestors and prediction accuracy has not reached a plateau when increasing sample size, aggregating data from several preceding cycles is recommended for predicting genetic values in subsequent cycles despite decreasing relatedness over time.

Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

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Alberto Muñoz

2016-10-01

Full Text Available Ecological Niche Models (ENMs are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models. Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species and taxonomy (amphibians and reptiles. Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural

Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

Science.gov (United States)

Santos, Xavier; Felicísimo, Ángel M.

2016-01-01

Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

Physicochemical state of the nanotopographic surface of commercially pure titanium following anodization-hydrothermal treatment reveals significantly improved hydrophilicity and surface energy profiles.

Science.gov (United States)

Takebe, Jun; Ito, Shigeki; Miura, Shingo; Miyata, Kyohei; Ishibashi, Kanji

2012-01-01

A method of coating commercially pure titanium (cpTi) implants with a highly crystalline, thin hydroxyapatite (HA) layer using discharge anodic oxidation followed by hydrothermal treatment (Spark discharged Anodic oxidation treatment ; SA-treated cpTi) has been reported for use in clinical dentistry. We hypothesized that a thin HA layer with high crystallinity and nanostructured anodic titanium oxide film on such SA-treated cpTi implant surfaces might be a crucial function of their surface-specific potential energy. To test this, we analyzed anodic oxide (AO) cpTi and SA-treated cpTi disks by SEM and AFM. Contact angles and surface free energy of each disk surface was measured using FAMAS software. High-magnification SEM and AFM revealed the nanotopographic structure of the anodic titanium oxide film on SA-treated cpTi; however, this was not observed on the AO cpTi surface. The contact angle and surface free energy measurements were also significantly different between AO cpTi and SA-treated cpTi surfaces (Tukey's, P<0.05). These data indicated that the change of physicochemical properties of an anodic titanium oxide film with HA crystals on an SA-treated cpTi surface may play a key role in the phenomenon of osteoconduction during the process of osseointegration. Copyright © 2011 Elsevier B.V. All rights reserved.

Expression and significance of Bax protein in model of radiation injury in mouse skin

International Nuclear Information System (INIS)

Feng Yizhong; Mo Yahong

2002-01-01

Objective: The study is to find some valuable criteria for diagnosis and treatment of radiation injury in skin. Methods: The expression of Bax protein was studied by SP immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Their relationship relating to radiation dose was also investigated. Results: The expression rates of Bax were 30%, 30%, 70%, 70% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively. There was no significant correlation between the expression of Bax and radiation groups. Conclusions: The experiment shows that radiation can increase the expression of Bax protein which might be related to poor healing in radiation skin injury

AUTOMATIC SUMMARIZATION OF WEB FORUMS AS SOURCES OF PROFESSIONALLY SIGNIFICANT INFORMATION

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K. I. Buraya

2016-07-01

assessment characteristics of the post text in general come to the fore, and also the features connected with structure of a thread as the text and the social graph. We have shown that efficiency of extraction of informative posts poorly depends on a way of keywords assignment while such dependence is essential to extraction of relevant posts. The way of keywords extraction, the most effective for real appendices has been revealed. We have shown that at extraction of relevant posts linear methods are better in efficiency in comparison with nonlinear, and the LDA model is intermediate; at the same time at extraction of informative posts linear and nonlinear methods are identical by efficiency, and the LDA model considerably concedes to both of them. We have proposed substantial model explaining the received results. Practical Relevance. The obtained results can provide background for creation of new and adequate application of the existing algorithms of web forums summarization that will allow reducing significantly user’s time and resource expenditure by receiving and studying the last minute professionally significant information.

Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

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Axel Kleespies

2005-10-01

Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

DEFF Research Database (Denmark)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

Model-independent and quasi-model-independent search for new physics at CDF

International Nuclear Information System (INIS)

Aaltonen, T.; Maki, T.; Mehtala, P.; Orava, R.; Osterberg, K.; Saarikko, H.; van Remortel, N.; Abulencia, A.; Budd, S.; Ciobanu, C. I.; Errede, D.; Errede, S.; Gerberich, H.; Grundler, U.; Junk, T. R.; Kraus, J.; Marino, C. P.; Neubauer, M. S.; Norniella, O.; Pitts, K.

2008-01-01

Data collected in run II of the Fermilab Tevatron are searched for indications of new electroweak scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with respect to the standard model prediction. A model-independent approach (Vista) considers the gross features of the data and is sensitive to new large cross section physics. A quasi-model-independent approach (Sleuth) searches for a significant excess of events with large summed transverse momentum and is particularly sensitive to new electroweak scale physics that appears predominantly in one final state. This global search for new physics in over 300 exclusive final states in 927 pb -1 of pp collisions at √(s)=1.96 TeV reveals no such significant indication of physics beyond the standard model.

Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

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Jatin Narula

2010-05-01

Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

Science.gov (United States)

Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

2017-12-01

The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and

How significant is the ‘significant other’? Associations between significant others’ health behaviors and attitudes and young adults’ health outcomes

Directory of Open Access Journals (Sweden)

Berge Jerica M

2012-04-01

Full Text Available Abstract Background Having a significant other has been shown to be protective against physical and psychological health conditions for adults. Less is known about the period of emerging young adulthood and associations between significant others’ weight and weight-related health behaviors (e.g. healthy dietary intake, the frequency of physical activity, weight status. This study examined the association between significant others’ health attitudes and behaviors regarding eating and physical activity and young adults’ weight status, dietary intake, and physical activity. Methods This study uses data from Project EAT-III, a population-based cohort study with emerging young adults from diverse ethnic and socioeconomic backgrounds (n = 1212. Logistic regression models examining cross-sectional associations, adjusted for sociodemographics and health behaviors five years earlier, were used to estimate predicted probabilities and calculate prevalence differences. Results Young adult women whose significant others had health promoting attitudes/behaviors were significantly less likely to be overweight/obese and were more likely to eat ≥ 5 fruits/vegetables per day and engage in ≥ 3.5 hours/week of physical activity, compared to women whose significant others did not have health promoting behaviors/attitudes. Young adult men whose significant other had health promoting behaviors/attitudes were more likely to engage in ≥ 3.5 hours/week of physical activity compared to men whose significant others did not have health promoting behaviors/attitudes. Conclusions Findings suggest the protective nature of the significant other with regard to weight-related health behaviors of young adults, particularly for young adult women. Obesity prevention efforts should consider the importance of including the significant other in intervention efforts with young adult women and potentially men.

Significance of uncertainties derived from settling tank model structure and parameters on predicting WWTP performance - A global sensitivity analysis study

DEFF Research Database (Denmark)

Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

2011-01-01

Uncertainty derived from one of the process models – such as one-dimensional secondary settling tank (SST) models – can impact the output of the other process models, e.g., biokinetic (ASM1), as well as the integrated wastewater treatment plant (WWTP) models. The model structure and parameter...... and from the last aerobic bioreactor upstream to the SST (Garrett/hydraulic method). For model structure uncertainty, two one-dimensional secondary settling tank (1-D SST) models are assessed, including a first-order model (the widely used Takács-model), in which the feasibility of using measured...... uncertainty of settler models can therefore propagate, and add to the uncertainties in prediction of any plant performance criteria. Here we present an assessment of the relative significance of secondary settling model performance in WWTP simulations. We perform a global sensitivity analysis (GSA) based...

RNA-Seq analysis during the life cycle of Cryptosporidium parvum reveals significant differential gene expression between proliferating stages in the intestine and infectious sporozoites.

Science.gov (United States)

Lippuner, Christoph; Ramakrishnan, Chandra; Basso, Walter U; Schmid, Marc W; Okoniewski, Michal; Smith, Nicholas C; Hässig, Michael; Deplazes, Peter; Hehl, Adrian B

2018-05-01

Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites. On the other hand, expression of 1259 genes was upregulated in intestinal stages (merozoites/gamonts) with a gene ontology enrichment for 63 biological processes and upregulation of 117 genes in 23 metabolic pathways. There was no clear stage specificity of expression of AP2-domain containing transcription factors, although sporozoites had a relatively small repertoire of these important regulators. Our RNA-Seq analysis revealed a new calcium-dependent protein kinase, bringing the total number of known calcium-dependent protein kinases (CDPKs) in C. parvum to 11. One of these, CDPK1, was expressed in all stages, strengthening the notion that it is a valid drug target. By comparing parasites grown in vivo (which produce bona fide thick-walled oocysts) and in vitro (which are arrested in sexual development prior to oocyst generation) we were able to confirm that genes encoding oocyst wall proteins are expressed in gametocytes and that the proteins are stockpiled rather than generated de novo in zygotes. RNA-Seq analysis of C. parvum revealed genes expressed in a stage-specific manner and others whose expression is required at all stages of development. The functional significance of these can now be addressed through recent advances in transgenics for C. parvum, and may lead to the identification of viable drug and vaccine

Significance of flow clustering and sequencing on sediment transport: 1D sediment transport modelling

Science.gov (United States)

Hassan, Kazi; Allen, Deonie; Haynes, Heather

2016-04-01

. Results illustrate that clustered flood events generated sediment loads up to an order of magnitude greater than that of individual events of the same flood volume. Correlations were significant for sediment volume compared to both maximum flow discharge (R2<0.8) and number of events (R2 -0.5 to -0.7) within the cluster. The strongest correlations occurred for clusters with a greater number of flow events only slightly above-threshold. This illustrates that the numerical model can capture a degree of the non-linear morphological response to flow magnitude. Analysis of the relationship between morphological change and the skewness of flow events within each cluster was also determined, illustrating only minor sensitivity to cluster peak distribution skewness. This is surprising and discussion is presented on model limitations, including the capability of sediment transport formulae to effectively account for temporal processes of antecedent flow, hysteresis, local supply etc.

Multiresolution wavelet-ANN model for significant wave height forecasting.

Digital Repository Service at National Institute of Oceanography (India)

Deka, P.C.; Mandal, S.; Prahlada, R.

Hybrid wavelet artificial neural network (WLNN) has been applied in the present study to forecast significant wave heights (Hs). Here Discrete Wavelet Transformation is used to preprocess the time series data (Hs) prior to Artificial Neural Network...

Methods for significance testing of categorical covariates in logistic regression models after multiple imputation: power and applicability analysis

NARCIS (Netherlands)

Eekhout, I.; Wiel, M.A. van de; Heymans, M.W.

2017-01-01

Background. Multiple imputation is a recommended method to handle missing data. For significance testing after multiple imputation, Rubin’s Rules (RR) are easily applied to pool parameter estimates. In a logistic regression model, to consider whether a categorical covariate with more than two levels

Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

Science.gov (United States)

Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

2015-01-01

Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii, during short-term exposure to irradiance stress reveals significant down regulation of several heat-shock proteins.

Science.gov (United States)

Mahong, Bancha; Roytrakul, Suttiruk; Phaonaklop, Narumon; Wongratana, Janewit; Yokthongwattana, Kittisak

2012-03-01

Oxygenic photosynthetic organisms often suffer from excessive irradiance, which cause harmful effects to the chloroplast proteins and lipids. Photoprotection and the photosystem II repair processes are the mechanisms that plants deploy to counteract the drastic effects from irradiance stress. Although the protective and repair mechanisms seemed to be similar in most plants, many species do confer different level of tolerance toward high light. Such diversity may originate from differences at the molecular level, i.e., perception of the light stress, signal transduction and expression of stress responsive genes. Comprehensive analysis of overall changes in the total pool of proteins in an organism can be performed using a proteomic approach. In this study, we employed 2-DE/LC-MS/MS-based comparative proteomic approach to analyze total proteins of the light sensitive model unicellular green alga Chlamydomonas reinhardtii in response to excessive irradiance. Results showed that among all the differentially expressed proteins, several heat-shock proteins and molecular chaperones were surprisingly down-regulated after 3-6 h of high light exposure. Discussions were made on the possible involvement of such down regulation and the light sensitive nature of this model alga.

Application of REVEAL-W to risk-based configuration control

International Nuclear Information System (INIS)

Dezfuli, H.; Meyer, J.; Modarres, M.

1994-01-01

Over the past two years, the concept of risk-based configuration control has been introduced to the US Nuclear Regulatory Commission and the nuclear industry. Converting much of the current, deterministically based regulation of nuclear power plants to risk-based regulation can result in lower levels of risk while relieving unnecessary burdens on power plant operators and regulatory staff. To achieve the potential benefits of risk-based configuration control, the risk models developed for nuclear power plants should be (1) flexible enough to effectively support necessary risk calculations, and (2) transparent enough to encourage their use by all parties. To address these needs, SCIENTECH, Inc., has developed the PC-based REVEAL W (formerly known as SMART). This graphic-oriented and user-friendly application software allows the user to develop transparent complex logic models based on the concept of the master plant logic diagram. The logic model is success-oriented and compact. The analytical capability built into REVEAL W is generic, so the software can support different types of risk-based evaluations, such as probabilistic safety assessment, accident sequence precursor analysis, design evaluation and configuration management. In this paper, we focus on the application of REVEAL W to support risk-based configuration control of nuclear power plants. (author)

Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

Directory of Open Access Journals (Sweden)

Snigdha Roy

Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

Data-driven modeling of sleep EEG and EOG reveals characteristics indicative of pre-Parkinson's and Parkinson's disease.

Science.gov (United States)

Christensen, Julie A E; Zoetmulder, Marielle; Koch, Henriette; Frandsen, Rune; Arvastson, Lars; Christensen, Søren R; Jennum, Poul; Sorensen, Helge B D

2014-09-30

Manual scoring of sleep relies on identifying certain characteristics in polysomnograph (PSG) signals. However, these characteristics are disrupted in patients with neurodegenerative diseases. This study evaluates sleep using a topic modeling and unsupervised learning approach to identify sleep topics directly from electroencephalography (EEG) and electrooculography (EOG). PSG data from control subjects were used to develop an EOG and an EEG topic model. The models were applied to PSG data from 23 control subjects, 25 patients with periodic leg movements (PLMs), 31 patients with idiopathic REM sleep behavior disorder (iRBD) and 36 patients with Parkinson's disease (PD). The data were divided into training and validation datasets and features reflecting EEG and EOG characteristics based on topics were computed. The most discriminative feature subset for separating iRBD/PD and PLM/controls was estimated using a Lasso-regularized regression model. The features with highest discriminability were the number and stability of EEG topics linked to REM and N3, respectively. Validation of the model indicated a sensitivity of 91.4% and a specificity of 68.8% when classifying iRBD/PD patients. The topics showed visual accordance with the manually scored sleep stages, and the features revealed sleep characteristics containing information indicative of neurodegeneration. This study suggests that the amount of N3 and the ability to maintain NREM and REM sleep have potential as early PD biomarkers. Data-driven analysis of sleep may contribute to the evaluation of neurodegenerative patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

Science.gov (United States)

Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

2017-07-01

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors.

Science.gov (United States)

Kiu, Raymond; Caim, Shabhonam; Alexander, Sarah; Pachori, Purnima; Hall, Lindsay J

2017-01-01

Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an "open" pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene) in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens -associated exotoxins genes including α-toxin ( plc ), enterotoxin ( cpe ), and Perfringolysin O ( pfo or pfoA ), although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56) of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes ( tet ) and anti-defensins genes ( mprF ) were consistently detected in silico ( tet : 75%; mprF : 100%). However, pre-antibiotic era strain genomes did not encode for tet , thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

Science.gov (United States)

Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

2014-07-01

The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

The significance of the heavy top quark

International Nuclear Information System (INIS)

Simmons, Elizabeth H.

1997-01-01

Experiment shows that the top quark is far heavier than the other elementary fermions. This finding has stimulated research on theories of electroweak and flavor symmetry breaking that include physics beyond the standard model. Efforts to accommodate a heavy top quark within existing frameworks have revealed constraints on model-building. Other investigations have started from the premise that a large top quark mass could signal a qualitative difference between the top quark and other fermions, perhaps in the form of new interactions peculiar to the top quark. Such new dynamics may also help answer existing questions about electroweak and flavor physics. This talk explores the implications of the heavy top quark in the context of weakly-coupled (e.g., SUSY) and strongly-coupled (e.g., technicolor) theories of electroweak symmetry breaking

Ecological Momentary Assessment of Pain, Fatigue, Depressive, and Cognitive Symptoms Reveals Significant Daily Variability in Multiple Sclerosis.

Science.gov (United States)

Kratz, Anna L; Murphy, Susan L; Braley, Tiffany J

2017-11-01

To describe the daily variability and patterns of pain, fatigue, depressed mood, and cognitive function in persons with multiple sclerosis (MS). Repeated-measures observational study of 7 consecutive days of home monitoring, including ecological momentary assessment (EMA) of symptoms. Multilevel mixed models were used to analyze data. General community. Ambulatory adults (N=107) with MS recruited through the University of Michigan and surrounding community. Not applicable. EMA measures of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale, collected 5 times a day for 7 days. Cognitive function and depressed mood exhibited more stable within-person patterns than pain and fatigue, which varied considerably within person. All symptoms increased in intensity across the day (all Pfatigue showing the most substantial increase. Notably, this diurnal increase varied by sex and age; women showed a continuous increase from wake to bedtime, whereas fatigue plateaued after 7 pm for men (wake-bed B=1.04, P=.004). For the oldest subgroup, diurnal increases were concentrated to the middle of the day compared with younger subgroups, which showed an earlier onset of fatigue increase and sustained increases until bed time (wake-3 pm B=.04, P=.01; wake-7 pm B=.03, P=.02). Diurnal patterns of cognitive function varied by education; those with advanced college degrees showed a more stable pattern across the day, with significant differences compared with those with bachelor-level degrees in the evening (wake-7 pm B=-.47, P=.02; wake-bed B=-.45, P=.04). Findings suggest that chronic symptoms in MS are not static, even over a short time frame; rather, symptoms-fatigue and pain in particular-vary dynamically across and within days. Incorporation of EMA methods should be considered in the assessment of these chronic MS symptoms to enhance assessment and treatment strategies. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier

Evidence of significant covalent bonding in Au(CN)(2)(-).

Science.gov (United States)

Wang, Xue-Bin; Wang, Yi-Lei; Yang, Jie; Xing, Xiao-Peng; Li, Jun; Wang, Lai-Sheng

2009-11-18

The Au(CN)(2)(-) ion is the most stable Au compound known for centuries, yet a detailed understanding of its chemical bonding is still lacking. Here we report direct experimental evidence of significant covalent bonding character in the Au-C bonds in Au(CN)(2)(-) using photoelectron spectroscopy and comparisons with its lighter congeners, Ag(CN)(2)(-) and Cu(CN)(2)(-). Vibrational progressions in the Au-C stretching mode were observed for all detachment transitions for Au(CN)(2)(-), in contrast to the atomic-like transitions for Cu(CN)(2)(-), revealing the Au-C covalent bonding character. In addition, rich electronic structural information was obtained for Au(CN)(2)(-) by employing 118 nm detachment photons. Density functional theory and high-level ab initio calculations were carried out to understand the photoelectron spectra and obtain insight into the nature of the chemical bonding in the M(CN)(2)(-) complexes. Significant covalent character in the Au-C bonding due to the strong relativistic effects was revealed in Au(CN)(2)(-), consistent with its high stability.

Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

Science.gov (United States)

Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

2015-04-01

Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited. © 2015 John Wiley & Sons Ltd.

A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

Directory of Open Access Journals (Sweden)

Ke Xu

2011-12-01

Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

Science.gov (United States)

Lai, Jonathan H; Fleming, Kirsten E; Ly, Thai Yen; Pasternak, Sylvia; Godlewski, Marek; Doucette, Steve; Walsh, Noreen M

2015-09-01

Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different biological subsets of the tumor exist led us to explore this diversity. In an Eastern Canadian cohort of cases (75 patients; mean age, 76 years [range, 43-91]; male/female ratio, 43:32; 51 [68%] pure and 24 [34%] combined tumors), we semiquantitatively compared the immunohistochemical expression of 3 cellular proteins (p53, Bcl-2, and c-kit) in pure versus combined groups. Viral status was known in a subset of cases. The significant overexpression of p53 in the combined group (mean [SD], 153.8 [117.8] versus 121.6 [77.9]; P = .01) and the increased epidermal expression of this protein (p53 patches) in the same group lend credence to a primary etiologic role for sun damage in these cases. Expression of Bcl-2 and c-kit did not differ significantly between the 2 morphological groups. A relative increase in c-kit expression was significantly associated with a virus-negative status (median [interquartile range], 100 [60-115] versus 70 [0-100]; P = .03). Emerging data reveal divergent biological pathways in Merkel cell carcinoma, each with a characteristic immunohistochemical profile. Virus-positive tumors (all pure) exhibit high retinoblastoma protein and low p53 expression, whereas virus-negative cases (few pure and all combined) show high p53 and relatively high c-kit expression. The potential biological implications of this dichotomy call for consistent stratification of these tumors in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Celecoxib does not significantly delay bone healing in a rat femoral osteotomy model: a bone histomorphometry study

Directory of Open Access Journals (Sweden)

Iwamoto J

2011-12-01

Full Text Available Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8, the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week group (positive control, n = 5, and the celecoxib administration (4 mg/kg orally, five times a week group (n = 8. After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

Coronary risk assessment by point-based vs. equation-based Framingham models: significant implications for clinical care.

Science.gov (United States)

Gordon, William J; Polansky, Jesse M; Boscardin, W John; Fung, Kathy Z; Steinman, Michael A

2010-11-01

US cholesterol guidelines use original and simplified versions of the Framingham model to estimate future coronary risk and thereby classify patients into risk groups with different treatment strategies. We sought to compare risk estimates and risk group classification generated by the original, complex Framingham model and the simplified, point-based version. We assessed 2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III) guidelines recommend formal risk stratification. For each subject, we calculated the 10-year risk of major coronary events using the original and point-based Framingham models, and then compared differences in these risk estimates and whether these differences would place subjects into different ATP-III risk groups (20% risk). Using standard procedures, all analyses were adjusted for survey weights, clustering, and stratification to make our results nationally representative. Among 39 million eligible adults, the original Framingham model categorized 71% of subjects as having "moderate" risk (20%) risk. Estimates of coronary risk by the original and point-based models often differed substantially. The point-based system classified 15% of adults (5.7 million) into different risk groups than the original model, with 10% (3.9 million) misclassified into higher risk groups and 5% (1.8 million) into lower risk groups, for a net impact of classifying 2.1 million adults into higher risk groups. These risk group misclassifications would impact guideline-recommended drug treatment strategies for 25-46% of affected subjects. Patterns of misclassifications varied significantly by gender, age, and underlying CHD risk. Compared to the original Framingham model, the point-based version misclassifies millions of Americans into risk groups for which guidelines recommend different treatment strategies.

Network motif frequency vectors reveal evolving metabolic network organisation.

Science.gov (United States)

Pearcy, Nicole; Crofts, Jonathan J; Chuzhanova, Nadia

2015-01-01

At the systems level many organisms of interest may be described by their patterns of interaction, and as such, are perhaps best characterised via network or graph models. Metabolic networks, in particular, are fundamental to the proper functioning of many important biological processes, and thus, have been widely studied over the past decade or so. Such investigations have revealed a number of shared topological features, such as a short characteristic path-length, large clustering coefficient and hierarchical modular structure. However, the extent to which evolutionary and functional properties of metabolism manifest via this underlying network architecture remains unclear. In this paper, we employ a novel graph embedding technique, based upon low-order network motifs, to compare metabolic network structure for 383 bacterial species categorised according to a number of biological features. In particular, we introduce a new global significance score which enables us to quantify important evolutionary relationships that exist between organisms and their physical environments. Using this new approach, we demonstrate a number of significant correlations between environmental factors, such as growth conditions and habitat variability, and network motif structure, providing evidence that organism adaptability leads to increased complexities in the resultant metabolic networks.

Networks of Food Sharing Reveal the Functional Significance of Multilevel Sociality in Two Hunter-Gatherer Groups.

Science.gov (United States)

Dyble, Mark; Thompson, James; Smith, Daniel; Salali, Gul Deniz; Chaudhary, Nikhil; Page, Abigail E; Vinicuis, Lucio; Mace, Ruth; Migliano, Andrea Bamberg

2016-08-08

Like many other mammalian and primate societies [1-4], humans are said to live in multilevel social groups, with individuals situated in a series of hierarchically structured sub-groups [5, 6]. Although this multilevel social organization has been described among contemporary hunter-gatherers [5], questions remain as to the benefits that individuals derive from living in such groups. Here, we show that food sharing among two populations of contemporary hunter-gatherers-the Palanan Agta (Philippines) and Mbendjele BaYaka (Republic of Congo)-reveals similar multilevel social structures, with individuals situated in households, within sharing clusters of 3-4 households, within the wider residential camps, which vary in size. We suggest that these groupings serve to facilitate inter-sexual provisioning, kin provisioning, and risk reduction reciprocity, three levels of cooperation argued to be fundamental in human societies [7, 8]. Humans have a suite of derived life history characteristics including a long childhood and short inter-birth intervals that make offspring energetically demanding [9] and have moved to a dietary niche that often involves the exploitation of difficult to acquire foods with highly variable return rates [10-12]. This means that human foragers face both day-to-day and more long-term energetic deficits that conspire to make humans energetically interdependent. We suggest that a multilevel social organization allows individuals access to both the food sharing partners required to buffer themselves against energetic shortfalls and the cooperative partners required for skill-based tasks such as cooperative foraging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcriptomic analysis of the late stages of grapevine (Vitis vinifera cv. Cabernet Sauvignon) berry ripening reveals significant induction of ethylene signaling and flavor pathways in the skin.

Science.gov (United States)

Cramer, Grant R; Ghan, Ryan; Schlauch, Karen A; Tillett, Richard L; Heymann, Hildegarde; Ferrarini, Alberto; Delledonne, Massimo; Zenoni, Sara; Fasoli, Marianna; Pezzotti, Mario

2014-12-19

Grapevine berry, a nonclimacteric fruit, has three developmental stages; the last one is when berry color and sugar increase. Flavors derived from terpenoid and fatty acid metabolism develop at the very end of this ripening stage. The transcriptomic response of pulp and skin of Cabernet Sauvignon berries in the late stages of ripening between 22 and 37 °Brix was assessed using whole-genome micorarrays. The transcript abundance of approximately 18,000 genes changed with °Brix and tissue type. There were a large number of changes in many gene ontology (GO) categories involving metabolism, signaling and abiotic stress. GO categories reflecting tissue differences were overrepresented in photosynthesis, isoprenoid metabolism and pigment biosynthesis. Detailed analysis of the interaction of the skin and pulp with °Brix revealed that there were statistically significantly higher abundances of transcripts changing with °Brix in the skin that were involved in ethylene signaling, isoprenoid and fatty acid metabolism. Many transcripts were peaking around known optimal fruit stages for flavor production. The transcript abundance of approximately two-thirds of the AP2/ERF superfamily of transcription factors changed during these developmental stages. The transcript abundance of a unique clade of ERF6-type transcription factors had the largest changes in the skin and clustered with genes involved in ethylene, senescence, and fruit flavor production including ACC oxidase, terpene synthases, and lipoxygenases. The transcript abundance of important transcription factors involved in fruit ripening was also higher in the skin. A detailed analysis of the transcriptome dynamics during late stages of ripening of grapevine berries revealed that these berries went through massive transcriptional changes in gene ontology categories involving chemical signaling and metabolism in both the pulp and skin, particularly in the skin. Changes in the transcript abundance of genes involved in

Clinical Significance of CK19 Negative Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Fujisue, Mamiko, E-mail: nishimura.reiki@cityhosp-kumamoto.jp; Nishimura, Reiki; Okumura, Yasuhiro [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Tashima, Rumiko [Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Nishiyama, Yasuyuki; Osako, Tomofumi [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Toyozumi, Yasuo; Arima, Nobuyuki [Department of Pathology, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan)

2012-12-21

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

Directory of Open Access Journals (Sweden)

Nobuyuki Arima

2012-12-01

Full Text Available Analysis of sentinel lymph nodes (SLNs by means of One-Step Nucleic Acid Amplification (OSNA is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19 which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

International Nuclear Information System (INIS)

Fujisue, Mamiko; Nishimura, Reiki; Okumura, Yasuhiro; Tashima, Rumiko; Nishiyama, Yasuyuki; Osako, Tomofumi; Toyozumi, Yasuo; Arima, Nobuyuki

2012-01-01

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

Directory of Open Access Journals (Sweden)

Claire A Hales

Full Text Available Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142, and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

Science.gov (United States)

Hales, Claire A; Robinson, Emma S J; Houghton, Conor J

2016-01-01

Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Applications of Living Fire PRA models to Fire Protection Significance Determination Process in Taiwan

International Nuclear Information System (INIS)

De-Cheng, Chen; Chung-Kung, Lo; Tsu-Jen, Lin; Ching-Hui, Wu; Lin, James C.

2004-01-01

The living fire probabilistic risk assessment (PRA) models for all three operating nuclear power plants (NPPs) in Taiwan had been established in December 2000. In that study, a scenario-based PRA approach was adopted to systematically evaluate the fire and smoke hazards and associated risks. Using these fire PRA models developed, a risk-informed application project had also been completed in December 2002 for the evaluation of cable-tray fire-barrier wrapping exemption. This paper presents a new application of the fire PRA models to fire protection issues using the fire protection significance determination process (FP SDP). The fire protection issues studied may involve the selection of appropriate compensatory measures during the period when an automatic fire detection or suppression system in a safety-related fire zone becomes inoperable. The compensatory measure can either be a 24-hour fire watch or an hourly fire patrol. The living fire PRA models were used to estimate the increase in risk associated with the fire protection issue in terms of changes in core damage frequency (CDF) and large early release frequency (LERF). In compliance with SDP at-power and the acceptance guidelines specified in RG 1.174, the fire protection issues in question can be grouped into four categories; red, yellow, white and green, in accordance with the guidelines developed for FD SDP. A 24-hour fire watch is suggested only required for the yellow condition, while an hourly fire patrol may be adopted for the white condition. More limiting requirement is suggested for the red condition, but no special consideration is needed for the green condition. For the calculation of risk measures, risk impacts from any additional fire scenarios that may have been introduced, as well as more severe initiating events and fire damages that may accompany the fire protection issue should be considered carefully. Examples are presented in this paper to illustrate the evaluation process. (authors)

Hydrothermal Fe cycling and deep ocean organic carbon scavenging: Model-based evidence for significant POC supply to seafloor sediments

Digital Repository Service at National Institute of Oceanography (India)

German, C.R.; Legendre, L.L.; Sander, S.G.;; Niquil, N.; Luther-III, G.W.; LokaBharathi, P.A.; Han, X.; LeBris, N.

by more than ~10% over background values, what the model does indicate is that scavenging of carbon in association with Fe-rich hydrothermal plume particles should play a significant role in the delivery of particulate organic carbon to deep ocean...

Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors

Directory of Open Access Journals (Sweden)

Raymond Kiu

2017-12-01

Full Text Available Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an “open” pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens-associated exotoxins genes including α-toxin (plc, enterotoxin (cpe, and Perfringolysin O (pfo or pfoA, although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56 of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes (tet and anti-defensins genes (mprF were consistently detected in silico (tet: 75%; mprF: 100%. However, pre-antibiotic era strain genomes did not encode for tet, thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

Predictive models of forest logging residues of Triplochiton ...

African Journals Online (AJOL)

The model developed indicated that logarithmic functions performed better than other form of equation. The findings of this study revealed that there is significant logging residues left to waste in the forest after timber harvest and quantifying this logging residue in terms of biomass model can serve as management tools in ...

Significant strain accumulation between the deformation front and landward out-of-sequence thrusts in accretionary wedge of SW Taiwan revealed by cGPS and SAR interferometry

Science.gov (United States)

Tsai, M. C.

2017-12-01

High strain accumulation across the fold-and-thrust belt in Southwestern Taiwan are revealed by the Continuous GPS (cGPS) and SAR interferometry. This high strain is generally accommodated by the major active structures in fold-and-thrust belt of western Foothills in SW Taiwan connected to the accretionary wedge in the incipient are-continent collision zone. The active structures across the high strain accumulation include the deformation front around the Tainan Tableland, the Hochiali, Hsiaokangshan, Fangshan and Chishan faults. Among these active structures, the deformation pattern revealed from cGPS and SAR interferometry suggest that the Fangshan transfer fault may be a left-lateral fault zone with thrust component accommodating the westward differential motion of thrust sheets on both side of the fault. In addition, the Chishan fault connected to the splay fault bordering the lower-slope and upper-slope of the accretionary wedge which could be the major seismogenic fault and an out-of-sequence thrust fault in SW Taiwan. The big earthquakes resulted from the reactivation of out-of-sequence thrusts have been observed along the Nankai accretionary wedge, thus the assessment of the major seismogenic structures by strain accumulation between the frontal décollement and out-of-sequence thrusts is a crucial topic. According to the background seismicity, the low seismicity and mid-crust to mantle events are observed inland and the lower- and upper- slope domain offshore SW Taiwan, which rheologically implies the upper crust of the accretionary wedge is more or less aseimic. This result may suggest that the excess fluid pressure from the accretionary wedge not only has significantly weakened the prism materials as well as major fault zone, but also makes the accretionary wedge landward extension, which is why the low seismicity is observed in SW Taiwan area. Key words: Continuous GPS, SAR interferometry, strain rate, out-of-sequence thrust.

Revealing Rembrandt

Directory of Open Access Journals (Sweden)

Andrew J Parker

2014-04-01

Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

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Hu, Bihui; Yang, Jinying; Huang, Qian; Bao, Junjie; Brennecke, Shaun Patrick; Liu, Huishu

2016-05-01

Preeclampsia is associated with an increased inflammatory response. Immune suppression might be an effective treatment. The aim of this study was to examine whether Cyclosporin A (CsA), an immunosuppressant, improves clinical characteristics of preeclampsia and suppresses inflammation in a lipopolysaccharide (LPS) induced preeclampsia rat model. Pregnant rats were randomly divided into 4 groups: group 1 (PE) rats each received LPS via tail vein on gestational day (GD) 14; group 2 (PE+CsA5) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (5mg/kg, ip) on GDs 16, 17 and 18; group 3 (PE+CsA10) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (10mg/kg, ip) on GDs 16, 17 and 18; group 4 (pregnant control, PC) rats were treated with the vehicle (saline) used for groups 1, 2 and 3. Systolic blood pressure, urinary albumin, biometric parameters and the levels of serum cytokines were measured on day 20. CsA treatment significantly reduced LPS-induced systolic blood pressure and the mean 24-h urinary albumin excretion. Pro-inflammatory cytokines IL-6, IL-17, IFN-γ and TNF-α were increased in the LPS treatment group but were reduced in (LPS+CsA) group (Ppreeclampsia signs and attenuated inflammatory responses in the LPS induced preeclampsia rat model which suggests that immunosuppressant might be an alternative management option for preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

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Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

2013-02-15

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

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Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

2016-06-01

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Cross-hemispheric dopamine projections have functional significance

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Fox, Megan E.; Mikhailova, Maria A.; Bass, Caroline E.; Takmakov, Pavel; Gainetdinov, Raul R.; Budygin, Evgeny A.; Wightman, R. Mark

2016-01-01

Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson’s disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine–lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres. PMID:27298371

High-Elevation Sierra Nevada Conifers Reveal Increasing Reliance on Snow Water with Changing Climate

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Lepley, K. S.; Meko, D. M.; Touchan, R.; Shamir, E.; Graham, R.

2017-12-01

Snowpack in the Sierra Nevada Mountains accounts for around one third of California's water supply. Melting snow can provide water into dry summer months characteristic of the region's Mediterranean climate. As climate changes, understanding patterns of snowpack, snowmelt, and biological response are critical in this region of agricultural, recreational, and ecological value. Tree rings can act as proxy records to inform scientists and resource managers of past climate variability where instrumental data is unavailable. Here we investigate relationships between tree rings of high-elevation, snow-adapted conifer trees (Tsuga mertensiana, Abies magnifica) and April 1st snow-water equivalent (SWE) in the northern Sierra Nevada Mountains. The 1st principal component of 29 highly correlated regional SWE time series was modeled using multiple linear regression of four tree-ring chronologies including two lagged chronologies. Split-period verification analysis of this model revealed poor predictive skill in the early half (1929 - 1966) of the calibration period (1929 - 2003). Further analysis revealed a significant (p time. Snow water is becoming a more limiting resource to tree growth as average temperatures rise and the hydrologic regime shifts. These results highlight the need for resource managers and policy makers to consider that biological response to climate is not static.

Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.

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Mohsen, Zaid; Sim, Hosung; Garcia-Galiano, David; Han, Xingfa; Bellefontaine, Nicole; Saunders, Thomas L; Elias, Carol F

2017-12-01

Prokineticin receptor 2 (PROKR2) is predominantly expressed in the mammalian central nervous system. Loss-of-function mutations of PROKR2 in humans are associated with Kallmann syndrome due to the disruption of gonadotropin releasing hormone neuronal migration and deficient olfactory bulb morphogenesis. PROKR2 has been also implicated in the neuroendocrine control of GnRH neurons post-migration and other physiological systems. However, the brain circuitry and mechanisms associated with these actions have been difficult to investigate mainly due to the widespread distribution of Prokr2-expressing cells, and the lack of animal models and molecular tools. Here, we describe the generation, validation and characterization of a new mouse model that expresses Cre recombinase driven by the Prokr2 promoter, using CRISPR-Cas9 technology. Cre expression was visualized using reporter genes, tdTomato and GFP, in males and females. Expression of Cre-induced reporter genes was found in brain sites previously described to express Prokr2, e.g., the paraventricular and the suprachiasmatic nuclei, and the area postrema. The Prokr2-Cre mouse model was further validated by colocalization of Cre-induced GFP and Prokr2 mRNA. No disruption of Prokr2 expression, GnRH neuronal migration or fertility was observed. Comparative analysis of Prokr2-Cre expression in male and female brains revealed a sexually dimorphic distribution confirmed by in situ hybridization. In females, higher Cre activity was found in the medial preoptic area, ventromedial nucleus of the hypothalamus, arcuate nucleus, medial amygdala and lateral parabrachial nucleus. In males, Cre was higher in the amygdalo-hippocampal area. The sexually dimorphic pattern of Prokr2 expression indicates differential roles in reproductive function and, potentially, in other physiological systems.

Significance of matrix diagonalization in modelling inelastic electron scattering

Energy Technology Data Exchange (ETDEWEB)

Lee, Z. [University of Ulm, Ulm 89081 (Germany); Hambach, R. [University of Ulm, Ulm 89081 (Germany); University of Jena, Jena 07743 (Germany); Kaiser, U.; Rose, H. [University of Ulm, Ulm 89081 (Germany)

2017-04-15

Electron scattering is always applied as one of the routines to investigate nanostructures. Nowadays the development of hardware offers more and more prospect for this technique. For example imaging nanostructures with inelastic scattered electrons may allow to produce component-sensitive images with atomic resolution. Modelling inelastic electron scattering is therefore essential for interpreting these images. The main obstacle to study inelastic scattering problem is its complexity. During inelastic scattering, incident electrons entangle with objects, and the description of this process involves a multidimensional array. Since the simulation usually involves fourdimensional Fourier transforms, the computation is highly inefficient. In this work we have offered one solution to handle the multidimensional problem. By transforming a high dimensional array into twodimensional array, we are able to perform matrix diagonalization and approximate the original multidimensional array with its twodimensional eigenvectors. Our procedure reduces the complicated multidimensional problem to a twodimensional problem. In addition, it minimizes the number of twodimensional problems. This method is very useful for studying multiple inelastic scattering. - Highlights: • 4D problems are involved in modelling inelastic electron scattering. • By means of matrix diagonalization, the 4D problems can be simplified as 2D problems. • The number of 2D problems is minimized by using this approach.

A mouse model of visual perceptual learning reveals alterations in neuronal coding and dendritic spine density in the visual cortex

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Yan eWang

2016-03-01

Full Text Available Visual perceptual learning (VPL can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS and a 55% gain in visual acuity (VA. Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1 than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

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Wang, Yan; Wu, Wei; Zhang, Xian; Hu, Xu; Li, Yue; Lou, Shihao; Ma, Xiao; An, Xu; Liu, Hui; Peng, Jing; Ma, Danyi; Zhou, Yifeng; Yang, Yupeng

2016-01-01

Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

Cytogenetical and morphological features reveal significant differences among Venezuelan and Brazilian samples of Mugil curema (Teleostei: Mugilidae

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Mauro Nirchio

Full Text Available Karyotype of M. curema from the Gulf of Mexico and Brazil have been reported as possessing chromosome complement with 2n=28 and FN=48, whereas specimens from Venezuela has been reported as possessing a diploid number 2n=24 and a conserved FN (48. Although at first sight this variation suggests the presence of a chromosomal intraspecific (interpopulational variability, the possibility that we are dealing with two different species was examined. This work revisit the karyotypes of M. curema from Venezuela and Brazil, including new data on C-banding, and NOR localization, and compares morphologic characteristics of samples from both localities. Thus, besides diploid number, the constitutive heterochromatin distribution and NORs location, mark other differences between M. curema Cytotype 1 (2n=28; FN=48 and Cytotype 2 (2n=24; NF=48. Moreover, morphologic comparison revealed differences in the scale counts and pectoral fin rays: 35 scales in the middle body line and 15 pectoral fin rays in specimens possessing the karyotype 2n=28, compared with 37-39 scales in the middle body line and 17 pectoral fin rays in specimens with the karyotype 2n=24. These differences lead us to suggest that both cytotypes are not related merely to geographic polytipic variations but could correspond to different species.

Pedestrian Walking Behavior Revealed through a Random Walk Model

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Hui Xiong

2012-01-01

Full Text Available This paper applies method of continuous-time random walks for pedestrian flow simulation. In the model, pedestrians can walk forward or backward and turn left or right if there is no block. Velocities of pedestrian flow moving forward or diffusing are dominated by coefficients. The waiting time preceding each jump is assumed to follow an exponential distribution. To solve the model, a second-order two-dimensional partial differential equation, a high-order compact scheme with the alternating direction implicit method, is employed. In the numerical experiments, the walking domain of the first one is two-dimensional with two entrances and one exit, and that of the second one is two-dimensional with one entrance and one exit. The flows in both scenarios are one way. Numerical results show that the model can be used for pedestrian flow simulation.

Structural mode significance using INCA. [Interactive Controls Analysis computer program

Science.gov (United States)

Bauer, Frank H.; Downing, John P.; Thorpe, Christopher J.

1990-01-01

Structural finite element models are often too large to be used in the design and analysis of control systems. Model reduction techniques must be applied to reduce the structural model to manageable size. In the past, engineers either performed the model order reduction by hand or used distinct computer programs to retrieve the data, to perform the significance analysis and to reduce the order of the model. To expedite this process, the latest version of INCA has been expanded to include an interactive graphical structural mode significance and model order reduction capability.

Genome-wide significant localization for working and spatial memory: Identifying genes for psychosis using models of cognition.

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Knowles, Emma E M; Carless, Melanie A; de Almeida, Marcio A A; Curran, Joanne E; McKay, D Reese; Sprooten, Emma; Dyer, Thomas D; Göring, Harald H; Olvera, Rene; Fox, Peter; Almasy, Laura; Duggirala, Ravi; Kent, Jack W; Blangero, John; Glahn, David C

2014-01-01

It is well established that risk for developing psychosis is largely mediated by the influence of genes, but identifying precisely which genes underlie that risk has been problematic. Focusing on endophenotypes, rather than illness risk, is one solution to this problem. Impaired cognition is a well-established endophenotype of psychosis. Here we aimed to characterize the genetic architecture of cognition using phenotypically detailed models as opposed to relying on general IQ or individual neuropsychological measures. In so doing we hoped to identify genes that mediate cognitive ability, which might also contribute to psychosis risk. Hierarchical factor models of genetically clustered cognitive traits were subjected to linkage analysis followed by QTL region-specific association analyses in a sample of 1,269 Mexican American individuals from extended pedigrees. We identified four genome wide significant QTLs, two for working and two for spatial memory, and a number of plausible and interesting candidate genes. The creation of detailed models of cognition seemingly enhanced the power to detect genetic effects on cognition and provided a number of possible candidate genes for psychosis. © 2013 Wiley Periodicals, Inc.

Dinosaurs reveal the geographical signature of an evolutionary radiation.

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O'Donovan, Ciara; Meade, Andrew; Venditti, Chris

2018-03-01

Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs' ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation-when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation.

Introduction of e-learning in dental radiology reveals significantly improved results in final examination.

Science.gov (United States)

Meckfessel, Sandra; Stühmer, Constantin; Bormann, Kai-Hendrik; Kupka, Thomas; Behrends, Marianne; Matthies, Herbert; Vaske, Bernhard; Stiesch, Meike; Gellrich, Nils-Claudius; Rücker, Martin

2011-01-01

Because a traditionally instructed dental radiology lecture course is very time-consuming and labour-intensive, online courseware, including an interactive-learning module, was implemented to support the lectures. The purpose of this study was to evaluate the perceptions of students who have worked with web-based courseware as well as the effect on their results in final examinations. Users (n(3+4)=138) had access to the e-program from any networked computer at any time. Two groups (n(3)=71, n(4)=67) had to pass a final exam after using the e-course. Results were compared with two groups (n(1)=42, n(2)=48) who had studied the same content by attending traditional lectures. In addition a survey of the students was statistically evaluated. Most of the respondents reported a positive attitude towards e-learning and would have appreciated more access to computer-assisted instruction. Two years after initiating the e-course the failure rate in the final examination dropped significantly, from 40% to less than 2%. The very positive response to the e-program and improved test scores demonstrated the effectiveness of our e-course as a learning aid. Interactive modules in step with clinical practice provided learning that is not achieved by traditional teaching methods alone. To what extent staff savings are possible is part of a further study. Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Species Richness and Diversity Reveal that Human-Modified ...

African Journals Online (AJOL)

Family diversity and richness showed no significant differences across the sites. The spider species consisted of primarily three functional groups: ground wanderers, web builders and plant wanderers, and showed no within-group differences in abundance between sites. Similarity index between the study sites revealed a ...

Bayesian spatial modelling and the significance of agricultural land use to scrub typhus infection in Taiwan.

Science.gov (United States)

Wardrop, Nicola A; Kuo, Chi-Chien; Wang, Hsi-Chieh; Clements, Archie C A; Lee, Pei-Fen; Atkinson, Peter M

2013-11-01

Scrub typhus is transmitted by the larval stage of trombiculid mites. Environmental factors, including land cover and land use, are known to influence breeding and survival of trombiculid mites and, thus, also the spatial heterogeneity of scrub typhus risk. Here, a spatially autoregressive modelling framework was applied to scrub typhus incidence data from Taiwan, covering the period 2003 to 2011, to provide increased understanding of the spatial pattern of scrub typhus risk and the environmental and socioeconomic factors contributing to this pattern. A clear spatial pattern in scrub typhus incidence was observed within Taiwan, and incidence was found to be significantly correlated with several land cover classes, temperature, elevation, normalized difference vegetation index, rainfall, population density, average income and the proportion of the population that work in agriculture. The final multivariate regression model included statistically significant correlations between scrub typhus incidence and average income (negatively correlated), the proportion of land that contained mosaics of cropland and vegetation (positively correlated) and elevation (positively correlated). These results highlight the importance of land cover on scrub typhus incidence: mosaics of cropland and vegetation represent a transitional land cover type which can provide favourable habitats for rodents and, therefore, trombiculid mites. In Taiwan, these transitional land cover areas tend to occur in less populated and mountainous areas, following the frontier establishment and subsequent partial abandonment of agricultural cultivation, due to demographic and socioeconomic changes. Future land use policy decision-making should ensure that potential public health outcomes, such as modified risk of scrub typhus, are considered.

Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

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Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

2016-05-15

Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

Do US Ambient Air Lead Levels Have a Significant Impact on Childhood Blood Lead Levels: Results of a National Study

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LuAnn L. Brink

2013-01-01

Full Text Available Introduction. Although lead paint and leaded gasoline have not been used in the US for thirty years, thousands of US children continue to have blood lead levels (BLLs of concern. Methods. We investigated the potential association of modeled air lead levels and BLLs ≥ 10 μg/dL using a large CDC database with BLLs on children aged 0–3 years. Percent of children with BLLs ≥ 10 μg/dL (2000–2007 by county and proportion of pre-50 housing and SES variables were merged with the US EPA's National Air Toxics Assessment (NATA modeled air lead data. Results. The proportion with BLL ≥ 10 μg/dL was 1.24% in the highest air lead counties, and the proportion with BLL ≥ 10 μg/dL was 0.36% in the lowest air lead counties, resulting in a crude prevalence ratio of 3.4. Further analysis using multivariate negative binomial regression revealed that NATA lead was a significant predictor of % BLL ≥ 10 μg/dL after controlling for percent pre-l950 housing, percent rural, and percent black. A geospatial regression revealed that air lead, percent older housing, and poverty were all significant predictors of % BLL ≥ 10 μg/dL. Conclusions. More emphasis should be given to potential sources of ambient air lead near residential areas.

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

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Brad A. Friedman

2018-01-01

Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

Science.gov (United States)

Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

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Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

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Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

2014-01-01

Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which

Statistically significant relational data mining :

Energy Technology Data Exchange (ETDEWEB)

Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

2014-02-01

This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

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Yonghua Bao

Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

Composition of fibrin glues significantly influences axial vascularization and degradation in isolation chamber model.

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Arkudas, Andreas; Pryymachuk, Galyna; Hoereth, Tobias; Beier, Justus P; Polykandriotis, Elias; Bleiziffer, Oliver; Gulle, Heinz; Horch, Raymund E; Kneser, Ulrich

2012-07-01

In this study, different fibrin sealants with varying concentrations of the fibrin components were evaluated in terms of matrix degradation and vascularization in the arteriovenous loop (AVL) model of the rat. An AVL was placed in a Teflon isolation chamber filled with 500 μl fibrin gel. The matrix was composed of commercially available fibrin gels, namely Beriplast (Behring GmbH, Marburg, Germany) (group A), Evicel (Omrix Biopharmaceuticals S.A., Somerville, New Jersey, USA) (group B), Tisseel VH S/D (Baxter, Vienna, Austria) with a thrombin concentration of 4 IU/ml and a fibrinogen concentration of 80 mg/ml [Tisseel S F80 (Baxter), group C] and with an fibrinogen concentration of 20 mg/ml [Tisseel S F20 (Baxter), group D]. After 2 and 4 weeks, five constructs per group and time point were investigated using micro-computed tomography, and histological and morphometrical analysis techniques. The aprotinin, factor XIII and thrombin concentration did not affect the degree of clot degradation. An inverse relationship was found between fibrin matrix degradation and sprouting of blood vessels. By reducing the fibrinogen concentration in group D, a significantly decreased construct weight and an increased generation of vascularized connective tissue were detected. There was an inverse relationship between matrix degradation and vascularization detectable. Fibrinogen as the major matrix component showed a significant impact on the matrix properties. Alteration of fibrin gel properties might optimize formation of blood vessels.

Can role models boost entrepreneurial attitudes?

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Fellnhofer, Katharina; Puumalainen, Kaisu

2017-01-01

This multi-country study used role models to boost perceptions of entrepreneurial feasibility and desirability. The results of a structural equation model based on a sample comprising 426 individuals who were primarily from Austria, Finland and Greece revealed a significant positive influence on perceived entrepreneurial desirability and feasibility. These findings support the argument for embedding entrepreneurial role models in entrepreneurship education courses to promote entrepreneurial activities. This direction is not only relevant for the academic community but also essential for nascent entrepreneurs, policymakers and society at large.

Double-layer structure model of the uranium generating bed in the land basins of the northwestern China and its significance

International Nuclear Information System (INIS)

Wang Zhilong

1988-04-01

The paper puts forward a double layer structure model of uranium generating bed in the land basins of Northwestern China, i.e. uranium ganerating bed = source layer of uranium+gathering uranium layer. The mechanism of its formation: Feldspar was hydromicatized. Some feldspar, quarts detrital silicate minerals were replaced to redden by the authigenesis of hematite and goethite. In the course of the oxidation, a little uranium is released from the detrital minerals. Because of the oxidation environment, the released uranium wasn't able to be precipitated, only to diffuse to the adjacent grey bed which has low Eh value with uranium-bearing 'stagnant water' fixed in pores during the dewatering process of the diagenesis and form minable uranium deposit. The significance of the model for uranium prospecting are as follows: (1) Uranium source range is much expanded concerning ruanium prospecting in sandstone. (2) For the potential assessment of basin and the selection of potential area, the model is an important prospecting criterion. (3) By using the main criterion uranium-generating bed-arkosic red beds well, the buried ore bodies can be found provided that arkosic red beds were regarded as a significant criterion of uranium-generating bed

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

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Chiao-Ling Lo

2016-08-01

Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

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Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

2016-08-01

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.

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Prasanna Vidyasekar

Full Text Available Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated and 2542 (downregulated genes (>2 fold in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated and 444 (downregulated genes (>2 fold under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2.

Analysis of significance of environmental factors in landslide susceptibility modeling: Case study Jemma drainage network, Ethiopia

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Vít Maca

2017-06-01

Full Text Available Aim of the paper is to describe methodology for calculating significance of environmental factors in landslide susceptibility modeling and present result of selected one. As a study area part of a Jemma basin in Ethiopian Highland is used. This locality is highly affected by mass movement processes. In the first part all major factors and their influence are described briefly. Majority of the work focuses on research of other methodologies used in susceptibility models and design of own methodology. This method is unlike most of the methods used completely objective, therefore it is not possible to intervene in the results. In article all inputs and outputs of the method are described as well as all stages of calculations. Results are illustrated on specific examples. In study area most important factor for landslide susceptibility is slope, on the other hand least important is land cover. At the end of article landslide susceptibility map is created. Part of the article is discussion of results and possible improvements of the methodology.

Light and electron microscopy of the European beaver (Castor fiber) stomach reveal unique morphological features with possible general biological significance.

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Ziółkowska, Natalia; Lewczuk, Bogdan; Petryński, Wojciech; Palkowska, Katarzyna; Prusik, Magdalena; Targońska, Krystyna; Giżejewski, Zygmunt; Przybylska-Gornowicz, Barbara

2014-01-01

Anatomical, histological, and ultrastructural studies of the European beaver stomach revealed several unique morphological features. The prominent attribute of its gross morphology was the cardiogastric gland (CGG), located near the oesophageal entrance. Light microscopy showed that the CGG was formed by invaginations of the mucosa into the submucosa, which contained densely packed proper gastric glands comprised primarily of parietal and chief cells. Mucous neck cells represented beaver stomach was the presence of specific mucus with a thickness up to 950 µm (in frozen, unfixed sections) that coated the mucosa. Our observations suggest that the formation of this mucus is complex and includes the secretory granule accumulation in the cytoplasm of pit cells, the granule aggregation inside cells, and the incorporation of degenerating cells into the mucus.

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

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Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.;

Statistical significance of cis-regulatory modules

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Smith Andrew D

2007-01-01

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

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Anna Ljungdahl

Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

Neglect Of Parameter Estimation Uncertainty Can Significantly Overestimate Structural Reliability

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Rózsás Árpád

2015-12-01

Full Text Available Parameter estimation uncertainty is often neglected in reliability studies, i.e. point estimates of distribution parameters are used for representative fractiles, and in probabilistic models. A numerical example examines the effect of this uncertainty on structural reliability using Bayesian statistics. The study reveals that the neglect of parameter estimation uncertainty might lead to an order of magnitude underestimation of failure probability.

A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

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Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

2016-06-01

Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs. Copyright © 2016 Elsevier Inc. All rights reserved.

Aquatic insect ecophysiological traits reveal phylogenetically based differences in dissolved cadmium susceptibility.

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Buchwalter, David B; Cain, Daniel J; Martin, Caitrin A; Xie, Lingtian; Luoma, Samuel N; Garland, Theodore

2008-06-17

We used a phylogenetically based comparative approach to evaluate the potential for physiological studies to reveal patterns of diversity in traits related to susceptibility to an environmental stressor, the trace metal cadmium (Cd). Physiological traits related to Cd bioaccumulation, compartmentalization, and ultimately susceptibility were measured in 21 aquatic insect species representing the orders Ephemeroptera, Plecoptera, and Trichoptera. We mapped these experimentally derived physiological traits onto a phylogeny and quantified the tendency for related species to be similar (phylogenetic signal). All traits related to Cd bioaccumulation and susceptibility exhibited statistically significant phylogenetic signal, although the signal strength varied among traits. Conventional and phylogenetically based regression models were compared, revealing great variability within orders but consistent, strong differences among insect families. Uptake and elimination rate constants were positively correlated among species, but only when effects of body size and phylogeny were incorporated in the analysis. Together, uptake and elimination rates predicted dramatic Cd bioaccumulation differences among species that agreed with field-based measurements. We discovered a potential tradeoff between the ability to eliminate Cd and the ability to detoxify it across species, particularly mayflies. The best-fit regression models were driven by phylogenetic parameters (especially differences among families) rather than functional traits, suggesting that it may eventually be possible to predict a taxon's physiological performance based on its phylogenetic position, provided adequate physiological information is available for close relatives. There appears to be great potential for evolutionary physiological approaches to augment our understanding of insect responses to environmental stressors in nature.

Molecular Chemical Structure of Barley Proteins Revealed by Ultra-Spatially Resolved Synchrotron Light Sourced FTIR Microspectroscopy: Comparison of Barley Varieties

International Nuclear Information System (INIS)

Yu, P.

2007-01-01

Barley protein structure affects the barley quality, fermentation, and degradation behavior in both humans and animals among other factors such as protein matrix. Publications show various biological differences among barley varieties such as Valier and Harrington, which have significantly different degradation behaviors. The objectives of this study were to reveal the molecular structure of barley protein, comparing various varieties (Dolly, Valier, Harrington, LP955, AC Metcalfe, and Sisler), and quantify protein structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling by using the ultra-spatially resolved synchrotron light sourced Fourier transform infrared microspectroscopy (SFTIRM). The items of the protein molecular structure revealed included protein structure α-helices, β-sheets, and others such as β-turns and random coils. The experiment was performed at the National Synchrotron Light Source in Brookhaven National Laboratory (BNL, US Department of Energy, NY). The results showed that with the SFTIRM, the molecular structure of barley protein could be revealed. Barley protein structures exhibited significant differences among the varieties in terms of proportion and ratio of model-fitted α-helices, β-sheets, and others. By using multi-component peaks modeling at protein amide I region of 1710-1576 cm -1 , the results show that barley protein consisted of approximately 18-34% of α-helices, 14-25% of β-sheets, and 44-69% others. AC Metcalfe, Sisler, and LP955 consisted of higher (P 0.05). The ratio of α-helices to others (0.3 to 1.0, P < 0.05) and that of β-sheets to others (0.2 to 0.8, P < 0.05) were different among the barley varieties. It needs to be pointed out that using a multi-peak modeling for protein structure analysis is only for making relative estimates and not exact determinations and only for the comparison purpose between varieties. The principal component analysis showed that protein amide I Fourier

Brief Group Psychoeducation for Bulimia Nervosa: Assessing the Clinical Significance of Change.

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Davis, Ron; And Others

1990-01-01

Brief intervention designed to promote symptom management was completed by 41 women with bulimia nervosa. Findings revealed diversity of outcomes that individuals reported following participation in intervention. Found differential reporting of clinically significant change in favor of specific eating psychopathology relative to personality…

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

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Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

2016-04-05

Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

VALORA: data base system for storage significant information used in the behavior modelling in the biosphere

International Nuclear Information System (INIS)

Valdes R, M.; Aguero P, A.; Perez S, D.; Cancio P, D.

2006-01-01

The nuclear and radioactive facilities can emit to the environment effluents that contain radionuclides, which are dispersed and/or its accumulate in the atmosphere, the terrestrial surface and the surface waters. As part of the evaluations of radiological impact, it requires to be carried out qualitative and quantitative analysis. In many of the cases it doesn't have the real values of the parameters that are used in the modelling, neither it is possible to carry out their measure, for that to be able to carry out the evaluation it needs to be carried out an extensive search of that published in the literature about the possible values of each parameter, under similar conditions to the object of study, this work can be extensive. In this work the characteristics of the VALORA Database System developed with the purpose of organizing and to automate significant information that it appears in different sources (scientific or technique literature) of the parameters that are used in the modelling of the behavior of the pollutants in the environment and the values assigned to these parameters that are used in the evaluation of the radiological impact potential is described; VALORA allows the consultation and selection of the characteristic parametric data of different situations and processes that are required by the calculation pattern implemented. The software VALORA it is a component of a group of tools computer that have as objective to help to the resolution of dispersion models and transfer of pollutants. (Author)

Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance.

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Wartenberg, Martin; Cibin, Silvia; Zlobec, Inti; Vassella, Erik; Eppenberger-Castori, Serenella M M; Terracciano, Luigi; Eichmann, Micha; Worni, Mathias; Gloor, Beat; Perren, Aurel; Karamitopoulou, Eva

2018-04-16

Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins. Previous data on FOXP3 were integrated. Immune-cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8. 2017), survival and epithelial-mesenchymal-transition (EMT)-like tumor budding.  Results: Three PDAC-subtypes were identified: the "immune-escape" (54%), poor in T- and B-cells and enriched in FOXP3+Tregs, with high-grade budding, frequent CDKN2A- , SMAD4- and PIK3CA-mutations and poor outcome; the "immune-rich" (35%), rich in T- and B-cells and poorer in FOXP3+Tregs, with infrequent budding, lower CDKN2A- and PIK3CA-mutation rate and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11, ATM) and the best outcome; and the "immune-exhausted" (11%) with immunogenic microenvironment and two subpopulations: one with PD-L1-expression and high PIK3CA-mutation rate and a microsatellite-unstable subpopulation with high prevalence of JAK3-mutations. The combination of low budding, low stromal FOXP3-counts, presence of TLTs and absence of CDKN2A-mutations confers significant survival advantage in PDAC-patients. Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance. Copyright ©2018

Significance of the expression of matrix metalloproteinase-9 (MMP-9) in brain tissue of rat models of experimental intracerebral haemorrhage (ICH)

International Nuclear Information System (INIS)

Wu Jiami; Liu Shengda

2005-01-01

Objective: To study the relationship between the brain tissue expression of MMP-9 and brain water content in rat models of experimental ICH. Methods: Rat models of ICH were prepared with intracerebral (caudate nuclei) injection of autologous noncoagulated blood (50 μl). Animals were sacrificed at 6h, 12h, 24h, 48h, 72h, 120h, lw, 2w and the MMP-9 expressions at the periphery of intracerebral hematoma were examined with immunohisto chemistry. The brain water content was also determined at the same time. Control models were prepared with intracerebral sham injection of normal saline. Results: (1) In the ICH models, the number of MMP-9 positive capillaries at the periphery of hematoma began to rise at 6h (vs that of sham group, P < 0.01 ) with peak at 48h, then gradually dropped. At lwk, the number was still significantly higher than that in the sham group (P <0.01 ). However, there were no expression at 2wk. (2) The brain water content in the ICH group was significantly increased at 12h (vs sham group, P < 0.05) with peak at 72h. At lwk, the brain water content was still significantly higher in the ICH group (P <0.01 ) but at 2wk, the brain water content was about the same in both groups. (3) Animals injected with different amounts of blood (30 μl, 50 μl, 100 μl) showed increased expression of MMP-9 along with the increase of dose (P<0.01). (4) The MMP-9 expression was positively correlated with the brain water content (r=0.8291, P<0.05). Conclusion: In the rat models, MMP-9 expression was activated after ICH. The increase paralleled that of the amount of haemorrhage and brain water content. It was postulated that MMP-9 enhanced development of brain edema through degrading of the blood brain barrier component substances. (authors)

An empirical model of the Baltic Sea reveals the importance of social dynamics for ecological regime shifts.

Science.gov (United States)

Lade, Steven J; Niiranen, Susa; Hentati-Sundberg, Jonas; Blenckner, Thorsten; Boonstra, Wiebren J; Orach, Kirill; Quaas, Martin F; Österblom, Henrik; Schlüter, Maja

2015-09-01

Regime shifts triggered by human activities and environmental changes have led to significant ecological and socioeconomic consequences in marine and terrestrial ecosystems worldwide. Ecological processes and feedbacks associated with regime shifts have received considerable attention, but human individual and collective behavior is rarely treated as an integrated component of such shifts. Here, we used generalized modeling to develop a coupled social-ecological model that integrated rich social and ecological data to investigate the role of social dynamics in the 1980s Baltic Sea cod boom and collapse. We showed that psychological, economic, and regulatory aspects of fisher decision making, in addition to ecological interactions, contributed both to the temporary persistence of the cod boom and to its subsequent collapse. These features of the social-ecological system also would have limited the effectiveness of stronger fishery regulations. Our results provide quantitative, empirical evidence that incorporating social dynamics into models of natural resources is critical for understanding how resources can be managed sustainably. We also show that generalized modeling, which is well-suited to collaborative model development and does not require detailed specification of causal relationships between system variables, can help tackle the complexities involved in creating and analyzing social-ecological models.

Brain Signals of Face Processing as Revealed by Event-Related Potentials

Directory of Open Access Journals (Sweden)

Ela I. Olivares

2015-01-01

Full Text Available We analyze the functional significance of different event-related potentials (ERPs as electrophysiological indices of face perception and face recognition, according to cognitive and neurofunctional models of face processing. Initially, the processing of faces seems to be supported by early extrastriate occipital cortices and revealed by modulations of the occipital P1. This early response is thought to reflect the detection of certain primary structural aspects indicating the presence grosso modo of a face within the visual field. The posterior-temporal N170 is more sensitive to the detection of faces as complex-structured stimuli and, therefore, to the presence of its distinctive organizational characteristics prior to within-category identification. In turn, the relatively late and probably more rostrally generated N250r and N400-like responses might respectively indicate processes of access and retrieval of face-related information, which is stored in long-term memory (LTM. New methods of analysis of electrophysiological and neuroanatomical data, namely, dynamic causal modeling, single-trial and time-frequency analyses, are highly recommended to advance in the knowledge of those brain mechanisms concerning face processing.

Solar journey: The significance of our galactic environment for the heliosphere and earth

CERN Document Server

Frisch, Priscilla C

2006-01-01

Humans evolved when the Sun was in the great void of the Local Bubble. The Sun entered the present environment of interstellar clouds only during the late Quaternary. Astronomical data reveal these long and short term changes in our galactic environment. Theoretical models then tell us how these changes affect interplanetary particles, planetary magnetospheres, and the Earth itself. Cosmic rays leave an isotopic signature in the paleoclimate record that helps trace the solar journey through space. "Solar Journey: The Significance of Our Galactic Environment for the Heliosphere and Earth" lays the foundation for an interdisciplinary study of the influence of interstellar material on the solar system and Earth as we travel through the Milky Way Galaxy. The solar wind bubble responds dynamically to interstellar material flowing past the Sun, regulating interstellar gas, dust, and cosmic particle fluxes in the interplanetary medium and the Earth. Cones of interstellar gas and dust focused by solar gravity, the ma...

Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

Directory of Open Access Journals (Sweden)

Peter A. Bell

2013-06-01

Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

What Population Reveals about Individual Cell Identity: Single-Cell Parameter Estimation of Models of Gene Expression in Yeast.

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Artémis Llamosi

2016-02-01

Full Text Available Significant cell-to-cell heterogeneity is ubiquitously observed in isogenic cell populations. Consequently, parameters of models of intracellular processes, usually fitted to population-averaged data, should rather be fitted to individual cells to obtain a population of models of similar but non-identical individuals. Here, we propose a quantitative modeling framework that attributes specific parameter values to single cells for a standard model of gene expression. We combine high quality single-cell measurements of the response of yeast cells to repeated hyperosmotic shocks and state-of-the-art statistical inference approaches for mixed-effects models to infer multidimensional parameter distributions describing the population, and then derive specific parameters for individual cells. The analysis of single-cell parameters shows that single-cell identity (e.g. gene expression dynamics, cell size, growth rate, mother-daughter relationships is, at least partially, captured by the parameter values of gene expression models (e.g. rates of transcription, translation and degradation. Our approach shows how to use the rich information contained into longitudinal single-cell data to infer parameters that can faithfully represent single-cell identity.

Multilevel linear modelling of the response-contingent learning of young children with significant developmental delays.

Science.gov (United States)

Raab, Melinda; Dunst, Carl J; Hamby, Deborah W

2018-02-27

The purpose of the study was to isolate the sources of variations in the rates of response-contingent learning among young children with multiple disabilities and significant developmental delays randomly assigned to contrasting types of early childhood intervention. Multilevel, hierarchical linear growth curve modelling was used to analyze four different measures of child response-contingent learning where repeated child learning measures were nested within individual children (Level-1), children were nested within practitioners (Level-2), and practitioners were nested within the contrasting types of intervention (Level-3). Findings showed that sources of variations in rates of child response-contingent learning were associated almost entirely with type of intervention after the variance associated with differences in practitioners nested within groups were accounted for. Rates of child learning were greater among children whose existing behaviour were used as the building blocks for promoting child competence (asset-based practices) compared to children for whom the focus of intervention was promoting child acquisition of missing skills (needs-based practices). The methods of analysis illustrate a practical approach to clustered data analysis and the presentation of results in ways that highlight sources of variations in the rates of response-contingent learning among young children with multiple developmental disabilities and significant developmental delays. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

Science.gov (United States)

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

International Nuclear Information System (INIS)

Teyssedre, G.; Laurent, C.; Vu, T. T. N.

2015-01-01

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10 −14 –10 −13  m 2  V −1  s −1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets

RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance

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Richard J. Bingham

2017-11-01

Full Text Available The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance.

Science.gov (United States)

Bingham, Richard J; Dykeman, Eric C; Twarock, Reidun

2017-11-17

The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

Science.gov (United States)

Teyssedre, G.; Vu, T. T. N.; Laurent, C.

2015-12-01

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30-60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10-14-10-13 m2 V-1 s-1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

relative discriminating powers of gge and ammi models

African Journals Online (AJOL)

Prof. Adipala Ekwamu

were evaluated at ten locations in Nigeria for grain yield and stability. The analysis of variance revealed significant (P < 0.05) GEI effect. ... Stability model of GGE biplot was superior, effective and informative ... Key Words: Glycine max, principal component analysis ... breeding programme in multi-environment trials. (MET).

Transcriptional and physiological data reveal the dehydration memory behavior in switchgrass (Panicum virgatum L.).

Science.gov (United States)

Zhang, Chao; Peng, Xi; Guo, Xiaofeng; Tang, Gaijuan; Sun, Fengli; Liu, Shudong; Xi, Yajun

2018-01-01

Switchgrass ( Panicum virgatum L.) is a model biofuel plant because of its high biomass, cellulose-richness, easy degradation to ethanol, and the availability of extensive genomic information. However, a little is currently known about the molecular responses of switchgrass plants to dehydration stress, especially multiple dehydration stresses. Studies on the transcriptional profiles of 35-day-old tissue culture plants revealed 741 dehydration memory genes. Gene Ontology and pathway analysis showed that these genes were enriched in phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Further analysis of specific pathways combined with physiological data suggested that switchgrass improved its dehydration resistance by changing various aspects of its responses to secondary dehydration stress (D2), including the regulation of abscisic acid (ABA) and jasmonic acid (JA) biosynthesis and signal transduction, the biosynthesis of osmolytes (l-proline, stachyose and trehalose), energy metabolism (i.e., metabolic process relating to photosynthetic systems, glycolysis, and the TCA cycle), and lignin biosynthesis. The transcriptional data and chemical substance assays showed that ABA was significantly accumulated during both primary (D1) and secondary (D2) dehydration stresses, whereas JA accumulated during D1 but became significantly less abundant during D2. This suggests the existence of a complicated signaling network of plant hormones in response to repeated dehydration stresses. A homology analysis focusing on switchgrass, maize, and Arabidopsis revealed the conservation and species-specific distribution of dehydration memory genes. The molecular responses of switchgrass plants to successive dehydration stresses have been systematically characterized, revealing a previously unknown transcriptional memory behavior. These results provide new insights into the mechanisms of dehydration stress responses in plants. The genes and

Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

Science.gov (United States)

Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

2016-03-01

Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux.

Directory of Open Access Journals (Sweden)

Nicola K Petty

2011-04-01

Full Text Available Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC and enterohaemorrhagic E. coli (EHEC and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease.

Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

KAUST Repository

Lovrics, Anna

2014-11-14

We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

Cardiac c-Kit Biology Revealed by Inducible Transgenesis.

Science.gov (United States)

Gude, Natalie A; Firouzi, Fareheh; Broughton, Kathleen M; Ilves, Kelli; Nguyen, Kristine P; Payne, Christina R; Sacchi, Veronica; Monsanto, Megan M; Casillas, Alexandria R; Khalafalla, Farid G; Wang, Bingyan J; Ebeid, David E; Alvarez, Roberto; Dembitsky, Walter P; Bailey, Barbara A; van Berlo, Jop; Sussman, Mark A

2018-06-22

Biological significance of c-Kit as a cardiac stem cell marker and role(s) of c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because of varied and discrepant findings. Alternative experimental models are required to contextualize and reconcile discordant published observations of cardiac c-Kit myocardial biology and provide meaningful insights regarding clinical relevance of c-Kit signaling for translational cell therapy. The main objectives of this study are as follows: demonstrating c-Kit myocardial biology through combined studies of both human and murine cardiac cells; advancing understanding of c-Kit myocardial biology through creation and characterization of a novel, inducible transgenic c-Kit reporter mouse model that overcomes limitations inherent to knock-in reporter models; and providing perspective to reconcile disparate viewpoints on c-Kit biology in the myocardium. In vitro studies confirm a critical role for c-Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit receptor promotes cell survival and proliferation in stem cells and cardiomyocytes of either human or murine origin. For creation of the mouse model, the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line. The combination of c-Kit transgenesis coupled to H2BEGFP readout provides sensitive, specific, inducible, and persistent tracking of c-Kit promoter activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in cardiac tissue from the knock-in model is 55% lower than that from our transgenic line. The c-Kit transgenic reporter model reveals intimate association of c-Kit expression with adult myocardial biology. Both cardiac stem cells and a subpopulation of cardiomyocytes express c-Kit in uninjured adult heart

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales.

Science.gov (United States)

Hummel, Jonathan; Pagkaliwangan, Mark; Gjoka, Xhorxhi; Davidovits, Terence; Stock, Rick; Ransohoff, Thomas; Gantier, Rene; Schofield, Mark

2018-01-17

The biopharmaceutical industry is evolving in response to changing market conditions, including increasing competition and growing pressures to reduce costs. Single-use (SU) technologies and continuous bioprocessing have attracted attention as potential facilitators of cost-optimized manufacturing for monoclonal antibodies. While disposable bioprocessing has been adopted at many scales of manufacturing, continuous bioprocessing has yet to reach the same level of implementation. In this study, the cost of goods of Pall Life Science's integrated, continuous bioprocessing (ICB) platform is modeled, along with that of purification processes in stainless-steel and SU batch formats. All three models include costs associated with downstream processing only. Evaluation of the models across a broad range of clinical and commercial scenarios reveal that the cost savings gained by switching from stainless-steel to SU batch processing are often amplified by continuous operation. The continuous platform exhibits the lowest cost of goods across 78% of all scenarios modeled here, with the SU batch process having the lowest costs in the rest of the cases. The relative savings demonstrated by the continuous process are greatest at the highest feed titers and volumes. These findings indicate that existing and imminent continuous technologies and equipment can become key enablers for more cost effective manufacturing of biopharmaceuticals. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On testing the significance of atmospheric response to smoke from the Kuwaiti oil fires using the Los Alamos general circulation model

Energy Technology Data Exchange (ETDEWEB)

Kao, C.J.; Glatzmaier, G.A.; Malone, R.C. [Los Alamos National Laboratory, Los Alamos, NM (United States)

1994-07-01

The response of the Los Alamos atmospheric general circulation model to the smoke from the Kuwaiti oil fires set in 1991 is examined. The model has an interactive soot transport module that uses a Lagrangian tracer particle scheme. The statistical significance of the results is evaluated using a methodology based on the classic Student`s t test. Among various estimated smoke emission rates and associated visible absorption coefficients, the worst- and best-case scenarios are selected. In each of the scenarios, an ensemble of 10 30-day June simulations are conducted with the smoke and are compared to the same 10 June simulations without the smoke. The results of the worst-case scneario show that a statistically significant wave train pattern propagates eastward-poleward downstream from the source. The signals favorably compare with the observed climate anomalies in summer 1991, albeit some possible El Nino-Southern Oscillation effects were involved in the actual climate. The results of the best-case (i.e., least-impact) scenario show that the significance is rather small but that its general pattern is quite similar to that in the worst-case scenario.

On testing the significance of atmospheric response to smoke from the Kuwaiti oil fires using the Los Alamos general circulation model

Energy Technology Data Exchange (ETDEWEB)

Chih-Yue Jim Kao; Glatzmaier, G.A.; Malone, R.C. [Los Alamos National Lab., NM (United States)

1994-07-20

The response of the Los Alamos atmospheric general circulation model to the smoke from the Kuwaiti oil fires set in 1991 is examined. The model has an interactive soot transport module that uses a Lagrangian tracer particle scheme. The statistical significance of the results is evaluated using a methodology based on the classic Student`s t test. Among various estimated smoke emission rates and associated visible absorption coefficients, the worst- and best-case scenarios are selected. In each of the scenarios, an ensemble of 10, 30-day June simulations are conducted with the smoke, and are compared to the same 10 June simulations without the smoke. The results of the worst-case scenario show that a statistically significant wave train pattern propagates eastward-poleward downstream from the source. The signals favorably compare with the observed climate anomalies in summer 1991, albeit some possible El Nino-Southern Oscillation effects were involved in the actual climate. The results of the best-case (i.e., least-impact) scenario show that the significance is rather small but that its general pattern is quite similar to that in the worst-case scenario. 24 refs., 5 figs.

Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.

Science.gov (United States)

An, X-K; Fang, J; Yu, Z-Z; Lin, Q; Lu, C-X; Qu, H-L; Ma, Q-L

2017-08-01

Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced limonene production in cyanobacteria reveals photosynthesis limitations.

Science.gov (United States)

Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y; Rentzepis, Peter M; Yuan, Joshua S

2016-12-13

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria.

Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

Energy Technology Data Exchange (ETDEWEB)

Rahman, Md. Mostafizar [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Yu, Peiqiang [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

2017-01-31

Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutrition models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.

A more robust model of the biodiesel reaction, allowing identification of process conditions for significantly enhanced rate and water tolerance.

Science.gov (United States)

Eze, Valentine C; Phan, Anh N; Harvey, Adam P

2014-03-01

A more robust kinetic model of base-catalysed transesterification than the conventional reaction scheme has been developed. All the relevant reactions in the base-catalysed transesterification of rapeseed oil (RSO) to fatty acid methyl ester (FAME) were investigated experimentally, and validated numerically in a model implemented using MATLAB. It was found that including the saponification of RSO and FAME side reactions and hydroxide-methoxide equilibrium data explained various effects that are not captured by simpler conventional models. Both the experiment and modelling showed that the "biodiesel reaction" can reach the desired level of conversion (>95%) in less than 2min. Given the right set of conditions, the transesterification can reach over 95% conversion, before the saponification losses become significant. This means that the reaction must be performed in a reactor exhibiting good mixing and good control of residence time, and the reaction mixture must be quenched rapidly as it leaves the reactor. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global terrestrial water storage connectivity revealed using complex climate network analyses

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Sun, A. Y.; Chen, J.; Donges, J.

2015-07-01

Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

Metabolomics Reveals Relationship between Plasma Inositols and Birth Weight: Possible Markers for Fetal Programming of Type 2 Diabetes

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Pia Marlene Nissen

2011-01-01

Full Text Available Epidemiological studies in man and with experimental animal models have shown that intrauterine growth restriction (IUGR resulting in low birth weight is associated with higher risk of programming welfare diseases in later life. In the pig, severe IUGR occurs naturally and contribute substantially to a large intralitter variation in birth weight and may therefore be a good model for man. In the present paper the natural form of IUGR in pigs was studied close to term by nuclear magnetic resonance (NMR-based metabolomics. The NMR-based investigations revealed different metabolic profiles of plasma samples from low-birth weight (LW and high-birth weight (HW piglets, respectively, and differences were assigned to levels of glucose and myo-inositol. Further studies by GC-MS revealed that LW piglets had a significant higher concentration of myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo-inositol and D-chiro-inositol have been coupled with glucose intolerance and insulin resistance in adults, and the present paper therefore suggests that IUGR is related to impaired glucose metabolism during fetal development, which may cause type 2 diabetes in adulthood.

Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

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Masanao Sato

Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

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Camilla Ceccatelli Berti

2015-04-01

Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

Do climate model predictions agree with long-term precipitation trends in the arid southwestern United States?

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Elias, E.; Rango, A.; James, D.; Maxwell, C.; Anderson, J.; Abatzoglou, J. T.

2016-12-01

Researchers evaluating climate projections across southwestern North America observed a decreasing precipitation trend. Aridification was most pronounced in the cold (non-monsoonal) season, whereas downward trends in precipitation were smaller in the warm (monsoonal) season. In this region, based upon a multimodel mean of 20 Coupled Model Intercomparison Project 5 models using a business-as-usual (Representative Concentration Pathway 8.5) trajectory, midcentury precipitation is projected to increase slightly during the monsoonal time period (July-September; 6%) and decrease slightly during the remainder of the year (October-June; -4%). We use observed long-term (1915-2015) monthly precipitation records from 16 weather stations to investigate how well measured trends corroborate climate model predictions during the monsoonal and non-monsoonal timeframe. Running trend analysis using the Mann-Kendall test for 15 to 101 year moving windows reveals that half the stations showed significant (p≤0.1), albeit small, increasing trends based on the longest term record. Trends based on shorter-term records reveal a period of significant precipitation decline at all stations representing the 1950s drought. Trends from 1930 to 2015 reveal significant annual, monsoonal and non-monsoonal increases in precipitation (Fig 1). The 1960 to 2015 time window shows no significant precipitation trends. The more recent time window (1980 to 2015) shows a slight, but not significant, increase in monsoonal precipitation and a larger, significant decline in non-monsoonal precipitation. GCM precipitation projections are consistent with more recent trends for the region. Running trends from the most recent time window (mid-1990s to 2015) at all stations show increasing monsoonal precipitation and decreasing Oct-Jun precipitation, with significant trends at 6 of 16 stations. Running trend analysis revealed that the long-term trends were not persistent throughout the series length, but depended

Seasonal succession in zooplankton feeding traits reveals trophic trait coupling

DEFF Research Database (Denmark)

Kenitz, Kasia; Visser, Andre; Mariani, Patrizio

2017-01-01

non-motile cells flourishing in spring and motile community dominating during summer. The zooplankton community is dominated by active feeding-current feeders with peak biomass in the late spring declining during summer. The model reveals how zooplankton grazing reinforces protist plankton seasonal...

A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton

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Sarah M. Carpanini

2014-06-01

Full Text Available Mutations in RAB18 have been shown to cause the heterogeneous autosomal recessive disorder Warburg Micro syndrome (WARBM. Individuals with WARBM present with a range of clinical symptoms, including ocular and neurological abnormalities. However, the underlying cellular and molecular pathogenesis of the disorder remains unclear, largely owing to the lack of any robust animal models that phenocopy both the ocular and neurological features of the disease. We report here the generation and characterisation of a novel Rab18-mutant mouse model of WARBM. Rab18-mutant mice are viable and fertile. They present with congenital nuclear cataracts and atonic pupils, recapitulating the characteristic ocular features that are associated with WARBM. Additionally, Rab18-mutant cells exhibit an increase in lipid droplet size following treatment with oleic acid. Lipid droplet abnormalities are a characteristic feature of cells taken from WARBM individuals, as well as cells taken from individuals with other neurodegenerative conditions. Neurological dysfunction is also apparent in Rab18-mutant mice, including progressive weakness of the hind limbs. We show that the neurological defects are, most likely, not caused by gross perturbations in synaptic vesicle recycling in the central or peripheral nervous system. Rather, loss of Rab18 is associated with widespread disruption of the neuronal cytoskeleton, including abnormal accumulations of neurofilament and microtubule proteins in synaptic terminals, and gross disorganisation of the cytoskeleton in peripheral nerves. Global proteomic profiling of peripheral nerves in Rab18-mutant mice reveals significant alterations in several core molecular pathways that regulate cytoskeletal dynamics in neurons. The apparent similarities between the WARBM phenotype and the phenotype that we describe here indicate that the Rab18-mutant mouse provides an important platform for investigation of the disease pathogenesis and therapeutic

A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton.

Science.gov (United States)

Carpanini, Sarah M; McKie, Lisa; Thomson, Derek; Wright, Ann K; Gordon, Sarah L; Roche, Sarah L; Handley, Mark T; Morrison, Harris; Brownstein, David; Wishart, Thomas M; Cousin, Michael A; Gillingwater, Thomas H; Aligianis, Irene A; Jackson, Ian J

2014-06-01

Mutations in RAB18 have been shown to cause the heterogeneous autosomal recessive disorder Warburg Micro syndrome (WARBM). Individuals with WARBM present with a range of clinical symptoms, including ocular and neurological abnormalities. However, the underlying cellular and molecular pathogenesis of the disorder remains unclear, largely owing to the lack of any robust animal models that phenocopy both the ocular and neurological features of the disease. We report here the generation and characterisation of a novel Rab18-mutant mouse model of WARBM. Rab18-mutant mice are viable and fertile. They present with congenital nuclear cataracts and atonic pupils, recapitulating the characteristic ocular features that are associated with WARBM. Additionally, Rab18-mutant cells exhibit an increase in lipid droplet size following treatment with oleic acid. Lipid droplet abnormalities are a characteristic feature of cells taken from WARBM individuals, as well as cells taken from individuals with other neurodegenerative conditions. Neurological dysfunction is also apparent in Rab18-mutant mice, including progressive weakness of the hind limbs. We show that the neurological defects are, most likely, not caused by gross perturbations in synaptic vesicle recycling in the central or peripheral nervous system. Rather, loss of Rab18 is associated with widespread disruption of the neuronal cytoskeleton, including abnormal accumulations of neurofilament and microtubule proteins in synaptic terminals, and gross disorganisation of the cytoskeleton in peripheral nerves. Global proteomic profiling of peripheral nerves in Rab18-mutant mice reveals significant alterations in several core molecular pathways that regulate cytoskeletal dynamics in neurons. The apparent similarities between the WARBM phenotype and the phenotype that we describe here indicate that the Rab18-mutant mouse provides an important platform for investigation of the disease pathogenesis and therapeutic interventions. �

Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

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Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

2016-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.

Elucidating the significance of spatial memory on movement decisions by African savannah elephants using state-space models.

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Polansky, Leo; Kilian, Werner; Wittemyer, George

2015-04-22

Spatial memory facilitates resource acquisition where resources are patchy, but how it influences movement behaviour of wide-ranging species remains to be resolved. We examined African elephant spatial memory reflected in movement decisions regarding access to perennial waterholes. State-space models of movement data revealed a rapid, highly directional movement behaviour almost exclusively associated with visiting perennial water. Behavioural change point (BCP) analyses demonstrated that these goal-oriented movements were initiated on average 4.59 km, and up to 49.97 km, from the visited waterhole, with the closest waterhole accessed 90% of the time. Distances of decision points increased when switching to different waterholes, during the dry season, or for female groups relative to males, while selection of the closest waterhole decreased when switching. Overall, our analyses indicated detailed spatial knowledge over large scales, enabling elephants to minimize travel distance through highly directional movement when accessing water. We discuss the likely cognitive and socioecological mechanisms driving these spatially precise movements that are most consistent with our findings. By applying modern analytic techniques to high-resolution movement data, this study illustrates emerging approaches for studying how cognition structures animal movement behaviour in different ecological and social contexts. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

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Staines, Katherine A; Javaheri, Behzad; Hohenstein, Peter; Fleming, Robert; Ikpegbu, Ekele; Unger, Erin; Hopkinson, Mark; Buttle, David J; Pitsillides, Andrew A; Farquharson, Colin

2017-11-01

The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn flox/flox (cKO) mice and their Pdpn flox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope.

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Art F Y Poon

2007-11-01

Full Text Available The third variable loop (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1 that founder effects in the evolutionary history of the sequences can be ignored, and; (2 that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%-40%. Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to

Mechanistic species distribution modeling reveals a niche shift during invasion.

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Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

2017-06-01

Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma

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Liu NQ

2015-03-01

Full Text Available Naiqing Liu,1,2,* Jingyu Zhang,2,* Shuxiang Sun,2 Liguang Yang,2 Zhongjin Zhou,2 Qinli Sun,2 Jun Niu11Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, Yishui Central Hospital, Linyi, People’s Republic of China*These authors contributed equally to this workBackground: The clinical significance of fibroblast growth factor 1 (FGF1 has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored.Patients and methods: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan–Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma.Results: Higher FGF1 expression rate is 56.7% (101/178 in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001. Expression of FGF1 is significantly associated with lymph node invasion (P<0.001, distant metastasis (P=0.013, and differentiation (P=0.015. Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021, and can be identified to be an independent unfavorable prognostic factor (P=0.004.Conclusion: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.Keywords: fibroblast growth factor 1, gastric adenocarcinoma, prognosis, biomarker, lymph node, gene fusion

The In Vitro Mass-Produced Model Mycorrhizal Fungus, Rhizophagus irregularis, Significantly Increases Yields of the Globally Important Food Security Crop Cassava

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Ceballos, Isabel; Ruiz, Michael; Fernández, Cristhian; Peña, Ricardo

2013-01-01

The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future. PMID:23950975

The in vitro mass-produced model mycorrhizal fungus, Rhizophagus irregularis, significantly increases yields of the globally important food security crop cassava.

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Isabel Ceballos

Full Text Available The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF and plant roots. The fungi provide the plant with inorganic phosphate (P. The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.

Hidden Markov model analysis reveals the advantage of analytic eye movement patterns in face recognition across cultures.

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Chuk, Tim; Crookes, Kate; Hayward, William G; Chan, Antoni B; Hsiao, Janet H

2017-12-01

It remains controversial whether culture modulates eye movement behavior in face recognition. Inconsistent results have been reported regarding whether cultural differences in eye movement patterns exist, whether these differences affect recognition performance, and whether participants use similar eye movement patterns when viewing faces from different ethnicities. These inconsistencies may be due to substantial individual differences in eye movement patterns within a cultural group. Here we addressed this issue by conducting individual-level eye movement data analysis using hidden Markov models (HMMs). Each individual's eye movements were modeled with an HMM. We clustered the individual HMMs according to their similarities and discovered three common patterns in both Asian and Caucasian participants: holistic (looking mostly at the face center), left-eye-biased analytic (looking mostly at the two individual eyes in addition to the face center with a slight bias to the left eye), and right-eye-based analytic (looking mostly at the right eye in addition to the face center). The frequency of participants adopting the three patterns did not differ significantly between Asians and Caucasians, suggesting little modulation from culture. Significantly more participants (75%) showed similar eye movement patterns when viewing own- and other-race faces than different patterns. Most importantly, participants with left-eye-biased analytic patterns performed significantly better than those using either holistic or right-eye-biased analytic patterns. These results suggest that active retrieval of facial feature information through an analytic eye movement pattern may be optimal for face recognition regardless of culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of ethylene responses by OsRTH1 overexpression reveals the biological significance of ethylene in rice seedling growth and development

Science.gov (United States)

Zhang, Wei; Zhou, Xin; Wen, Chi-Kuang

2012-01-01

Overexpression of Arabidopsis Reversion-To-ethylene Sensitivity1 (RTE1) results in whole-plant ethylene insensitivity dependent on the ethylene receptor gene Ethylene Response1 (ETR1). However, overexpression of the tomato RTE1 homologue Green Ripe (GR) delays fruit ripening but does not confer whole-plant ethylene insensitivity. It was decided to investigate whether aspects of ethylene-induced growth and development of the monocotyledonous model plant rice could be modulated by rice RTE1 homologues (OsRTH genes). Results from a cross-species complementation test in Arabidopsis showed that OsRTH1 overexpression complemented the rte1-2 loss-of-function mutation and conferred whole-plant ethylene insensitivity in an ETR1-dependent manner. In contrast, OsRTH2 and OsRTH3 overexpression did not complement rte1-2 or confer ethylene insensitivity. In rice, OsRTH1 overexpression substantially prevented ethylene-induced alterations in growth and development, including leaf senescence, seedling leaf elongation and development, coleoptile elongation or curvature, and adventitious root development. Results of subcellular localizations of OsRTHs, each fused with the green fluorescent protein, in onion epidermal cells suggested that the three OsRTHs were predominantly localized to the Golgi. OsRTH1 may be an RTE1 orthologue of rice and modulate rice ethylene responses. The possible roles of auxins and gibberellins in the ethylene-induced alterations in growth were evaluated and the biological significance of ethylene in the early stage of rice seedling growth is discussed. PMID:22451723

Seismic tomography model reveals mantle magma sources of recent volcanic activity at El Hierro Island (Canary Islands, Spain)

Science.gov (United States)

García-Yeguas, Araceli; Ibáñez, Jesús M.; Koulakov, Ivan; Jakovlev, Andrey; Romero-Ruiz, M. Carmen; Prudencio, Janire

2014-12-01

We present a 3-D model of P and S velocities beneath El Hierro Island, constructed using the traveltime data of more than 13 000 local earthquakes recorded by the Instituto Geográfico Nacional (IGN, Spain) in the period from 2011 July to 2012 September. The velocity models were performed using the LOTOS code for iterative passive source tomography. The results of inversion were thoroughly verified using different resolution and robustness tests. The results reveal that the majority of the onshore area of El Hierro is associated with a high-velocity anomaly observed down to 10-12-km depth. This anomaly is interpreted as the accumulation of solid igneous rocks erupted during the last 1 Myr and intrusive magmatic bodies. Below this high-velocity pattern, we observe a low-velocity anomaly, interpreted as a batch of magma coming from the mantle located beneath El Hierro. The boundary between the low- and high-velocity anomalies is marked by a prominent seismicity cluster, thought to represent anomalous stresses due to the interaction of the batch of magma with crust material. The areas of recent eruptions, Orchilla and La Restinga, are associated with low-velocity anomalies surrounding the main high-velocity block. These eruptions took place around the island where the crust is much weaker than the onshore area and where the melted material cannot penetrate. These results put constraints on the geological model that could explain the origin of the volcanism in oceanic islands, such as in the Canaries, which is not yet clearly understood.

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

Energy Technology Data Exchange (ETDEWEB)

Teyssedre, G., E-mail: gilbert.teyssedre@laplace.univ-tlse.fr; Laurent, C. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); CNRS, LAPLACE, F-31062 Toulouse (France); Vu, T. T. N. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); Electric Power University, 235 Hoang Quoc Viet, 10000 Hanoi (Viet Nam)

2015-12-21

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10{sup −14}–10{sup −13} m{sup 2} V{sup −1} s{sup −1} for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery.

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Savage, Lisa M; Hall, Joseph M; Resende, Leticia S

2012-06-01

Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.

Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

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Matthew J. Birket

2015-10-01

Full Text Available Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC model of hypertrophic cardiomyopathy (HCM. A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

THRESHOLD OF SIGNIFICANCE IN STRESS MANAGEMENT

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Elena RUSE

2015-12-01

Full Text Available Stress management is the individual's ability to handle any situation, external conditions, to match the demands of the external environment. The researchers revealed several stages in the stress response. A first phase was called ‘‘alert reaction'' or ‘‘immediate reaction to stress‘‘, phase in which there are physiological modifications and manifestations that occur under psychological aspect. Adaptation phase is the phase in which the reactions from the first phase diminishes or disappears. Exhaustion phase is related to the diversity of stress factors and time and may exceed the resources of the human body to adapt. Influencing factors may be: limited, cognitive, perceptual, and a priori. But there is a threshold of significance in stress management. Once the reaction to external stimuli occurs, awareness is needed. The capability effect occurs, any side effect goes away and comes out the ''I AM'' effect.

Participatory Water Resources Modeling in a Water-Scarce Basin (Rio Sonora, Mexico) Reveals Uncertainty in Decision-Making

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Mayer, A. S.; Vivoni, E. R.; Halvorsen, K. E.; Kossak, D.

2014-12-01

The Rio Sonora Basin (RSB) in northwest Mexico has a semi-arid and highly variable climate along with urban and agricultural pressures on water resources. Three participatory modeling workshops were held in the RSB in spring 2013. A model of the water resources system, consisting of a watershed hydrology model, a model of the water infrastructure, and groundwater models, was developed deliberatively in the workshops, along with scenarios of future climate and development. Participants were asked to design water resources management strategies by choosing from a range of supply augmentation and demand reduction measures associated with water conservation. Participants assessed water supply reliability, measured as the average daily supply divided by daily demand for historical and future periods, by probing with the climate and development scenarios. Pre- and post-workshop-surveys were developed and administered, based on conceptual models of workshop participants' beliefs regarding modeling and local water resources. The survey results indicate that participants believed their modeling abilities increased and beliefs in the utility of models increased as a result of the workshops. The selected water resources strategies varied widely among participants. Wastewater reuse for industry and aquifer recharge were popular options, but significant numbers of participants thought that inter-basin transfers and desalination were viable. The majority of participants indicated that substantial increases in agricultural water efficiency could be achieved. On average, participants chose strategies that produce reliabilities over the historical and future periods of 95%, but more than 20% of participants were apparently satisfied with reliabilities lower than 80%. The wide range of strategies chosen and associated reliabilities indicate that there is a substantial degree of uncertainty in how future water resources decisions could be made in the region.

Prognostic factors in advanced breast cancer: Race and receptor status are significant after development of metastasis.

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Ren, Zhiyong; Li, Yufeng; Shen, Tiansheng; Hameed, Omar; Siegal, Gene P; Wei, Shi

2016-01-01

Prognostic factors are well established in early-stage breast cancer (BC), but less well-defined in advanced disease. We analyzed 323 BC patients who had distant relapse during follow-up from 1997 to 2010 to determine the significant clinicopathologic factors predicting survival outcomes. By univariate analysis, race, tumor grade, estrogen and progesterone receptors (ER/PR) and HER2 status were significantly associated with overall survival (OS) and post-metastasis survival (PMS). Applying a Cox regression model revealed that all these factors remained significant for PMS, while race, tumor grade and HER2 were independent factors for OS. Tumor grade was the only significant factor for metastasis-free survival by univariate and multivariate analyses. Our findings demonstrated that being Caucasian, hormonal receptor positive (HR+) and HER2 positive (HER2+) were all associated with a decreased hazard of death and that patients with HR+/HER2+ tumors had superior outcomes to those with HR+/HER2- disease. Further, PR status held a prognostic value over ER, thus reflecting the biologic mechanism of the importance of the functional ER pathway and the heterogeneity in the response to endocrine therapy. These observations indicate that the patients' genetic makeup and the intrinsic nature of the tumor principally govern BC progression and prognosticate the long-term outcomes in advanced disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

Master stability functions reveal diffusion-driven pattern formation in networks

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Brechtel, Andreas; Gramlich, Philipp; Ritterskamp, Daniel; Drossel, Barbara; Gross, Thilo

2018-03-01

We study diffusion-driven pattern formation in networks of networks, a class of multilayer systems, where different layers have the same topology, but different internal dynamics. Agents are assumed to disperse within a layer by undergoing random walks, while they can be created or destroyed by reactions between or within a layer. We show that the stability of homogeneous steady states can be analyzed with a master stability function approach that reveals a deep analogy between pattern formation in networks and pattern formation in continuous space. For illustration, we consider a generalized model of ecological meta-food webs. This fairly complex model describes the dispersal of many different species across a region consisting of a network of individual habitats while subject to realistic, nonlinear predator-prey interactions. In this example, the method reveals the intricate dependence of the dynamics on the spatial structure. The ability of the proposed approach to deal with this fairly complex system highlights it as a promising tool for ecology and other applications.

Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

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Mahavadi, Poornima; Sasikumar, Satish; Cushing, Leah; Hyland, Tessa; Rosser, Ann E.; Riccardi, Daniela; Lu, Jining; Kalin, Tanya V.; Kalinichenko, Vladimir V.; Guenther, Andreas; Ramirez, Maria I.; Pardo, Annie; Selman, Moisés; Warburton, David

2013-01-01

Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity. PMID:24375798

Qualitative ubiquitome unveils the potential significances of protein lysine ubiquitination in hyphal growth of Aspergillus nidulans.

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Chu, Xin-Ling; Feng, Ming-Guang; Ying, Sheng-Hua

2016-02-01

Protein ubiquitination is an evolutionarily conserved post-translational modification process in eukaryotes, and it plays an important role in many biological processes. Aspergillus nidulans, a model filamentous fungus, contributes to our understanding of cellular physiology, metabolism and genetics, but its ubiquitination is not completely revealed. In this study, the ubiquitination sites in the proteome of A. nidulans were identified using a highly sensitive mass spectrometry combined with immuno-affinity enrichment of the ubiquitinated peptides. The 4816 ubiquitination sites were identified in 1913 ubiquitinated proteins, accounting for 18.1% of total proteins in A. nidulans. Bioinformatic analysis suggested that the ubiquitinated proteins associated with a number of biological functions and displayed various sub-cellular localisations. Meanwhile, seven motifs were revealed from the ubiquitinated peptides, and significantly over-presented in the different pathways. Comparison of the enriched functional catalogues indicated that the ubiquitination functions divergently during growth of A. nidulans and Saccharomyces cerevisiae. Additionally, the proteins in A. nidulans-specific sub-category (cell growth/morphogenesis) were subjected to the protein interaction analysis which demonstrated that ubiquitination is involved in the comprehensive protein interactions. This study presents a first proteomic view of ubiquitination in the filamentous fungus, and provides an initial framework for exploring the physiological roles of ubiquitination in A. nidulans.

The significance of the choice of radiobiological (NTCP) models in treatment plan objective functions

International Nuclear Information System (INIS)

Miller, J.; Fuller, M.; Vinod, S.; Holloway, L.

2009-01-01

Full text: A Clinician's discrimination between radiation therapy treatment plans is traditionally a subjective process, based on experience and existing protocols. A more objective and quantitative approach to distinguish between treatment plans is to use radiobiological or dosimetric objective functions, based on radiobiological or dosimetric models. The efficacy of models is not well understood, nor is the correlation of the rank of plans resulting from the use of models compared to the traditional subjective approach. One such radiobiological model is the Normal Tissue Complication Probability (NTCP). Dosimetric models or indicators are more accepted in clinical practice. In this study, three radiobiological models, Lyman NTCP, critical volume NTCP and relative seriality NTCP, and three dosimetric models, Mean Lung Dose (MLD) and the Lung volumes irradiated at lOGy (V|0) and 20 G y (V20), were used to rank a series of treatment plans using, harm to normal (Lung) tissue as the objective criterion. None of the models considered in this study showed consistent correlation with the Radiation Oncologists plan ranking. If radiobiological or dosimetric models are to be used in objective functions for lung treatments, based on this study it is recommended that the Lyman NTCP model be used because it will provide most consistency with traditional clinician ranking.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

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Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

Science.gov (United States)

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

Science.gov (United States)

Hoover, Malachia; Adamian, Yvess; Brown, Mark; Maawy, Ali; Chang, Alexander; Lee, Jacqueline; Gharibi, Armen; Katz, Matthew H; Fleming, Jason; Hoffman, Robert M; Bouvet, Michael; Doebler, Robert; Kelber, Jonathan A

2017-01-24

Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies.

MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.

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Hoye, Mariah L; Koval, Erica D; Wegener, Amy J; Hyman, Theodore S; Yang, Chengran; O'Brien, David R; Miller, Rebecca L; Cole, Tracy; Schoch, Kathleen M; Shen, Tao; Kunikata, Tomonori; Richard, Jean-Philippe; Gutmann, David H; Maragakis, Nicholas J; Kordasiewicz, Holly B; Dougherty, Joseph D; Miller, Timothy M

2017-05-31

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease

The new galaxy evolution paradigm revealed by the Herschel surveys

Science.gov (United States)

Eales, Stephen; Smith, Dan; Bourne, Nathan; Loveday, Jon; Rowlands, Kate; van der Werf, Paul; Driver, Simon; Dunne, Loretta; Dye, Simon; Furlanetto, Cristina; Ivison, R. J.; Maddox, Steve; Robotham, Aaron; Smith, Matthew W. L.; Taylor, Edward N.; Valiante, Elisabetta; Wright, Angus; Cigan, Philip; De Zotti, Gianfranco; Jarvis, Matt J.; Marchetti, Lucia; Michałowski, Michał J.; Phillipps, Steven; Viaene, Sebastien; Vlahakis, Catherine

2018-01-01

The Herschel Space Observatory has revealed a very different galaxyscape from that shown by optical surveys which presents a challenge for galaxy-evolution models. The Herschel surveys reveal (1) that there was rapid galaxy evolution in the very recent past and (2) that galaxies lie on a single Galaxy Sequence (GS) rather than a star-forming 'main sequence' and a separate region of 'passive' or 'red-and-dead' galaxies. The form of the GS is now clearer because far-infrared surveys such as the Herschel ATLAS pick up a population of optically red star-forming galaxies that would have been classified as passive using most optical criteria. The space-density of this population is at least as high as the traditional star-forming population. By stacking spectra of H-ATLAS galaxies over the redshift range 0.001 high stellar masses, high star-formation rates but, even several billion years in the past, old stellar populations - they are thus likely to be relatively recent ancestors of early-type galaxies in the Universe today. The form of the GS is inconsistent with rapid quenching models and neither the analytic bathtub model nor the hydrodynamical EAGLE simulation can reproduce the rapid cosmic evolution. We propose a new gentler model of galaxy evolution that can explain the new Herschel results and other key properties of the galaxy population.

Ecological succession reveals potential signatures of marine-terrestrial transition in salt marsh fungal communities.

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Dini-Andreote, Francisco; Pylro, Victor Satler; Baldrian, Petr; van Elsas, Jan Dirk; Salles, Joana Falcão

2016-08-01

Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in β-diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal β-diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem.

An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II.

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Sonia Chelouah

Full Text Available F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II. The antitumor activity of F14512 in human tumor models is significantly higher than that of other epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the demonstrated superiority of F14512 over other Topo II poisons might not result solely from its preferential uptake by cancer cells, but could also be due to unique effects on Topo II interactions with DNA. To further dissect the mechanism of action of F14512, we used Drosophila melanogaster mutants whose genetic background leads to an easily scored phenotype that is sensitive to changes in Topo II activity and/or localization. F14512 has antiproliferative properties in Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique sites located in moderately repeated sequences, suggesting that the drug specifically targets a select and limited subset of genomic sequences. Feeding F14512 to developing mutant Drosophila larvae led to the recovery of flies expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a first thoracic segment. Other recovered F14512-induced gain- and loss-of-function phenotypes similarly correspond to precise genetic dysfunctions. These complex in vivo results obtained in a whole developing organism can be reconciled with known genetic anomalies and constitute a remarkable instance of specific alterations of gene expression by ingestion of a drug. "Drosophila-based anticancer pharmacology" hence reveals unique properties for F14512, demonstrating the usefulness of an assay system that provides a low-cost, rapid and effective complement to mammalian models and permits the elucidation of fundamental mechanisms of

Fourier decomposition of spatial localization errors reveals an idiotropic dominance of an internal model of gravity.

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De Sá Teixeira, Nuno Alexandre

2014-12-01

Given its conspicuous nature, gravity has been acknowledged by several research lines as a prime factor in structuring the spatial perception of one's environment. One such line of enquiry has focused on errors in spatial localization aimed at the vanishing location of moving objects - it has been systematically reported that humans mislocalize spatial positions forward, in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, spatial localization errors were found to evolve dynamically with time in a pattern congruent with an anticipated trajectory (representational trajectory). The present study attempts to ascertain the degree to which vestibular information plays a role in these phenomena. Human observers performed a spatial localization task while tilted to varying degrees and referring to the vanishing locations of targets moving along several directions. A Fourier decomposition of the obtained spatial localization errors revealed that although spatial errors were increased "downward" mainly along the body's longitudinal axis (idiotropic dominance), the degree of misalignment between the latter and physical gravity modulated the time course of the localization responses. This pattern is surmised to reflect increased uncertainty about the internal model when faced with conflicting cues regarding the perceived "downward" direction.

Comparative metatranscriptomics reveals decline of a neustonic planktonic population

KAUST Repository

Mojib, Nazia; Thimma, Manjula; Kumaran, M.; Sougrat, Rachid; Irigoien, Xabier

2016-01-01

The neuston layer in tropical seas provides a good model to study the effects of increased levels of different stressors (e.g., temperature, ultraviolet radiation and Trichodesmium blooms). Here, we use a comparative in situ metatranscriptomics approach to reveal the functional genomic composition of metabolically active neustonic mesozooplankton community in response to the summer conditions in the Red Sea. The neustonic population exhibited changes in composition and abundance with a significant decline in copepods and appendicularia in July, when Trichodesmium cells were more abundant along with high temperatures and UV-B radiation. Nearly 23,000 genes were differentially expressed at the community level when the metatranscriptomes of the neustonic zooplankton were compared in April, July, and October. On a wider Phylum level, the genes related to oxidative phosphorylation, carbon, nucleotides, amino acids, and lipids were significantly overrepresented in both arthropods and chordates in April and October. On organism level for copepods, expression of genes responsive to oxidative stress, defense against bacteria, immune response, and virus reproduction were increased along with the observed increased appearance of copepod carcasses in the samples collected during July. The differences in expression correspond either to secondary effects of the Trichodesmium bloom or more likely to the increased UV-B radiation in July. Given the dearth of information on the zooplankton gene expression in response to environmental stimuli, our study provides the first transcriptome landscape of the mesozooplankton community during a period of increased mortality of the copepod and appendicularia population.

Comparative metatranscriptomics reveals decline of a neustonic planktonic population

KAUST Repository

Mojib, Nazia

2016-10-20

The neuston layer in tropical seas provides a good model to study the effects of increased levels of different stressors (e.g., temperature, ultraviolet radiation and Trichodesmium blooms). Here, we use a comparative in situ metatranscriptomics approach to reveal the functional genomic composition of metabolically active neustonic mesozooplankton community in response to the summer conditions in the Red Sea. The neustonic population exhibited changes in composition and abundance with a significant decline in copepods and appendicularia in July, when Trichodesmium cells were more abundant along with high temperatures and UV-B radiation. Nearly 23,000 genes were differentially expressed at the community level when the metatranscriptomes of the neustonic zooplankton were compared in April, July, and October. On a wider Phylum level, the genes related to oxidative phosphorylation, carbon, nucleotides, amino acids, and lipids were significantly overrepresented in both arthropods and chordates in April and October. On organism level for copepods, expression of genes responsive to oxidative stress, defense against bacteria, immune response, and virus reproduction were increased along with the observed increased appearance of copepod carcasses in the samples collected during July. The differences in expression correspond either to secondary effects of the Trichodesmium bloom or more likely to the increased UV-B radiation in July. Given the dearth of information on the zooplankton gene expression in response to environmental stimuli, our study provides the first transcriptome landscape of the mesozooplankton community during a period of increased mortality of the copepod and appendicularia population.

Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

International Nuclear Information System (INIS)

Niu Tingxian; Shi Zhiyong; Luo Jianjun

2009-01-01

Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

Corruption Significantly Increases the Capital Cost of Power Plants in Developing Contexts

Directory of Open Access Journals (Sweden)

Kumar Biswajit Debnath

2018-03-01

Full Text Available Emerging economies with rapidly growing population and energy demand, own some of the most expensive power plants in the world. We hypothesized that corruption has a relationship with the capital cost of power plants in developing countries such as Bangladesh. For this study, we analyzed the capital cost of 61 operational and planned power plants in Bangladesh. Initial comparison study revealed that the mean capital cost of a power plant in Bangladesh is twice than that of the global average. Then, the statistical analysis revealed a significant correlation between corruption and the cost of power plants, indicating that higher corruption leads to greater capital cost. The high up-front cost can be a significant burden on the economy, at present and in the future, as most are financed through international loans with extended repayment terms. There is, therefore, an urgent need for the review of the procurement and due diligence process of establishing power plants, and for the implementation of a more transparent system to mitigate adverse effects of corruption on megaprojects.

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

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Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Impact of lifetime model selections on the reliability prediction of IGBT modules in modular multilevel converters

DEFF Research Database (Denmark)

Zhang, Yi; Wang, Huai; Wang, Zhongxu

2017-01-01

, this paper benchmarks the most commonly-employed lifetime models of power semiconductor devices for offshore Modular Multilevel Converters (MMC) based wind farms. The benchmarking reveals that the lifetime model selection has a significant impact on the lifetime estimation. The use of analytical lifetime...

Modeling, Analysis, and Control of a Hypersonic Vehicle with Significant Aero-Thermo-Elastic-Propulsion Interactions: Elastic, Thermal and Mass Uncertainty

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Khatri, Jaidev

This thesis examines themodeling, analysis, and control system design issues for scramjet powered hypersonic vehicles. A nonlinear three degrees of freedom longitudinal model which includes aero-propulsion-elasticity effects was used for all analyses. This model is based upon classical compressible flow and Euler-Bernouli structural concepts. Higher fidelity computational fluid dynamics and finite element methods are needed for more precise intermediate and final evaluations. The methods presented within this thesis were shown to be useful for guiding initial control relevant design. The model was used to examine the vehicle's static and dynamic characteristics over the vehicle's trimmable region. The vehicle has significant longitudinal coupling between the fuel equivalency ratio (FER) and the flight path angle (FPA). For control system design, a two-input two-output plant (FER - elevator to speed-FPA) with 11 states (including 3 flexible modes) was used. Velocity, FPA, and pitch were assumed to be available for feedback. Aerodynamic heat modeling and design for the assumed TPS was incorporated to original Bolender's model to study the change in static and dynamic properties. De-centralized control stability, feasibility and limitations issues were dealt with the change in TPS elasticity, mass and physical dimension. The impact of elasticity due to TPS mass, TPS physical dimension as well as prolonged heating was also analyzed to understand performance limitations of de-centralized control designed for nominal model.

Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

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Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

2017-01-01

Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

Site-directed mutagenesis under the direction of in silico protein docking modeling reveals the active site residues of 3-ketosteroid-Δ1-dehydrogenase from Mycobacterium neoaurum.

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Qin, Ning; Shen, Yanbing; Yang, Xu; Su, Liqiu; Tang, Rui; Li, Wei; Wang, Min

2017-07-01

3-Ketosteroid-Δ 1 -dehydrogenases (KsdD) from Mycobacterium neoaurum could transform androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione. This reaction has a significant effect on the product of pharmaceutical steroid. The crystal structure and active site residues information of KsdD from Mycobacterium is not yet available, which result in the engineering of KsdD is tedious. In this study, by the way of protein modeling and site-directed mutagenesis, we find that, Y122, Y125, S138, E140 and Y541 from the FAD-binding domain and Y365 from the catalytic domain play a key role in this transformation. Compared with the wild type, the decline in AD conversion for mutants illustrated that Y125, Y365, and Y541 were essential to the function of KsdD. Y122, S138 and E140 contributed to the catalysis of KsdD. The following analysis revealed the catalysis mechanism of these mutations in KsdD of Mycobacterium. These information presented here facilitate the manipulation of the catalytic properties of the enzyme to improve its application in the pharmaceutical steroid industry.

Source model and Coulomb stress change of 2017 Mw 6.5 Philippine (Ormoc) Earthquake revealed by SAR interferometry

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Tsai, M. C.; Hu, J. C.; Yang, Y. H.; Hashimoto, M.; Aurelio, M.; Su, Z.; Escudero, J. A.

2017-12-01

Multi-sight and high spatial resolution interferometric SAR data enhances our ability for mapping detailed coseismic deformation to estimate fault rupture model and to infer the Coulomb stress change associated with a big earthquake. Here, we use multi-sight coseismic interferograms acquired by ALOS-2 and Sentinel-1A satellites to estimate the fault geometry and slip distribution on the fault plane of the 2017 Mw 6.5 Ormoc Earthquake in Leyte island of Philippine. The best fitting model predicts that the coseismic rupture occurs along a fault plane with strike of 325.8º and dip of 78.5ºE. This model infers that the rupture of 2017 Ormoc earthquake is dominated by left-lateral slip with minor dip-slip motion, consistent with the left-lateral strike-slip Philippine fault system. The fault tip has propagated to the ground surface, and the predicted coseismic slip on the surface is about 1 m located at 6.5 km Northeast of Kananga city. Significant slip is concentrated on the fault patches at depth of 0-8 km and an along-strike distance of 20 km with varying slip magnitude from 0.3 m to 2.3 m along the southwest segment of this seismogenic fault. Two minor coseismic fault patches are predicted underneath of the Tononan geothermal field and the creeping segment of the northwest portion of this seismogenic fault. This implies that the high geothermal gradient underneath of the Tongonan geothermal filed could prevent heated rock mass from the coseismic failure. The seismic moment release of our preferred fault model is 7.78×1018 Nm, equivalent to Mw 6.6 event. The Coulomb failure stress (CFS) calculated by the preferred fault model predicts significant positive CFS change on the northwest segment of the Philippine fault in Leyte Island which has coseismic slip deficit and is absent from aftershocks. Consequently, this segment should be considered to have increasing of risk for future seismic hazard.

Tax Policy Trends: Republicans Reveal Proposed Tax Overhaul

Directory of Open Access Journals (Sweden)

Philip Bazel

2017-10-01

Full Text Available REPUBLICANS REVEAL PROPOSED TAX OVERHAUL The White House and Congressional Republicans have revealed their much-anticipated proposal for reform of the U.S. personal and corporate tax systems. The proposal titled, “UNIFIED FRAMEWORK FOR FIXING OUR BROKEN TAX CODE” outlines a number of central policy changes, which will significantly alter the U.S. corporate tax system. The proposal includes a top federal marginal rate reduction for the sole proprietorships, partnerships and S corporation—small business equivalents— from 39.6% to 25% (state income tax rates would no longer be deductible. Large corporations would also see a meaningful federal rate reduction given the proposed drop in the federal corporate income tax rate from 35% to 20%. Additionally, the proposal includes a generous temporary measure intended to stimulate investment, full capital expensing for machinery with a partial limitation of interest deductions.

Innovations in individual feature history management - The significance of feature-based temporal model

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Choi, J.; Seong, J.C.; Kim, B.; Usery, E.L.

2008-01-01

A feature relies on three dimensions (space, theme, and time) for its representation. Even though spatiotemporal models have been proposed, they have principally focused on the spatial changes of a feature. In this paper, a feature-based temporal model is proposed to represent the changes of both space and theme independently. The proposed model modifies the ISO's temporal schema and adds new explicit temporal relationship structure that stores temporal topological relationship with the ISO's temporal primitives of a feature in order to keep track feature history. The explicit temporal relationship can enhance query performance on feature history by removing topological comparison during query process. Further, a prototype system has been developed to test a proposed feature-based temporal model by querying land parcel history in Athens, Georgia. The result of temporal query on individual feature history shows the efficiency of the explicit temporal relationship structure. ?? Springer Science+Business Media, LLC 2007.

Metal and Isotope Analysis of Bird Feathers in a Contaminated Estuary Reveals Bioaccumulation, Biomagnification, and Potential Toxic Effects.

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Einoder, L D; MacLeod, C K; Coughanowr, C

2018-07-01

The Derwent estuary, in south east Tasmania, is highly contaminated with heavy metals, mainly due to past industrial pollution. This study sought to determine the extent of contamination, bioaccumulation, and biomagnification in the resident bird community and therefore to infer the potential for adverse effects in birds. Thirteen metals were measured from breast feathers (n = 51 individuals) of eight sympatric species of aquatic bird. Stable carbon (δ 13 C) and nitrogen (δ 15 N) isotopes were used to identify dietary sources of contaminants, trophic level, and potential biomagnification through food chains. Generalised linear models revealed that metal burdens were often poorly correlated with δ 13 C, indicating their uptake from a range of freshwater, brackish, and marine carbon sources-not surprising due to widespread contamination across the tidal estuary. Feather mercury increased significantly with trophic level (inferred from δ 15 N). White-bellied Sea-eagle Haliaeetus leucogaster samples contained 240 times more mercury than feral Goose Anser cygnoides. Feather arsenic and copper concentrations were significantly higher in birds feeding lower in the food chain. For several piscivorous species, both chick and adults were sampled revealing significantly higher feather mercury, zinc, and selenium in adults. Feathers from birds found dead along the banks of the estuary had significantly higher lead loads than from live birds, and numerous individuals had levels of mercury, zinc, and lead above toxic thresholds reported in other studies. These results highlight the need to include biota from higher trophic levels in contaminant monitoring programs to understand fully the fate and broader implications of contaminants in the environment.

Clinical significance of perceptible fetal motion.

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Rayburn, W F

1980-09-15

The monitoring of fetal activity during the last trimester of pregnancy has been proposed to be useful in assessing fetal welfare. The maternal perception of fetal activity was tested among 82 patients using real-time ultrasonography. All perceived fetal movements were visualized on the scanner and involved motion of the lower limbs. Conversely, 82% of all visualized motions of fetal limbs were perceived by the patients. All combined motions of fetal trunk with limbs were preceived by the patients and described as strong movements, whereas clusters of isolated, weak motions of the fetal limbs were less accurately perceived (56% accuracy). The number of fetal movements perceived during the 15-minute test period was significantly (p fetal motion was present (44 of 45 cases) than when it was absent (five of 10 cases). These findings reveal that perceived fetal motion is: (1) reliable; (2) related to the strength of lower limb motion; (3) increased with ruptured amniotic membranes; and (4) reassuring if considered to be active.

Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

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Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-07

Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

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Dominik Schreiber

2017-08-01

Full Text Available Inflammatory bowel diseases (IBD, which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml, TNF-α (10 ng/ml, and IL-1β (5 ng/ml. Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

Ensenanzas en un gimnasio: an investigation of modeling and verbal rehearsal on the motor performance of Hispanic limited English proficient children.

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Meaney, K S; Edwards, R

1996-03-01

This study investigated the effects of modeling and verbal rehearsal on the motor performance of English-speaking and limited English proficient (LEP) children. Children (N = 64) in 4th-grade classes were randomly assigned to conditions in a 2 x 2 x 2 x 2 (Gender x Primary Language x Model Type x Rehearsal) factorial design. Boys and girls whose primary language was English or Spanish were assigned to either a verbal model or no-model condition as well as to a verbal rehearsal or no-rehearsal condition of the motor skills required to be performed. Analysis of variance revealed a significant Model Type x Primary Language interaction as well as a significant Rehearsal x Primary Language interaction. Follow-up analyses revealed that English-speaking children provided with a verbal rehearsal strategy recalled significantly more skills than English-speaking children in the no-rehearsal condition; for LEP children, there were no differences due to rehearsal. Moreover, LEP children presented with a verbal model recalled significantly more skills than LEP children in the no-model condition; for English-speaking children, there were no differences attributed to model type. These results indicate that effective modeling conditions that are provided with verbal cues in English are related to children's primary language.

Predator-prey interaction reveals local effects of high-altitude insect migration

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High-altitude nocturnal insect migrations represent significant pulses of resources, yet are difficult to study and poorly understood. Predator-prey interactions, specifically migratory moth consumption by high-flying bats, potentially reveal flows of migratory insects across a landscape. In North...

Sensitivity of fluvial sediment source apportionment to mixing model assumptions: A Bayesian model comparison.

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Cooper, Richard J; Krueger, Tobias; Hiscock, Kevin M; Rawlins, Barry G

2014-11-01

Mixing models have become increasingly common tools for apportioning fluvial sediment load to various sediment sources across catchments using a wide variety of Bayesian and frequentist modeling approaches. In this study, we demonstrate how different model setups can impact upon resulting source apportionment estimates in a Bayesian framework via a one-factor-at-a-time (OFAT) sensitivity analysis. We formulate 13 versions of a mixing model, each with different error assumptions and model structural choices, and apply them to sediment geochemistry data from the River Blackwater, Norfolk, UK, to apportion suspended particulate matter (SPM) contributions from three sources (arable topsoils, road verges, and subsurface material) under base flow conditions between August 2012 and August 2013. Whilst all 13 models estimate subsurface sources to be the largest contributor of SPM (median ∼76%), comparison of apportionment estimates reveal varying degrees of sensitivity to changing priors, inclusion of covariance terms, incorporation of time-variant distributions, and methods of proportion characterization. We also demonstrate differences in apportionment results between a full and an empirical Bayesian setup, and between a Bayesian and a frequentist optimization approach. This OFAT sensitivity analysis reveals that mixing model structural choices and error assumptions can significantly impact upon sediment source apportionment results, with estimated median contributions in this study varying by up to 21% between model versions. Users of mixing models are therefore strongly advised to carefully consider and justify their choice of model structure prior to conducting sediment source apportionment investigations. An OFAT sensitivity analysis of sediment fingerprinting mixing models is conductedBayesian models display high sensitivity to error assumptions and structural choicesSource apportionment results differ between Bayesian and frequentist approaches.

Mechanistic issues for modeling radiation-induced segregation

International Nuclear Information System (INIS)

Simonen, E.P.; Bruemmer, S.M.

1993-03-01

Model calculations of radiation-induced chromium depletion and radiation-induced nickel enrichment at grain boundaries are compared to measured depletions and enrichments. The model is calibrated to fit chromium depletion in commercial purity 304 stainless steel irradiated in boiling water reactor (BWR) environments. Predicted chromium depletion profiles and the dose dependence of chromium concentration at grain boundaries are in accord with measured trends. Evaluation of chromium and nickel profiles in three neutron, and two ion, irradiation environments reveal significant inconsistencies between measurements and predictions

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

Institute of Scientific and Technical Information of China (English)

Cuiping Yang; Changchun Cai; Xiaojin Yang; Yanping Yang; Zhigang Zhou; Jianhua Liu; Heping Ye; Hongjiao Wan

2012-01-01

An experimental model of schizophrenia was established using dizocilpine (MK-801). Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease.

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Matthias Hübenthal

Full Text Available The diagnosis of inflammatory bowel disease (IBD still remains a clinical challenge and the most accurate diagnostic procedure is a combination of clinical tests including invasive endoscopy. In this study we evaluated whether systematic miRNA expression profiling, in conjunction with machine learning techniques, is suitable as a non-invasive test for the major IBD phenotypes (Crohn's disease (CD and ulcerative colitis (UC. Based on microarray technology, expression levels of 863 miRNAs were determined for whole blood samples from 40 CD and 36 UC patients and compared to data from 38 healthy controls (HC. To further discriminate between disease-specific and general inflammation we included miRNA expression data from other inflammatory diseases (inflammation controls (IC: 24 chronic obstructive pulmonary disease (COPD, 23 multiple sclerosis, 38 pancreatitis and 45 sarcoidosis cases as well as 70 healthy controls from previous studies. Classification problems considering 2, 3 or 4 groups were solved using different types of penalized support vector machines (SVMs. The resulting models were assessed regarding sparsity and performance and a subset was selected for further investigation. Measured by the area under the ROC curve (AUC the corresponding median holdout-validated accuracy was estimated as ranging from 0.75 to 1.00 (including IC and 0.89 to 0.98 (excluding IC, respectively. In combination, the corresponding models provide tools for the distinction of CD and UC as well as CD, UC and HC with expected classification error rates of 3.1 and 3.3%, respectively. These results were obtained by incorporating not more than 16 distinct miRNAs. Validated target genes of these miRNAs have been previously described as being related to IBD. For others we observed significant enrichment for IBD susceptibility loci identified in earlier GWAS. These results suggest that the proposed miRNA signature is of relevance for the etiology of IBD. Its diagnostic

Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer.

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Niu, Yanyang; Li, Fang; Tang, Bo; Shi, Yan; Hao, Yingxue; Yu, Peiwu

2014-01-01

This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.

Neural correlates reveal sub-lexical orthography and phonology during reading aloud: A review

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Kalinka eTimmer

2014-08-01

Full Text Available The sub-lexical conversion of graphemes-to-phonemes (GPC during reading has been investigated extensively with behavioral measures, as well as event-related potentials (ERPs. Most research utilizes silent reading (e.g., lexical decision task for which phonological activation is not a necessity. However, recent research employed reading aloud to capture sub-lexical GPC. The masked priming paradigm avoids strategic processing and is therefore well suitable for capturing sub-lexical processing instead of lexical effects. By employing ERPs, the on-line time course of sub-lexical GPC can be observed before the overt response. ERPs have revealed that besides phonological activation, as revealed by behavioral studies, there is also early orthographic activation. This review describes studies in one’s native language, in one’s second language, and in a cross-language situation. We discuss the implications the ERP results have on different (computational models. First, the ERP results show that computational models should assume an early locus of the grapheme-to-phoneme-conversion (GPC. Second, cross-language studies reveal that the phonological representations from both languages of a bilingual become activated automatically and the phonology belonging to the context is selected rapidly. Therefore, it is important to extend the scope of computational models of reading (aloud to multiple lexicons.

The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP): Overview and Description of Models, Simulations and Climate Diagnostics

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Lamarque, J.-F.; Shindell, D. T.; Naik, V.; Plummer, D.; Josse, B.; Righi, M.; Rumbold, S. T.; Schulz, M.; Skeie, R. B.; Strode, S.;

Hedgehog pathway activity in the LADY prostate tumor model

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Kasper Susan

2007-03-01

Full Text Available Abstract Background Robust Hedgehog (Hh signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined. Results We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin. Conclusion Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.

Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model

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Celli, Jonathan P.; Rizvi, Imran; Evans, Conor L.; Abu-Yousif, Adnan O.; Hasan, Tayyaba

2010-09-01

Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with increasing mean size. At day 10, cultures are treated with either carboplatin or photodynamic therapy (PDT). We quantify size-dependent cytotoxic response for each treatment on a nodule by nodule basis using automated segmentation combined with ratiometric batch-processing of calcein and ethidium bromide fluorescence intensity data (indicating live and dead cells, respectively). Both treatments reduce viability, though carboplatin leaves micronodules largely structurally intact with a size distribution similar to untreated cultures. In contrast, PDT treatment disrupts micronodular structure, causing punctate regions of toxicity, shifting the distribution toward smaller sizes, and potentially increasing vulnerability to subsequent chemotherapeutic treatment.

Deeper Insight into the Diels-Alder Reaction through the Activation Strain Model

NARCIS (Netherlands)

Fernandez, I.; Bickelhaupt, F.M.

2016-01-01

The Diels–Alder (DA) cycloaddition reaction has the ability to significantly increase molecular complexity regioselectively and stereospecifically in a single synthetic step. In this review it is discussed how the activation strain model of chemical reactivity reveals the physical factors that

Communication Games Reveal Preparation Contextuality

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Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

2017-12-01

A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug

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Mamidala Praveen

2012-01-01

Full Text Available Abstract Background Bed bugs (Cimex lectularius are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. Results We performed a next-generation RNA sequencing (RNA-Seq experiment to find differentially expressed genes between pesticide-resistant (PR and pesticide-susceptible (PS strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs and our previous 454 pyrosequenced database (21,088 ESTs. The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2 revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. Conclusions We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide

Inspiration and Intellect: Significant Learning in Musical Forms and Analysis

Science.gov (United States)

Kelley, Bruce C.

2009-01-01

In his book "Creating Significant Learning Experiences" (2003), Dee Fink challenges professors to create a deep vision for the courses they teach. Educators often have a vision for what their courses could be, but often lack a model for instituting change. Fink's book provides that model. In this article, the author describes how this model helped…

MRI and morphological observation in C6 glioma model rats and significance

International Nuclear Information System (INIS)

Zhou Ying; Yuan Bo; Wang Hao; Lu Jin; Yuan Changji; Ma Yue; Tong Dan; Zhang Kun; Gao Feng; Wu Xiaogang

2013-01-01

Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×10 6 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

Optimization of rootkit revealing system resources – A game theoretic approach

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K. Muthumanickam

2015-10-01

Full Text Available Malicious rootkit is a collection of programs designed with the intent of infecting and monitoring the victim computer without the user’s permission. After the victim has been compromised, the remote attacker can easily cause further damage. In order to infect, compromise and monitor, rootkits adopt Native Application Programming Interface (API hooking technique. To reveal the hidden rootkits, current rootkit detection techniques check different data structures which hold reference to Native APIs. To verify these data structures, a large amount of system resources are required. This is because of the number of APIs in these data structures being quite large. Game theoretic approach is a useful mathematical tool to simulate network attacks. In this paper, a mathematical model is framed to optimize resource consumption using game-theory. To the best of our knowledge, this is the first work to be proposed for optimizing resource consumption while revealing rootkit presence using game theory. Non-cooperative game model is taken to discuss the problem. Analysis and simulation results show that our game theoretic model can effectively reduce the resource consumption by selectively monitoring the number of APIs in windows platform.

Significant genetic differentiation within the population of the Island of Corsica (France) revealed by y-chromosome analysis.

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Ghiani, Maria Elena; Varesi, Laurent; Mitchell, Robert John; Vona, Giuseppe

2009-12-01

Using 10 Y-chromosome short tandem repeat allelic and haplotypic frequencies, we examined genetic variation within the population of Corsica and its relationship with other Mediterranean populations. The most significant finding is the high level of genetic differentiation within Corsica, with strong evidence of an effective barrier to male-mediated gene flow between the south and the rest of the island. This internal differentiation most probably results from low exogamy among small isolated populations and also from the orography of the island, with a central mountain chain running the length of the island restricting human movement. This physical barrier is reflected not only in present-day intraisland linguistic and genetic differences but also in the relatedness of Corsican regions to other Mediterranean groups. Northwest and Central Corsica are much closer to West Mediterranean populations, whereas South Corsica is closer to Central-North Sardinia and East Mediterranean populations.

Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

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Abhijeet Kapoor

Full Text Available Human dopamine β-hydroxylase (DBH is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering.Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function.The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and

Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

Science.gov (United States)

Kapoor, Abhijeet; Shandilya, Manish; Kundu, Suman

2011-01-01

Human dopamine β-hydroxylase (DBH) is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs) have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering. Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function. The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and provides

[Severe pulmonary embolism revealed by status epilepticus].

Science.gov (United States)

Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J

2016-12-01

High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Genetic Algorithm Based Microscale Vehicle Emissions Modelling

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Sicong Zhu

2015-01-01

Full Text Available There is a need to match emission estimations accuracy with the outputs of transport models. The overall error rate in long-term traffic forecasts resulting from strategic transport models is likely to be significant. Microsimulation models, whilst high-resolution in nature, may have similar measurement errors if they use the outputs of strategic models to obtain traffic demand predictions. At the microlevel, this paper discusses the limitations of existing emissions estimation approaches. Emission models for predicting emission pollutants other than CO2 are proposed. A genetic algorithm approach is adopted to select the predicting variables for the black box model. The approach is capable of solving combinatorial optimization problems. Overall, the emission prediction results reveal that the proposed new models outperform conventional equations in terms of accuracy and robustness.

Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer

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Ling XL

2015-06-01

Full Text Available Xiao-Ling Ling,* Tao Zhang,* Xiao-Ming Hou, Da Zhao Department of Oncology, The First Hospital of Lanzhou University (The Branch Hospital of Donggang, Lanzhou, Gansu Province, People’s Republic of China *These authors contributed equally to this work Purpose: Fascin-1 promotes the formation of filopodia, lamellipodia, and microspikes of cell membrane after its cross-linking with F-actin, thereby enhancing the cell movement and metastasis and invasion of tumor cells. This study explored the fascin-1 protein’s expression in non-small cell lung cancer (NSCLC tissues and its relationship with clinical pathology and prognostic indicators.Methods: Immunohistochemical analysis was used to determine the expression of fascin-1 in NSCLC tissues. We used quantitative real-time polymerase chain reaction and western blot analysis to further verify the results. The fascin-1 expression and statistical method for clinical pathological parameters are examined by χ2. Kaplan–Meier method is used for survival analysis. Cox’s Proportional Hazard Model was used to conduct a combined-effect analysis for each covariate.Results: In 73 of the 128 cases, NSCLC cancer tissues (57.0% were found with high expression of fascin-1, which was significantly higher than the adjacent tissues (35/128, 27.3%. The results suggested that the high expression of fascin-1 was significantly correlated with lymph node metastasis (P=0.022 and TNM stage (P=0.042. The high fascin-1 expression patients survived shorter than those NSCLC patients with low fascin-1 expression (P<0.05. Univariate analysis revealed that lymph node metastasis, TNM stage, and fascin-1 expression status were correlated with the overall survival. Similarly, lymph node metastasis, TNM stage, and fascin-1 expression status were significantly associated with the overall survival in multivariate analyses by using the Cox regression model.Conclusion: The fascin-1 protein may be a useful prognostic indicator and

Revealing transboundary and local air pollutant sources affecting Metro Manila through receptor modeling studies

International Nuclear Information System (INIS)

Pabroa, Preciosa Corazon B.; Bautista VII, Angel T.; Santos, Flora L.; Racho, Joseph Michael D.

2011-01-01

Ambient fine particulate matter (PM 2 .5) levels at the Metro Manila air sampling stations of the Philippine Nuclear Research Research Institute were found to be above the WHO guideline value of 10 μg m 3 indicating, in general, very poor air quality in the area. The elemental components of the fine particulate matter were obtained using the energy-dispersive x-ray fluorescence spectrometry. Positive matrix factorization, a receptor modelling tool, was used to identify and apportion air pollution sources. Location of probable transboundary air pollutants were evaluated using HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) while location of probable local air pollutant sources were determined using the conditional probability function (CPF). Air pollutant sources can either be natural or anthropogenic. This study has shown natural air pollutant sources such as volcanic eruptions from Bulusan volcano in 2006 and from Anatahan volcano in 2005 to have impacted on the region. Fine soils was shown to have originated from China's Mu US Desert some time in 2004. Smoke in the fine fraction in 2006 show indications of coming from forest fires in Sumatra and Borneo. Fine particulate Pb in Valenzuela was shown to be coming from the surrounding area. Many more significant air pollution impacts can be evaluated with the identification of probable air pollutant sources with the use of elemental fingerprints and locating these sources with the use of HYSPLIT and CPF. (author)

DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

International Nuclear Information System (INIS)

Yang, Jun; Wang, Yuwei; Leconte, Jérémy; Forget, François; Wolf, Eric T.; Goldblatt, Colin; Feldl, Nicole; Merlis, Timothy; Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S.

2016-01-01

An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m 2 ; differences in shortwave reach up to 60 W m 2 , especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m 2 in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

Energy Technology Data Exchange (ETDEWEB)

Yang, Jun; Wang, Yuwei [Department of Atmospheric and Oceanic Sciences, School of Physics, Peking University, Beijing (China); Leconte, Jérémy; Forget, François [Laboratoire de Météorologie Dynamique, Institut Pierre Simon Laplace, CNRS, Paris (France); Wolf, Eric T. [Laboratory for Atmospheric and Space Physics, University of Colorado in Boulder, CO (United States); Goldblatt, Colin [School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada); Feldl, Nicole [Division of Geological and Planetary Sciences, California Institute of Technology, CA (United States); Merlis, Timothy [Department of Atmospheric and Oceanic Sciences at McGill University, Montréal (Canada); Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S., E-mail: junyang@pku.edu.cn, E-mail: abbot@uchicago.edu [Department of the Geophysical Sciences, University of Chicago, Chicago, IL (United States)

2016-08-01

An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m{sup 2}; differences in shortwave reach up to 60 W m{sup 2}, especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m{sup 2} in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

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Karin Voordeckers

2015-11-01

Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

Combined effects of climate models, hydrological model structures and land use scenarios on hydrological impacts of climate change

DEFF Research Database (Denmark)

Karlsson, Ida B.; Sonnenborg, Torben O.; Refsgaard, Jens Christian

2016-01-01

Impact studies of the hydrological response of future climate change are important for the water authorities when risk assessment, management and adaptation to a changing climate are carried out. The objective of this study was to model the combined effect of land use and climate changes...... use scenarios. The results revealed that even though the hydrological models all showed similar performance during calibration, the mean discharge response to climate change varied up to 30%, and the variations were even higher for extreme events (1th and 99th percentile). Land use changes appeared...... to cause little change in mean hydrological responses and little variation between hydrological models. Differences in hydrological model responses to land use were, however, significant for extremes due to dissimilarities in hydrological model structure and process equations. The climate model choice...

Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

DEFF Research Database (Denmark)

Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana

2008-01-01

Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p...... penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML.......42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete...

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

Commensurate comparisons of models with energy budget observations reveal consistent climate sensitivities

Science.gov (United States)

Armour, K.

2017-12-01

Global energy budget observations have been widely used to constrain the effective, or instantaneous climate sensitivity (ICS), producing median estimates around 2°C (Otto et al. 2013; Lewis & Curry 2015). A key question is whether the comprehensive climate models used to project future warming are consistent with these energy budget estimates of ICS. Yet, performing such comparisons has proven challenging. Within models, values of ICS robustly vary over time, as surface temperature patterns evolve with transient warming, and are generally smaller than the values of equilibrium climate sensitivity (ECS). Naively comparing values of ECS in CMIP5 models (median of about 3.4°C) to observation-based values of ICS has led to the suggestion that models are overly sensitive. This apparent discrepancy can partially be resolved by (i) comparing observation-based values of ICS to model values of ICS relevant for historical warming (Armour 2017; Proistosescu & Huybers 2017); (ii) taking into account the "efficacies" of non-CO2 radiative forcing agents (Marvel et al. 2015); and (iii) accounting for the sparseness of historical temperature observations and differences in sea-surface temperature and near-surface air temperature over the oceans (Richardson et al. 2016). Another potential source of discrepancy is a mismatch between observed and simulated surface temperature patterns over recent decades, due to either natural variability or model deficiencies in simulating historical warming patterns. The nature of the mismatch is such that simulated patterns can lead to more positive radiative feedbacks (higher ICS) relative to those engendered by observed patterns. The magnitude of this effect has not yet been addressed. Here we outline an approach to perform fully commensurate comparisons of climate models with global energy budget observations that take all of the above effects into account. We find that when apples-to-apples comparisons are made, values of ICS in models are

The Comparative Study of Collaborative Learning and SDLC Model to develop IT Group Projects

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Sorapak Pukdesree

2017-11-01

Full Text Available The main objectives of this research were to compare the attitudes of learners between applying SDLC model with collaborative learning and typical SDLC model and to develop electronic courseware as group projects. The research was a quasi-experimental research. The populations of the research were students who took Computer Organization and Architecture course in the academic year 2015. There were 38 students who participated to the research. The participants were divided voluntary into two groups including an experimental group with 28 students using SDLC model with collaborative learning and a control group with 10 students using typical SDLC model. The research instruments were attitude questionnaire, semi-structured interview and self-assessment questionnaire. The collected data was analysed by arithmetic mean, standard deviation, and independent sample t-test. The results of the questionnaire revealed that the attitudes of the learners using collaborative learning and SDLC model were statistically significant difference between the mean score for experimental group and control group at a significance level of 0.05. The independent statistical analyses were significantly different between the two groups at a significance level of 0.05. The results of the interviewing revealed that most of the learners had the corresponding opinions that collaborative learning was very useful with highest level of their attitudes comparing with the previous methodology. Learners had left some feedbacks that collaborative learning should be applied to other courses.

Levels of Interaction Provided by Online Distance Education Models

Science.gov (United States)

Alhih, Mohammed; Ossiannilsson, Ebba; Berigel, Muhammet

2017-01-01

Interaction plays a significant role to foster usability and quality in online education. It is one of the quality standard to reveal the evidence of practice in online distance education models. This research study aims to evaluate levels of interaction in the practices of distance education centres. It is aimed to provide online distance…

Polynomial regression analysis and significance test of the regression function

International Nuclear Information System (INIS)

Gao Zhengming; Zhao Juan; He Shengping

2012-01-01

In order to analyze the decay heating power of a certain radioactive isotope per kilogram with polynomial regression method, the paper firstly demonstrated the broad usage of polynomial function and deduced its parameters with ordinary least squares estimate. Then significance test method of polynomial regression function is derived considering the similarity between the polynomial regression model and the multivariable linear regression model. Finally, polynomial regression analysis and significance test of the polynomial function are done to the decay heating power of the iso tope per kilogram in accord with the authors' real work. (authors)

Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

Science.gov (United States)

Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

2012-01-01

Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

MOTORCYCLE CRASH PREDICTION MODEL FOR NON-SIGNALIZED INTERSECTIONS

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S. HARNEN

2003-01-01

Full Text Available This paper attempts to develop a prediction model for motorcycle crashes at non-signalized intersections on urban roads in Malaysia. The Generalized Linear Modeling approach was used to develop the model. The final model revealed that an increase in motorcycle and non-motorcycle flows entering an intersection is associated with an increase in motorcycle crashes. Non-motorcycle flow on major road had the greatest effect on the probability of motorcycle crashes. Approach speed, lane width, number of lanes, shoulder width and land use were also found to be significant in explaining motorcycle crashes. The model should assist traffic engineers to decide the need for appropriate intersection treatment that specifically designed for non-exclusive motorcycle lane facilities.

Breast Cancer Epidemiology of the Working-Age Female Population Reveals Significant Implications for the South Korean Economy.

Science.gov (United States)

Park, Jeong Hyun; Lee, Se Kyung; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin; Kim, Ji-Yeon; Ahn, Jin-Seok; Park, Won; Yu, Jonghan; Park, Yeon Hee

2018-03-01

In this study, we aimed to evaluate the economic loss due to the diagnosis of breast cancer within the female South Korean working-age population. A population-based cost analysis was performed for cancer-related diagnoses between 1999 and 2014, using respective public government funded databases. Among the five most common cancers, breast cancer mortality was strongly associated with the growth in gross domestic product between 1999 and 2014 (R=0.98). In the female population, breast cancer represented the greatest productivity loss among all cancers, which was a consequence of the peak in the incidence of breast cancer during mid-working age in the working-age population, in addition to being the most common and fastest growing cancer among South Korean women. Our study shows that breast cancer not only represents a significant disease burden for individual patients, but also contributes a real, nonnegligible loss in productivity in the South Korean economy.

Observations and operational model simulations reveal the impact of Hurricane Matthew (2016) on the Gulf Stream and coastal sea level

Science.gov (United States)

Ezer, Tal; Atkinson, Larry P.; Tuleya, Robert

2017-12-01

In October 7-9, 2016, Hurricane Matthew moved along the southeastern coast of the U.S., causing major flooding and significant damage, even to locations farther north well away from the storm's winds. Various observations, such as tide gauge data, cable measurements of the Florida Current (FC) transport, satellite altimeter data and high-frequency radar data, were analyzed to evaluate the impact of the storm. The data show a dramatic decline in the FC flow and increased coastal sea level along the U.S. coast. Weakening of the Gulf Stream (GS) downstream from the storm's area contributed to high coastal sea levels farther north. Analyses of simulations of an operational hurricane-ocean coupled model reveal the disruption that the hurricane caused to the GS flow, including a decline in transport of ∼20 Sv (1 Sv = 106 m3 s-1). In comparison, the observed FC reached a maximum transport of ∼40 Sv before the storm on September 10 and a minimum of ∼20 Sv after the storm on October 12. The hurricane impacts both the geostrophic part of the GS and the wind-driven currents, generating inertial oscillations with velocities of up to ±1 m s-1. Analysis of the observed FC transport since 1982 indicated that the magnitude of the current weakening in October 2016 was quite rare (outside 3 standard deviations from the mean). Such a large FC weakening in the past occurred more often in October and November, but is extremely rare in June-August. Similar impacts on the FC from past tropical storms and hurricanes suggest that storms may contribute to seasonal and interannual variations in the FC. The results also demonstrated the extended range of coastal impacts that remote storms can cause through their influence on ocean currents.

Spatial models reveal the microclimatic buffering capacity of old-growth forests.

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Frey, Sarah J K; Hadley, Adam S; Johnson, Sherri L; Schulze, Mark; Jones, Julia A; Betts, Matthew G

2016-04-01

Climate change is predicted to cause widespread declines in biodiversity, but these predictions are derived from coarse-resolution climate models applied at global scales. Such models lack the capacity to incorporate microclimate variability, which is critical to biodiversity microrefugia. In forested montane regions, microclimate is thought to be influenced by combined effects of elevation, microtopography, and vegetation, but their relative effects at fine spatial scales are poorly known. We used boosted regression trees to model the spatial distribution of fine-scale, under-canopy air temperatures in mountainous terrain. Spatial models predicted observed independent test data well (r = 0.87). As expected, elevation strongly predicted temperatures, but vegetation and microtopography also exerted critical effects. Old-growth vegetation characteristics, measured using LiDAR (light detection and ranging), appeared to have an insulating effect; maximum spring monthly temperatures decreased by 2.5°C across the observed gradient in old-growth structure. These cooling effects across a gradient in forest structure are of similar magnitude to 50-year forecasts of the Intergovernmental Panel on Climate Change and therefore have the potential to mitigate climate warming at local scales. Management strategies to conserve old-growth characteristics and to curb current rates of primary forest loss could maintain microrefugia, enhancing biodiversity persistence in mountainous systems under climate warming.

Gemtuzumab Ozogamicin (GO Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia

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Cathy C Zhang

2018-01-01

Full Text Available Gemtuzumab ozogamicin (GO is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML. Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs. Herein, we use cell line and patient-derived xenograft (PDX AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34. In vivo, the two chemoresistant subpopulations (CLL1+/CD117− and CD34+/CD38+ showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs.

GeoSciML v3.0 - a significant upgrade of the CGI-IUGS geoscience data model

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Raymond, O.; Duclaux, G.; Boisvert, E.; Cipolloni, C.; Cox, S.; Laxton, J.; Letourneau, F.; Richard, S.; Ritchie, A.; Sen, M.; Serrano, J.-J.; Simons, B.; Vuollo, J.

2012-04-01

GeoSciML version 3.0 (http://www.geosciml.org), released in late 2011, is the latest version of the CGI-IUGS* Interoperability Working Group geoscience data interchange standard. The new version is a significant upgrade and refactoring of GeoSciML v2 which was released in 2008. GeoSciML v3 has already been adopted by several major international interoperability initiatives, including OneGeology, the EU INSPIRE program, and the US Geoscience Information Network, as their standard data exchange format for geoscience data. GeoSciML v3 makes use of recently upgraded versions of several Open Geospatial Consortium (OGC) and ISO data transfer standards, including GML v3.2, SWE Common v2.0, and Observations and Measurements v2 (ISO 19156). The GeoSciML v3 data model has been refactored from a single large application schema with many packages, into a number of smaller, but related, application schema modules with individual namespaces. This refactoring allows the use and future development of modules of GeoSciML (eg; GeologicUnit, GeologicStructure, GeologicAge, Borehole) in smaller, more manageable units. As a result of this refactoring and the integration with new OGC and ISO standards, GeoSciML v3 is not backwardly compatible with previous GeoSciML versions. The scope of GeoSciML has been extended in version 3.0 to include new models for geomorphological data (a Geomorphology application schema), and for geological specimens, geochronological interpretations, and metadata for geochemical and geochronological analyses (a LaboratoryAnalysis-Specimen application schema). In addition, there is better support for borehole data, and the PhysicalProperties model now supports a wider range of petrophysical measurements. The previously used CGI_Value data type has been superseded in favour of externally governed data types provided by OGC's SWE Common v2 and GML v3.2 data standards. The GeoSciML v3 release includes worked examples of best practice in delivering geochemical

Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.

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Le Roy, Caroline Ivanne; Passey, Jade Louise; Woodward, Martin John; La Ragione, Roberto Marcello; Claus, Sandrine Paule

2017-06-01

Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1 H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro bioassays reveal that additives are significant contributors to the toxicity of commercial household pesticides.

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van de Merwe, Jason P; Neale, Peta A; Melvin, Steven D; Leusch, Frederic D L

2018-06-01

Pesticides commonly used around households can contain additives of unknown concentrations and toxicity. Given the likelihood of these chemicals washing into urban waterways, it is important to understand the effects that these additives may have on aquatic organisms. The aim of this study was to compare the toxicity of commercially available household pesticides to that of the active ingredient(s) alone. The toxicity of five household pesticides (three herbicides and two insecticides) was investigated using a bacterial cytotoxicity bioassay and an algal photosynthesis bioassay. The commercial products were up to an order of magnitude more toxic than the active ingredient(s) alone. In addition, two commercial products with the same listed active ingredients in the same ratio had a 600× difference in potency. These results clearly demonstrate that additives in commercial formulations are significant contributors to the toxicity of household pesticides. The toxicity of pesticides in aquatic systems is therefore likely underestimated by conventional chemical monitoring and risk assessment when only the active ingredients are considered. Regulators and customers should require more clarity from pesticide manufacturers about the nature and concentrations of not only the active ingredients, but also additives used in commercial formulations. In addition, monitoring programmes and chemical risk assessments schemes should develop a structured approach to assessing the toxic effects of commercial formulations, including additives, rather than simply those of the listed active ingredients. Copyright © 2018. Published by Elsevier B.V.

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

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Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

2016-03-01

Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

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Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

2015-01-01

Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

Increasing the statistical significance of entanglement detection in experiments

Energy Technology Data Exchange (ETDEWEB)

Jungnitsch, Bastian; Niekamp, Soenke; Kleinmann, Matthias; Guehne, Otfried [Institut fuer Quantenoptik und Quanteninformation, Innsbruck (Austria); Lu, He; Gao, Wei-Bo; Chen, Zeng-Bing [Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei (China); Chen, Yu-Ao; Pan, Jian-Wei [Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei (China); Physikalisches Institut, Universitaet Heidelberg (Germany)

2010-07-01

Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. We show this to be the case for an error model in which the variance of an observable is interpreted as its error and for the standard error model in photonic experiments. Specifically, we demonstrate that the Mermin inequality yields a Bell test which is statistically more significant than the Ardehali inequality in the case of a photonic four-qubit state that is close to a GHZ state. Experimentally, we observe this phenomenon in a four-photon experiment, testing the above inequalities for different levels of noise.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering

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Mehanathan eMuthamilarasan

2015-11-01

Full Text Available Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl, callose (Gsl and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2 and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering.

Science.gov (United States)

Muthamilarasan, Mehanathan; Khan, Yusuf; Jaishankar, Jananee; Shweta, Shweta; Lata, Charu; Prasad, Manoj

2015-01-01

Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si) is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl), callose (Gsl) and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD) and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2, and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Four not six: Revealing culturally common facial expressions of emotion.

Science.gov (United States)

Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

2016-06-01

As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells

International Nuclear Information System (INIS)

Askmyr, M; Ågerstam, H; Lilljebjörn, H; Hansen, N; Karlsson, C; Palffy, S von; Landberg, N; Högberg, C; Lassen, C; Rissler, M; Richter, J; Ehinger, M; Järås, M; Fioretos, T

2014-01-01

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34 + cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML

Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

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Jian-Ping Zhou

Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

The performance of FLake in the Met Office Unified Model

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Gabriel Gerard Rooney

2013-12-01

Full Text Available We present results from the coupling of FLake to the Met Office Unified Model (MetUM. The coupling and initialisation are first described, and the results of testing the coupled model in local and global model configurations are presented. These show that FLake has a small statistical impact on screen temperature, but has the potential to modify the weather in the vicinity of areas of significant inland water. Examination of FLake lake ice has revealed that the behaviour of lakes in the coupled model is unrealistic in some areas of significant sub-grid orography. Tests of various modifications to ameliorate this behaviour are presented. The results indicate which of the possible model changes best improve the annual cycle of lake ice. As FLake has been developed and tuned entirely outside the Unified Model system, these results can be interpreted as a useful objective measure of the performance of the Unified Model in terms of its near-surface characteristics.

The Ambulatory Integration of the Medical and Social (AIMS) model: A retrospective evaluation.

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Rowe, Jeannine M; Rizzo, Victoria M; Shier Kricke, Gayle; Krajci, Kate; Rodriguez-Morales, Grisel; Newman, Michelle; Golden, Robyn

2016-01-01

An exploratory, retrospective evaluation of Ambulatory Integration of the Medical and Social (AIMS), a care coordination model designed to integrate medical and non-medical needs of patients and delivered exclusively by social workers was conducted to examine mean utilization of costly health care services for older adult patients. Results reveal mean utilization of 30-day hospital readmissions, emergency department (ED) visits, and hospital admissions are significantly lower for the study sample compared to the larger patient population. Comparisons with national population statistics reveal significantly lower mean utilization of 30-day admissions and ED visits for the study sample. The findings offer preliminary support regarding the value of AIMS.

Climate model biases in seasonality of continental water storage revealed by satellite gravimetry

Science.gov (United States)

Swenson, Sean; Milly, P.C.D.

2006-01-01

Satellite gravimetric observations of monthly changes in continental water storage are compared with outputs from five climate models. All models qualitatively reproduce the global pattern of annual storage amplitude, and the seasonal cycle of global average storage is reproduced well, consistent with earlier studies. However, global average agreements mask systematic model biases in low latitudes. Seasonal extrema of low‐latitude, hemispheric storage generally occur too early in the models, and model‐specific errors in amplitude of the low‐latitude annual variations are substantial. These errors are potentially explicable in terms of neglected or suboptimally parameterized water stores in the land models and precipitation biases in the climate models.

Estimating the consequences of significant fracture flow at Yucca Mountain

International Nuclear Information System (INIS)

Gauthier, J.H.; Wilson, M.L.; Lauffer, F.C.

1992-01-01

In this paper a simple model is proposed for investigating the possibility of significant fracture flow at Yucca Mountain, Nevada. The model allows an estimate of the number of flowing fractures at Yucca Mountain based on the size of the fractures and the yearly volume of infiltrating water. Given the number of flowing fractures, the number of waste containers they contact is estimated by a geometric argument. Preliminary results indicate that the larger the flowing fractures, the lower the releases of radionuclides. Also, even with significant fracture flow, releases could be well below the limits set by the Environmental Protection Agency

Estimating the consequences of significant fracture flow at Yucca Mountain

International Nuclear Information System (INIS)

Gauthier, J.H.; Wilson, M.L.; Lauffer, F.C.

1991-01-01

A simple model is proposed for investigating the possibility of significant fracture flow at Yucca Mountain, Nevada. The model allows an estimate of the number of flowing fractures at Yucca Mountain based on the size of the fractures and the yearly volume of infiltrating water. Given the number of flowing fractures, the number of waste containers they contact is estimated by a geometric argument. Preliminary results indicate that the larger the flowing fractures, the lower the releases of radionuclides. Also, even with significant fracture flow, releases could be well below the limits set by the Environmental Protection Agency

PA positioning significantly reduces testicular dose during sacroiliac joint radiography

Energy Technology Data Exchange (ETDEWEB)

Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

2010-11-15

Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

Sectional modeling of nanoparticle size and charge distributions in dusty plasmas

International Nuclear Information System (INIS)

Agarwal, Pulkit; Girshick, Steven L

2012-01-01

Sectional models of the dynamics of aerosol populations are well established in the aerosol literature but have received relatively less attention in numerical models of dusty plasmas, where most modeling studies have assumed the existence of monodisperse dust particles. In the case of plasmas in which nanoparticles nucleate and grow, significant polydispersity can exist in particle size distributions, and stochastic charging can cause particles of given size to have a broad distribution of charge states. Sectional models, while computationally expensive, are well suited to treating such distributions. This paper presents an overview of sectional modeling of nanodusty plasmas, and presents examples of simulation results that reveal important qualitative features of the spatiotemporal evolution of such plasmas, many of which could not be revealed by models that consider only monodisperse dust particles and average particle charge. These features include the emergence of bimodal particle populations consisting of very small neutral particles and larger negatively charged particles, the effects of size and charge distributions on coagulation, spreading and structure of the particle cloud, and the dynamics of dusty plasma afterglows. (paper)

Revealed access to haemodialysis facilities in northeastern Iran: Factors that matter in rural and urban areas.

Science.gov (United States)

Kiani, Behzad; Bagheri, Nasser; Tara, Ahmad; Hoseini, Benyamin; Tabesh, Hamed; Tara, Mahmood

2017-11-07

Poor access to haemodialysis facilities is associated with high mortality and morbidity rates. This study investigated factors affecting revealed access to the haemodialysis facilities considering patients living in rural and urban areas without any haemodialysis facility (Group A) and those living urban areas with haemodialysis facilities (Group B). This study is based on selfreported Actual Access Time (AAT) to referred haemodialysis facilities and other information regarding travel to haemodialysis facilities from patients. All significant variables on univariate analysis were entered into a univariate general linear model in order to identify factors associated with AAT. Both spatial (driving time and distance) and non-spatial factors (sex, income level, caregivers, transportation mode, education level, ethnicity and personal vehicle ownership) influenced the revealed access identified in Group A. The non-spatial factors for Group B patients were the same as for Group A, but no spatial factor was identified in Group B. It was found that accessibility is strongly underestimated when driving time is chosen as accessibility measure to haemodialysis facilities. Analysis of revealed access determinants provides policymakers with an appropriate decision base for making appropriate decisions and finding solutions to decrease the access time for patients under haemodialysis therapy. Driving time alone is not a good proxy for measuring access to haemodialysis facilities as there are many other potential obstacles, such as women's special travel problems, poor other transportation possibilities, ethnicity disparities, low education levels, low caregiver status and low-income.

Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT.

Science.gov (United States)

Christel, Stephan; Herold, Malte; Bellenberg, Sören; El Hajjami, Mohamed; Buetti-Dinh, Antoine; Pivkin, Igor V; Sand, Wolfgang; Wilmes, Paul; Poetsch, Ansgar; Dopson, Mark

2017-11-17

Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilum T applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilum T DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS 2 ). Leptospirillum ferriphilum T adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron-oxidizers in the context of acidic and metal rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilum T coupled with functional omics data provides new insights into its metabolic properties, such as the

End-to-end models for marine ecosystems: Are we on the precipice of a significant advance or just putting lipstick on a pig?

Directory of Open Access Journals (Sweden)

Kenneth A. Rose

2012-02-01

Full Text Available There has been a rapid rise in the development of end-to-end models for marine ecosystems over the past decade. Some reasons for this rise include need for predicting effects of climate change on biota and dissatisfaction with existing models. While the benefits of a well-implemented end-to-end model are straightforward, there are many challenges. In the short term, my view is that the major role of end-to-end models is to push the modelling community forward, and to identify critical data so that these data can be collected now and thus be available for the next generation of end-to-end models. I think we should emulate physicists and build theoretically-oriented models first, and then collect the data. In the long-term, end-to-end models will increase their skill, data collection will catch up, and end-to-end models will move towards site-specific applications with forecasting and management capabilities. One pathway into the future is individual efforts, over-promise, and repackaging of poorly performing component submodels (“lipstick on a pig”. The other pathway is a community-based collaborative effort, with appropriate caution and thoughtfulness, so that the needed improvements are achieved (“significant advance”. The promise of end-to-end modelling is great. We should act now to avoid missing a great opportunity.

Investigation of significantly high barrier height in Cu/GaN Schottky diode

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Manjari Garg

2016-01-01

Full Text Available Current-voltage (I-V measurements combined with analytical calculations have been used to explain mechanisms for forward-bias current flow in Copper (Cu Schottky diodes fabricated on Gallium Nitride (GaN epitaxial films. An ideality factor of 1.7 was found at room temperature (RT, which indicated deviation from thermionic emission (TE mechanism for current flow in the Schottky diode. Instead the current transport was better explained using the thermionic field-emission (TFE mechanism. A high barrier height of 1.19 eV was obtained at room temperature. X-ray photoelectron spectroscopy (XPS was used to investigate the plausible reason for observing Schottky barrier height (SBH that is significantly higher than as predicted by the Schottky-Mott model for Cu/GaN diodes. XPS measurements revealed the presence of an ultrathin cuprous oxide (Cu2O layer at the interface between Cu and GaN. With Cu2O acting as a degenerate p-type semiconductor with high work function of 5.36 eV, a high barrier height of 1.19 eV is obtained for the Cu/Cu2O/GaN Schottky diode. Moreover, the ideality factor and barrier height were found to be temperature dependent, implying spatial inhomogeneity of barrier height at the metal semiconductor interface.

Comparative evaluation of kinetic, equilibrium and semi-equilibrium models for biomass gasification

Energy Technology Data Exchange (ETDEWEB)

Buragohain, Buljit [Center for Energy, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India); Chakma, Sankar; Kumar, Peeush [Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India); Mahanta, Pinakeswar [Center for Energy, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India); Department of Mechanical Engineering, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India); Moholkar, Vijayanand S. [Center for Energy, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India); Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati – 781 039, Assam (India)

2013-07-01

Modeling of biomass gasification has been an active area of research for past two decades. In the published literature, three approaches have been adopted for the modeling of this process, viz. thermodynamic equilibrium, semi-equilibrium and kinetic. In this paper, we have attempted to present a comparative assessment of these three types of models for predicting outcome of the gasification process in a circulating fluidized bed gasifier. Two model biomass, viz. rice husk and wood particles, have been chosen for analysis, with gasification medium being air. Although the trends in molar composition, net yield and LHV of the producer gas predicted by three models are in concurrence, significant quantitative difference is seen in the results. Due to rather slow kinetics of char gasification and tar oxidation, carbon conversion achieved in single pass of biomass through the gasifier, calculated using kinetic model, is quite low, which adversely affects the yield and LHV of the producer gas. Although equilibrium and semi-equilibrium models reveal relative insensitivity of producer gas characteristics towards temperature, the kinetic model shows significant effect of temperature on LHV of the gas at low air ratios. Kinetic models also reveal volume of the gasifier to be an insignificant parameter, as the net yield and LHV of the gas resulting from 6 m and 10 m riser is same. On a whole, the analysis presented in this paper indicates that thermodynamic models are useful tools for quantitative assessment of the gasification process, while kinetic models provide physically more realistic picture.

Time series modelling of overflow structures

DEFF Research Database (Denmark)

Carstensen, J.; Harremoës, P.

1997-01-01

The dynamics of a storage pipe is examined using a grey-box model based on on-line measured data. The grey-box modelling approach uses a combination of physically-based and empirical terms in the model formulation. The model provides an on-line state estimate of the overflows, pumping capacities...... and available storage capacity in the pipe as well as predictions of future states. A linear overflow relation is found, differing significantly from the traditional modelling approach. This is due to complicated overflow structures in a hydraulic sense where the overflow is governed by inertia from the inflow...... to the overflow structures. The capacity of a pump draining the storage pipe has been estimated for two rain events, revealing that the pump was malfunctioning during the first rain event. The grey-box modelling approach is applicable for automated on-line surveillance and control. (C) 1997 IAWQ. Published...

Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

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Marie-Noëlle Delyfer

Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

Radiologically revealed spine osteoporosis in male with hypertension and coronary heart disease

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P A Chizhov

2005-01-01

Full Text Available Radiologically revealed spine osteoporosis in male with hypertension and coronary heart disease Objective. To study prevalence and intensity of spine osteoporosis (OP in men suffering from hypertension (H and coronary heart disease (CHD. Material and methods. 101 men with H and CHD aged 50 to 78 years (mean age 60,6±0,85 years and 37 men of control group without cardiovascular diseases aged 50-66 years (mean age 58,6±0,74 years were examined. Clinical examination, radiological, radiomorphometric spine examination and echocardioscopy were performed. Results. OP was revealed in 34,65% of main group pts what is 3,2 times more frequent than in control group (10,8%, p<0,05. OP intensity in men with H and CHD was significantly higher than in healthy people. Vfertebral fractures were revealed in 12,87+3,3% of main group pts and only in 2,7±2,7% in control group (p<0,05. OP development dependence from cardiac history duration and cardiac pathology severity was demonstrated. Conclusion. The results of the study show significantly higher prevalence of spine OP among men suffering from H and CHD. Long history and severity of cardiovascular pathology clinical signs promote OP frequency and severity increase.

A fractional factorial probabilistic collocation method for uncertainty propagation of hydrologic model parameters in a reduced dimensional space

Science.gov (United States)

Wang, S.; Huang, G. H.; Huang, W.; Fan, Y. R.; Li, Z.

2015-10-01

In this study, a fractional factorial probabilistic collocation method is proposed to reveal statistical significance of hydrologic model parameters and their multi-level interactions affecting model outputs, facilitating uncertainty propagation in a reduced dimensional space. The proposed methodology is applied to the Xiangxi River watershed in China to demonstrate its validity and applicability, as well as its capability of revealing complex and dynamic parameter interactions. A set of reduced polynomial chaos expansions (PCEs) only with statistically significant terms can be obtained based on the results of factorial analysis of variance (ANOVA), achieving a reduction of uncertainty in hydrologic predictions. The predictive performance of reduced PCEs is verified by comparing against standard PCEs and the Monte Carlo with Latin hypercube sampling (MC-LHS) method in terms of reliability, sharpness, and Nash-Sutcliffe efficiency (NSE). Results reveal that the reduced PCEs are able to capture hydrologic behaviors of the Xiangxi River watershed, and they are efficient functional representations for propagating uncertainties in hydrologic predictions.

Core-level photoemission revealing the Mott transition

International Nuclear Information System (INIS)

Kim, Hyeong-Do; Noh, Han-Jin; Kim, K.H.; Oh, S.-J.

2005-01-01

Ru 3d core-level X-ray photoemission spectra of various ruthenates are examined. They show in general two-peak structures, which can be assigned as the screened and unscreened peaks. The screened peak is absent in a Mott insulator, but develops into a main peak as the correlation strength becomes weak. This spectral behavior is well explained by the dynamical mean-field theory calculation for the single-band Hubbard model with the on-site core-hole potential using the exact diagonalization method. The new mechanism of the core-level photoemission satellite can be utilized to reveal the Mott transition phenomenon in various strongly correlated electron systems

The significance of fructose and MSG in affecting lipid and docosahexaenoic acid (DHA) production of Aurantiochytrium sp. SW1

Science.gov (United States)

Rahman, Shariffah Nurhidayah Syed Abdul; Kalil, Mohd Sahaid; Hamid, Aidil Abdul

2018-04-01

Optimization of fermentation medium for the production of docosahexaenoic acid (DHA) by Aurantiochytrium sp. SW1 was carried out. In this study, levels of fructose, monosodium glutamate (MSG) and sea salt were optimized for enhanced lipid and DHA production using response surface methodology (RSM). The design contains a total of 20 runs with 6 central points replication. Cultivation was carried out in 500 mL flasks containing 100 mL nitrogen limited medium at 30°C for 96h. Sequential model sum of squares (SS) revealed that the system was adequately represented by a quadratic model (p<0.0001). ANOVA results showed that fructose and MSG as a single factor has significant positive effect on the DHA content of SW1. The estimated optimal levels of the factors were 100 g/L fructose, 8 g/L MSG and 47% sea salt. Subsequent cultivation employing the suggested values confirmed that the predicted response values were experimentally achievable and reproducible, where 8.82 g/L DHA (51.34% g/g lipid) was achieved.

Surface tensions of multi-component mixed inorganic/organic aqueous systems of atmospheric significance: measurements, model predictions and importance for cloud activation predictions

Directory of Open Access Journals (Sweden)

D. O. Topping

2007-01-01

Full Text Available In order to predict the physical properties of aerosol particles, it is necessary to adequately capture the behaviour of the ubiquitous complex organic components. One of the key properties which may affect this behaviour is the contribution of the organic components to the surface tension of aqueous particles in the moist atmosphere. Whilst the qualitative effect of organic compounds on solution surface tensions has been widely reported, our quantitative understanding on mixed organic and mixed inorganic/organic systems is limited. Furthermore, it is unclear whether models that exist in the literature can reproduce the surface tension variability for binary and higher order multi-component organic and mixed inorganic/organic systems of atmospheric significance. The current study aims to resolve both issues to some extent. Surface tensions of single and multiple solute aqueous solutions were measured and compared with predictions from a number of model treatments. On comparison with binary organic systems, two predictive models found in the literature provided a range of values resulting from sensitivity to calculations of pure component surface tensions. Results indicate that a fitted model can capture the variability of the measured data very well, producing the lowest average percentage deviation for all compounds studied. The performance of the other models varies with compound and choice of model parameters. The behaviour of ternary mixed inorganic/organic systems was unreliably captured by using a predictive scheme and this was dependent on the composition of the solutes present. For more atmospherically representative higher order systems, entirely predictive schemes performed poorly. It was found that use of the binary data in a relatively simple mixing rule, or modification of an existing thermodynamic model with parameters derived from binary data, was able to accurately capture the surface tension variation with concentration. Thus

Non-parametric Bayesian graph models reveal community structure in resting state fMRI

DEFF Research Database (Denmark)

Andersen, Kasper Winther; Madsen, Kristoffer H.; Siebner, Hartwig Roman

2014-01-01

Modeling of resting state functional magnetic resonance imaging (rs-fMRI) data using network models is of increasing interest. It is often desirable to group nodes into clusters to interpret the communication patterns between nodes. In this study we consider three different nonparametric Bayesian...... models for node clustering in complex networks. In particular, we test their ability to predict unseen data and their ability to reproduce clustering across datasets. The three generative models considered are the Infinite Relational Model (IRM), Bayesian Community Detection (BCD), and the Infinite...... between clusters. BCD restricts the between-cluster link probabilities to be strictly lower than within-cluster link probabilities to conform to the community structure typically seen in social networks. IDM only models a single between-cluster link probability, which can be interpreted as a background...

Principles of proteome allocation are revealed using proteomic data and genome-scale models

DEFF Research Database (Denmark)

Yang, Laurence; Yurkovich, James T.; Lloyd, Colton J.

2016-01-01

to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the "generalist" (wild-type) E. coli proteome and phenotype across diverse growth environments. Across 15 growth conditions......Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked...... of these sectors for the general stress response sigma factor sigma(S). Finally, the sector constraints represent a general formalism for integrating omics data from any experimental condition into constraint-based ME models. The constraints can be fine-grained (individual proteins) or coarse-grained (functionally...

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

Science.gov (United States)

Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

2011-01-07

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

Science.gov (United States)

Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

2018-04-20

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

Science.gov (United States)

Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

2016-12-01

Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P guinea pig, and describe a unique distribution of intimal formation that results in both species

Broken home or drug using peers : "Significant relations"?

NARCIS (Netherlands)

Quensel, S; McArdle, P; Brinkley, A; Wiegersma, A; Blom, M; Fitzgerald, M; Johnson, R; Kolte, B; Michels, [No Value; Pierolini, A; Pos, R; Stoeckel, [No Value

2002-01-01

This study reports the results of a comparative survey with representative samples of 3,386 school attending youths, most of whom were 15 years of age and residing in five European cities. We found significant but low correlations between the type of family structure (intact family, model family,

DETERMINATION OF MOST SIGNIFICANT FACTORS FOR ANALYSIS OF HIGHWAY OPERATING CONDITIONS

Directory of Open Access Journals (Sweden)

M. G. Solodkaya

2017-01-01

Full Text Available Traffic circulation on highways is a random process. Therefore automotive damage rate and, respectively, roads on which they are moving is subjected to regularities of random processes. Dynamic processes of vehicle-road interaction are determined to various extents by a host of factors that include road pavement evenness and characteristics of moving vehicles. For this reason the following task has been set: to reveal the most significant factors and mathematically correlate values of vehicle dynamic loads with a quality of road pavement and vehicle speed. Such task statement has not been solved adequately and this situation determines importance and novelty of the investigations in the given direction. While solving the mentioned task the investigations which have been carried out under real-life conditions and with the help of real-life objects are considered as the most reliable ones. However, preparation and execution of such experiments as needed significantly complicates their implementation. In this regard it looks rather expediential to combine a factorial experiment with the tests of a checked model while using ECM with stage-by-stage parameter fixation of working processes passing in “vehicle-road” system, comprehensive assessment pertaining to influence of the selected factors and selection of their optimum combination. Mathematical dependence has been obtained to evaluate influence of several external factors on optimization of vehicle dynamic load on the road. This component makes it possible to attain a simplified and adequate description of element interaction in “vehicle – road” system. While investigating influence of pavement irregularities on maximum dynamic loads on the road influence rate of the selected factors is determined in the following sequence: vehicle weight, pavement evenness and speed of transport facility.

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

Science.gov (United States)

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Nutritional significance of a winter-flowering succulent for opportunistic avian nectarivores

CSIR Research Space (South Africa)

Symes, CT

2010-01-01

Full Text Available the enriched crassulacean acid metabolism (CAM) isotopic signature of nectar ()12.6 ± 0.5&). This relatively small contribution of A. marlothii nectar to assimilated carbon in whole blood contrasted with that of exhaled CO2 in Afri- can Red-eyed Bulbuls... Pycnonotus nigricans and Cape White-eyes Zosterops capensis. In both these species, the d13C of breath samples was significantly enriched compared with blood and feathers, and closely resembled that of the nectar, revealing combustion of ingested nectar...

Insight into model mechanisms through automatic parameter fitting: a new methodological framework for model development.

Science.gov (United States)

Tøndel, Kristin; Niederer, Steven A; Land, Sander; Smith, Nicolas P

2014-05-20

Striking a balance between the degree of model complexity and parameter identifiability, while still producing biologically feasible simulations using modelling is a major challenge in computational biology. While these two elements of model development are closely coupled, parameter fitting from measured data and analysis of model mechanisms have traditionally been performed separately and sequentially. This process produces potential mismatches between model and data complexities that can compromise the ability of computational frameworks to reveal mechanistic insights or predict new behaviour. In this study we address this issue by presenting a generic framework for combined model parameterisation, comparison of model alternatives and analysis of model mechanisms. The presented methodology is based on a combination of multivariate metamodelling (statistical approximation of the input-output relationships of deterministic models) and a systematic zooming into biologically feasible regions of the parameter space by iterative generation of new experimental designs and look-up of simulations in the proximity of the measured data. The parameter fitting pipeline includes an implicit sensitivity analysis and analysis of parameter identifiability, making it suitable for testing hypotheses for model reduction. Using this approach, under-constrained model parameters, as well as the coupling between parameters within the model are identified. The methodology is demonstrated by refitting the parameters of a published model of cardiac cellular mechanics using a combination of measured data and synthetic data from an alternative model of the same system. Using this approach, reduced models with simplified expressions for the tropomyosin/crossbridge kinetics were found by identification of model components that can be omitted without affecting the fit to the parameterising data. Our analysis revealed that model parameters could be constrained to a standard deviation of on

Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

Science.gov (United States)

Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

2002-10-15

Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

Uncertainty from the choice of microphysics scheme in convection-permitting models significantly exceeds aerosol effects

Directory of Open Access Journals (Sweden)

B. White

2017-10-01

Full Text Available This study investigates the hydrometeor development and response to cloud droplet number concentration (CDNC perturbations in convection-permitting model configurations. We present results from a real-data simulation of deep convection in the Congo basin, an idealised supercell case, and a warm-rain large-eddy simulation (LES. In each case we compare two frequently used double-moment bulk microphysics schemes and investigate the response to CDNC perturbations. We find that the variability among the two schemes, including the response to aerosol, differs widely between these cases. In all cases, differences in the simulated cloud morphology and precipitation are found to be significantly greater between the microphysics schemes than due to CDNC perturbations within each scheme. Further, we show that the response of the hydrometeors to CDNC perturbations differs strongly not only between microphysics schemes, but the inter-scheme variability also differs between cases of convection. Sensitivity tests show that the representation of autoconversion is the dominant factor that drives differences in rain production between the microphysics schemes in the idealised precipitating shallow cumulus case and in a subregion of the Congo basin simulations dominated by liquid-phase processes. In this region, rain mass is also shown to be relatively insensitive to the radiative effects of an overlying layer of ice-phase cloud. The conversion of cloud ice to snow is the process responsible for differences in cold cloud bias between the schemes in the Congo. In the idealised supercell case, thermodynamic impacts on the storm system using different microphysics parameterisations can equal those due to aerosol effects. These results highlight the large uncertainty in cloud and precipitation responses to aerosol in convection-permitting simulations and have important implications not only for process studies of aerosol–convection interaction, but also for

Revealed social preference for potable groundwater: An Eastern Iowa case study

Science.gov (United States)

Raunikar, R. P.; Bernknopf, R. L.; Forney, W.; Mishra, S.

2011-12-01

The spatially explicit land use and land cover information provided by Landsat moderate-resolution land imagery (MRLI) is needed to more efficiently balance the production of goods and services over landscapes. For example, economic trade-offs are needed to provide both clean groundwater resources and other non-environmental goods and services produced by activities that affect the vadose zone and thus contribute to contamination of groundwater. These trade-off choices are made by numerous economic agents and are constrained by many social institutions including governmental regulations at many levels, contractual obligations and traditions. In effect, on a social level, society acts as if it values groundwater by foregoing other goods to protect these resources. The result of the protection afforded to groundwater resources is observable by measuring contamination in well samples. This observed level of groundwater contamination risk is the revealed preference of society as a whole for clean groundwater. We observed the risk of groundwater contamination in a sampling of well data from our study area (35 counties of Eastern Iowa.) We used a proportional hazard model to quantify the nitrate contamination survival implied by the panel of 19,873 well data, where remaining below a 10 mg/ml maximum contamination level (MCL) is defined as survival. We tested the data for evidence that the levels of protection provided to these resources is correlated with aquifer and vadose zone characteristics and geographic location and whether it changed over time and with economic and other conditions. We demonstrate the use of a nitrate conditioned hazard function for projecting the survival of wells based on nitrate exposure information over the 1940 to 2010 time period. We discuss results of simulations of the survival process that demonstrate the economic significance of this approach. We find that aquifer survival has been significantly improving over time. The principle of

Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

Science.gov (United States)

Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

2016-01-01

Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

Development of the information model for consumer assessment of key quality indicators by goods labelling

Science.gov (United States)

Koshkina, S.; Ostrinskaya, L.

2018-04-01

An information model for “key” quality indicators of goods has been developed. This model is based on the assessment of f standardization existing state and the product labeling quality. According to the authors’ opinion, the proposed “key” indicators are the most significant for purchasing decision making. Customers will be able to use this model through their mobile technical devices. The developed model allows to decompose existing processes in data flows and to reveal the levels of possible architectural solutions. In-depth analysis of the presented information model decomposition levels will allow determining the stages of its improvement and to reveal additional indicators of the goods quality that are of interest to customers in the further research. Examining the architectural solutions for the customer’s information environment functioning when integrating existing databases will allow us to determine the boundaries of the model flexibility and customizability.

Hierarchical models for informing general biomass equations with felled tree data

Science.gov (United States)

Brian J. Clough; Matthew B. Russell; Christopher W. Woodall; Grant M. Domke; Philip J. Radtke

2015-01-01

We present a hierarchical framework that uses a large multispecies felled tree database to inform a set of general models for predicting tree foliage biomass, with accompanying uncertainty, within the FIA database. Results suggest significant prediction uncertainty for individual trees and reveal higher errors when predicting foliage biomass for larger trees and for...

Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

Science.gov (United States)

Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

2013-02-01

Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

Science.gov (United States)

Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

2015-01-01

Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3

Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

Directory of Open Access Journals (Sweden)

Marie Thérèse Besson

Full Text Available Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93. We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD, the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

Science.gov (United States)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Activity based costing model for inventory valuation

Directory of Open Access Journals (Sweden)

Vineet Chouhan

2017-03-01

Full Text Available Activity-Based-Model (ABC is used for the purpose of significant improvement for overhead accounting systems by providing the best information required for managerial decision. This pa-per discusses implacability of ABC technique on inventory valuation as a management account-ing innovation. In order to prove the applicability of ABC for inventory control a material driven medium-sized and privately owned company from engineering (iron and steel industry is select-ed and by analysis of its production process and its material dependency and use of indirect in-ventory, an ABC model is explored for better inventory control. The case revealed that the ne-cessity of ABC in the area of inventory control is significant. The company is not only able to increase its quality of decision but also it can significantly analyze its cost of direct material cost, valuation of direct material and use its implications for better decision making.

A revealed-preference study of behavioural impacts of real-time traffic information

NARCIS (Netherlands)

Knockaert, J.S.A.; Tseng, Y.; Verhoef, E.T.

2013-01-01

In the present study, we investigate the impact of real-time traffic information on traveller behaviour by using repeated day-to-day revealed-preference (RP) observations from a reward experiment. We estimate a trip scheduling model of morning peak behaviour that allows us to determine the impact of

Memory functions reveal structural properties of gene regulatory networks

Science.gov (United States)

Perez-Carrasco, Ruben

2018-01-01

Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection. By first converting a thermodynamic state ensemble model of gene regulation into mass action reactions we derive a general method that produces a set of time evolution equations for a subset of components of a network. The influence of the rest of the network, the bulk, is captured by memory functions that describe how the subnetwork reacts to its own past state via components in the bulk. These memory functions provide probes of near-steady state dynamics, revealing information not easily accessible otherwise. We illustrate the method on a simple cross-repressive transcriptional motif to show that memory functions not only simplify the analysis of the subnetwork but also have a natural interpretation. We then apply the approach to a GRN from the vertebrate neural tube, a well characterised developmental transcriptional network composed of four interacting transcription factors. The memory functions reveal the function of specific links within the neural tube network and identify features of the regulatory structure that specifically increase the robustness of the network to initial conditions. Taken together, the study provides evidence that Zwanzig-Mori projections offer powerful and effective tools for simplifying and exploring the behaviour of GRNs. PMID:29470492

Cross-species transcriptomic approach reveals genes in hamster implantation sites.

Science.gov (United States)

Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

2014-12-01

The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

Neural correlates of the LSD experience revealed by multimodal neuroimaging.

Science.gov (United States)

Carhart-Harris, Robin L; Muthukumaraswamy, Suresh; Roseman, Leor; Kaelen, Mendel; Droog, Wouter; Murphy, Kevin; Tagliazucchi, Enzo; Schenberg, Eduardo E; Nest, Timothy; Orban, Csaba; Leech, Robert; Williams, Luke T; Williams, Tim M; Bolstridge, Mark; Sessa, Ben; McGonigle, John; Sereno, Martin I; Nichols, David; Hellyer, Peter J; Hobden, Peter; Evans, John; Singh, Krish D; Wise, Richard G; Curran, H Valerie; Feilding, Amanda; Nutt, David J

2016-04-26

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Revealing Invisible Water: Moisture Recycling as an Ecosystem Service.

Science.gov (United States)

Keys, Patrick W; Wang-Erlandsson, Lan; Gordon, Line J

2016-01-01

An ecosystem service is a benefit derived by humanity that can be traced back to an ecological process. Although ecosystem services related to surface water have been thoroughly described, the relationship between atmospheric water and ecosystem services has been mostly neglected, and perhaps misunderstood. Recent advances in land-atmosphere modeling have revealed the importance of terrestrial ecosystems for moisture recycling. In this paper, we analyze the extent to which vegetation sustains the supply of atmospheric moisture and precipitation for downwind beneficiaries, globally. We simulate land-surface evaporation with a global hydrology model and track changes to moisture recycling using an atmospheric moisture budget model, and we define vegetation-regulated moisture recycling as the difference in moisture recycling between current vegetation and a hypothetical desert world. Our results show that nearly a fifth of annual average precipitation falling on land is from vegetation-regulated moisture recycling, but the global variability is large, with many places receiving nearly half their precipitation from this ecosystem service. The largest potential impacts for changes to this ecosystem service are land-use changes across temperate regions in North America and Russia. Likewise, in semi-arid regions reliant on rainfed agricultural production, land-use change that even modestly reduces evaporation and subsequent precipitation, could significantly affect human well-being. We also present a regional case study in the Mato Grosso region of Brazil, where we identify the specific moisture recycling ecosystem services associated with the vegetation in Mato Grosso. We find that Mato Grosso vegetation regulates some internal precipitation, with a diffuse region of benefit downwind, primarily to the south and east, including the La Plata River basin and the megacities of Sao Paulo and Rio de Janeiro. We synthesize our global and regional results into a generalized

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

OpenAIRE

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the exis...

Respiratory neuroplasticity - Overview, significance and future directions.

Science.gov (United States)

Fuller, David D; Mitchell, Gordon S

2017-01-01

Neuroplasticity is an important property of the neural system controlling breathing. However, our appreciation for its importance is still relatively new, and we have much to learn concerning different forms of plasticity, their underlying mechanisms, and their biological and clinical significance. In this brief review, we discuss several well-studied models of respiratory plasticity, including plasticity initiated by inactivity in the respiratory system, intermittent and sustained hypoxia, and traumatic injury to the spinal cord. Other aspects of respiratory plasticity are considered in other contributions to this special edition of Experimental Neurology on respiratory plasticity. Finally, we conclude with discussions concerning the biological and clinical significance of respiratory motor plasticity, and areas in need of future research effort. Copyright © 2016. Published by Elsevier Inc.

On discourse space modeling

OpenAIRE

Казыдуб, Надежда

2013-01-01

Discourse space is a complex structure that incorporates different levels and dimensions. The paper focuses on developing a multidisciplinary approach that is congruent to the complex character of the modern discourse. Two models of discourse space are proposed here. The Integrated Model reveals the interaction of different categorical mechanisms in the construction of the discourse space. The Evolutionary Model describes the historical roots of the modern discourse. It also reveals historica...

Assessing clinical significance of treatment outcomes using the DASS-21.

Science.gov (United States)

Ronk, Fiona R; Korman, James R; Hooke, Geoffrey R; Page, Andrew C

2013-12-01

Standard clinical significance classifications are based on movement between the "dysfunctional" and "functional" distributions; however, this dichotomy ignores heterogeneity within the "dysfunctional" population. Based on the methodology described by Tingey, Lambert, Burlingame, and Hansen (1996), the present study sought to present a 3-distribution clinical significance model for the 21-item version of the Depression Anxiety Stress Scales (DASS-21; P. F. Lovibond & Lovibond, 1995) using data from a normative sample (n = 2,914), an outpatient sample (n = 1,000), and an inpatient sample (n = 3,964). DASS-21 scores were collected at pre- and post-treatment for both clinical samples, and patients were classified into 1 of 5 categories based on whether they had made a reliable change and whether they had moved into a different functional range. Evidence supported the validity of the 3-distribution model for the DASS-21, since inpatients who were classified as making a clinically significant change showed lower symptom severity, higher perceived quality of life, and higher clinician-rated functioning than those who did not make a clinically significant change. Importantly, results suggest that the new category of recovering is an intermediate point between recovered and making no clinically significant change. Inpatients and outpatients have different treatment goals and therefore use of the concept of clinical significance needs to acknowledge differences in what constitutes a meaningful change. (c) 2013 APA, all rights reserved.

Prevalence and clinical significance of cathepsin G antibodies in systemic sclerosis

Directory of Open Access Journals (Sweden)

M. Favaro

2011-09-01

Full Text Available Objectives: To evaluate the prevalence and clinical significance of cathepsin G antibodies in patients affected with systemic sclerosis (SSc, scleroderma. Methods: 115 patients affected by SSc, 55 (47,8% with diffuse scleroderma (dSSc and 60 (52,2% with limited scleroderma (lSSc, were tested for cathepsin G antibodies by ELISA method. Moreover these sera were evaluated by indirect immunofluorescence (IIF on ethanol and formalin fixed human neutrophils. Results: By means of the ELISA method 16 (13,9% patients were found to be sera positive for anti-cathepsin G, 2 (12.5% of which showed a perinuclear fluorescence pattern (P-ANCA and 4 (25% an atypical ANCA staining, while 10 (62,5% were negative on IIF. The IIF on scleroderma sera revealed 5 (4,3% P-ANCA and 18 (15,7% atypical ANCA patterns. The anti-cathepsin G antibodies significantly prevailed in scleroderma sera (p=0.02 when their frequency was compared with that of healthy controls; while they were not significantly associated to any clinical or serological features of SSc patients. Conclusions: The anti-cathepsin G antibodies were significantly frequent in scleroderma sera; however, no clinical correlations were found. Thus, the significance of their presence in SSc still needs to be clarified.

NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

Directory of Open Access Journals (Sweden)

Joshua M. Baughman

2016-07-01

Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

Radiation induced muscositis as space flight risk. Model studies on X-ray and heavy ion irradiated typical oral mucosa models

International Nuclear Information System (INIS)

Tschachojan, Viktoria

2014-01-01

Humans in exomagnetospheric space are exposed to highly energetic heavy ion radiation which can be hardly shielded. Since radiation-induced mucositis constitutes a severe complication of heavy ion radiotherapy, it would also implicate a serious medical safety risk for the crew members during prolonged space flights such as missions to Moon or Mars. For assessment of risk developing radiation-induced mucositis, three-dimensional organotypic cultures of immortalized human keratinocytes and fibroblasts were irradiated with a 12 C particle beam at high energies or X-Rays. Immunofluorescence stainings were done from cryosections and radiation induced release of cytokines and chemokines was quantified by ELISA from culture supernatants. The major focuses of this study were on 4, 8, 24 and 48 hours after irradiation. The conducted analyses of our mucosa model showed many structural similarities with the native oral mucosa and authentic immunological responses to radiation exposure. Quantification of the DNA damage in irradiated mucosa models revealed about twice as many DSB after heavy-ion irradiation compared to X-rays at definite doses and time points, suggesting a higher gene toxicity of heavy ions. Nuclear factor κB activation was observed after treatment with X-rays or 12 C particles. An activation of NF κB p65 in irradiated samples could not be detected. ELISA analyses showed significantly higher interleukin 6 and interleukin 8 levels after irradiation with X-rays and 12 C particles compared to non-irradiated controls. However, only X-rays induced significantly higher levels of interleukin 1β. Analyses of TNF-α and IFN-γ showed no radiation-induced effects. Further analyses revealed a radiation-induced reduction in proliferation and loss of compactness in irradiated oral mucosa model, which would lead to local lesions in vivo. In this study we revealed that several pro-inflammatory markers and structural changes are induced by X-rays and heavy-ion irradiation

The Significance of Farm Size in the Evaluation of Labour Productivity in Agriculture

Directory of Open Access Journals (Sweden)

Martina Novotná

2016-01-01

Full Text Available The paper deal with the analysis of difference in labour productivity of farms categorised according to their size, to determine if the set subsidy system influences labour productivity in the size groups of the farms. The source of data for enterprises analysis was the firms database, which contains accounting data of 926 farms with at least one employee. The observed data were from the 6 year period (2007–2012. The farms were divided, according to their size into four categories defined by the European Commission: micro, small, medium and large enterprises. The analysis of the labour productivity I based on the added value and labour costs revealed that there are big differences of the labour productivity levels in particular size groups of farms. The further analysis revealed that an adjustment of the farm approach of the labour productivity, when the paid operation subsidies are added (labour productivity II, changes this conclusion and the differences between particular size groups of farms decreased. Using σ-convergence, it was proved that the relative variability of the labour productivity II values decreased significantly in the case of the medium-sized farms. We can say that subsidies significantly influence the labour productivity in farms. On one hand, there is decrease of differences between the level values of particular size groups of farms; on the other hand, there is no significant decrease its variability (except the medium-sized farms.

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

Science.gov (United States)

El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

2018-06-20

Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

Energy Technology Data Exchange (ETDEWEB)

Donius, Amalie E., E-mail: amalie.donius@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Obbard, Rachel W., E-mail: Rachel.W.Obbard@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Burger, Joan N., E-mail: ridge.of.the.ancients@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Hunger, Philipp M., E-mail: philipp.m.hunger@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Baker, Ian, E-mail: Ian.Baker@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Doherty, Roger D., E-mail: dohertrd@drexel.edu [Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Wegst, Ulrike G.K., E-mail: ulrike.wegst@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States)

2014-07-01

Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment.

Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

International Nuclear Information System (INIS)

Donius, Amalie E.; Obbard, Rachel W.; Burger, Joan N.; Hunger, Philipp M.; Baker, Ian; Doherty, Roger D.; Wegst, Ulrike G.K.

2014-01-01

Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment

PA positioning significantly reduces testicular dose during sacroiliac joint radiography

International Nuclear Information System (INIS)

Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

2010-01-01

Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump.

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Tejral, Gracian; Sopko, Bruno; Necas, Alois; Schoner, Wilhelm; Amler, Evzen

2017-01-01

Hydrolysis of ATP by Na + /K + -ATPase, a P-Type ATPase, catalyzing active Na + and K + transport through cellular membranes leads transiently to a phosphorylation of its catalytical α -subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp 369 to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ -phosphate group of ATP to the Asp 369 is achieved, analogous molecular modeling of the M 4 -M 5 loop of ATPase was performed using the crystal data of Na + /K + -ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr 338 and Ile 760 of the α 2 -subunit of Na + /K + -ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe 475 in the N-domain, the other one close to Asp 369 in the P-domain. However, binding of Mg 2+ •ATP to any of these sites in the "open conformation" may not lead to phosphorylation of Asp 369 . Additional conformations of the cytoplasmic loop were found wobbling between "open conformation"  "semi-open conformation  "closed conformation" in the absence of 2Mg 2+ •ATP. The cytoplasmic loop's conformational change to the "semi-open conformation"-characterized by a hydrogen bond between Arg 543 and Asp 611 -triggers by binding of 2Mg 2+ •ATP to a single ATP site and conversion to the "closed conformation" the phosphorylation of Asp 369 in the P-domain, and hence the start of Na + /K + -activated ATP hydrolysis.

Significance of Shear Wall in Multi-Storey Structure With Seismic Analysis

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Bongilwar, Rajat; Harne, V. R.; Chopade, Aditya

2018-03-01

In past decades, shear walls are one of the most appropriate and important structural component in multi-storied building. Therefore, it would be very interesting to study the structural response and their systems in multi-storied structure. Shear walls contribute the stiffness and strength during earthquakes which are often neglected during design of structure and construction. This study shows the effect of shear walls which significantly affect the vulnerability of structures. In order to test this hypothesis, G+8 storey building was considered with and without shear walls and analyzed for various parameters like base shear, storey drift ratio, lateral displacement, bending moment and shear force. Significance of shear wall has been studied with the help of two models. First model is without shear wall i.e. bare frame and other another model is with shear wall considering opening also in it. For modeling and analysis of both the models, FEM based software ETABS 2016 were used. The analysis of all models was done using Equivalent static method. The comparison of results has been done based on same parameters like base shear, storey drift ratio, lateral displacement, bending moment and shear force.

The significance of GW-SW interactions for biogeochemical processes in sandy streambeds

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Arnon, Shai; De Falco, Natalie; Fox, Aryeh; Laube, Gerrit; Schmidt, Christian; Fleckenstein, Jan; Boano, Fulvio

2015-04-01

Stream-groundwater interactions have a major impact on hyporheic exchange fluxes in sandy streambeds. However, the physical complexity of natural streams has limited our ability to study these types of interactions systematically, and to evaluate their importance to biogeochemical processes and nutrient cycling. In this work we were able to quantify the effect of losing and gaining fluxes on hyporheic exchange and nutrient cycling in homogeneous and heterogeneous streambeds by combining experiments in laboratory flumes and modeling. Tracer experiments for measuring hyporheic exchange were done using dyes and NaCl under various combinations of overlying water velocity and losing or gaining fluxes. Nutrient cycling experiments were conducted after growing a benthic biofilm by spiking with Sodium Benzoate (as a source of labile dissolved organic carbon, DOC) and measuring DOC and oxygen dynamics. The combination of experimental observations and modeling revealed that interfacial transport increases with the streambed hydraulic conductivity and proportional to the square of the overlying water velocity. Hyporheic exchange fluxes under losing and gaining flow conditions were similar, and became smaller when the losing or gaining flux increases. Increasing in streambed hydraulic conductivity led to higher hyporheic fluxes and reduction in the effects of losing and gaining flow conditions to constrain exchange. Despite the evident effect of flow conditions on hyporheic exchange, labile DOC uptake was positively linked to increasing overlying water velocity but was not affected by losing and gaining fluxes. This is because microbial aerobic activity was taking place at the upper few millimeters of the streambed as shown by local oxygen consumption rates, which was measured using microelectrodes. Based on modeling work, it is expected that GW-SW interaction will be more significant for less labile DOC and anaerobic processes. Our results enable us to study systematically

Large diameter femoral heads impose significant alterations on the strains developed on femoral component and bone: a finite element analysis.

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Theodorou, E G; Provatidis, C G; Babis, G C; Georgiou, C S; Megas, P D

2011-01-01

Total Hip Arthroplasty aims at fully recreating a functional hip joint. Over the past years modular implant systems have become common practice and are widely used, due to the surgical options they provide. In addition Big Femoral Heads have also been implemented in the process, providing more flexibility for the surgeon. The current study aims at investigating the effects that femoral heads of bigger diameter may impose on the mechanical behavior of the bone-implant assembly. Using data acquired by Computed Tomographies and a Coordinate Measurement Machine, a cadaveric femur and a Profemur-E modular stem were fully digitized, leading to a three dimensional finite element model in ANSYS Workbench. Strains and stresses were then calculated, focusing on areas of clinical interest, based on Gruen zones: the calcar and the corresponding below the greater trochanter area in the proximal femur, the stem tip region and a profile line along linea aspera. The performed finite elements analysis revealed that the use of large diameter heads produces significant changes in strain development within the bone volume, especially in the lateral side. The application of Frost's law in bone remodeling, validated the hypothesis that for all diameters normal bone growth occurs. However, in the calcar area lower strain values were recorded, when comparing with the reference model featuring a 28mm femoral head. Along line aspera and for the stem tip area, higher values were recorded. Finally, stresses calculated on the modular neck revealed increased values, but without reaching the yield strength of the titanium alloy used.

Revealing Amphiphilic Nanodornains of Anti-Biofouling Polymer Coatings

Energy Technology Data Exchange (ETDEWEB)

Amadei, CA; Yang, R; Chiesa, M; Gleason, KK; Santos, S

2014-04-09

Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be similar to 1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

Kernel density surface modelling as a means to identify significant concentrations of vulnerable marine ecosystem indicators.

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Ellen Kenchington

Full Text Available The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify "significant concentrations" of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores, and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here

Garrison's model of self-directed learning: preliminary validation and relationship to academic achievement.

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Abd-El-Fattah, Sabry M

2010-11-01

In this project, 119 undergraduates responded to a questionnaire tapping three psychological constructs implicated in Garrison's model of self-directed learning: self-management, self-monitoring, and motivation. Mediation analyses showed that these psychological constructs are interrelated and that motivation mediates the relationship between self-management and self-monitoring. Path modeling analyses revealed that self-management and self-monitoring significantly predicted academic achievement over two semesters with self-management being the strongest predictor. Motivation significantly predicted academic achievement over the second semester only. Implications of these findings for self-directed learning and academic achievement in a traditional classroom setting are discussed.

Exoplanets, Exo-Solar Life, and Human Significance

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Wiseman, Jennifer

2011-01-01

With the recent detection of over 500 extrasolar planets, the existence of "other worlds", perhaps even other Earths, is no longer in the realm of science fiction. The study of exoplanets rapidly moved from an activity on the fringe of astronomy to one of the highest priorities of the world's astronomical programs. Actual images of extrasolar planets were revealed over the past two years for the first time. NASA's Hubble Space Telescope is already characterizing the atmospheres of Jupiter-like planets, in other systems. And the recent launch of the NASA Kepler space telescope is enabling the first statistical assessment of how common solar systems like our own really are. As we begin to characterize these "other worlds" and assess their habitability, the question of the significance and uniqueness of life on Earth will impact our society as never before. I will provide a comprehensive overview of the techniques and status of exoplanet detection, followed by reflections as to the societal impact of finding out that Earths are common, or rare. Will finding other potentially habitable planets create another "Copernican Revolution"? Will perceptions of the significance of life on Earth change when we find other Earth-like planets? I will discuss the plans of the scientific community for future telescopes that will be abe to survey our solar neighborhood for Earth-like planets, study their atmospheres, and search for biological signs of life.

High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

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Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

2014-11-01

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract

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Satoshi Inoue

2018-03-01

Full Text Available Using preclinical models, we have recently found that ELK1, a transcriptional factor that activates downstream targets, including c-fos proto-oncogene, induces bladder cancer outgrowth. Here, we immunohistochemically determined the expression status of phospho-ELK1, an activated form of ELK1, in upper urinary tract urothelial carcinoma (UUTUC. Overall, phospho-ELK1 was positive in 47 (47.5%; 37 weak (1+ and 10 moderate (2+ of 99 UUTUCs, which was significantly (P = 0.002 higher than in benign urothelium (21 (25.3% of 83; 17 1+ and 4 2+ and was also associated with androgen receptor expression (P = 0.001. Thirteen (35.1% of 37 non-muscle-invasive versus 34 (54.8% of 62 muscle-invasive UUTUCs (P = 0.065 were immunoreactive for phospho-ELK1. Lymphovascular invasion was significantly (P = 0.014 more often seen in phospho-ELK1(2+ tumors (80.0% than in phospho-ELK1(0/1+ tumors (36.0%. There were no statistically significant associations between phospho-ELK1 expression and tumor grade, presence of concurrent carcinoma in situ or hydronephrosis, or pN status. Kaplan-Meier and log-rank tests revealed that patients with phospho-ELK1(2+ tumor had marginally and significantly higher risks of disease progression (P = 0.055 and cancer-specific mortality (P = 0.008, respectively, compared to those with phospho-ELK1(0/1+ tumor. The current results thus support our previous observations in bladder cancer and further suggest that phospho-ELK1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.

Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

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Colin Klein

2018-02-01

Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.

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Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John

2009-03-01

To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

Revealing the Driving Forces of Mid-Cities Urban Growth Patterns Using Spatial Modeling: a Case Study of Los Ángeles, Chile

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Mauricio I. Aguayo

2007-06-01

Full Text Available City growth and changes in land-use patterns cause various important social and environmental impacts. To understand the spatial and temporal dynamics of these processes, the factors that drive urban development must be identified and analyzed, especially those factors that can be used to predict future changes and their potential environmental effects. Our objectives were to quantify the relationship between urban growth and its driving forces and to predict the spatial growth pattern based on historical land-use changes for the city of Los Ángeles in central Chile. This involved the analysis of images from 1978, 1992, and 1998 and characterization of the spatial pattern of land-use change; the construction of digital coverage in GIS; the selection of predictive variables through univariate analysis; the construction of logistic regression models using growth vs. nongrowth for 1978-1992 as the dependent variable; and the prediction of the probability of land-use change by applying the regression model to the 1992-1998 period. To investigate the influence of spatial scale, we constructed several sets of models that contained (1 only distance variables, e.g., distance to highways; (2 only scale-dependent density variables, e.g., density of urban area within a 600-m radius; (3 both distance and density variables; and (4 both distance and density variables at several spatial scales. The environmental variables were included in all models. The combination of distance and density variables at several scales is required to appropriately capture the multiscale urban growth process. The best models correctly predict ~90% of the observed land-use changes for 1992-1998. The distance to access roads, densities of the urban road system and urbanized area at various scales, and soil type were the strongest predictors of the growth pattern. Other variables were less important or not significant in explaining the urban growth process. Our approach, which

Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.

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Haixin Chang

Full Text Available Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place within the confinement of a reproductive tract. In this report, we quantitatively assessed sea urchin and mouse sperm chemotaxis using a recently developed microfluidic model and high-speed imaging. Results demonstrated that sea urchin Arbacia punctulata sperm were chemotactic toward the peptide resact with high chemotactic sensitivity, with an average velocity Vx up the chemical gradient as high as 20% of its average speed (238 μm/s, while mouse sperm displayed no statistically significant chemotactic behavior in progesterone gradients, which had been proposed to guide mammalian sperm toward eggs. This work demonstrates the validity of a microfluidic model for quantitative sperm chemotaxis studies, and reveals a biological insight that chemotaxis up a progesterone gradient may not be a universal strategy for mammalian sperm to reach eggs.

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

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Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

2017-09-01

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

International Nuclear Information System (INIS)

Palumbo, Tiziana; Poultsides, George A.; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

2016-01-01

Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. The online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users

Wind energy: Overcoming inadequate wind and modeling uncertainties

Energy Technology Data Exchange (ETDEWEB)

Kane, Vivek

2010-09-15

'Green Energy' is the call of the day, and significance of Wind Energy can never be overemphasized. But the key question here is - What if the wind resources are inadequate? Studies reveal that the probability of finding favorable wind at a given place on land is only 15%. Moreover, there are inherent uncertainties associated with wind business. Can we overcome inadequate wind resources? Can we scientifically quantify uncertainty and model it to make business sense? This paper proposes a solution, by way of break-through Wind Technologies, combined with advanced tools for Financial Modeling, enabling vital business decisions.

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription.

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Singh, Prashant K; Long, Mark D; Battaglia, Sebastiano; Hu, Qiang; Liu, Song; Sucheston-Campbell, Lara E; Campbell, Moray J

2015-01-01

The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1α,25(OH)2D3. Across all models, 111 miRNAs were significantly modulated by 1α,25(OH)2D3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1α,25(OH)2D3-regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.

Collaborative Workshops and Student Academic Performance in Introductory College Mathematics Courses: A Study of a Treisman Model Math Excel Program.

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Duncan, Hollis; Dick, Thomas

2000-01-01

Describes the Treisman model which involves supplemental workshops in which college students solve problems in collaborative learning groups. Reports on the effectiveness of Math Excel, an implementation of the Treisman model for introductory mathematics courses at Oregon State University over five academic terms. Reveals a significant effect on…

Modeling the building blocks of biodiversity.

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Lucas N Joppa

Full Text Available BACKGROUND: Networks of single interaction types, such as plant-pollinator mutualisms, are biodiversity's "building blocks". Yet, the structure of mutualistic and antagonistic networks differs, leaving no unified modeling framework across biodiversity's component pieces. METHODS/PRINCIPAL FINDINGS: We use a one-dimensional "niche model" to predict antagonistic and mutualistic species interactions, finding that accuracy decreases with the size of the network. We show that properties of the modeled network structure closely approximate empirical properties even where individual interactions are poorly predicted. Further, some aspects of the structure of the niche space were consistently different between network classes. CONCLUSIONS/SIGNIFICANCE: These novel results reveal fundamental differences between the ability to predict ecologically important features of the overall structure of a network and the ability to predict pair-wise species interactions.

Equation-free analysis of two-component system signalling model reveals the emergence of co-existing phenotypes in the absence of multistationarity.

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Rebecca B Hoyle

Full Text Available Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long transient excursions from a stable state to an unstable excited state, and the switching on and off of a reaction network according to the availability of a constituent chemical species. Here we analyse a detailed stochastic kinetic model of two-component system signalling in bacteria, and show that alternative phenotypes emerge in the absence of these features. We perform a bifurcation analysis of deterministic reaction rate equations derived from the model, and find that they cannot reproduce the whole range of qualitative responses to external signals demonstrated by direct stochastic simulations. In particular, the mixed mode, where stochastic switching and a graded response are seen simultaneously, is absent. However, probabilistic and equation-free analyses of the stochastic model that calculate stationary states for the mean of an ensemble of stochastic trajectories reveal that slow transcription of either response regulator or histidine kinase leads to the coexistence of an approximate basal solution and a graded response that combine to produce the mixed mode, thus establishing its essential stochastic nature. The same techniques also show that stochasticity results in the observation of an all-or-none bistable response over a much wider range of external signals than would be expected on deterministic grounds. Thus we demonstrate the application of numerical equation-free methods to a detailed biochemical reaction network model, and show that it can provide new insight into the role of stochasticity in the emergence of phenotypic diversity.

Evaluation of a novel dry eye model induced by oral administration of finasteride.

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Li, Kai; Zhang, Chuanwei; Yang, Zichao; Wang, Yuliang; Si, Haipeng

2017-12-01

Dry eye is a common eye disease, and suitable animal models are indispensable for investigating the pathogenesis and developing treatments for dry eye. The present study was conducted to develop an androgen deficiency dry eye model induced by finasteride, and to evaluate ocular surface status and inflammatory cytokine gene expression in the lacrimal gland using a cytokine antibody array system. The results revealed that the antiandrogenic drug finasteride induced significant tear deficiency, and the histopathology results revealed significant inflammatory cell infiltration in the lacrimal gland. The cytokine antibody array system identified increased B7‑2 (also known as cluster of differentiation 86), interleukin (IL)‑1β, IL‑4, IL‑6, IL‑10, matrix metalloproteinase‑8, Fas ligand, tumor necrosis factor (TNF)‑α and metalloproteinase inhibitor 1 levels in the lacrimal gland of the dry eye model. These cytokines were validated as candidate markers through the use of western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Both analyses confirmed a significant increase in proinflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and anti‑inflammatory cytokines, including IL‑4 and IL‑10. The aforementioned data suggested that inflammation in antiandrogenic models resulted from a balance between inflammatory and anti‑inflammatory responses. Thus, direct finasteride administration may produce an applicable model for dry eye mediated by androgen deficiency. In addition, there may be a correlation between sex, steroid deficiency and the inflammatory response. The findings of the present study have provided useful information for the pathogenesis and diagnosis of dry eye mediated by androgen deficiency.

Dimensional Model for Estimating Factors influencing Childhood Obesity: Path Analysis Based Modeling

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Maryam Kheirollahpour

2014-01-01

Full Text Available The main objective of this study is to identify and develop a comprehensive model which estimates and evaluates the overall relations among the factors that lead to weight gain in children by using structural equation modeling. The proposed models in this study explore the connection among the socioeconomic status of the family, parental feeding practice, and physical activity. Six structural models were tested to identify the direct and indirect relationship between the socioeconomic status and parental feeding practice general level of physical activity, and weight status of children. Finally, a comprehensive model was devised to show how these factors relate to each other as well as to the body mass index (BMI of the children simultaneously. Concerning the methodology of the current study, confirmatory factor analysis (CFA was applied to reveal the hidden (secondary effect of socioeconomic factors on feeding practice and ultimately on the weight status of the children and also to determine the degree of model fit. The comprehensive structural model tested in this study suggested that there are significant direct and indirect relationships among variables of interest. Moreover, the results suggest that parental feeding practice and physical activity are mediators in the structural model.

ICT evaluation models and performance of medium and small enterprises

Directory of Open Access Journals (Sweden)

Bayaga Anass

2014-01-01

Full Text Available Building on prior research related to (1 impact of information communication technology (ICT and (2 operational risk management (ORM in the context of medium and small enterprises (MSEs, the focus of this study was to investigate the relationship between (1 ICT operational risk management (ORM and (2 performances of MSEs. To achieve the focus, the research investigated evaluating models for understanding the value of ICT ORM in MSEs. Multiple regression, Repeated-Measures Analysis of Variance (RM-ANOVA and Repeated-Measures Multivariate Analysis of Variance (RM-MANOVA were performed. The findings of the distribution revealed that only one variable made a significant percentage contribution to the level of ICT operation in MSEs, the Payback method (β = 0.410, p < .000. It may thus be inferred that the Payback method is the prominent variable, explaining the variation in level of evaluation models affecting ICT adoption within MSEs. Conclusively, in answering the two questions (1 degree of variability explained and (2 predictors, the results revealed that the variable contributed approximately 88.4% of the variations in evaluation models affecting ICT adoption within MSEs. The analysis of variance also revealed that the regression coefficients were real and did not occur by chance

Modeling the mechanical properties of liver fibrosis in rats.

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Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

2016-06-14

The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. Copyright © 2016 Elsevier Ltd. All rights reserved.

A mistletoe tale: postglacial invasion of Psittacanthus schiedeanus (Loranthaceae) to Mesoamerican cloud forests revealed by molecular data and species distribution modeling.

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Ornelas, Juan Francisco; Gándara, Etelvina; Vásquez-Aguilar, Antonio Acini; Ramírez-Barahona, Santiago; Ortiz-Rodriguez, Andrés Ernesto; González, Clementina; Mejía Saules, María Teresa; Ruiz-Sanchez, Eduardo

2016-04-12

Ecological adaptation to host taxa is thought to result in mistletoe speciation via race formation. However, historical and ecological factors could also contribute to explain genetic structuring particularly when mistletoe host races are distributed allopatrically. Using sequence data from nuclear (ITS) and chloroplast (trnL-F) DNA, we investigate the genetic differentiation of 31 Psittacanthus schiedeanus (Loranthaceae) populations across the Mesoamerican species range. We conducted phylogenetic, population and spatial genetic analyses on 274 individuals of P. schiedeanus to gain insight of the evolutionary history of these populations. Species distribution modeling, isolation with migration and Bayesian inference methods were used to infer the evolutionary transition of mistletoe invasion, in which evolutionary scenarios were compared through posterior probabilities. Our analyses revealed shallow levels of population structure with three genetic groups present across the sample area. Nine haplotypes were identified after sequencing the trnL-F intergenic spacer. These haplotypes showed phylogeographic structure, with three groups with restricted gene flow corresponding to the distribution of individuals/populations separated by habitat (cloud forest localities from San Luis Potosí to northwestern Oaxaca and Chiapas, localities with xeric vegetation in central Oaxaca, and localities with tropical deciduous forests in Chiapas), with post-glacial population expansions and potentially corresponding to post-glacial invasion types. Similarly, 44 ITS ribotypes suggest phylogeographic structure, despite the fact that most frequent ribotypes are widespread indicating effective nuclear gene flow via pollen. Gene flow estimates, a significant genetic signal of demographic expansion, and range shifts under past climatic conditions predicted by species distribution modeling suggest post-glacial invasion of P. schiedeanus mistletoes to cloud forests. However, Approximate

Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding.

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Joshua G X Wong

Full Text Available Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients.We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188, and those without (n = 4,195. Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization.On admission, female gender (p38°C (p38°C (aOR 1.81; 95% CI: 1.27-2.61, nausea/vomiting (aOR 1.39; 95% CI: 0.94-2.12, ANC (aOR 1.3; 95% CI: 1.15-1.46, ALC (aOR 0.4; 95% CI: 0.25-0.64, hematocrit percentage (aOR 0.96; 95% CI: 0.92-1.002 and platelet count (aOR 0.993; 95% CI: 0.988-0.998. At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98.Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre-identifying those less likely to develop clinically significant bleeding.

Revealing effective classifiers through network comparison

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Gallos, Lazaros K.; Fefferman, Nina H.

2014-11-01

The ability to compare complex systems can provide new insight into the fundamental nature of the processes captured, in ways that are otherwise inaccessible to observation. Here, we introduce the n-tangle method to directly compare two networks for structural similarity, based on the distribution of edge density in network subgraphs. We demonstrate that this method can efficiently introduce comparative analysis into network science and opens the road for many new applications. For example, we show how the construction of a “phylogenetic tree” across animal taxa according to their social structure can reveal commonalities in the behavioral ecology of the populations, or how students create similar networks according to the University size. Our method can be expanded to study many additional properties, such as network classification, changes during time evolution, convergence of growth models, and detection of structural changes during damage.

Statistical significant changes in ground thermal conditions of alpine Austria during the last decade

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Kellerer-Pirklbauer, Andreas

2016-04-01

Longer data series (e.g. >10 a) of ground temperatures in alpine regions are helpful to improve the understanding regarding the effects of present climate change on distribution and thermal characteristics of seasonal frost- and permafrost-affected areas. Beginning in 2004 - and more intensively since 2006 - a permafrost and seasonal frost monitoring network was established in Central and Eastern Austria by the University of Graz. This network consists of c.60 ground temperature (surface and near-surface) monitoring sites which are located at 1922-3002 m a.s.l., at latitude 46°55'-47°22'N and at longitude 12°44'-14°41'E. These data allow conclusions about general ground thermal conditions, potential permafrost occurrence, trend during the observation period, and regional pattern of changes. Calculations and analyses of several different temperature-related parameters were accomplished. At an annual scale a region-wide statistical significant warming during the observation period was revealed by e.g. an increase in mean annual temperature values (mean, maximum) or the significant lowering of the surface frost number (F+). At a seasonal scale no significant trend of any temperature-related parameter was in most cases revealed for spring (MAM) and autumn (SON). Winter (DJF) shows only a weak warming. In contrast, the summer (JJA) season reveals in general a significant warming as confirmed by several different temperature-related parameters such as e.g. mean seasonal temperature, number of thawing degree days, number of freezing degree days, or days without night frost. On a monthly basis August shows the statistically most robust and strongest warming of all months, although regional differences occur. Despite the fact that the general ground temperature warming during the last decade is confirmed by the field data in the study region, complications in trend analyses arise by temperature anomalies (e.g. warm winter 2006/07) or substantial variations in the winter

Significance of thymic scintigraphy

International Nuclear Information System (INIS)

Baba, Hiromi; Oshiumi, Yoshihiko; Nakayama, Chikashi; Morita, Kazunori; Koga, Ichinari

1978-01-01

Thymic scintigraphy by 67 Ga-citrate and 75 Se-methionine was done on 6 cases of thymoma, and 5 cases of myasthenia gravis. Scan was positive on 5 of 6 cases of thymoma. All patients with malignant thymoma were positive. Among the 7 cases of myasthenia gravis, scintigrams revealed 2 thymomas and 1 hyperplasia on whom no thymic mass suspected. Thymic scintigraphy is useful examination when dealing with myasthenia gravis. (auth.)

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

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Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

2017-02-01

Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

Statistical significance of trends in monthly heavy precipitation over the US

KAUST Repository

Mahajan, Salil

2011-05-11

Trends in monthly heavy precipitation, defined by a return period of one year, are assessed for statistical significance in observations and Global Climate Model (GCM) simulations over the contiguous United States using Monte Carlo non-parametric and parametric bootstrapping techniques. The results from the two Monte Carlo approaches are found to be similar to each other, and also to the traditional non-parametric Kendall\\'s τ test, implying the robustness of the approach. Two different observational data-sets are employed to test for trends in monthly heavy precipitation and are found to exhibit consistent results. Both data-sets demonstrate upward trends, one of which is found to be statistically significant at the 95% confidence level. Upward trends similar to observations are observed in some climate model simulations of the twentieth century, but their statistical significance is marginal. For projections of the twenty-first century, a statistically significant upwards trend is observed in most of the climate models analyzed. The change in the simulated precipitation variance appears to be more important in the twenty-first century projections than changes in the mean precipitation. Stochastic fluctuations of the climate-system are found to be dominate monthly heavy precipitation as some GCM simulations show a downwards trend even in the twenty-first century projections when the greenhouse gas forcings are strong. © 2011 Springer-Verlag.

Validated predictive modelling of the environmental resistome.

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Amos, Gregory C A; Gozzard, Emma; Carter, Charlotte E; Mead, Andrew; Bowes, Mike J; Hawkey, Peter M; Zhang, Lihong; Singer, Andrew C; Gaze, William H; Wellington, Elizabeth M H

2015-06-01

Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome.