GW182 controls Drosophila circadian behavior and PDF-Receptor signaling

PubMed Central

Zhang, Yong; Emery, Patrick

2013-01-01

The neuropeptide PDF is crucial for Drosophila circadian behavior: it keeps circadian neurons synchronized. Here, we identify GW182 as a key regulator of PDF signaling. Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function. GW182 mediates miRNA-dependent gene silencing through its interaction with AGO1. Consistently, GW182's AGO1 interaction domain is required for GW182's circadian function. Moreover, our results indicate that GW182 modulates PDFR signaling by silencing the expression of the cAMP phosphodiesterase DUNCE. Importantly, this repression is under photic control, and GW182 activity level - which is limiting in circadian neurons - influences the responses of the circadian neural network to light. We propose that GW182's gene silencing activity functions as a rheostat for PDFR signaling, and thus profoundly impacts the circadian neural network and its response to environmental inputs. PMID:23583112

Background controlled QTL mapping in pure-line genetic populations derived from four-way crosses

PubMed Central

Zhang, S; Meng, L; Wang, J; Zhang, L

2017-01-01

Pure lines derived from multiple parents are becoming more important because of the increased genetic diversity, the possibility to conduct replicated phenotyping trials in multiple environments and potentially high mapping resolution of quantitative trait loci (QTL). In this study, we proposed a new mapping method for QTL detection in pure-line populations derived from four-way crosses, which is able to control the background genetic variation through a two-stage mapping strategy. First, orthogonal variables were created for each marker and used in an inclusive linear model, so as to completely absorb the genetic variation in the mapping population. Second, inclusive composite interval mapping approach was implemented for one-dimensional scanning, during which the inclusive linear model was employed to control the background variation. Simulation studies using different genetic models demonstrated that the new method is efficient when considering high detection power, low false discovery rate and high accuracy in estimating quantitative trait loci locations and effects. For illustration, the proposed method was applied in a reported wheat four-way recombinant inbred line population. PMID:28722705

Background controlled QTL mapping in pure-line genetic populations derived from four-way crosses.

PubMed

Zhang, S; Meng, L; Wang, J; Zhang, L

2017-10-01

Pure lines derived from multiple parents are becoming more important because of the increased genetic diversity, the possibility to conduct replicated phenotyping trials in multiple environments and potentially high mapping resolution of quantitative trait loci (QTL). In this study, we proposed a new mapping method for QTL detection in pure-line populations derived from four-way crosses, which is able to control the background genetic variation through a two-stage mapping strategy. First, orthogonal variables were created for each marker and used in an inclusive linear model, so as to completely absorb the genetic variation in the mapping population. Second, inclusive composite interval mapping approach was implemented for one-dimensional scanning, during which the inclusive linear model was employed to control the background variation. Simulation studies using different genetic models demonstrated that the new method is efficient when considering high detection power, low false discovery rate and high accuracy in estimating quantitative trait loci locations and effects. For illustration, the proposed method was applied in a reported wheat four-way recombinant inbred line population.

A Genetic RNAi Screen for IP3/Ca2+ Coupled GPCRs in Drosophila Identifies the PdfR as a Regulator of Insect Flight

PubMed Central

Agrawal, Tarjani; Sadaf, Sufia; Hasan, Gaiti

2013-01-01

Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP3 receptor. Among the 108 GPCRs screened, we discovered 5 IP3/Ca2+ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior. PMID:24098151

Genetic background in nonalcoholic fatty liver disease: A comprehensive review

PubMed Central

Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

2015-01-01

In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

Unexpected effects of different genetic backgrounds on identification of genomic rearrangements via whole-genome next generation sequencing.

PubMed

Chen, Zhangguo; Gowan, Katherine; Leach, Sonia M; Viboolsittiseri, Sawanee S; Mishra, Ameet K; Kadoishi, Tanya; Diener, Katrina; Gao, Bifeng; Jones, Kenneth; Wang, Jing H

2016-10-21

Whole genome next generation sequencing (NGS) is increasingly employed to detect genomic rearrangements in cancer genomes, especially in lymphoid malignancies. We recently established a unique mouse model by specifically deleting a key non-homologous end-joining DNA repair gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in germinal center B cells. This mouse model spontaneously develops mature B cell lymphomas (termed G1XP lymphomas). Here, we attempt to employ whole genome NGS to identify novel structural rearrangements, in particular inter-chromosomal translocations (CTXs), in these G1XP lymphomas. We sequenced six lymphoma samples, aligned our NGS data with mouse reference genome (in C57BL/6J (B6) background) and identified CTXs using CREST algorithm. Surprisingly, we detected widespread CTXs in both lymphomas and wildtype control samples, majority of which were false positive and attributable to different genetic backgrounds. In addition, we validated our NGS pipeline by sequencing multiple control samples from distinct tissues of different genetic backgrounds of mouse (B6 vs non-B6). Lastly, our studies showed that widespread false positive CTXs can be generated by simply aligning sequences from different genetic backgrounds of mouse. We conclude that mapping and alignment with reference genome might not be a preferred method for analyzing whole-genome NGS data obtained from a genetic background different from reference genome. Given the complex genetic background of different mouse strains or the heterogeneity of cancer genomes in human patients, in order to minimize such systematic artifacts and uncover novel CTXs, a preferred method might be de novo assembly of personalized normal control genome and cancer cell genome, instead of mapping and aligning NGS data to mouse or human reference genome. Thus, our studies have critical impact on the manner of data analysis for cancer genomics.

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families.

PubMed

Page, Joshua; Constantino, John Nicholas; Zambrana, Katherine; Martin, Eden; Tunc, Ilker; Zhang, Yi; Abbacchi, Anna; Messinger, Daniel

2016-01-01

Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability

Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

PubMed

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-03-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

PubMed Central

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-01-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

PubMed

Shafer, Orie T; Kim, Dong Jo; Dunbar-Yaffe, Richard; Nikolaev, Viacheslav O; Lohse, Martin J; Taghert, Paul H

2008-04-24

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

Gene interaction at seed-awning loci in the genetic background of wild rice.

PubMed

Ikemoto, Mai; Otsuka, Mitsuharu; Thanh, Pham Thien; Phan, Phuong Dang Thai; Ishikawa, Ryo; Ishii, Takashige

2017-09-12

Seed awning is one of the important traits for successful propagation in wild rice. During the domestication of rice by ancient humans, plants with awnless seeds may have been selected because long awns hindered collection and handling activities. To investigate domestication of awnless rice, QTL analysis for seed awning was first carried out using backcross recombinant inbred lines between Oryza sativa Nipponbare (recurrent parent) and O. rufipogon W630 (donor parent). Two strong QTLs were detected in the same regions as known major seed-awning loci, An-1 and RAE2. Subsequent causal mutation surveying and fine mapping confirmed that O. rufipogon W630 has functional alleles at both loci. The gene effects and interactions at these loci were examined using two backcross populations with reciprocal genetic backgrounds of O. sativa Nipponbare and O. rufipogon W630. As awn length in wild rice varied among seeds even in the same plant, awn length was measured based on spikelet position. In the genetic background of cultivated rice, the wild alleles at An-1 and RAE2 had awning effects, and plants having both wild homozygous alleles produced awns whose length was about 70% of those of the wild parent. On the other hand, in the genetic background of wild rice, the substitution of cultivated alleles at An-1 and RAE2 contributed little to awn length reduction. These results indicate that the domestication process of awnless seeds was complicated because many genes are involved in awn formation in wild rice.

New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

PubMed

Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

2008-05-30

Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial

The GABAA Receptor RDL Acts in Peptidergic PDF Neurons to Promote Sleep in Drosophila

PubMed Central

Chung, Brian Y.; Kilman, Valerie L.; Keath, J. Russel; Pitman, Jena L.; Allada, Ravi

2011-01-01

SUMMARY Sleep is regulated by a circadian clock that largely times sleep and wake to occur at specific times of day and a sleep homeostat that drives sleep as a function of duration of prior wakefulness[1]. To better understand the role of the circadian clock in sleep regulation, we have been using the fruit fly Drosophila melanogaster[2]. Fruit flies display all of the core behavioral features of sleep including relative immobility, elevated arousal thresholds and homeostatic regulation[2, 3]. We assessed sleep-wake modulation by a core set of 20 circadian pacemaker neurons that express the neuropeptide PDF. We find that PDF neuron ablation, loss of pdf or its receptor pdfr results in increased sleep during the late night in light:dark (LD) conditions and more prominent increases on the first subjective day of constant darkness (DD). Flies deploy similar genetic and neurotransmitter pathways to regulate sleep as their mammalian counterparts, including GABA[4]. We find that RNAi-mediated knockdown of the GABAA receptor gene, Resistant to dieldrin (Rdl), in PDF neurons, reduced sleep consistent with a role for GABA in inhibiting PDF neuron function. Patch clamp electrophysiology reveals GABA-activated picrotoxin-sensitive chloride currents on PDF+ neurons. In addition, RDL is detectable most strongly on the large subset of PDF+ pacemaker neurons. These results suggest that GABAergic inhibition of arousal promoting PDF neurons is an important mode of sleep-wake regulation in vivo. PMID:19230663

The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep in Drosophila.

PubMed

Chung, Brian Y; Kilman, Valerie L; Keath, J Russel; Pitman, Jena L; Allada, Ravi

2009-03-10

Sleep is regulated by a circadian clock that times sleep and wake to specific times of day and a homeostat that drives sleep as a function of prior wakefulness. To analyze the role of the circadian clock, we have used the fruit fly Drosophila. Flies display the core behavioral features of sleep, including relative immobility, elevated arousal thresholds, and homeostatic regulation. We assessed sleep-wake modulation by a core set of circadian pacemaker neurons that express the neuropeptide PDF. We find that disruption of PDF function increases sleep during the late night in light:dark and the first subjective day of constant darkness. Flies deploy genetic and neurotransmitter pathways to regulate sleep that are similar to those of their mammalian counterparts, including GABA. We find that RNA interference-mediated knockdown of the GABA(A) receptor gene, Resistant to dieldrin (Rdl), in PDF neurons reduces sleep, consistent with a role for GABA in inhibiting PDF neuron function. Patch-clamp electrophysiology reveals GABA-activated picrotoxin-sensitive chloride currents on PDF+ neurons. In addition, RDL is detectable most strongly on the large subset of PDF+ pacemaker neurons. These results suggest that GABAergic inhibition of arousal-promoting PDF neurons is an important mode of sleep-wake regulation in vivo.

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome

PubMed Central

Kamiyoshi, Naohiro; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-01-01

Background and objectives Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. Design, setting, participants, & measurements We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport–related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. Results The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte–related genes. Conclusions The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive

The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila.

PubMed

Duvall, Laura B; Taghert, Paul H

2012-01-01

The neuropeptide Pigment Dispersing Factor (PDF) is essential for normal circadian function in Drosophila. It synchronizes the phases of M pacemakers, while in E pacemakers it decelerates their cycling and supports their amplitude. The PDF receptor (PDF-R) is present in both M and subsets of E cells. Activation of PDF-R stimulates cAMP increases in vitro and in M cells in vivo. The present study asks: What is the identity of downstream signaling components that are associated with PDF receptor in specific circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells. Genetic disruptions of AC3 specifically disrupt PDF responses: they do not affect other Gs-coupled GPCR signaling in M cells, they can be rescued, and they do not represent developmental alterations. Knockdown of the Drosophila AKAP-like scaffolding protein Nervy also reduces PDF responses. Flies with AC3 alterations show behavioral syndromes consistent with known roles of M pacemakers as mediated by PDF. Surprisingly, disruption of AC3 does not alter PDF responses in E cells--the PDF-R(+) LNd. Within M pacemakers, PDF-R couples preferentially to a single AC, but PDF-R association with a different AC(s) is needed to explain PDF signaling in the E pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into "circadian signalosomes," whose compositions differ between E and M pacemaker cell types.

Leveraging Genetic-Background Effects in Saccharomyces cerevisiae To Improve Lignocellulosic Hydrolysate Tolerance

DOE PAGES

Sardi, Maria; Rovinskiy, Nikolay; Zhang, Yaoping; ...

2016-07-22

We report a major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in different Saccharomyces cerevisiae (yeast)more » strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six different S. cerevisiae strains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Lastly, our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.« less

Genetics Home Reference: lymphangioleiomyomatosis

MedlinePlus

... Genetics Share: Email Facebook Twitter Home Health Conditions LAM Lymphangioleiomyomatosis Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Lymphangioleiomyomatosis ( LAM ) is a condition that affects the lungs , the ...

Genetics Home Reference: homocystinuria

MedlinePlus

... reductase deficiency Orphanet: Homocystinuria without methylmalonic aciduria Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (6 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) CLIMB: ...

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.

PubMed

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-30

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-01

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit. PMID:28134281

Genetics Home Reference: citrullinemia

MedlinePlus

... Type II MalaCards: citrullinemia, classic Orphanet: Citrullinemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (5 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) National ...

Genetic background effects of keratin 8 and 18 in a DDC-induced hepatotoxicity and Mallory-Denk body formation mouse model.

PubMed

Haybaeck, Johannes; Stumptner, Cornelia; Thueringer, Andrea; Kolbe, Thomas; Magin, Thomas M; Hesse, Michael; Fickert, Peter; Tsybrovskyy, Oleksiy; Müller, Heimo; Trauner, Michael; Zatloukal, Kurt; Denk, Helmut

2012-06-01

Keratin 8 (K8) and keratin 18 (K18) form the major hepatocyte cytoskeleton. We investigated the impact of genetic loss of either K8 or K18 on liver homeostasis under toxic stress with the hypothesis that K8 and K18 exert different functions. krt8⁻/⁻ and krt18⁻/⁻ mice crossed into the same 129-ola genetic background were treated by acute and chronic administration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). In acutely DDC-intoxicated mice, macrovesicular steatosis was more pronounced in krt8⁻/⁻ and krt18⁻/⁻ compared with wild-type (wt) animals. Mallory-Denk bodies (MDBs) appeared in krt18⁻/⁻ mice already at an early stage of intoxication in contrast to krt8⁻/⁻ mice that did not display MDB formation when fed with DDC. Keratin-deficient mice displayed significantly lower numbers of apoptotic hepatocytes than wt animals. krt8⁻/⁻, krt18⁻/⁻ and control mice displayed comparable cell proliferation rates. Chronically DDC-intoxicated krt18⁻/⁻ and wt mice showed a similarly increased degree of steatohepatitis with hepatocyte ballooning and MDB formation. In krt8⁻/⁻ mice, steatosis was less, ballooning, and MDBs were absent. krt18⁻/⁻ mice developed MDBs whereas krt8⁻/⁻ mice on the same genetic background did not, highlighting the significance of different structural properties of keratins. They are independent of the genetic background as an intrinsic factor. By contrast, toxicity effects may depend on the genetic background. krt8⁻/⁻ and krt18⁻/⁻ mice on the same genetic background show similar sensitivity to DDC intoxication and almost resemble wt animals regarding survival, degree of porphyria, liver-to-body weight ratio, serum bilirubin and liver enzyme levels. This stands in contrast to previous work where krt8⁻/⁻ and krt18⁻/⁻ mice on different genetic backgrounds were investigated.

Web Standard: PDF - When to Use, Document Metadata, PDF Sections

EPA Pesticide Factsheets

PDF files provide some benefits when used appropriately. PDF files should not be used for short documents ( 5 pages) unless retaining the format for printing is important. PDFs should have internal file metadata and meet section 508 standards.

Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice.

PubMed

Narahara, Shun; Matsushima, Haruna; Sakai, Eiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki

2012-04-01

Osteoclasts (OCLs) are multinucleated giant cells and are formed by the fusion of mononuclear progenitors of monocyte/macrophage lineage. It is known that macrophages derived from different genetic backgrounds exhibit quite distinct characteristics of immune responses. However, it is unknown whether OCLs from different genetic backgrounds show distinct characteristics. In this study, we showed that bone-marrow macrophages (BMMs) derived from C57BL/6, BALB/c and ddY mice exhibited considerably distinct morphological characteristics and cell differentiation into OCLs. The differentiation of BMMs into OCLs was comparatively quicker in the C57BL/6 and ddY mice, while that of BALB/c mice was rather slow. Morphologically, ddY OCLs showed a giant cell with a round shape, C57BL/6 OCLs were of a moderate size with many protrusions and BALB/c OCLs had the smallest size with fewer nuclei. The intracellular signaling of differentiation and expression levels of marker proteins of OCLs were different in the respective strains. Treatment of BMMs from the three different strains with the reducing agent N-acetylcysteine (NAC) or with the oxidation agent hydrogen peroxide (H(2)O(2)) induced changes in the shape and sizes of the cells and caused distinct patterns of cell differentiation and survival. Thus, genetic backgrounds and redox conditions regulate the morphological characteristics and cell differentiation of OCLs.

Genetics Home Reference: keratoconus

MedlinePlus

... Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Home Health Conditions Keratoconus Keratoconus Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Keratoconus ...

Cardiac Teratogenicity in Mouse Maternal Phenylketonuria: Defining phenotype parameters and genetic background influences

PubMed Central

Seagraves, Nikki J.; McBride, Kim L.

2012-01-01

Maternal phenylketonuria (MPKU) is a syndrome including cardiovascular malformations (CVMs), microcephaly, intellectual impairment, and small for gestational age, caused by in-utero exposure to elevated serum phenylalanine (Phe) due to PKU in the mother. It is becoming a public health concern as more women with PKU reach child bearing age. Although a mouse model of PKU, BTBR Pahenu2, has been available for 20 years, it has not been well utilized for studying MPKU. We used this model to delineate critical parameters in Phe cardiovascular teratogenicity and study the effect of genetic background. Dosing and timing experiments were performed with the BTBR Pahenu2 mouse. A dose response curve was noted, with CVM rates at maternal serum Phe levels <360 μM (control), 360 – 600 μM (low), 600 – 900 μM (mid), and >900μM (high) of 11.86%, 16.67%, 30.86%, and 46.67% respectively. A variety of CVMs were noted on the BTBR background, including double outlet right ventricle (DORV), aortic arch artery (AAA)abnormalities, and ventricular septal defects (VSDs). Timed exposure experiments identified a teratogenic window from embryonic day 8.5-13.5, with higher rates of conotruncal and valve defects occurring in early exposure time and persistent truncus arteriosus (PTA) and aortic arch branching abnormalities occurring with late exposure. Compared to the BTBR strain, N10+ Pahenu2 congenics on the C3H/HeJ background had higher rates of CVMs in general and propensity to left ventricular outflow tract (LVOT) malformations, while the C57B/L6 background had similar CVM rates but predominately AAA abnormalities. We have delineated key parameters of Phe cardiovascular teratogenicity, demonstrated the utility of this MPKU model on different mouse strains, and shown how genetic background profoundly affects the phenotype. PMID:22951387

The Circadian Neuropeptide PDF Signals Preferentially through a Specific Adenylate Cyclase Isoform AC3 in M Pacemakers of Drosophila

PubMed Central

Duvall, Laura B.; Taghert, Paul H.

2012-01-01

The neuropeptide Pigment Dispersing Factor (PDF) is essential for normal circadian function in Drosophila. It synchronizes the phases of M pacemakers, while in E pacemakers it decelerates their cycling and supports their amplitude. The PDF receptor (PDF-R) is present in both M and subsets of E cells. Activation of PDF-R stimulates cAMP increases in vitro and in M cells in vivo. The present study asks: What is the identity of downstream signaling components that are associated with PDF receptor in specific circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells. Genetic disruptions of AC3 specifically disrupt PDF responses: they do not affect other Gs-coupled GPCR signaling in M cells, they can be rescued, and they do not represent developmental alterations. Knockdown of the Drosophila AKAP-like scaffolding protein Nervy also reduces PDF responses. Flies with AC3 alterations show behavioral syndromes consistent with known roles of M pacemakers as mediated by PDF. Surprisingly, disruption of AC3 does not alter PDF responses in E cells—the PDF-R(+) LNd. Within M pacemakers, PDF-R couples preferentially to a single AC, but PDF-R association with a different AC(s) is needed to explain PDF signaling in the E pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into “circadian signalosomes,” whose compositions differ between E and M pacemaker cell types. PMID:22679392

Conservational PDF Equations of Turbulence

NASA Technical Reports Server (NTRS)

Shih, Tsan-Hsing; Liu, Nan-Suey

2010-01-01

Recently we have revisited the traditional probability density function (PDF) equations for the velocity and species in turbulent incompressible flows. They are all unclosed due to the appearance of various conditional means which are modeled empirically. However, we have observed that it is possible to establish a closed velocity PDF equation and a closed joint velocity and species PDF equation through conditions derived from the integral form of the Navier-Stokes equations. Although, in theory, the resulted PDF equations are neither general nor unique, they nevertheless lead to the exact transport equations for the first moment as well as all higher order moments. We refer these PDF equations as the conservational PDF equations. This observation is worth further exploration for its validity and CFD application

The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background

PubMed Central

Halberg, Richard B.; Chen, Xiaodi; Amos-Landgraf, James M.; White, Alanna; Rasmussen, Kristin; Clipson, Linda; Pasch, Cheri; Sullivan, Ruth; Pitot, Henry C.; Dove, William F.

2008-01-01

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes. PMID:18723878

The pleiotropic phenotype of Apc mutations in the mouse: allele specificity and effects of the genetic background.

PubMed

Halberg, Richard B; Chen, Xiaodi; Amos-Landgraf, James M; White, Alanna; Rasmussen, Kristin; Clipson, Linda; Pasch, Cheri; Sullivan, Ruth; Pitot, Henry C; Dove, William F

2008-09-01

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes.

Genetic Background and Environment Influence the Effects of Mutations in pykF and Help Reveal Mechanisms Underlying Their Benefit

DTIC Science & Technology

2015-08-01

another trait (Losos 2011). All of these factors make it hard to identify adaptations. Mutations are the ultimate source of genetic variation that is...effects when added to the same evolved background (See Table 2.2 for results of one-way ANOVAs). Genetic background explains most (~ 88%) of the variation ...in fitness whereas the variation explained by different pykF alleles is negligible (~2%) compared to statistical noise (~8%) (Table 2.3). These

A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior.

PubMed

Lear, Bridget C; Merrill, C Elaine; Lin, Jui-Ming; Schroeder, Analyne; Zhang, Luoying; Allada, Ravi

2005-10-20

The neuropeptide Pigment-Dispersing Factor (PDF) plays a critical role in mediating circadian control of behavior in Drosophila. Here we identify mutants (groom-of-PDF; gop) that display phase-advanced evening activity and poor free-running rhythmicity, phenocopying pdf mutants. In gop mutants, a spontaneous retrotransposon disrupts a coding exon of a G protein-coupled receptor, CG13758. Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop. Yet PDF oscillations themselves remain robust in gop mutants, suggesting that GOP acts downstream of PDF. gop is expressed most strongly in the dorsal brain in regions that lie in proximity to PDF-containing nerve terminals. Taken together, these studies implicate GOP as a PDF receptor in Drosophila.

Genetics Home Reference: isovaleric acidemia

MedlinePlus

... Consortium of Metabolic Programs Orphanet: Isovaleric acidemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) CLIMB (Children Living With Inherited Metabolic Diseases) (UK) National Organization ...

Genetics Home Reference: propionic acidemia

MedlinePlus

... Consortium of Metabolic Programs Orphanet: Propionic acidemia Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (6 links) CLIMB (Children Living With Inherited Metabolic Diseases) (UK) National Organization ...

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

PubMed Central

Choi, Lin; DeNieu, Michael; Sonnenschein, Anne; Hummel, Kristen; Marier, Christian; Victory, Andrew; Porter, Cody; Mammel, Anna; Holms, Julie; Sivaratnam, Gayatri

2017-01-01

For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis. PMID:29166655

Age, experience and genetic background influence treadmill walking in mice

PubMed Central

Wooley, Christine M.; Xing, Shuqin; Burgess, Robert W.; Cox, Gregory A.; Seburn, Kevin L.

2009-01-01

WOOLEY, C.M., S. XING, R.W. BURGESS, G.A. COX, AND K.L. SEBURN. Age, experience and genetic background influence treadmill walking in mice. PHYSIOL. BEHAV. XX(X), XXX-XXX, 2008 – The use of a treadmill to gather data for gait analysis in mice is a convenient, sensitive method to evaluate motor performance. However, evidence from several species, including mice, shows that treadmill locomotion is a novel task that is not equivalent to over ground locomotion and that may be particularly sensitive to the test environment and protocol. We investigated the effects of age, genetic background and repeated trials on treadmill walking in mice and show that these factors are important considerations in the interpretation of gait data. Specifically we report that as C57BL/6J (B6) mice age, the animals use progressively longer, less frequent strides to maintain the same walking speed. The increase is most rapid between 1 and 6 months of age and is explained, in part, by changes in size and weight. We also extended previous findings showing that repeat trials cause mice to modify their treadmill gait pattern. In general, B6 mice tend to take shorter, more frequent steps and adopt a wider dynamic stance with repeated walking trials. The nature and extent of the response changes with both the number and timing of the trials and was observed with inter-trial intervals as long as 3 months. Finally, we compared the gait pattern of an additional seven inbred strains of mice and found significant variation in the length and frequency of strides used to maintain the same walking speed. The combined results offer the bases for further mechanistic studies and can be used to guide optimal experimental design. PMID:19027767

Effect of genetic background on the contribution of New Zealand Black loci to autoimmune lupus nephritis

PubMed Central

Rozzo, Stephen J.; Vyse, Timothy J.; Drake, Charles G.; Kotzin, Brian L.

1996-01-01

Autoimmune diseases such as systemic lupus erythematosus are complex genetic traits with contributions from major histocompatibility complex (MHC) genes and multiple unknown non-MHC genes. Studies of animal models of lupus have provided important insight into the immunopathogenesis of disease, and genetic analyses of these models overcome certain obstacles encountered when studying human patients. Genome-wide scans of different genetic crosses have been used to map several disease-linked loci in New Zealand hybrid mice. Although some consensus exists among studies mapping the New Zealand Black (NZB) and New Zealand White (NZW) loci that contribute to lupus-like disease, considerable variability is also apparent. A variable in these studies is the genetic background of the non-autoimmune strain, which could influence genetic contributions from the affected strain. A direct examination of this question was undertaken in the present study by mapping NZB nephritis-linked loci in backcrosses involving different non-autoimmune backgrounds. In a backcross with MHC-congenic C57BL/6J mice, H2z appeared to be the strongest genetic determinant of severe lupus nephritis, whereas in a backcross with congenic BALB/cJ mice, H2z showed no influence on disease expression. NZB loci on chromosomes 1, 4, 11, and 14 appeared to segregate with disease in the BALB/cJ cross, but only the influence of the chromosome 1 locus spanned both crosses and showed linkage with disease when all mice were considered. Thus, the results indicate that contributions from disease-susceptibility loci, including MHC, may vary markedly depending on the non-autoimmune strain used in a backcross analysis. These studies provide insight into variables that affect genetic heterogeneity and add an important dimension of complexity for linkage analyses of human autoimmune disease. PMID:8986781

The Joint Effects of Background Selection and Genetic Recombination on Local Gene Genealogies

PubMed Central

Zeng, Kai; Charlesworth, Brian

2011-01-01

Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data. PMID:21705759

The joint effects of background selection and genetic recombination on local gene genealogies.

PubMed

Zeng, Kai; Charlesworth, Brian

2011-09-01

Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data.

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

PubMed

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Genetics Home Reference: holocarboxylase synthetase deficiency

MedlinePlus

... holocarboxylase synthetase deficiency Orphanet: Multiple carboxylase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases Organic Acidemia Association ...

Genetics Home Reference: beta-ketothiolase deficiency

MedlinePlus

... Beta Ketothiolase Deficiency Orphanet: Beta-ketothiolase deficiency Screening, Technology And Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (2 links) Children Living with Inherited Metabolic Diseases Organic Acidemia Association ...

Genetic background of supernumerary teeth

PubMed Central

Subasioglu, Asli; Savas, Selcuk; Kucukyilmaz, Ebru; Kesim, Servet; Yagci, Ahmet; Dundar, Munis

2015-01-01

Supernumerary teeth (ST) are odontostomatologic anomaly characterized by as the existence excessive number of teeth in relation to the normal dental formula. This condition is commonly seen with several congenital genetic disorders such as Gardner's syndrome, cleidocranial dysostosis and cleft lip and palate. Less common syndromes that are associated with ST are; Fabry Disease, Ellis-van Creveld syndrome, Nance-Horan syndrome, Rubinstein-Taybi Syndrome and Trico–Rhino–Phalangeal syndrome. ST can be an important component of a distinctive disorder and an important clue for early diagnosis. Certainly early detecting the abnormalities gives us to make correct management of the patient and also it is important for making well-informed decisions about long-term medical care and treatment. In this review, the genetic syndromes that are related with ST were discussed. PMID:25713500

Genetic background of supernumerary teeth.

PubMed

Subasioglu, Asli; Savas, Selcuk; Kucukyilmaz, Ebru; Kesim, Servet; Yagci, Ahmet; Dundar, Munis

2015-01-01

Supernumerary teeth (ST) are odontostomatologic anomaly characterized by as the existence excessive number of teeth in relation to the normal dental formula. This condition is commonly seen with several congenital genetic disorders such as Gardner's syndrome, cleidocranial dysostosis and cleft lip and palate. Less common syndromes that are associated with ST are; Fabry Disease, Ellis-van Creveld syndrome, Nance-Horan syndrome, Rubinstein-Taybi Syndrome and Trico-Rhino-Phalangeal syndrome. ST can be an important component of a distinctive disorder and an important clue for early diagnosis. Certainly early detecting the abnormalities gives us to make correct management of the patient and also it is important for making well-informed decisions about long-term medical care and treatment. In this review, the genetic syndromes that are related with ST were discussed.

Identification of mutant phenotypes associated with loss of individual microRNAs in sensitized genetic backgrounds in Caenorhabditis elegans

PubMed Central

Brenner, John L.; Jasiewicz, Kristen L.; Fahley, Alisha F.; Kemp, Benedict J.; Abbott, Allison L.

2010-01-01

Summary MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the translation and/or the stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single gene knockouts did not result in detectable mutant phenotypes [1]. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes [2]. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways [3]. Using these two approaches, mutant phenotypes were identified for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis. PMID:20579881

Genetics Home Reference: Leydig cell hypoplasia

MedlinePlus

... Twitter Home Health Conditions Leydig cell hypoplasia Leydig cell hypoplasia Printable PDF Open All Close All Enable ... consumer genetic testing? What are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Sensitivity to Pigment-Dispersing Factor (PDF) Is Cell-Type Specific among PDF-Expressing Circadian Clock Neurons in the Madeira Cockroach.

PubMed

Gestrich, Julia; Giese, Maria; Shen, Wen; Zhang, Yi; Voss, Alexandra; Popov, Cyril; Stengl, Monika; Wei, HongYing

2018-02-01

Transplantation studies have pinpointed the circadian clock of the Madeira cockroach to the accessory medulla (AME) of the brain's optic lobes. The AME is innervated by approximately 240 adjacent neuropeptidergic neurons, including 12 pigment-dispersing factor (PDF)-expressing neurons anterior to the AME (aPDFMEs). Four of the aPDFMEs project contralaterally, controlling locomotor activity rhythms of the night-active cockroach. The present in vitro Ca 2+ imaging analysis focuses on contralaterally projecting AME neurons and their responses to PDF, GABA, and acetylcholine (ACh). First, rhodamine-dextran backfills from the contralateral optic stalk identified contralaterally projecting AME neurons, which were then dispersed in primary cell cultures. After characterization of PDF, GABA, and ACh responses, PDF immunocytochemistry identified ipsilaterally and contralaterally projecting PDFMEs. All PDF-sensitive clock neurons, PDF-immunoreactive clock neurons, and the majority of ipsilaterally and contralaterally projecting cells were excited by ACh. GABA inhibited all PDF-expressing clock neurons, and about half of other ipsilaterally projecting and most contralaterally projecting clock neurons. For the first time, we identified PDF autoreceptors in PDF-secreting cockroach circadian pacemakers. The medium-sized aPDFMEs and all other contralaterally projecting PDF-sensitive clock cells were inhibited by PDF. The ipsilaterally remaining small PDF-sensitive clock cells were activated by PDF. Only the largest aPDFME did not express PDF autoreceptors. We hypothesize that opposing PDF signaling generates 2 different ensembles of clock cells with antiphasic activity, regulating and maintaining a constant phase relationship between rest and activity cycles of the night-active cockroach.

GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE

EPA Science Inventory

Genetic Background but not Metallothionein Phenotype Dictates Sensitivity to
Cadmium-Induced Testicular Injury in Mice

Jie Liu1,2, Chris Corton3, David J. Dix4, Yaping Liu1, Michael P. Waalkes2
and Curtis D. Klaassen1

ABSTRACT

Parenteral administrati...

Temperature effect on triacylglycerol species in seed oil from high stearic sunflower lines with different genetic backgrounds.

PubMed

Izquierdo, Natalia G; Martínez-Force, Enrique; Garcés, Rafael; Aguirrezábal, Luis An; Zambelli, Andrés; Reid, Roberto

2016-10-01

This study characterized the influence of temperature during grain filling on the saturated fatty acid distribution in triacylglycerol molecules from high stearic sunflower lines with different genetic backgrounds. Two growth chamber experiments were conducted with day/night temperatures of 16/16, 26/16, 26/26 and 32/26 °C. In all genotypes, independently of the genetic background, higher temperatures increased palmitic and oleic acid and reduced linoleic acid concentrations. Increasing night temperature produced an increase in saturated-unsaturated-saturated species, indicating a more symmetrical distribution of saturated fatty acids. The solid fat index was more affected by temperature during grain filling in lines with high linoleic than high oleic background. Higher variations in symmetry among night temperatures were observed in lines with high oleic background, which are more stable in fatty acid composition. The effect of temperature on triacylglycerol composition is not completely explained by its effect on fatty acid composition. Thus night temperature affects oil properties via its effects on fatty acid synthesis and on the distribution of fatty acids in the triacylglycerol molecules. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

PubMed

Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

PubMed Central

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and

Nutrigenetics: links between genetic background and response to Mediterranean-type diets.

PubMed

Lairon, Denis; Defoort, Catherine; Martin, Jean-Charles; Amiot-Carlin, Marie-Jo; Gastaldi, Marguerite; Planells, Richard

2009-09-01

It has been substantiated that the onset of most major diseases (CVD, diabetes, obesity, cancers, etc.) is modulated by the interaction between genetic traits (susceptibility) and environmental factors, especially diet. We aim to report more specific observations relating the effects of Mediterranean-type diets on cardiovascular risk factors and the genetic background of subjects. In the first part, general concepts about nutrigenetics are briefly presented. Human genome has, overall, only marginally changed since its origin but it is thought that minor changes (polymorphisms) of common genes that occurred during evolution are now widespread in human populations, and can alter metabolic pathways and response to diets. In the second part, we report the data obtained during the Medi-RIVAGE intervention study performed in the South-East of France. Data obtained in 169 subjects at moderate cardiovascular risk after a 3-month dietary intervention indicate that some of the twenty-three single nucleotide polymorphisms (SNP) studied exhibit interactions with diets regarding changes of particular parameters after 3-month regimens. Detailed examples are presented, such as interactions between SNP in genes coding for microsomial transfer protein (MTTP) or intestinal fatty acid binding protein (FABP2) and triglyceride, LDL-cholesterol or Framigham score lowering in responses to Mediterranean-type diets. The data provided add further evidence of the interaction between particular SNP and metabolic responses to diets. Finally, improvement in dietary recommendations by taking into account known genetic variability has been discussed.

Genetics Home Reference: mitochondrial trifunctional protein deficiency

MedlinePlus

... protein deficiency Orphanet: Mitochondrial trifunctional protein deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases (CLIMB) Children's Mitochondrial ...

Developmental analysis and influence of genetic background on the Lhx3 W227ter mouse model of combined pituitary hormone deficiency disease.

PubMed

Prince, Kelly L; Colvin, Stephanie C; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A; Rhodes, Simon J

2013-02-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3(W227ter/W227ter) mouse model. Lhx3(W227ter/W227ter) embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3(W227ter/W227ter) genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3(W227ter/W227ter) animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3(W227ter/W227ter) mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3(W227ter/W227ter) mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases.

Developmental Analysis and Influence of Genetic Background on the Lhx3 W227ter Mouse Model of Combined Pituitary Hormone Deficiency Disease

PubMed Central

Prince, Kelly L.; Colvin, Stephanie C.; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A.

2013-01-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3W227ter/W227ter mouse model. Lhx3W227ter/W227ter embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3W227ter/W227ter genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3W227ter/W227ter animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3W227ter/W227ter mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3W227ter/W227ter mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases. PMID:23288907

Electrical silencing of PDF neurons advances the phase of non-PDF clock neurons in Drosophila.

PubMed

Wu, Ying; Cao, Guan; Nitabach, Michael N

2008-04-01

Drosophila clock neurons exhibit self-sustaining cellular oscillations that rely in part on rhythmic transcriptional feedback loops. We have previously determined that electrical silencing of the pigment dispersing factor (PDF)-expressing lateral-ventral (LN(V)) pacemaker subset of fly clock neurons via expression of an inward-rectifier K(+) channel (Kir2.1) severely disrupts free-running rhythms of locomotor activity-most flies are arrhythmic and those that are not exhibit weak short-period rhythms-and abolishes LN(V) molecular oscillation in constant darkness. PDF is known to be an important LN(V) output signal. Here we examine the effects of electrical silencing of the LN(V) pacemakers on molecular rhythms in other, nonsilenced, subsets of clock neurons. In contrast to previously described cell-autonomous abolition of free-running molecular rhythms, we find that electrical silencing of the LN(V) pacemakers via Kir2.1 expression does not impair molecular rhythms in LN(D), DN1, and DN2 subsets of clock neurons. However, free-running molecular rhythms in these non-LN(V) clock neurons occur with advanced phase. Electrical silencing of LN(V)s phenocopies PDF null mutation (pdf (01) ) at both behavioral and molecular levels except for the complete abolition of free-running cellular oscillation in the LN(V)s themselves. LN(V) electrically silenced or pdf 01 flies exhibit weak free-running behavioral rhythms with short period, and the molecular oscillation in non-LN(V) neurons phase advances in constant darkness. That LN( V) electrical silencing leads to the same behavioral and non-LN( V) molecular phenotypes as pdf 01 suggests that persistence of LN(V) molecular oscillation in pdf 01 flies has no functional effect, either on behavioral rhythms or on non-LN(V) molecular rhythms. We thus conclude that functionally relevant signals from LN(V)s to non-LN(V) clock neurons and other downstream targets rely both on PDF signaling and LN(V) electrical activity, and that LN( V

Genetics Home Reference: glutaric acidemia type I

MedlinePlus

... Acidemia I Orphanet: Glutaryl-CoA dehydrogenase deficiency Screening, Technology and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) National Organization ...

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

PubMed

Petkau, T L; Hill, A; Leavitt, B R

2016-02-19

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

PubMed Central

Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

2013-01-01

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

PubMed

Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E

2013-07-01

Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

PDF approach for compressible turbulent reacting flows

NASA Technical Reports Server (NTRS)

Hsu, A. T.; Tsai, Y.-L. P.; Raju, M. S.

1993-01-01

The objective of the present work is to develop a probability density function (pdf) turbulence model for compressible reacting flows for use with a CFD flow solver. The probability density function of the species mass fraction and enthalpy are obtained by solving a pdf evolution equation using a Monte Carlo scheme. The pdf solution procedure is coupled with a compressible CFD flow solver which provides the velocity and pressure fields. A modeled pdf equation for compressible flows, capable of capturing shock waves and suitable to the present coupling scheme, is proposed and tested. Convergence of the combined finite-volume Monte Carlo solution procedure is discussed, and an averaging procedure is developed to provide smooth Monte-Carlo solutions to ensure convergence. Two supersonic diffusion flames are studied using the proposed pdf model and the results are compared with experimental data; marked improvements over CFD solutions without pdf are observed. Preliminary applications of pdf to 3D flows are also reported.

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

PubMed Central

Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

2015-01-01

The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

PubMed

Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J; Foster, Russell G; Peirson, Stuart N; Nolan, Patrick M

2015-01-01

The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-variate joint PDF for non-Gaussianities: exact formulation and generic approximations

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

Verde, Licia; Jimenez, Raul; Alvarez-Gaume, Luis

2013-06-01

We provide an exact expression for the multi-variate joint probability distribution function of non-Gaussian fields primordially arising from local transformations of a Gaussian field. This kind of non-Gaussianity is generated in many models of inflation. We apply our expression to the non-Gaussianity estimation from Cosmic Microwave Background maps and the halo mass function where we obtain analytical expressions. We also provide analytic approximations and their range of validity. For the Cosmic Microwave Background we give a fast way to compute the PDF which is valid up to more than 7σ for f{sub NL} values (both true and sampled) not ruledmore » out by current observations, which consists of expressing the PDF as a combination of bispectrum and trispectrum of the temperature maps. The resulting expression is valid for any kind of non-Gaussianity and is not limited to the local type. The above results may serve as the basis for a fully Bayesian analysis of the non-Gaussianity parameter.« less

Layout-aware text extraction from full-text PDF of scientific articles

PubMed Central

2012-01-01

Background The Portable Document Format (PDF) is the most commonly used file format for online scientific publications. The absence of effective means to extract text from these PDF files in a layout-aware manner presents a significant challenge for developers of biomedical text mining or biocuration informatics systems that use published literature as an information source. In this paper we introduce the ‘Layout-Aware PDF Text Extraction’ (LA-PDFText) system to facilitate accurate extraction of text from PDF files of research articles for use in text mining applications. Results Our paper describes the construction and performance of an open source system that extracts text blocks from PDF-formatted full-text research articles and classifies them into logical units based on rules that characterize specific sections. The LA-PDFText system focuses only on the textual content of the research articles and is meant as a baseline for further experiments into more advanced extraction methods that handle multi-modal content, such as images and graphs. The system works in a three-stage process: (1) Detecting contiguous text blocks using spatial layout processing to locate and identify blocks of contiguous text, (2) Classifying text blocks into rhetorical categories using a rule-based method and (3) Stitching classified text blocks together in the correct order resulting in the extraction of text from section-wise grouped blocks. We show that our system can identify text blocks and classify them into rhetorical categories with Precision1 = 0.96% Recall = 0.89% and F1 = 0.91%. We also present an evaluation of the accuracy of the block detection algorithm used in step 2. Additionally, we have compared the accuracy of the text extracted by LA-PDFText to the text from the Open Access subset of PubMed Central. We then compared this accuracy with that of the text extracted by the PDF2Text system, 2commonly used to extract text from PDF. Finally, we discuss

A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

PubMed

Read, Timothy; Richmond, Phillip A; Dowell, Robin D

2016-01-01

Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome.

PubMed

Kamiyoshi, Naohiro; Nozu, Kandai; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-08-08

Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an

Genetic Background Has a Major Impact on Differences in Sleep Resulting from Environmental Influences in Drosophila

PubMed Central

Zimmerman, John E.; Chan, May T.; Jackson, Nicholas; Maislin, Greg; Pack, Allan I.

2012-01-01

Study Objectives: To determine the effect of different genetic backgrounds on demographic and environmental interventions that affect sleep and evaluate variance of these measures; and to evaluate sleep and variance of sleep behaviors in 6 divergent laboratory strains of common origin. Design: Assessment of the effects of age, sex, mating status, food sources, and social experience using video analysis of sleep behavior in 2 different strains of Drosophila, white1118ex (w1118ex) and white Canton-S (wCS10). Sleep was also determined for 6 laboratory strains of Canton-S and 3 inbred lines. The variance of total sleep was determined for all groups and conditions. Measurements and Results: The circadian periods and the effects of age upon sleep were the same between w1118ex and wCS10 strains. However, the w1118ex and wCS10 strains demonstrated genotype-dependent differences in the effects upon sleep of sex, mating status, social experience, and being on different foods. Variance of total sleep was found to differ in a genotype dependent manner for interventions between the w1118ex and wCS10 strains. Six different laboratory Canton-S strains were found to have significantly different circadian periods (P < 0.001) and sleep phenotypes (P < 0.001). Three inbred lines showed reduced variance for sleep measurements. Conclusions: One must control environmental conditions in a rigorously consistent manner to ensure that sleep data may be compared between experiments. Genetic background has a significant impact upon changes in sleep behavior and variance of behavior due to demographic factors and environmental interventions. This represents an opportunity to discover new genes that modify sleep/wake behavior. Citation: Zimmerman JE; Chan MT; Jackson N; Maislin G; Pack AI. Genetic background has a major impact on differences in sleep resulting from environmental influences in Drosophila. SLEEP 2012;35(4):545-557. PMID:22467993

Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

PubMed

Yang, Wan-Lin; Kouyos, Roger D; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Scherrer, Alexandra U; Shilaih, Mohaned; Hinkley, Trevor; Petropoulos, Christos; Bonhoeffer, Sebastian; Günthard, Huldrych F

2015-03-01

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

Pdf - Transport equations for chemically reacting flows

NASA Technical Reports Server (NTRS)

Kollmann, W.

1989-01-01

The closure problem for the transport equations for pdf and the characteristic functions of turbulent, chemically reacting flows is addressed. The properties of the linear and closed equations for the characteristic functional for Eulerian and Lagrangian variables are established, and the closure problem for the finite-dimensional case is discussed for pdf and characteristic functions. It is shown that the closure for the scalar dissipation term in the pdf equation developed by Dopazo (1979) and Kollmann et al. (1982) results in a single integral, in contrast to the pdf, where double integration is required. Some recent results using pdf methods obtained for turbulent flows with combustion, including effects of chemical nonequilibrium, are discussed.

Creating an Interactive PDF

ERIC Educational Resources Information Center

Branzburg, Jeffrey

2008-01-01

There are many ways to begin a PDF document using Adobe Acrobat. The easiest and most popular way is to create the document in another application (such as Microsoft Word) and then use the Adobe Acrobat software to convert it to a PDF. In this article, the author describes how he used Acrobat's many tools in his project--an interactive…

PKCepsilon overexpression, irrespective of genetic background, sensitizes skin to UVR-induced development of squamous-cell carcinomas.

PubMed

Sand, Jordan M; Aziz, Moammir H; Dreckschmidt, Nancy E; Havighurst, Thomas C; Kim, KyungMann; Oberley, Terry D; Verma, Ajit K

2010-01-01

Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKCepsilon) transgenic mice on FVB/N background, which overexpress PKCepsilon protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKCepsilon and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKCepsilon FVB/N transgenic mice with SKH-1 hairless mice to generate PKCepsilon-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCepsilon SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1-2 KJ m(-2)) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKCepsilon overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKCepsilon level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis.

The Neuropeptides FLP-2 and PDF-1 Act in Concert To Arouse Caenorhabditis elegans Locomotion.

PubMed

Chen, Didi; Taylor, Kelsey P; Hall, Qi; Kaplan, Joshua M

2016-11-01

During larval molts, Caenorhabditis elegans exhibits a sleep-like state (termed lethargus) that is characterized by the absence of feeding and profound locomotion quiescence. The rhythmic pattern of locomotion quiescence and arousal linked to the molting cycle is mediated by reciprocal changes in sensory responsiveness, whereby arousal is associated with increased responsiveness. Sensory neurons arouse locomotion via release of a neuropeptide (PDF-1) and glutamate. Here we identify a second arousing neuropeptide (FLP-2). We show that FLP-2 acts via an orexin-like receptor (FRPR-18), and that FLP-2 and PDF-1 secretion are regulated by reciprocal positive feedback. These results suggest that the aroused behavioral state is stabilized by positive feedback between two neuropeptides. Copyright © 2016 by the Genetics Society of America.

Genetics Home Reference: 3-methylcrotonyl-CoA carboxylase deficiency

MedlinePlus

... Targets Orphanet: 3-methylcrotonyl-CoA carboxylase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Organic ...

Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements.

PubMed

Sanders, Anne M; Stehle, John R; Blanks, Michael J; Riedlinger, Gregory; Kim-Shapiro, Jung W; Monjazeb, Arta M; Adams, Jonathan M; Willingham, Mark C; Cui, Zheng

2010-03-31

Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/). SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was

Recent progress in the joint velocity-scalar PDF method

NASA Technical Reports Server (NTRS)

Anand, M. S.

1995-01-01

This viewgraph presentation discusses joint velocity-scalar PDF method; turbulent combustion modeling issues for gas turbine combustors; PDF calculations for a recirculating flow; stochastic dissipation model; joint PDF calculations for swirling flows; spray calculations; reduced kinetics/manifold methods; parallel processing; and joint PDF focus areas.

A computer simulated phantom study of tomotherapy dose optimization based on probability density functions (PDF) and potential errors caused by low reproducibility of PDF.

PubMed

Sheng, Ke; Cai, Jing; Brookeman, James; Molloy, Janelle; Christopher, John; Read, Paul

2006-09-01

Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can be converted to a probability density function (PDF), which describes the probability of the tumor at a certain position, for PDF based treatment planning. Using this method in simulated sequential tomotherapy, we study the dose reduction of normal tissues and more important, the effect of PDF reproducibility on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The first PDF was accumulated from a 300 s scan and the second PDF was calculated from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam fluences based on the second PDF were delivered to the hypothetical gross target volume (GTV) of a lung phantom that moved following the first PDF The reproducibility between two PDFs varied from low (78%) to high (94.8%) when the second scan time increased from 5 s to 300 s. When a highly reproducible PDF was used in optimization, the dose coverage of GTV was maintained; phantom lung receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom lung dose was reduced by 9.6%. However, optimization based on PDF with low reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased nearly exponentially as the PDF error increased. Therefore, although the dose of the tumor surrounding tissue can be theoretically reduced by PDF based treatment planning, the reliability and applicability of this method highly depend on if a reproducible PDF exists and is measurable. By correlating the dosimetric error and PDF error together, a useful guideline for PDF data acquisition and patient qualification for PDF based planning can be derived.

A computer simulated phantom study of tomotherapy dose optimization based on probability density functions (PDF) and potential errors caused by low reproducibility of PDF

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

Sheng, Ke; Cai Jing; Brookeman, James

2006-09-15

Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can be converted to a probability density function (PDF), which describes the probability of the tumor at a certain position, for PDF based treatment planning. Using this method in simulated sequential tomotherapy, we study the dose reduction of normal tissues and more important, the effect of PDF reproducibility on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The first PDF was accumulated from a 300 s scan and the second PDF wasmore » calculated from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam fluences based on the second PDF were delivered to the hypothetical gross target volume (GTV) of a lung phantom that moved following the first PDF. The reproducibility between two PDFs varied from low (78%) to high (94.8%) when the second scan time increased from 5 s to 300 s. When a highly reproducible PDF was used in optimization, the dose coverage of GTV was maintained; phantom lung receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom lung dose was reduced by 9.6%. However, optimization based on PDF with low reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased nearly exponentially as the PDF error increased. Therefore, although the dose of the tumor surrounding tissue can be theoretically reduced by PDF based treatment planning, the reliability and applicability of this method highly depend on if a reproducible PDF exists and is measurable. By correlating the dosimetric error and PDF error together, a useful guideline for PDF data acquisition and patient qualification for PDF based planning can be derived.« less

SAP modulates B cell functions in a genetic background-dependent manner.

PubMed

Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

2013-06-01

Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

How biological background assumptions influence scientific risk evaluation of stacked genetically modified plants: an analysis of research hypotheses and argumentations.

PubMed

Rocca, Elena; Andersen, Fredrik

2017-08-14

Scientific risk evaluations are constructed by specific evidence, value judgements and biological background assumptions. The latter are the framework-setting suppositions we apply in order to understand some new phenomenon. That background assumptions co-determine choice of methodology, data interpretation, and choice of relevant evidence is an uncontroversial claim in modern basic science. Furthermore, it is commonly accepted that, unless explicated, disagreements in background assumptions can lead to misunderstanding as well as miscommunication. Here, we extend the discussion on background assumptions from basic science to the debate over genetically modified (GM) plants risk assessment. In this realm, while the different political, social and economic values are often mentioned, the identity and role of background assumptions at play are rarely examined. We use an example from the debate over risk assessment of stacked genetically modified plants (GM stacks), obtained by applying conventional breeding techniques to GM plants. There are two main regulatory practices of GM stacks: (i) regulate as conventional hybrids and (ii) regulate as new GM plants. We analyzed eight papers representative of these positions and found that, in all cases, additional premises are needed to reach the stated conclusions. We suggest that these premises play the role of biological background assumptions and argue that the most effective way toward a unified framework for risk analysis and regulation of GM stacks is by explicating and examining the biological background assumptions of each position. Once explicated, it is possible to either evaluate which background assumptions best reflect contemporary biological knowledge, or to apply Douglas' 'inductive risk' argument.

Daily rhythms in locomotor circuits in Drosophila involve PDF

PubMed Central

Pírez, Nicolás; Christmann, Bethany L.

2013-01-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

Daily rhythms in locomotor circuits in Drosophila involve PDF.

PubMed

Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

2013-08-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep.

Genetics Home Reference: short/branched chain acyl-CoA dehydrogenase deficiency

MedlinePlus

... PDF) Orphanet: 2-methylbutyryl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Patient Support and Advocacy Resources (2 links) Children Living with Inherited Metabolic Diseases (CLIMB) Organic Acidemia ...

PDF receptor signaling in Caenorhabditis elegans modulates locomotion and egg-laying.

PubMed

Meelkop, Ellen; Temmerman, Liesbet; Janssen, Tom; Suetens, Nick; Beets, Isabel; Van Rompay, Liesbeth; Shanmugam, Nilesh; Husson, Steven J; Schoofs, Liliane

2012-09-25

In Caenorhabditis elegans, pdfr-1 encodes three receptors of the secretin receptor family. These G protein-coupled receptors are activated by three neuropeptides, pigment dispersing factors 1a, 1b and 2, which are encoded by pdf-1 and pdf-2. We isolated a PDF receptor loss-of-function allele (lst34) by means of a mutagenesis screen and show that the PDF signaling system is involved in locomotion and egg-laying. We demonstrate that the pdfr-1 mutant phenocopies the defective locomotor behavior of the pdf-1 mutant and that pdf-1 and pdf-2 behave antagonistically. All three PDF receptor splice variants are involved in the regulation of locomotor behavior. Cell specific rescue experiments show that this pdf mediated behavior is regulated by neurons rather than body wall muscles. We also show that egg-laying patterns of pdf-1 and pdf-2 mutants are affected, but not those of pdfr-1 mutants, pointing to a novel role for the PDF-system in the regulation of egg-laying. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A compression algorithm for the combination of PDF sets.

PubMed

Carrazza, Stefano; Latorre, José I; Rojo, Juan; Watt, Graeme

The current PDF4LHC recommendation to estimate uncertainties due to parton distribution functions (PDFs) in theoretical predictions for LHC processes involves the combination of separate predictions computed using PDF sets from different groups, each of which comprises a relatively large number of either Hessian eigenvectors or Monte Carlo (MC) replicas. While many fixed-order and parton shower programs allow the evaluation of PDF uncertainties for a single PDF set at no additional CPU cost, this feature is not universal, and, moreover, the a posteriori combination of the predictions using at least three different PDF sets is still required. In this work, we present a strategy for the statistical combination of individual PDF sets, based on the MC representation of Hessian sets, followed by a compression algorithm for the reduction of the number of MC replicas. We illustrate our strategy with the combination and compression of the recent NNPDF3.0, CT14 and MMHT14 NNLO PDF sets. The resulting compressed Monte Carlo PDF sets are validated at the level of parton luminosities and LHC inclusive cross sections and differential distributions. We determine that around 100 replicas provide an adequate representation of the probability distribution for the original combined PDF set, suitable for general applications to LHC phenomenology.

The pdf approach to turbulent flow

NASA Technical Reports Server (NTRS)

Kollmann, W.

1990-01-01

This paper provides a detailed discussion of the theory and application of probability density function (pdf) methods, which provide a complete statistical description of turbulent flow fields at a single point or a finite number of points. The basic laws governing the flow of Newtonian fluids are set up in the Eulerian and the Lagrangian frame, and the exact and linear equations for the characteristic functionals in those frames are discussed. Pdf equations in both frames are derived as Fourier transforms of the equations of the characteristic functions. Possible formulations for the nonclosed terms in the pdf equation are discussed, their properties are assessed, and closure modes for the molecular-transport and the fluctuating pressure-gradient terms are reviewed. The application of pdf methods to turbulent combustion flows, supersonic flows, and the interaction of turbulence with shock waves is discussed.

Comments on PDF methods

NASA Technical Reports Server (NTRS)

Chen, J.-Y.

1992-01-01

Viewgraphs are presented on the following topics: the grand challenge of combustion engineering; research of probability density function (PDF) methods at Sandia; experiments of turbulent jet flames (Masri and Dibble, 1988); departures from chemical equilibrium; modeling turbulent reacting flows; superequilibrium OH radical; pdf modeling of turbulent jet flames; scatter plot for CH4 (methane) and O2 (oxygen); methanol turbulent jet flames; comparisons between predictions and experimental data; and turbulent C2H4 jet flames.

PDF for Healthcare and Child Health Data Forms.

PubMed

Zuckerman, Alan E; Schneider, Joseph H; Miller, Ken

2008-11-06

PDF-H is a new best practices standard that uses XFA forms and embedded JavaScript to combine PDF forms with XML data. Preliminary experience with AAP child health forms shows that the combination of PDF with XML is a more effective method to visualize familiar data on paper and the web than the traditional use of XML and XSLT. Both PDF-H and HL7 Clinical Document Architecture can co-exist using the same data for different display formats.

BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer: hope or reality?

PubMed Central

Tagliaferri, Pierosandro; Ventura, Monica; Baudi, Francesco; Cucinotto, Iole; Arbitrio, Mariamena; Di Martino, Maria Teresa; Tassone, Pierfrancesco

2009-01-01

Ovarian epithelial tumors are an hallmark of hereditary cancer syndromes which are related to the germ-line inheritance of cancer predisposing mutations in BRCA1 and BRCA2 genes. Although these genes have been associated with multiple different physiologic functions, they share an important role in DNA repair mechanisms and therefore in the whole genomic integrity control. These findings have risen a variety of issues in terms of treatment and prevention of breast and ovarian tumors arising in this context. Enhanced sensitivity to platinum-based anticancer drugs has been related to BRCA1/2 functional loss. Retrospective studies disclosed differential chemosensitivity profiles of BRCA1/2-related as compared to "sporadic" ovarian cancer and led to the identification of a "BRCA-ness" phenotype of ovarian cancer, which includes inherited BRCA1/2 germ-line mutations, a serous high grade histology highly sensitive to platinum derivatives. Molecularly-based tailored treatments of human tumors are an emerging issue in the "era" of molecular targeted drugs and molecular profiling technologies. We will critically discuss if the genetic background of ovarian cancer can indeed represent a determinant issue for decision making in the treatment selection and how the provocative preclinical findings might be translated in the therapeutic scenario. The presently available preclinical and clinical evidence clearly indicates that genetic background has an emerging role in treatment individualization for ovarian cancer patients. PMID:19825178

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study.

PubMed

San-Cristobal, Rodrigo; Navas-Carretero, Santiago; Livingstone, Katherine M; Celis-Morales, Carlos; Macready, Anna L; Fallaize, Rosalind; O'Donovan, Clare B; Lambrinou, Christina P; Moschonis, George; Marsaux, Cyril F M; Manios, Yannis; Jarosz, Miroslaw; Daniel, Hannelore; Gibney, Eileen R; Brennan, Lorraine; Drevon, Christian A; Gundersen, Thomas E; Gibney, Mike; Saris, Wim H M; Lovegrove, Julie A; Grimaldi, Keith; Parnell, Laurence D; Bouwman, Jildau; Van Ommen, Ben; Mathers, John C; Martinez, J Alfredo

2017-10-11

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers.

Is Genetic Background Important in Lung Cancer Survival?

PubMed Central

Lindström, Linda S.; Hall, Per; Hartman, Mikael; Wiklund, Fredrik; Czene, Kamila

2009-01-01

Background In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. Methods Our population-based Swedish family database included three million families and over 58 100 lung cancer patients. We modelled the proband (parent, sibling, spouse) survival utilizing a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse) was analysed with a Cox model. Findings By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99), compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65). Finally, in spouses no correlation in survival was found. Interpretation Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed. PMID:19478952

Genetics Home Reference: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

MedlinePlus

... Targets Orphanet: 3-hydroxy-3-methylglutaric aciduria Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (3 links) Children Living with Inherited Metabolic Diseases (CLIMB) (UK) FOD ( ...

The Genetic Background of Neonatal Disease.

PubMed

Göpel, Wolfgang; Westermann, Eva; Pagel, Friederike

2018-01-01

More than 27,000 human genes have been sequenced and described. Only a few of these genes are relevant for common human diseases with regard to diagnostic or therapeutic purposes. This review describes the genetics of common traits and diseases with a particular focus on perspectives for drug discovery and drug therapy in neonates. © 2018 S. Karger AG, Basel.

Genetics Home Reference: very long-chain acyl-CoA dehydrogenase deficiency

MedlinePlus

... Very long chain acyl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children's Mitochondrial Disease Network (UK) FOD (Fatty Oxidation Disorders) ...

Genetics Home Reference: long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

MedlinePlus

... Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Screening, Technology, and Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases (CLIMB) Children's Mitochondrial ...

Life extension and the position of the hormetic zone depends on sex and genetic background in Drosophila melanogaster.

PubMed

Sarup, Pernille; Loeschcke, Volker

2011-04-01

Hormesis, the beneficial effect of a mild stress, has been proposed as a means to prolong the period of healthy ageing as it can increase the average lifespan of a cohort. However, if we want to use hormesis therapeutically it is important that the treatment is beneficial on the individual level and not just on average at the population level. Long lived lines have been shown not to benefit from a, in other lines, hormesis inducing heat treatment in Drosophila melanogaster, D. buzzatii and mice. Also in many experiments hormesis has been reported to occur in one sex only, usually males but not in females. Here we investigated the interaction between the hormetic response and genetic background, sex and duration of a mild heat stress in D. melanogaster, using three replicate lines that have been selected for increased longevity and their respective control lines. We found that genetic background influences the position of the hormetic zone. The implication of this result could be that in a genetically diverse populations a treatment that is life prolonging in one individual could be life shortening in other individuals. However, we did find a hormetic response in all combinations of line and sex in at least one of the experiments which suggests that if it is possible to identify the optimal hormetic dose individually hormesis might become a therapeutic treatment.

Application and Evaluation of Interactive 3D PDF for Presenting and Sharing Planning Results for Liver Surgery in Clinical Routine

PubMed Central

Newe, Axel; Becker, Linda; Schenk, Andrea

2014-01-01

Background & Objectives The Portable Document Format (PDF) is the de-facto standard for the exchange of electronic documents. It is platform-independent, suitable for the exchange of medical data, and allows for the embedding of three-dimensional (3D) surface mesh models. In this article, we present the first clinical routine application of interactive 3D surface mesh models which have been integrated into PDF files for the presentation and the exchange of Computer Assisted Surgery Planning (CASP) results in liver surgery. We aimed to prove the feasibility of applying 3D PDF in medical reporting and investigated the user experience with this new technology. Methods We developed an interactive 3D PDF report document format and implemented a software tool to create these reports automatically. After more than 1000 liver CASP cases that have been reported in clinical routine using our 3D PDF report, an international user survey was carried out online to evaluate the user experience. Results Our solution enables the user to interactively explore the anatomical configuration and to have different analyses and various resection proposals displayed within a 3D PDF document covering only a single page that acts more like a software application than like a typical PDF file (“PDF App”). The new 3D PDF report offers many advantages over the previous solutions. According to the results of the online survey, the users have assessed the pragmatic quality (functionality, usability, perspicuity, efficiency) as well as the hedonic quality (attractiveness, novelty) very positively. Conclusion The usage of 3D PDF for reporting and sharing CASP results is feasible and well accepted by the target audience. Using interactive PDF with embedded 3D models is an enabler for presenting and exchanging complex medical information in an easy and platform-independent way. Medical staff as well as patients can benefit from the possibilities provided by 3D PDF. Our results open the door for a

PDF4LHC recommendations for LHC Run II

DOE PAGES

Butterworth, Jon; Carrazza, Stefano; Cooper-Sarkar, Amanda; ...

2016-01-06

We provide an updated recommendation for the usage of sets of parton distribution functions (PDFs) and the assessment of PDF and PDF+αs uncertainties suitable for applications at the LHC Run II. We review developments since the previous PDF4LHC recommendation, and discuss and compare the new generation of PDFs, which include substantial information from experimental data from the Run I of the LHC. We then propose a new prescription for the combination of a suitable subset of the available PDF sets, which is presented in terms of a single combined PDF set. Lastly, we finally discuss tools which allow for themore » delivery of this combined set in terms of optimized sets of Hessian eigenvectors or Monte Carlo replicas, and their usage, and provide some examples of their application to LHC phenomenology.« less

Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background.

PubMed

Saqui-Salces, Milena; Tsao, Amy C; Gillilland, Merritt G; Merchant, Juanita L

2017-01-01

The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male C57BL/6J mice on the HiE diets ate less, whereas males on the HiE diets compared with the STD diets gained weight. All diet treatments reduced energy expenditure in females but in males only those on the HiE + O diet. Gut microbiota composition differed in the C57BL/6J females but not the males. Hybrid B6SJLF1/J mice showed similar weight gain on all test diets. In contrast, mixed strain male mice fed a HiE + O diet gained ∼40% more weight than females on the same diet. In addition to increased weight gain, mixed genetic mice on the HiE + O diet cleared glucose normally but secreted more insulin. We concluded that sex and genetic background define weight gain and metabolic responses of mice on high caloric diets and OM. Copyright © 2017 the American Physiological Society.

Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background

PubMed Central

Tsao, Amy C.; Gillilland, Merritt G.; Merchant, Juanita L.

2016-01-01

The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male C57BL/6J mice on the HiE diets ate less, whereas males on the HiE diets compared with the STD diets gained weight. All diet treatments reduced energy expenditure in females but in males only those on the HiE + O diet. Gut microbiota composition differed in the C57BL/6J females but not the males. Hybrid B6SJLF1/J mice showed similar weight gain on all test diets. In contrast, mixed strain male mice fed a HiE + O diet gained ∼40% more weight than females on the same diet. In addition to increased weight gain, mixed genetic mice on the HiE + O diet cleared glucose normally but secreted more insulin. We concluded that sex and genetic background define weight gain and metabolic responses of mice on high caloric diets and OM. PMID:27810953

Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

PubMed Central

Cook, Matthew S.; Munger, Steven C.; Nadeau, Joseph H.; Capel, Blanche

2011-01-01

Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1Ter/Ter mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1Ter/Ter mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1Ter/Ter; Bax–/– double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1Ter/Ter germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27Kip1 and p21Cip1. P27Kip1 and P21Cip1 protein are both significantly decreased in Dnd1Ter/Ter germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility. PMID:21115610

Deep PDF parsing to extract features for detecting embedded malware.

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

Munson, Miles Arthur; Cross, Jesse S.

2011-09-01

The number of PDF files with embedded malicious code has risen significantly in the past few years. This is due to the portability of the file format, the ways Adobe Reader recovers from corrupt PDF files, the addition of many multimedia and scripting extensions to the file format, and many format properties the malware author may use to disguise the presence of malware. Current research focuses on executable, MS Office, and HTML formats. In this paper, several features and properties of PDF Files are identified. Features are extracted using an instrumented open source PDF viewer. The feature descriptions of benignmore » and malicious PDFs can be used to construct a machine learning model for detecting possible malware in future PDF files. The detection rate of PDF malware by current antivirus software is very low. A PDF file is easy to edit and manipulate because it is a text format, providing a low barrier to malware authors. Analyzing PDF files for malware is nonetheless difficult because of (a) the complexity of the formatting language, (b) the parsing idiosyncrasies in Adobe Reader, and (c) undocumented correction techniques employed in Adobe Reader. In May 2011, Esparza demonstrated that PDF malware could be hidden from 42 of 43 antivirus packages by combining multiple obfuscation techniques [4]. One reason current antivirus software fails is the ease of varying byte sequences in PDF malware, thereby rendering conventional signature-based virus detection useless. The compression and encryption functions produce sequences of bytes that are each functions of multiple input bytes. As a result, padding the malware payload with some whitespace before compression/encryption can change many of the bytes in the final payload. In this study we analyzed a corpus of 2591 benign and 87 malicious PDF files. While this corpus is admittedly small, it allowed us to test a system for collecting indicators of embedded PDF malware. We will call these indicators features

Identification of salt-tolerant QTLs with strong genetic background effect using two sets of reciprocal introgression lines in rice.

PubMed

Cheng, Lirui; Wang, Yun; Meng, Lijun; Hu, Xia; Cui, Yanru; Sun, Yong; Zhu, Linghua; Ali, Jauhar; Xu, Jianlong; Li, Zhikang

2012-01-01

Effect of genetic background on detection of quantitative trait locus (QTL) governing salinity tolerance (ST) was studied using two sets of reciprocal introgression lines (ILs) derived from a cross between a moderately salinity tolerant japonica variety, Xiushui09 from China, and a drought tolerant but salinity susceptible indica breeding line, IR2061-520-6-9 from the Philippines. Salt toxicity symptoms (SST) on leaves, days to seedling survival (DSS), and sodium and potassium uptake by shoots were measured under salinity stress of 140 mmol/L of NaCl. A total of 47 QTLs, including 26 main-effect QTLs (M-QTLs) and 21 epistatic QTLs (E-QTLs), were identified from the two sets of reciprocal ILs. Among the 26 M-QTLs, only four (15.4%) were shared in the reciprocal backgrounds while no shared E-QTLs were detected, indicating that ST QTLs, especially E-QTLs, were very specific to the genetic background. Further, 78.6% of the M-QTLs for SST and DSS identified in the reciprocal ILs were also detected in the recombinant inbred lines (RILs) from the same cross, which clearly brings out the background effect on ST QTL detection and its utilization in ST breeding. The detection of ILs with various levels of pyramiding of nonallelic M-QTL alleles for ST from Xiushui09 into IR2061-520-6-9 allowed us to further improve the ST in rice.

Recent advances in PDF modeling of turbulent reacting flows

NASA Technical Reports Server (NTRS)

Leonard, Andrew D.; Dai, F.

1995-01-01

This viewgraph presentation concludes that a Monte Carlo probability density function (PDF) solution successfully couples with an existing finite volume code; PDF solution method applied to turbulent reacting flows shows good agreement with data; and PDF methods must be run on parallel machines for practical use.

Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.

PubMed

Fun, Axel; Leitner, Thomas; Vandekerckhove, Linos; Däumer, Martin; Thielen, Alexander; Buchholz, Bernd; Hoepelman, Andy I M; Gisolf, Elizabeth H; Schipper, Pauline J; Wensing, Annemarie M J; Nijhuis, Monique

2018-01-05

Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance. Using deep sequencing we analyzed the integrase coding sequence (CDS) in longitudinal samples from five patients who initiated raltegravir plus optimized background therapy at viral loads > 5000 copies/ml. To investigate the role of the HIV-1 genetic background we created recombinant viruses containing the viral integrase coding region from pre-raltegravir samples from two patients in whom raltegravir resistance developed through different pathways. The in vitro selections performed with these recombinant viruses were designed to mimic natural population bottlenecks. Deep sequencing analysis of the viral integrase CDS revealed that the virological response to raltegravir containing therapy inversely correlated with the relative amount of unique sequence variants that emerged suggesting diversifying selection during drug pressure. In 4/5 patients multiple signature mutations representing different resistance pathways were observed. Interestingly, the resistant population can consist of a single resistant variant that completely dominates the population but also of multiple variants from different resistance pathways that coexist in the viral population. We also found evidence for increased diversification after stronger bottlenecks. In vitro selections with low viral titers, mimicking population bottlenecks, revealed that both recombinant viruses and HXB2 reference virus were able to select mutations from different resistance pathways, although typically only one resistance pathway

Transcriptional regulation of the human mitochondrial peptide deformylase (PDF).

PubMed

Pereira-Castro, Isabel; Costa, Luís Teixeira da; Amorim, António; Azevedo, Luisa

2012-05-18

The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formyl-methionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner. Copyright © 2012 Elsevier Inc. All rights reserved.

Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum

PubMed Central

Drury, Douglas W.; Wade, Michael J.

2010-01-01

Hybrids from crosses between populations of the flour beetle, Tribolium castaneum, express varying degrees of inviability and morphological abnormalities. The proportion of allopatric population hybrids exhibiting these negative hybrid phenotypes varies widely, from 3% to 100%, depending upon the pair of populations crossed. We crossed three populations and measured two fitness components, fertility and adult offspring numbers from successful crosses, to determine how genes segregating within populations interact in inter-population hybrids to cause the negative phenotypes. With data from crosses of 40 sires from each of three populations to groups of 5 dams from their own and two divergent populations, we estimated the genetic variance and covariance for breeding value of fitness between the intra- and inter-population backgrounds and the sire × dam-population interaction variance. The latter component of the variance in breeding values estimates the change in genic effects between backgrounds owing to epistasis. Interacting genes with a positive effect, prior to fixation, in the sympatric background but a negative effect in the hybrid background cause reproductive incompatibility in the Dobzhansky-Muller speciation model. Thus, the sire × dam-population interaction provides a way to measure the progress toward speciation of genetically differentiating populations on a trait by trait basis using inter-population hybrids. PMID:21044199

Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

PubMed

Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

PubMed Central

Funk, Nico W.; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

PDF modeling of near-wall turbulent flows

NASA Astrophysics Data System (ADS)

Dreeben, Thomas David

1997-06-01

Pdf methods are extended to include modeling of wall- bounded turbulent flows. For flows in which resolution of the viscous sublayer is desired, a Pdf near-wall model is developed in which the Generalized Langevin model is combined with an exact model for viscous transport. Durbin's method of elliptic relaxation is used to incorporate the wall effects into the governing equations without the use of wall functions or damping functions. Close to the wall, the Generalized Langevin model provides an analogy to the effect of the fluctuating continuity equation. This enables accurate modeling of the near-wall turbulent statistics. Demonstrated accuracy for fully-developed channel flow is achieved with a Pdf/Monte Carlo simulation, and with its related Reynolds-stress closure. For flows in which the details of the viscous sublayer are not important, a Pdf wall- function method is developed with the Simplified Langevin model.

PDF and cAMP enhance PER stability in Drosophila clock neurons

PubMed Central

Li, Yue; Guo, Fang; Shen, James; Rosbash, Michael

2014-01-01

The neuropeptide PDF is important for Drosophila circadian rhythms: pdf01 (pdf-null) animals are mostly arrhythmic or short period in constant darkness and have an advanced activity peak in light–dark conditions. PDF contributes to the amplitude, synchrony, as well as the pace of circadian rhythms within clock neurons. PDF is known to increase cAMP levels in PDR receptor (PDFR)-containing neurons. However, there is no known connection of PDF or of cAMP with the Drosophila molecular clockworks. We discovered that the mutant period gene perS ameliorates the phenotypes of pdf-null flies. The period protein (PER) is a well-studied repressor of clock gene transcription, and the perS protein (PERS) has a markedly short half-life. The result therefore suggests that the PDF-mediated increase in cAMP might lengthen circadian period by directly enhancing PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in S2 tissue culture cells and in fly circadian neurons. Adding PDF to fly brains in vitro has a similar effect. Consistent with these relationships, a light pulse causes more prominent PER degradation in pdf01 circadian neurons than in wild-type neurons. The results indicate that PDF contributes to clock neuron synchrony by increasing cAMP and PKA, which enhance PER stability and decrease clock speed in intrinsically fast-paced PDFR-containing clock neurons. We further suggest that the more rapid degradation of PERS bypasses PKA regulation and makes the pace of clock neurons more uniform, allowing them to avoid much of the asynchrony caused by the absence of PDF. PMID:24707054

PDF and cAMP enhance PER stability in Drosophila clock neurons.

PubMed

Li, Yue; Guo, Fang; Shen, James; Rosbash, Michael

2014-04-01

The neuropeptide PDF is important for Drosophila circadian rhythms: pdf(01) (pdf-null) animals are mostly arrhythmic or short period in constant darkness and have an advanced activity peak in light-dark conditions. PDF contributes to the amplitude, synchrony, as well as the pace of circadian rhythms within clock neurons. PDF is known to increase cAMP levels in PDR receptor (PDFR)-containing neurons. However, there is no known connection of PDF or of cAMP with the Drosophila molecular clockworks. We discovered that the mutant period gene per(S) ameliorates the phenotypes of pdf-null flies. The period protein (PER) is a well-studied repressor of clock gene transcription, and the per(S) protein (PERS) has a markedly short half-life. The result therefore suggests that the PDF-mediated increase in cAMP might lengthen circadian period by directly enhancing PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in S2 tissue culture cells and in fly circadian neurons. Adding PDF to fly brains in vitro has a similar effect. Consistent with these relationships, a light pulse causes more prominent PER degradation in pdf(01) circadian neurons than in wild-type neurons. The results indicate that PDF contributes to clock neuron synchrony by increasing cAMP and PKA, which enhance PER stability and decrease clock speed in intrinsically fast-paced PDFR-containing clock neurons. We further suggest that the more rapid degradation of PERS bypasses PKA regulation and makes the pace of clock neurons more uniform, allowing them to avoid much of the asynchrony caused by the absence of PDF.

Publications - PDF 96-18 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 96-18 Publication Details Title: Major and trace element analyses of Cretaceous plutonic Bibliographic Reference Newberry, R.J., 1996, Major and trace element analyses of Cretaceous plutonic rocks in pdf1996_018.pdf (571.0 K) Keywords Geochemistry; Geology; Igneous Rocks; Major Oxides; Plutonic Rocks

Neuropeptide Y-Y2 receptor knockout mice: influence of genetic background on anxiety-related behaviors.

PubMed

Zambello, E; Zanetti, L; Hédou, G F; Angelici, O; Arban, R; Tasan, R O; Sperk, G; Caberlotto, L

2011-03-10

Neuropeptide Y (NPY) has been extensively studied in relation to anxiety and depression but of the seven NPY receptors known to date, it is not yet clear which one is mainly involved in mediating its effects in emotional behavior. Mice lacking the NPY-Y2 receptors were previously shown to be less anxious due to their improved ability to cope with stressful situations. In the present study, the behavioral phenotype including the response to challenges was analyzed in NPY-Y2 knockout (KO) mice backcrossed in to congenic C57BL/6 background. In the elevated plus-maze (EPM) and the forced swim test (FST), the anxiolytic-like or antidepressant-like phenotype of the NPY-Y2 KO mice could not be confirmed, although this study differs from the previous one only with regard to the genetic background of the mice. In addition, no differences in response to acute stress or to the antidepressant desipramine in the FST were detected between wild type (WT) and NPY-Y2 KO animals. These results suggest that the genetic background of the animals appears to have a strong influence on the behavioral phenotype of NPY-Y2 KO mice. Additionally, to further characterize the animals by their biochemical response to a challenge, the neurochemical changes induced by the anxiogenic compound yohimbine were measured in the medial prefrontal cortex (mPFC) of NPY-Y2 KO and compared to WT mice. Dopamine (DA) levels were significantly increased by yohimbine in the WT but unaffected in the KO mice, suggesting that NPY-Y2 receptor exerts a direct control over both the tonic and phasic release of DA and that, although the anxiety-like behavior of these NPY-Y2 KO mice is unaltered, there are clear modifications of DA dynamics. However, yohimbine led to a significant increase in noradrenaline (NA) concentration and a slight reduction in serotonin concentration that were identical for both phenotypes. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Conditional probability distribution function of "energy transfer rate" (PDF(ɛ|PVI)) as compared with its counterpart of temperature (PDF(T|PVI)) at the same condition of fluctuation

NASA Astrophysics Data System (ADS)

He, Jiansen; Wang, Yin; Pei, Zhongtian; Zhang, Lei; Tu, Chuanyi

2017-04-01

Energy transfer rate of turbulence is not uniform everywhere but suggested to follow a certain distribution, e.g., lognormal distribution (Kolmogorov 1962). The inhomogeneous transfer rate leads to emergence of intermittency, which may be identified with some parameter, e.g., normalized partial variance increments (PVI) (Greco et al., 2009). Large PVI of magnetic field fluctuations are found to have a temperature distribution with the median and mean values higher than that for small PVI level (Osman et al., 2012). However, there is a large proportion of overlap between temperature distributions associated with the smaller and larger PVIs. So it is recognized that only PVI cannot fully determine the temperature, since the one-to-one mapping relationship does not exist. One may be curious about the reason responsible for the considerable overlap of conditional temperature distribution for different levels of PVI. Usually the hotter plasma with higher temperature is speculated to be heated more with more dissipation of turbulence energy corresponding to more energy cascading rate, if the temperature fluctuation of the eigen wave mode is not taken into account. To explore the statistical relationship between turbulence cascading and plasma thermal state, we aim to study and reveal, for the first time, the conditional probability function of "energy transfer rate" under different levels of PVI condition (PDF(ɛ|PVI)), and compare it with the conditional probability function of temperature. The conditional probability distribution function, PDF(ɛ|PVI), is derived from PDF(PVI|ɛ)·PDF(ɛ)/PDF(PVI) according to the Bayesian theorem. PDF(PVI) can be obtained directly from the data. PDF(ɛ) is derived from the conjugate-gradient inversion of PDF(PVI) by assuming reasonably that PDF(δB|σ) is a Gaussian distribution, where PVI=|δB|/ σ and σ ( ɛι)1/3. PDF(ɛ) can also be acquired from fitting PDF(δB) with an integral function ∫PDF(δB|σ)PDF(σ)d σ. As a result

Antibiotic Resistance, Virulence, and Genetic Background of Community-Acquired Uropathogenic Escherichia coli from Algeria.

PubMed

Yahiaoui, Merzouk; Robin, Frédéric; Bakour, Rabah; Hamidi, Moufida; Bonnet, Richard; Messai, Yamina

2015-10-01

The aim of the study was to investigate antibiotic resistance mechanisms, virulence traits, and genetic background of 150 nonrepetitive community-acquired uropathogenic Escherichia coli (CA-UPEC) from Algeria. A rate of 46.7% of isolates was multidrug resistant. bla genes detected were blaTEM (96.8% of amoxicillin-resistant isolates), blaCTX-M-15 (4%), overexpressed blaAmpC (4%), blaSHV-2a, blaTEM-4, blaTEM-31, and blaTEM-35 (0.7%). All tetracycline-resistant isolates (51.3%) had tetA and/or tetB genes. Sulfonamides and trimethoprim resistance genes were sul2 (60.8%), sul1 (45.9%), sul3 (6.7%), dfrA14 (25.4%), dfrA1 (18.2%), dfrA12 (16.3%), and dfrA25 (5.4%). High-level fluoroquinolone resistance (22.7%) was mediated by mutations in gyrA (S83L-D87N) and parC (S80I-E84G/V or S80I) genes. qnrB5, qnrS1, and aac(6')-Ib-cr were rare (5.3%). Class 1 and/or class 2 integrons were detected (40.7%). Isolates belonged to phylogroups B2+D (50%), A+B1 (36%), and F+C+Clade I (13%). Most of D (72.2%) and 38.6% of B2 isolates were multidrug resistant; they belong to 14 different sequence types, including international successful ST131, ST73, and ST69, reported for the first time in the community in Algeria and new ST4494 and ST4529 described in this study. Besides multidrug resistance, B2 and D isolates possessed virulence factors of colonization, invasion, and long-term persistence. The study highlighted multidrug-resistant CA-UPEC with high virulence traits and an epidemic genetic background.

Cyclic AMP imaging sheds light on PDF signaling in circadian clock neurons.

PubMed

Tomchik, Seth M; Davis, Ronald L

2008-04-24

In Drosophila, the neuropeptide PDF is required for circadian rhythmicity, but it is unclear where PDF acts. In this issue of Neuron, Shafer et al. use a novel bioimaging methodology to demonstrate that PDF elevates cAMP in nearly all clock neurons. Thus, PDF apparently exerts more widespread effects on the circadian clock network than suggested by previous studies of PDF receptor expression.

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

PubMed Central

Marsh, Sharon; Hu, Junbo; Feng, Wenke

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.

PubMed

Vecsey, Christopher G; Pírez, Nicolás; Griffith, Leslie C

2014-03-01

Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding.

The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons

PubMed Central

Vecsey, Christopher G.; Pírez, Nicolás

2013-01-01

Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding. PMID:24353297

An Overview of the NCC Spray/Monte-Carlo-PDF Computations

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, Nan-Suey (Technical Monitor)

2000-01-01

This paper advances the state-of-the-art in spray computations with some of our recent contributions involving scalar Monte Carlo PDF (Probability Density Function), unstructured grids and parallel computing. It provides a complete overview of the scalar Monte Carlo PDF and Lagrangian spray computer codes developed for application with unstructured grids and parallel computing. Detailed comparisons for the case of a reacting non-swirling spray clearly highlight the important role that chemistry/turbulence interactions play in the modeling of reacting sprays. The results from the PDF and non-PDF methods were found to be markedly different and the PDF solution is closer to the reported experimental data. The PDF computations predict that some of the combustion occurs in a predominantly premixed-flame environment and the rest in a predominantly diffusion-flame environment. However, the non-PDF solution predicts wrongly for the combustion to occur in a vaporization-controlled regime. Near the premixed flame, the Monte Carlo particle temperature distribution shows two distinct peaks: one centered around the flame temperature and the other around the surrounding-gas temperature. Near the diffusion flame, the Monte Carlo particle temperature distribution shows a single peak. In both cases, the computed PDF's shape and strength are found to vary substantially depending upon the proximity to the flame surface. The results bring to the fore some of the deficiencies associated with the use of assumed-shape PDF methods in spray computations. Finally, we end the paper by demonstrating the computational viability of the present solution procedure for its use in 3D combustor calculations by summarizing the results of a 3D test case with periodic boundary conditions. For the 3D case, the parallel performance of all the three solvers (CFD, PDF, and spray) has been found to be good when the computations were performed on a 24-processor SGI Origin work-station.

Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background

PubMed Central

Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

2016-01-01

Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. PMID:27406785

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

PubMed Central

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

2015-01-01

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

Organic micropollutants paracetamol and ibuprofen-toxicity, biodegradation, and genetic background of their utilization by bacteria.

PubMed

Żur, Joanna; Piński, Artur; Marchlewicz, Ariel; Hupert-Kocurek, Katarzyna; Wojcieszyńska, Danuta; Guzik, Urszula

2018-06-19

Currently, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are classified as one of the most emerging group of xenobiotics and have been detected in various natural matrices. Among them, monocyclic paracetamol and ibuprofen, widely used to treat mild and moderate pain are the most popular. Since long-term adverse effects of these xenobiotics and their biological and pharmacokinetic activity especially at environmentally relevant concentrations are better understood, degradation of such contaminants has become a major concern. Moreover, to date, conventional wastewater treatment plants (WWTPs) are not fully adapted to remove that kind of micropollutants. Bioremediation processes, which utilize bacterial strains with increased degradation abilities, seem to be a promising alternative to the chemical methods used so far. Nevertheless, despite the wide prevalence of paracetamol and ibuprofen in the environment, toxicity and mechanism of their microbial degradation as well as genetic background of these processes remain not fully characterized. In this review, we described the current state of knowledge about toxicity and biodegradation mechanisms of paracetamol and ibuprofen and provided bioinformatics analysis concerning the genetic bases of these xenobiotics decomposition.

Background Selection in Partially Selfing Populations

PubMed Central

Roze, Denis

2016-01-01

Self-fertilizing species often present lower levels of neutral polymorphism than their outcrossing relatives. Indeed, selfing automatically increases the rate of coalescence per generation, but also enhances the effects of background selection and genetic hitchhiking by reducing the efficiency of recombination. Approximations for the effect of background selection in partially selfing populations have been derived previously, assuming tight linkage between deleterious alleles and neutral loci. However, loosely linked deleterious mutations may have important effects on neutral diversity in highly selfing populations. In this article, I use a general method based on multilocus population genetics theory to express the effect of a deleterious allele on diversity at a linked neutral locus in terms of moments of genetic associations between loci. Expressions for these genetic moments at equilibrium are then computed for arbitrary rates of selfing and recombination. An extrapolation of the results to the case where deleterious alleles segregate at multiple loci is checked using individual-based simulations. At high selfing rates, the tight linkage approximation underestimates the effect of background selection in genomes with moderate to high map length; however, another simple approximation can be obtained for this situation and provides accurate predictions as long as the deleterious mutation rate is not too high. PMID:27075726

Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background.

PubMed

Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

2016-08-01

Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

A PDF closure model for compressible turbulent chemically reacting flows

NASA Technical Reports Server (NTRS)

Kollmann, W.

1992-01-01

The objective of the proposed research project was the analysis of single point closures based on probability density function (pdf) and characteristic functions and the development of a prediction method for the joint velocity-scalar pdf in turbulent reacting flows. Turbulent flows of boundary layer type and stagnation point flows with and without chemical reactions were be calculated as principal applications. Pdf methods for compressible reacting flows were developed and tested in comparison with available experimental data. The research work carried in this project was concentrated on the closure of pdf equations for incompressible and compressible turbulent flows with and without chemical reactions.

Design and application of PDF model for extracting

NASA Astrophysics Data System (ADS)

Xiong, Lei

2013-07-01

In order to change the steps of contributions in editorial department system from two steps to one, this paper advocates that the technology of extracting the information of PDF files should be transplanted from PDF reader into IEEE Xplore contribution system and that it should be combined with uploading in batch skillfully to enable editors to upload PDF files about 1GB in batch for once. Computers will extract the information of the title, author, address, mailbox, abstract and key words of thesis voluntarily for later retrieval so as to save plenty of labor, material and finance for editorial department.

High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington's disease CAG knock-in mice across multiple genetic backgrounds.

PubMed

Ament, Seth A; Pearl, Jocelynn R; Grindeland, Andrea; St Claire, Jason; Earls, John C; Kovalenko, Marina; Gillis, Tammy; Mysore, Jayalakshmi; Gusella, James F; Lee, Jong-Min; Kwak, Seung; Howland, David; Lee, Min Young; Baxter, David; Scherler, Kelsey; Wang, Kai; Geman, Donald; Carroll, Jeffrey B; MacDonald, Marcy E; Carlson, George; Wheeler, Vanessa C; Price, Nathan D; Hood, Leroy E

2017-03-01

Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improvements and new features in the PDF module

NASA Technical Reports Server (NTRS)

Norris, Andrew T.

1995-01-01

This viewgraph presentation discusses what models are used in this package and what their advantages and disadvantages are, how the probability density function (PDF) model is implemented and the features of the program, and what can be expected in the future from the NASA Lewis PDF code.

Persistent Deterioration of Functioning (PDF) and change in well-being in older persons.

PubMed

Jonker, Angèle A; Comijs, Hannie C; Knipscheer, Kees C; Deeg, Dorly J

2008-10-01

It is often assumed that aging is accompanied by diverse and constant functional and cognitive decline, and it is therefore surprising that the well-being of older persons does not appear to decline in the same way. This study investigates longitudinally whether well-being in older persons changes due to Persistent Deterioration of Functioning (PDF). Data were collected in the context of the Longitudinal Aging Study Amsterdam (LASA). Conditions of PDF are persistent decline in cognitive functioning, physical functioning and increase in chronic diseases. Measurements of well-being included life satisfaction, positive affect, and valuation of life. T-tests were used to analyse mean difference scores for well-being, and univariate and multivariate regression analyses were performed to examine changes in three well-being outcomes in relation to PDF. Cross-sectional analyses showed significant differences and associations between the two PDF subgroups and non- PDF for well-being at T3. In longitudinal analyses, we found significant decreases in and associations with wellbeing over time in respondents fulfilling one PDF condition (mild PDF). For respondents fulfilling two or more PDF conditions (severe PDF), longitudinally no significant associations were found. Cognitive aspects of well-being (life satisfaction and valuation of life) and the affective element (positive affect) of well-being appear to be influenced negatively by mild PDF, whereas well-being does not seem to be diminished in persons with more severe PDF. This may be due to the ability to accept finally the inevitable situation of severe PDF.

A GPU accelerated PDF transparency engine

NASA Astrophysics Data System (ADS)

Recker, John; Lin, I.-Jong; Tastl, Ingeborg

2011-01-01

As commercial printing presses become faster, cheaper and more efficient, so too must the Raster Image Processors (RIP) that prepare data for them to print. Digital press RIPs, however, have been challenged to on the one hand meet the ever increasing print performance of the latest digital presses, and on the other hand process increasingly complex documents with transparent layers and embedded ICC profiles. This paper explores the challenges encountered when implementing a GPU accelerated driver for the open source Ghostscript Adobe PostScript and PDF language interpreter targeted at accelerating PDF transparency for high speed commercial presses. It further describes our solution, including an image memory manager for tiling input and output images and documents, a PDF compatible multiple image layer blending engine, and a GPU accelerated ICC v4 compatible color transformation engine. The result, we believe, is the foundation for a scalable, efficient, distributed RIP system that can meet current and future RIP requirements for a wide range of commercial digital presses.

Application of PDF methods to compressible turbulent flows

NASA Astrophysics Data System (ADS)

Delarue, B. J.; Pope, S. B.

1997-09-01

A particle method applying the probability density function (PDF) approach to turbulent compressible flows is presented. The method is applied to several turbulent flows, including the compressible mixing layer, and good agreement is obtained with experimental data. The PDF equation is solved using a Lagrangian/Monte Carlo method. To accurately account for the effects of compressibility on the flow, the velocity PDF formulation is extended to include thermodynamic variables such as the pressure and the internal energy. The mean pressure, the determination of which has been the object of active research over the last few years, is obtained directly from the particle properties. It is therefore not necessary to link the PDF solver with a finite-volume type solver. The stochastic differential equations (SDE) which model the evolution of particle properties are based on existing second-order closures for compressible turbulence, limited in application to low turbulent Mach number flows. Tests are conducted in decaying isotropic turbulence to compare the performances of the PDF method with the Reynolds-stress closures from which it is derived, and in homogeneous shear flows, at which stage comparison with direct numerical simulation (DNS) data is conducted. The model is then applied to the plane compressible mixing layer, reproducing the well-known decrease in the spreading rate with increasing compressibility. It must be emphasized that the goal of this paper is not as much to assess the performance of models of compressibility effects, as it is to present an innovative and consistent PDF formulation designed for turbulent inhomogeneous compressible flows, with the aim of extending it further to deal with supersonic reacting flows.

Comparative analysis of Pdf-mediated circadian behaviors between Drosophila melanogaster and D. virilis.

PubMed

Bahn, Jae Hoon; Lee, Gyunghee; Park, Jae H

2009-03-01

A group of small ventrolateral neurons (s-LN(v)'s) are the principal pacemaker for circadian locomotor rhythmicity of Drosophila melanogaster, and the pigment-dispersing factor (Pdf) neuropeptide plays an essential role as a clock messenger within these neurons. In our comparative studies on Pdf-associated circadian rhythms, we found that daily locomotor activity patterns of D. virilis were significantly different from those of D. melanogaster. Activities of D. virilis adults were mainly restricted to the photophase under light:dark cycles and subsequently became arrhythmic or weakly rhythmic in constant conditions. Such activity patterns resemble those of Pdf(01) mutant of D. melanogaster. Intriguingly, endogenous D. virilis Pdf (DvPdf) expression was not detected in the s-LN(v)-like neurons in the adult brains, implying that the Pdf(01)-like behavioral phenotypes of D. virilis are attributed in part to the lack of DvPdf in the s-LN(v)-like neurons. Heterologous transgenic analysis showed that cis-regulatory elements of the DvPdf transgene are capable of directing their expression in all endogenous Pdf neurons including s-LN(v)'s, as well as in non-Pdf clock neurons (LN(d)'s and fifth s-LN(v)) in a D. melanogaster host. Together these findings suggest a significant difference in the regulatory mechanisms of Pdf transcription between the two species and such a difference is causally associated with species-specific establishment of daily locomotor activity patterns.

Pressure algorithm for elliptic flow calculations with the PDF method

NASA Technical Reports Server (NTRS)

Anand, M. S.; Pope, S. B.; Mongia, H. C.

1991-01-01

An algorithm to determine the mean pressure field for elliptic flow calculations with the probability density function (PDF) method is developed and applied. The PDF method is a most promising approach for the computation of turbulent reacting flows. Previous computations of elliptic flows with the method were in conjunction with conventional finite volume based calculations that provided the mean pressure field. The algorithm developed and described here permits the mean pressure field to be determined within the PDF calculations. The PDF method incorporating the pressure algorithm is applied to the flow past a backward-facing step. The results are in good agreement with data for the reattachment length, mean velocities, and turbulence quantities including triple correlations.

A multi-scalar PDF approach for LES of turbulent spray combustion

NASA Astrophysics Data System (ADS)

Raman, Venkat; Heye, Colin

2011-11-01

A comprehensive joint-scalar probability density function (PDF) approach is proposed for large eddy simulation (LES) of turbulent spray combustion and tests are conducted to analyze the validity and modeling requirements. The PDF method has the advantage that the chemical source term appears closed but requires models for the small scale mixing process. A stable and consistent numerical algorithm for the LES/PDF approach is presented. To understand the modeling issues in the PDF method, direct numerical simulation of a spray flame at three different fuel droplet Stokes numbers and an equivalent gaseous flame are carried out. Assumptions in closing the subfilter conditional diffusion term in the filtered PDF transport equation are evaluated for various model forms. In addition, the validity of evaporation rate models in high Stokes number flows is analyzed.

Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein Treacle.

PubMed

Dixon, Jill; Dixon, Michael James

2004-04-01

Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain-dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA-derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Copyright 2004 Wiley-Liss, Inc.

[Practical experience about the compatibility of PDF converter in ECG information system].

PubMed

Yang, Gang; Lu, Weishi; Zhou, Jiacheng

2009-11-01

To find a way to view ECG from different manufacturers in electrocardiogram information system. Different format ECG data were transmitted to ECG center by different ways. Corresponding analysis software was used to make the diagnosis reports in the center. Then we use PDF convert to change all ECG reports into PDF format. The electrocardiogram information system manage these PDF format ECG data for clinic user. The ECG reports form several major ECG manufacturers were transformed to PDF format successfully. In the electrocardiogram information system it is freely to view the ECG figure. PDF format ECG report is a practicable way to solve the compatibility problem in electrocardiogram information system.

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

PubMed

Talsma, Aaron D; Christov, Christo P; Terriente-Felix, Ana; Linneweber, Gerit A; Perea, Daniel; Wayland, Matthew; Shafer, Orie T; Miguel-Aliaga, Irene

2012-07-24

The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system.

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila

PubMed Central

Talsma, Aaron D.; Christov, Christo P.; Terriente-Felix, Ana; Linneweber, Gerit A.; Perea, Daniel; Wayland, Matthew; Shafer, Orie T.; Miguel-Aliaga, Irene

2012-01-01

The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system. PMID:22778427

Mammographic texture synthesis using genetic programming and clustered lumpy background

NASA Astrophysics Data System (ADS)

Castella, Cyril; Kinkel, Karen; Descombes, François; Eckstein, Miguel P.; Sottas, Pierre-Edouard; Verdun, Francis R.; Bochud, François O.

2006-03-01

In this work we investigated the digital synthesis of images which mimic real textures observed in mammograms. Such images could be produced in an unlimited number with tunable statistical properties in order to study human performance and model observer performance in perception experiments. We used the previously developed clustered lumpy background (CLB) technique and optimized its parameters with a genetic algorithm (GA). In order to maximize the realism of the textures, we combined the GA objective approach with psychophysical experiments involving the judgments of radiologists. Thirty-six statistical features were computed and averaged, over 1000 real mammograms regions of interest. The same features were measured for the synthetic textures, and the Mahalanobis distance was used to quantify the similarity of the features between the real and synthetic textures. The similarity, as measured by the Mahalanobis distance, was used as GA fitness function for evolving the free CLB parameters. In the psychophysical approach, experienced radiologists were asked to qualify the realism of synthetic images by considering typical structures that are expected to be found on real mammograms: glandular and fatty areas, and fiber crossings. Results show that CLB images found via optimization with GA are significantly closer to real mammograms than previously published images. Moreover, the psychophysical experiments confirm that all the above mentioned structures are reproduced well on the generated images. This means that we can generate an arbitrary large database of textures mimicking mammograms with traceable statistical properties.

PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila.

PubMed

Cusumano, Paola; Klarsfeld, André; Chélot, Elisabeth; Picot, Marie; Richier, Benjamin; Rouyer, François

2009-11-01

Morning and evening circadian oscillators control the bimodal activity of Drosophila in light-dark cycles. The lateral neurons evening oscillator (LN-EO) is important for promoting diurnal activity at dusk. We found that the LN-EO autonomously synchronized to light-dark cycles through either the cryptochrome (CRY) that it expressed or the visual system. In conditions in which CRY was not activated, flies depleted for pigment-dispersing factor (PDF) or its receptor lost the evening activity and displayed reversed PER oscillations in the LN-EO. Rescue experiments indicated that normal PER cycling and the presence of evening activity relied on PDF secretion from the large ventral lateral neurons and PDF receptor function in the LN-EO. The LN-EO thus integrates light inputs and PDF signaling to control Drosophila diurnal behavior, revealing a new clock-independent function for PDF.

PDF Receptor Expression Reveals Direct Interactions between Circadian Oscillators in Drosophila

PubMed Central

Im, Seol Hee; Taghert, Paul H.

2010-01-01

Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest the network is divisible into M and E oscillators which normally interact and synchronize. Sixteen oscillator neurons (the small and large LNvs) express a neuropeptide called pigment dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a ~70 kB PDF receptor (pdfr) transgene which does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye. PMID:20394051

Statistical Analysis of PDF's for Na Released by Photons from Solid Surfaces

NASA Astrophysics Data System (ADS)

Gamborino, D.; Wurz, P.

2018-05-01

We analyse the adequacy of three model speed PDF's previously used to describe the desorption of Na from a solid surface either by ESD or PSD. We found that the Maxwell PDF is too wide compared to measurements and non-thermal PDF's are better suited.

Genetic background contributes to the co-morbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment.

PubMed

Sarkisova, Karine Yu; Fedotova, Irina B; Surina, Natalia M; Nikolaev, Georgy M; Perepelkina, Olga V; Kostina, Zoya A; Poletaeva, Inga I

2017-03-01

Anxiety and depression are the most frequent comorbidities of different types of convulsive and non-convulsive epilepsies. Increased anxiety and depression-like phenotype have been described in the genetic absence epilepsy models as well as in models of limbic epilepsy and acquired seizure models, suggesting a neurobiological connection. However, whether anxiety and/or depression are comorbid to audiogenic epilepsy remains unclear. The aim of this study was to investigate whether anxiety or depression-like behavior can be found in rat strains with different susceptibility to audiogenic seizures (AS) and whether chronic fluoxetine treatment affects this co-morbidity. Behavior in the elevated plus-maze and the forced swimming test was studied in four strains: Wistar rats non-susceptible to AS; Krushinsky-Molodkina (KM) strain, selectively bred for AS propensity from outbred Wistar rats; and a selection lines bred for maximal AS expression (strain "4") and for a lack of AS (strain "0") from KM×Wistar F2 hybrids. Effects of chronic antidepressant treatment on AS and behavior were also evaluated. Anxiety and depression levels were higher in KM rats (with AS) compared with Wistar rats (without AS), indicating the comorbidity with AS. However, in strains "4" and "0" with contrasting AS expression, but with a genetic background close to KM rats, anxiety and depression were not as divergent as in KMs versus Wistars. Fluoxetine treatment exerted an antidepressant effect in all rat strains irrespective of its effect on AS. Genetic background contributes substantively to the co-morbidity of anxiety and depression with AS propensity. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of the reproducibility of lung motion probability distribution function (PDF) using dynamic MRI.

PubMed

Cai, Jing; Read, Paul W; Altes, Talissa A; Molloy, Janelle A; Brookeman, James R; Sheng, Ke

2007-01-21

Treatment planning based on probability distribution function (PDF) of patient geometries has been shown a potential off-line strategy to incorporate organ motion, but the application of such approach highly depends upon the reproducibility of the PDF. In this paper, we investigated the dependences of the PDF reproducibility on the imaging acquisition parameters, specifically the scan time and the frame rate. Three healthy subjects underwent a continuous 5 min magnetic resonance (MR) scan in the sagittal plane with a frame rate of approximately 10 f s-1, and the experiments were repeated with an interval of 2 to 3 weeks. A total of nine pulmonary vessels from different lung regions (upper, middle and lower) were tracked and the dependences of their displacement PDF reproducibility were evaluated as a function of scan time and frame rate. As results, the PDF reproducibility error decreased with prolonged scans and appeared to approach equilibrium state in subjects 2 and 3 within the 5 min scan. The PDF accuracy increased in the power function with the increase of frame rate; however, the PDF reproducibility showed less sensitivity to frame rate presumably due to the randomness of breathing which dominates the effects. As the key component of the PDF-based treatment planning, the reproducibility of the PDF affects the dosimetric accuracy substantially. This study provides a reference for acquiring MR-based PDF of structures in the lung.

Optic nerve regeneration in the mouse is a complex trait modulated by genetic background

PubMed Central

Wang, Jiaxing; Li, Ying; King, Rebecca; Struebing, Felix L.

2018-01-01

Purpose The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains (C57BL/6J and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adenoassociated virus (AAV) delivery of shRNA, and a mild inflammatory response was induced with an intravitreal injection of zymosan with CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by cholera toxin B, and 2 days later, the regenerating axons within the optic nerve were examined. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that five axons had grown down the nerve and the longest distance a single axon reached. Results The analysis revealed a considerable amount of differential axonal regeneration across the seven BXD strains and the parental strains. There was a statistically significant difference (p=0.014 Mann–Whitney U test) in the regenerative capacity in the number of axons reaching 0.5 mm from a low of 236.1±24.4 axons in the BXD102 mice to a high of 759.8±79.2 axons in the BXD29 mice. There were also statistically significant differences (p=0.014 Mann–Whitney U test) in the distance axons traveled. Looking at a minimum of five axons, the shortest distance was 787.2±46.5 µm in the BXD102 mice, and the maximum distance was 2025.5±223.3 µm in the BXD29 mice. Conclusions Differences in genetic background can have a profound effect on axonal regeneration causing a threefold increase in the number of regenerating axons at 0.5 mm from the crush site and a 2.5-fold increase in the distance traveled by at least five axons in the damaged optic nerve. PMID:29463955

PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila.

PubMed

Im, Seol Hee; Taghert, Paul H

2010-06-01

Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment-dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a approximately 70-kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye. (c) 2009 Wiley-Liss, Inc.

PDF approach for turbulent scalar field: Some recent developments

NASA Technical Reports Server (NTRS)

Gao, Feng

1993-01-01

The probability density function (PDF) method has been proven a very useful approach in turbulence research. It has been particularly effective in simulating turbulent reacting flows and in studying some detailed statistical properties generated by a turbulent field There are, however, some important questions that have yet to be answered in PDF studies. Our efforts in the past year have been focused on two areas. First, a simple mixing model suitable for Monte Carlo simulations has been developed based on the mapping closure. Secondly, the mechanism of turbulent transport has been analyzed in order to understand the recently observed abnormal PDF's of turbulent temperature fields generated by linear heat sources.

Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.

PubMed

Depetris-Chauvin, Ana; Fernández-Gamba, Agata; Gorostiza, E Axel; Herrero, Anastasia; Castaño, Eduardo M; Ceriani, M Fernanda

2014-10-01

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

PubMed Central

Depetris-Chauvin, Ana; Fernández-Gamba, Ágata; Gorostiza, E. Axel; Herrero, Anastasia; Castaño, Eduardo M.; Ceriani, M. Fernanda

2014-01-01

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior. PMID:25356918

HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

PubMed

Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

2018-04-01

HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior.

PubMed

Lear, Bridget C; Zhang, Luoying; Allada, Ravi

2009-07-01

Discrete clusters of circadian clock neurons temporally organize daily behaviors such as sleep and wake. In Drosophila, a network of just 150 neurons drives two peaks of timed activity in the morning and evening. A subset of these neurons expresses the neuropeptide pigment dispersing factor (PDF), which is important for promoting morning behavior as well as maintaining robust free-running rhythmicity in constant conditions. Yet, how PDF acts on downstream circuits to mediate rhythmic behavior is unknown. Using circuit-directed rescue of PDF receptor mutants, we show that PDF targeting of just approximately 30 non-PDF evening circadian neurons is sufficient to drive morning behavior. This function is not accompanied by large changes in core molecular oscillators in light-dark, indicating that PDF RECEPTOR likely regulates the output of these cells under these conditions. We find that PDF also acts on this focused set of non-PDF neurons to regulate both evening activity phase and period length, consistent with modest resetting effects on core oscillators. PDF likely acts on more distributed pacemaker neuron targets, including the PDF neurons themselves, to regulate rhythmic strength. Here we reveal defining features of the circuit-diagram for PDF peptide function in circadian behavior, revealing the direct neuronal targets of PDF as well as its behavioral functions at those sites. These studies define a key direct output circuit sufficient for multiple PDF dependent behaviors.

E AND M CIRCADIAN PACEMAKER NEURONS USE DIFFERENT PDF RECEPTOR SIGNALOSOME COMPONENTS IN DROSOPHILA

PubMed Central

Duvall, Laura B.

2014-01-01

We used real-time imaging to detect cAMP levels in neurons of intact fly brains to study mechanisms of circadian pacemaker synchronization by the neuropeptide PDF in Drosophila. PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker sub-classes and is coupled to Gsα in both cases. We previously reported that PDF-R in M pacemakers elevates cAMP levels by activating the ortholog of mammalian Adenylate Cyclase 3 (AC3), but that AC3 disruptions had no effect on E pacemaker sensitivity to PDF. Here we show that PDF-R in E pacemakers activates a different AC isoform, AC78C, an ortholog of mammalian AC8. Knockdown of AC78C by transgenic RNAi substantially reduces, but does not completely abrogate, PDF responses in these E pacemakers. The knockdown effect is intact when restricted to mature stages, suggesting a physiological and not a development role for AC78C in E pacemakers. The AC78C phenotype is rescued by over-expression of AC78C, but not by over-expression of the rutabaga AC. AC78C over-expression does not disrupt PDF responses in these E pacemakers, and neither AC78C knockdown nor its over-expression disrupted locomotor rhythms. Finally, knockdown of two AKAPs, nervy and AKAP 200 partially reduces LNd PDF responses. These findings begin to identify the components of E pacemaker PDF-R signalosomes and indicate they are distinct from PDF-R signalosomes in M pacemakers: we propose they contain AC78C and at least one other AC. PMID:23929551

E and M circadian pacemaker neurons use different PDF receptor signalosome components in drosophila.

PubMed

Duvall, Laura B; Taghert, Paul H

2013-08-01

We used real-time imaging to detect cAMP levels in neurons of intact fly brains to study the mechanisms of circadian pacemaker synchronization by the neuropeptide pigment dispersing factor (PDF) in Drosophila. PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker subclasses and is coupled to G(sα) in both cases. We previously reported that PDF-R in M pacemakers elevates cAMP levels by activating the ortholog of mammalian adenylate cyclase 3 (AC3) but that AC3 disruptions had no effect on E pacemaker sensitivity to PDF. Here, we show that PDF-R in E pacemakers activates a different AC isoform, AC78C, an ortholog of mammalian AC8. Knockdown of AC78C by transgenic RNAi substantially reduces, but does not completely abrogate, PDF responses in these E pacemakers. The knockdown effect is intact when restricted to mature stages, suggesting a physiological and not a development role for AC78C in E pacemakers. The AC78C phenotype is rescued by the overexpression of AC78C but not by overexpression of the rutabaga AC. AC78C overexpression does not disrupt PDF responses in these E pacemakers, and neither AC78C knockdown nor its overexpression disrupted locomotor rhythms. Finally, knockdown of 2 AKAPs, nervy and AKAP200, partially reduces LNd PDF responses. These findings begin to identify the components of E pacemaker PDF-R signalosomes and indicate that they are distinct from PDF-R signalosomes in M pacemakers: we propose they contain AC78C and at least 1 other AC.

PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors.

PubMed

Mertens, Inge; Vandingenen, Anick; Johnson, Erik C; Shafer, Orie T; Li, W; Trigg, J S; De Loof, Arnold; Schoofs, Liliane; Taghert, Paul H

2005-10-20

The neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems.

PDF text classification to leverage information extraction from publication reports.

PubMed

Bui, Duy Duc An; Del Fiol, Guilherme; Jonnalagadda, Siddhartha

2016-06-01

Data extraction from original study reports is a time-consuming, error-prone process in systematic review development. Information extraction (IE) systems have the potential to assist humans in the extraction task, however majority of IE systems were not designed to work on Portable Document Format (PDF) document, an important and common extraction source for systematic review. In a PDF document, narrative content is often mixed with publication metadata or semi-structured text, which add challenges to the underlining natural language processing algorithm. Our goal is to categorize PDF texts for strategic use by IE systems. We used an open-source tool to extract raw texts from a PDF document and developed a text classification algorithm that follows a multi-pass sieve framework to automatically classify PDF text snippets (for brevity, texts) into TITLE, ABSTRACT, BODYTEXT, SEMISTRUCTURE, and METADATA categories. To validate the algorithm, we developed a gold standard of PDF reports that were included in the development of previous systematic reviews by the Cochrane Collaboration. In a two-step procedure, we evaluated (1) classification performance, and compared it with machine learning classifier, and (2) the effects of the algorithm on an IE system that extracts clinical outcome mentions. The multi-pass sieve algorithm achieved an accuracy of 92.6%, which was 9.7% (p<0.001) higher than the best performing machine learning classifier that used a logistic regression algorithm. F-measure improvements were observed in the classification of TITLE (+15.6%), ABSTRACT (+54.2%), BODYTEXT (+3.7%), SEMISTRUCTURE (+34%), and MEDADATA (+14.2%). In addition, use of the algorithm to filter semi-structured texts and publication metadata improved performance of the outcome extraction system (F-measure +4.1%, p=0.002). It also reduced of number of sentences to be processed by 44.9% (p<0.001), which corresponds to a processing time reduction of 50% (p=0.005). The rule-based multi

The Human Proteome Project: Unlocking the Mysteries of Human Life and Unleashing Its Potential

DTIC Science & Technology

2011-02-16

Australasian Genetics Resource Book. June 2007. Accessed September 27, 2010. www.genetics.com.au/pdf/factsheets/fs24.pdf. 2 White House, Office of...Project and Beyond." The Australasian Genetics Resource Book. June 2007. Accessed September 27, 2010. www.genetics.com.au/pdf/factsheets/fs24.pdf...9 Centre for Genetics Education. "The Human Genetic Code – The Human Genome Project and Beyond." The Australasian Genetics Resource Book. June

An assumed joint-Beta PDF approach for supersonic turbulent combustion

NASA Technical Reports Server (NTRS)

Baurle, R. A.; Alexopoulos, G. A.; Hassan, H. A.; Drummond, J. P.

1992-01-01

In a recent experiment, Cheng et al. (1991) used ultraviolet spontaneous vibrational Raman scattering and laser-induced predissociative fluorescence techniques for simultaneous measurements of temperature and concentrations of O2, H2, H2O, OH, and N2 (and their rms) in supersonic turbulent reacting shear layers. Because present computational techniques are not suited for prediction of all of the above measurements, a new approach has been developed and is being used to predict all relevant flow properties and their rms (where appropriate). The approach explores the use of a joint-Beta PDF for concentrations. It was found that the general expression of this PDF was impractical because of decoding problems resulting from determining the various parameters of the PDF. Thus, a special case of this general expression was considered. Calculations using this simplified version of the joint-Beta PDF were not consistent with the available data from the experiment.

Blocking endocytosis in Drosophila's circadian pacemaker neurons interferes with the endogenous clock in a PDF-dependent way.

PubMed

Wülbeck, Corinna; Grieshaber, Eva; Helfrich-Förster, Charlotte

2009-10-01

The neuropeptide pigment-dispersing factor (PDF) plays an essential role in the circadian clock of the fruit fly Drosophila melanogaster, but many details of PDF signaling in the clock network are still unknown. We tried to interfere with PDF signaling by blocking the GTPase Shibire in PDF neurons. Shibire is an ortholog of the mammalian Dynamins and is essential for endocytosis of clathrin-coated vesicles at the plasma membrane. Such endocytosis is used for neurotransmitter reuptake by presynaptic neurons, which is a prerequisite of synaptic vesicle recycling, and receptor-mediated endocytosis in the postsynaptic neuron, which leads to signal termination. By blocking Shibire function via overexpression of a dominant negative mutant form of Shibire in PDF neurons, we slowed down the behavioral rhythm by 3 h. This effect was absent in PDF receptor null mutants, indicating that we interfered with PDF receptor-mediated endocytosis. Because we obtained similar behavioral phenotypes by increasing the PDF level in regions close to PDF neurons, we conclude that blocking Shibire did prolong PDF signaling in the neurons that respond to PDF. Obviously, terminating the PDF signaling via receptor-mediated endocytosis is a crucial step in determining the period of behavioral rhythms.

Comments on the present state and future directions of PDF methods

NASA Technical Reports Server (NTRS)

Obrien, E. E.

1992-01-01

The one point probability density function (PDF) method is examined in light of its use in actual engineering problems. The PDF method, although relatively complicated, appears to be the only format available to handle the nonlinear stochastic difficulties caused by typical reaction kinetics. Turbulence modeling, if it is to play a central role in combustion modeling, has to be integrated with the chemistry in a way which produces accurate numerical solutions to combustion problems. It is questionable whether the development of turbulent models in isolation from the peculiar statistics of reactant concentrations is a fruitful line of development as far as propulsion is concerned. There are three issues for which additional viewgraphs are prepared: the one point pdf method; the amplitude mapping closure; and a hybrid strategy for replacing a full two point pdf treatment of reacting flows by a single point pdf and correlation functions. An appeal is made for the establishment of an adequate data base for compressible flow with reactions for Mach numbers of unity or higher.

Multiple Genetic Backgrounds of the Amplified Plasmodium falciparum Multidrug Resistance (pfmdr1) Gene and Selective Sweep of 184F Mutation in Cambodia

PubMed Central

Vinayak, Sumiti; Alam, Md Tauqeer; Sem, Rithy; Shah, Naman K.; Susanti, Augustina I.; Lim, Pharath; Muth, Sinuon; Maguire, Jason D.; Rogers, William O.; Fandeur, Thierry; Barnwell, John W.; Escalante, Ananias A.; Wongsrichanalai, Chansuda; Ariey, Frederick; Meshnick, Steven R.; Udhayakumar, Venkatachalam

2011-01-01

Background The emergence of artesunate-mefloquine (AS+MQ)–resistant Plasmodium falciparum in the Thailand-Cambodia region is a major concern for malaria control. Studies indicate that copy number increase and key alleles in the pfmdr1 gene are associated with AS+MQ resistance. In the present study, we investigated evidence for a selective sweep around pfmdr1 because of the spread of adaptive mutation and/or multiple copies of this gene in the P. falciparum population in Cambodia. Methods We characterized 13 microsatellite loci flanking (± 99 kb) pfmdr1 in 93 single-clone P. falciparum infections, of which 31 had multiple copies and 62 had a single copy of the pfmdr1 gene. Results Genetic analysis revealed no difference in the mean (± standard deviation) expected heterozygosity (He) at loci around single (0.75 ± 0.03) and multiple (0.76 ± 0.04) copies of pfmdr1. Evidence of genetic hitchhiking with the selective sweep of certain haplotypes was seen around mutant (184F) pfmdr1 allele, irrespective of the copy number. There was an overall reduction of 28% in mean He (± SD) around mutant allele (0.56 ± 0.05), compared with wild-type allele (0.84 ± 0.02). Significant linkage disequilibrium was also observed between the loci flanking mutant pfmdr1 allele. Conclusion The 184F mutant allele is under selection, whereas amplification of pfmdr1 gene in this population occurs on multiple genetic backgrounds. PMID:20367478

The Severity of Retinal Degeneration in Rp1h Gene-Targeted Mice Is Dependent on Genetic Background

PubMed Central

Liu, Qin; Saveliev, Alexei; Pierce, Eric A.

2009-01-01

Purpose The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1htm1Eap) on several different genetic backgrounds and analyzed their retinal phenotypes. Methods The Rp1htm1Eap allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretino-graphic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. Results Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h+/tm1Eap, DBA.129S(B6)-Rp1h+/tm1Eap, and A.129S(B6)-Rp1h+/tm1Eap mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h+/tm1Eap mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h+/tm1Eap mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h+/tm1Eap mice remain healthy up to 18 months. Conclusions The severity of the retinal degeneration caused by the Rp1htm1Eap allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h+/tm1Eap and A.129S(B6)-Rp1h+/tm1Eap congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease. PMID:19060274

The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background.

PubMed

Liu, Qin; Saveliev, Alexei; Pierce, Eric A

2009-04-01

The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h(tm1Eap)) on several different genetic backgrounds and analyzed their retinal phenotypes. The Rp1h(tm1Eap) allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h(+/tm1Eap), DBA.129S(B6)-Rp1h(+/tm1Eap), and A.129S(B6)-Rp1h(+/tm1Eap) mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h(+/tm1Eap) mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h(+/tm1Eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h(+/tm1Eap) mice remain healthy up to 18 months. The severity of the retinal degeneration caused by the Rp1h(tm1Eap) allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h(+/tm1Eap) and A.129S(B6)-Rp1h(+/tm1Eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.

Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila.

PubMed

Isaac, R Elwyn; Johnson, Erik C; Audsley, Neil; Shirras, Alan D

2007-12-01

Recent studies have firmly established pigment dispersing factor (PDF), a C-terminally amidated octodecapeptide, as a key neurotransmitter regulating rhythmic circadian locomotory behaviours in adult Drosophila melanogaster. The mechanisms by which PDF functions as a circadian peptide transmitter are not fully understood, however; in particular, nothing is known about the role of extracellular peptidases in terminating PDF signalling at synapses. In this study we show that PDF is susceptible to hydrolysis by neprilysin, an endopeptidase that is enriched in synaptic membranes of mammals and insects. Neprilysin cleaves PDF at the internal Ser7-Leu8 peptide bond to generate PDF1-7 and PDF8-18. Neither of these fragments were able to increase intracellular cAMP levels in HEK293 cells cotransfected with the Drosophila PDF receptor cDNA and a firefly luciferase reporter gene, confirming that such cleavage results in PDF inactivation. The Ser7-Leu8 peptide bond was also the principal cleavage site when PDF was incubated with membranes prepared from heads of adult Drosophila. This endopeptidase activity was inhibited by the neprilysin inhibitors phosphoramidon (IC(50,) 0.15 micromol l(-1)) and thiorphan (IC(50,) 1.2 micromol l(-1)). We propose that cleavage by a member of the Drosophila neprilysin family of endopeptidases is the most likely mechanism for inactivating synaptic PDF and that neprilysin might have an important role in regulating PDF signals within circadian neural circuits.

Cross-reference identification within a PDF document

NASA Astrophysics Data System (ADS)

Li, Sida; Gao, Liangcai; Tang, Zhi; Yu, Yinyan

2015-01-01

Cross-references, such like footnotes, endnotes, figure/table captions, references, are a common and useful type of page elements to further explain their corresponding entities in the target document. In this paper, we focus on cross-reference identification in a PDF document, and present a robust method as a case study of identifying footnotes and figure references. The proposed method first extracts footnotes and figure captions, and then matches them with their corresponding references within a document. A number of novel features within a PDF document, i.e., page layout, font information, lexical and linguistic features of cross-references, are utilized for the task. Clustering is adopted to handle the features that are stable in one document but varied in different kinds of documents so that the process of identification is adaptive with document types. In addition, this method leverages results from the matching process to provide feedback to the identification process and further improve the algorithm accuracy. The primary experiments in real document sets show that the proposed method is promising to identify cross-reference in a PDF document.

A time dependent mixing model to close PDF equations for transport in heterogeneous aquifers

NASA Astrophysics Data System (ADS)

Schüler, L.; Suciu, N.; Knabner, P.; Attinger, S.

2016-10-01

Probability density function (PDF) methods are a promising alternative to predicting the transport of solutes in groundwater under uncertainty. They make it possible to derive the evolution equations of the mean concentration and the concentration variance, used in moment methods. The mixing model, describing the transport of the PDF in concentration space, is essential for both methods. Finding a satisfactory mixing model is still an open question and due to the rather elaborate PDF methods, a difficult undertaking. Both the PDF equation and the concentration variance equation depend on the same mixing model. This connection is used to find and test an improved mixing model for the much easier to handle concentration variance. Subsequently, this mixing model is transferred to the PDF equation and tested. The newly proposed mixing model yields significantly improved results for both variance modelling and PDF modelling.

Improved biocompatibility of bicarbonate/lactate-buffered PDF is not related to pH.

PubMed

Zareie, Mohammad; Keuning, Eelco D; ter Wee, Piet M; Schalkwijk, Casper G; Beelen, Robert H J; van den Born, Jacob

2006-01-01

Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo. Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n=7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n=8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n=5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n=7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n=8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed. Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters P<0.05), accompanied by increased glucose absorption and reduced ultrafiltration capacity. Daily exposure to standard or acidified bicarbonate/lactate-buffered PDF improved the performance of the peritoneal membrane, evidenced by reduced new vessel formation in omentum (P<0.02) and parietal peritoneum (P<0.008), reduced fibrosis (P<0.02) and improved ultrafiltration capacity. No significant differences were found between standard and acidified bicarbonate/lactate-buffered PDF. During PET, acidic PDF was neutralized within 15 to 20 min. The bicarbonate/lactate-buffered PDF, acidity per se did not contribute

A Lagrangian mixing frequency model for transported PDF modeling

NASA Astrophysics Data System (ADS)

Turkeri, Hasret; Zhao, Xinyu

2017-11-01

In this study, a Lagrangian mixing frequency model is proposed for molecular mixing models within the framework of transported probability density function (PDF) methods. The model is based on the dissipations of mixture fraction and progress variables obtained from Lagrangian particles in PDF methods. The new model is proposed as a remedy to the difficulty in choosing the optimal model constant parameters when using conventional mixing frequency models. The model is implemented in combination with the Interaction by exchange with the mean (IEM) mixing model. The performance of the new model is examined by performing simulations of Sandia Flame D and the turbulent premixed flame from the Cambridge stratified flame series. The simulations are performed using the pdfFOAM solver which is a LES/PDF solver developed entirely in OpenFOAM. A 16-species reduced mechanism is used to represent methane/air combustion, and in situ adaptive tabulation is employed to accelerate the finite-rate chemistry calculations. The results are compared with experimental measurements as well as with the results obtained using conventional mixing frequency models. Dynamic mixing frequencies are predicted using the new model without solving additional transport equations, and good agreement with experimental data is observed.

Constraints on the gluon PDF from top quark pair production at hadron colliders

NASA Astrophysics Data System (ADS)

Czakon, Michal; Mangano, Michelangelo L.; Mitov, Alexander; Rojo, Juan

2013-07-01

Using the recently derived NNLO cross sections [1], we provide NNLO+NNLL theoretical predictions for top quark pair production based on all the available NNLO PDF sets, and compare them with the most precise LHC and Tevatron data. In this comparison we study in detail the PDF uncertainty and the scale, m t and α s dependence of the theoretical predictions for each PDF set. Next, we observe that top quark pair production provides a powerful direct constraint on the gluon PDF at large x, and include Tevatron and LHC top pair data consistently into a global NNLO PDF fit. We then explore the phenomenological consequences of the reduced gluon PDF uncertainties, by showing how they can improve predictions for Beyond the Standard Model processes at the LHC. Finally, we update to full NNLO+NNLL the theoretical predictions for the ratio of top quark cross sections between different LHC center of mass energies, as well as the cross sections for hypothetical heavy fourth-generation quark production at the LHC.

PDF methods for turbulent reactive flows

NASA Technical Reports Server (NTRS)

Hsu, Andrew T.

1995-01-01

Viewgraphs are presented on computation of turbulent combustion, governing equations, closure problem, PDF modeling of turbulent reactive flows, validation cases, current projects, and collaboration with industry and technology transfer.

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation.

PubMed

Klose, Markus; Duvall, Laura; Li, Weihua; Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H

2016-05-18

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional PDF Signaling in the Drosophila Circadian Neural Circuit is Gated by Ral A-Dependent Modulation

PubMed Central

Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H.

2016-01-01

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness, does not require endogenous ligand (PDF) signaling, or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additional, cell autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. PMID:27161526

A hybrid Reynolds averaged/PDF closure model for supersonic turbulent combustion

NASA Technical Reports Server (NTRS)

Frankel, Steven H.; Hassan, H. A.; Drummond, J. Philip

1990-01-01

A hybrid Reynolds averaged/assumed pdf approach has been developed and applied to the study of turbulent combustion in a supersonic mixing layer. This approach is used to address the 'laminar-like' treatment of the thermochemical terms that appear in the conservation equations. Calculations were carried out for two experiments involving H2-air supersonic turbulent mixing. Two different forms of the pdf were implemented. In general, the results show modest improvement from previous calculations. Moreover, the results appear to be somewhat independent of the form of the assumed pdf.

Differential Antidepressant-Like Response to Lithium Treatment between Mouse Strains: Effects of Sex, Maternal Care, and Mixed Genetic Background

PubMed Central

Can, Adem; Piantadosi, Sean C.; Gould, Todd D.

2013-01-01

Background Lithium is a mood stabilizer with both antidepressant and antimanic properties, though its mechanism of action is unclear. Identifying the genetic factors that influence lithium's therapeutic actions will be an important step to assist in identifying such mechanisms. We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain. Objectives To assess the roles of both genetic, and non-genetic factors such as sex and non-shared environmental factors that may mediate differential behavioral responses to lithium. Methods Mice were treated with lithium for ten days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal. We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains. Results Neither sex nor maternal care significantly influenced the differential antidepressant-like profile of lithium. Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain, but had no effects in BALB/cJ mice. Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain. Conclusions Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains. Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium's therapeutic actions. PMID:23503701

The CRYPTOCHROME photoreceptor gates PDF neuropeptide signaling to set circadian network hierarchy in Drosophila.

PubMed

Zhang, Luoying; Lear, Bridget C; Seluzicki, Adam; Allada, Ravi

2009-12-15

Circadian clocks in the brain are organized as coupled oscillators that integrate seasonal cues such as light and temperature to time daily behaviors. In Drosophila, the PIGMENT DISPERSING FACTOR (PDF) neuropeptide-expressing morning (M) and non-PDF evening (E) cells are coupled cell groups important for morning and evening behavior, respectively. Depending on day length, either M cells (short days) or E cells (long days) dictate both the morning and the evening phase, a phenomenon that we term network hierarchy. To examine the role of PDF in light-dark conditions, we examined flies lacking both the PDF receptor (PDFR) and the circadian photoreceptor CRYPTOCHROME (CRY). We found that subsets of E cells exhibit molecular oscillations antiphase to those of wild-type flies, single cry mutants, or single Pdfr mutants, demonstrating a potent role for PDF in light-mediated entrainment, specifically in the absence of CRY. Moreover, we find that the evening behavioral phase is more strongly reset by PDF(+) M cells in the absence of CRY. On the basis of our findings, we propose that CRY can gate PDF signaling to determine behavioral phase and network hierarchy.

Eimeria Species and Genetic Background Influence the Serum Protein Profile of Broilers with Coccidiosis

PubMed Central

Gilbert, Elizabeth R.; Cox, Chasity M.; Williams, Patricia M.; McElroy, Audrey P.; Dalloul, Rami A.; Ray, W. Keith; Barri, Adriana; Emmerson, Derek A.; Wong, Eric A.; Webb, Kenneth E.

2011-01-01

Background Coccidiosis is an intestinal disease caused by protozoal parasites of the genus Eimeria. Despite the advent of anti-coccidial drugs and vaccines, the disease continues to result in substantial annual economic losses to the poultry industry. There is still much unknown about the host response to infection and to date there are no reports of protein profiles in the blood of Eimeria-infected animals. The objective of this study was to evaluate the serum proteome of two genetic lines of broiler chickens after infection with one of three species of Eimeria. Methodology/Principal Findings Birds from lines A and B were either not infected or inoculated with sporulated oocysts from one of the three Eimeria strains at 15 d post-hatch. At 21 d (6 d post-infection), whole blood was collected and lesion scoring was performed. Serum was harvested and used for 2-dimensional gel electrophoresis. A total of 1,266 spots were quantitatively assessed by densitometry. Protein spots showing a significant effect of coccidia strain and/or broiler genetic line on density at P<0.05−0.01 (250 spots), P<0.01−0.001 (248 spots), and P<0.001 (314 spots) were excised and analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Proteins were identified in 172 spots. A total of 46 different proteins were identified. Of the spots with a corresponding protein identification, 57 showed a main effect of coccidia infection and/or 2-way interaction of coccidia infection×broiler genetic line at P<0.001. Conclusions/Significance Several of the metabolic enzymes identified in this study are potential candidates for early diagnostic markers of E. acervulina infection including malate dehydrogenase 2, NADH dehydrogenase 1 alpha subcomplex 9, and an ATP synthase. These proteins were detected only in Line A birds that were inoculated with E. acervulina. Results from this study provide a basic framework for future research aimed at uncovering the complex

Graph-based layout analysis for PDF documents

NASA Astrophysics Data System (ADS)

Xu, Canhui; Tang, Zhi; Tao, Xin; Li, Yun; Shi, Cao

2013-03-01

To increase the flexibility and enrich the reading experience of e-book on small portable screens, a graph based method is proposed to perform layout analysis on Portable Document Format (PDF) documents. Digital born document has its inherent advantages like representing texts and fractional images in explicit form, which can be straightforwardly exploited. To integrate traditional image-based document analysis and the inherent meta-data provided by PDF parser, the page primitives including text, image and path elements are processed to produce text and non text layer for respective analysis. Graph-based method is developed in superpixel representation level, and page text elements corresponding to vertices are used to construct an undirected graph. Euclidean distance between adjacent vertices is applied in a top-down manner to cut the graph tree formed by Kruskal's algorithm. And edge orientation is then used in a bottom-up manner to extract text lines from each sub tree. On the other hand, non-textual objects are segmented by connected component analysis. For each segmented text and non-text composite, a 13-dimensional feature vector is extracted for labelling purpose. The experimental results on selected pages from PDF books are presented.

Direct photon production and PDF fits reloaded

DOE PAGES

Campbell, John M.; Rojo, Juan; Slade, Emma; ...

2018-06-09

Direct photon production in hadronic collisions provides a handle on the gluon PDF by means of the QCD Compton scattering process. In this work we revisit the impact of direct photon production on a global PDF analysis, motivated by the recent availability of the next-to-next-to-leading (NNLO) calculation for this process. We demonstrate that the inclusion of NNLO QCD and leading-logarithmic electroweak corrections leads to a good quantitative agreement with the ATLAS measurements at 8 and 13 TeV, except for the most forward rapidity region in the former case. By including the ATLAS 8 TeV direct photon production data in themore » NNPDF3.1 NNLO global analysis, we assess its impact on the medium-x gluon. We also study the constraining power of the direct photon production measurements on PDF fits based on different datasets, in particular on the NNPDF3.1 no-LHC and collider-only fits. Here, we also present updated NNLO theoretical predictions for direct photon production at 13 TeV that include the constraints from the 8 TeV measurements.« less

Direct photon production and PDF fits reloaded

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

Campbell, John M.; Rojo, Juan; Slade, Emma

Direct photon production in hadronic collisions provides a handle on the gluon PDF by means of the QCD Compton scattering process. In this work we revisit the impact of direct photon production on a global PDF analysis, motivated by the recent availability of the next-to-next-to-leading (NNLO) calculation for this process. We demonstrate that the inclusion of NNLO QCD and leading-logarithmic electroweak corrections leads to a good quantitative agreement with the ATLAS measurements at 8 and 13 TeV, except for the most forward rapidity region in the former case. By including the ATLAS 8 TeV direct photon production data in themore » NNPDF3.1 NNLO global analysis, we assess its impact on the medium-x gluon. We also study the constraining power of the direct photon production measurements on PDF fits based on different datasets, in particular on the NNPDF3.1 no-LHC and collider-only fits. Here, we also present updated NNLO theoretical predictions for direct photon production at 13 TeV that include the constraints from the 8 TeV measurements.« less

Direct photon production and PDF fits reloaded

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

Campbell, John M.; Rojo, Juan; Slade, Emma

2018-02-08

Direct photon production in hadronic collisions provides a handle on the gluon PDF by means of the QCD Compton scattering process. In this work we revisit the impact of direct photon production on a global PDF analysis, motivated by the recent availability of the next-to-next-to-leading (NNLO) calculation for this process. We demonstrate that the inclusion of NNLO QCD and leading-logarithmic electroweak corrections leads to a good quantitative agreement with the ATLAS measurements at 8 TeV and 13 TeV, except for the most forward rapidity region in the former case. By including the ATLAS 8 TeV direct photon production data inmore » the NNPDF3.1 NNLO global analysis, we assess its impact on the medium-x gluon. We also study the constraining power of the direct photon production measurements on PDF fits based on different datasets, in particular on the NNPDF3.1 no-LHC and collider-only fits. We also present updated NNLO theoretical predictions for direct photon production at 13 TeV that include the constraints from the 8 TeV measurements.« less

Modeling of turbulent supersonic H2-air combustion with a multivariate beta PDF

NASA Technical Reports Server (NTRS)

Baurle, R. A.; Hassan, H. A.

1993-01-01

Recent calculations of turbulent supersonic reacting shear flows using an assumed multivariate beta PDF (probability density function) resulted in reduced production rates and a delay in the onset of combustion. This result is not consistent with available measurements. The present research explores two possible reasons for this behavior: use of PDF's that do not yield Favre averaged quantities, and the gradient diffusion assumption. A new multivariate beta PDF involving species densities is introduced which makes it possible to compute Favre averaged mass fractions. However, using this PDF did not improve comparisons with experiment. A countergradient diffusion model is then introduced. Preliminary calculations suggest this to be the cause of the discrepancy.

A New LES/PDF Method for Computational Modeling of Turbulent Reacting Flows

NASA Astrophysics Data System (ADS)

Turkeri, Hasret; Muradoglu, Metin; Pope, Stephen B.

2013-11-01

A new LES/PDF method is developed for computational modeling of turbulent reacting flows. The open source package, OpenFOAM, is adopted as the LES solver and combined with the particle-based Monte Carlo method to solve the LES/PDF model equations. The dynamic Smagorinsky model is employed to account for the subgrid-scale motions. The LES solver is first validated for the Sandia Flame D using a steady flamelet method in which the chemical compositions, density and temperature fields are parameterized by the mean mixture fraction and its variance. In this approach, the modeled transport equations for the mean mixture fraction and the square of the mixture fraction are solved and the variance is then computed from its definition. The results are found to be in a good agreement with the experimental data. Then the LES solver is combined with the particle-based Monte Carlo algorithm to form a complete solver for the LES/PDF model equations. The in situ adaptive tabulation (ISAT) algorithm is incorporated into the LES/PDF method for efficient implementation of detailed chemical kinetics. The LES/PDF method is also applied to the Sandia Flame D using the GRI-Mech 3.0 chemical mechanism and the results are compared with the experimental data and the earlier PDF simulations. The Scientific and Technical Research Council of Turkey (TUBITAK), Grant No. 111M067.

Differences in genetic background influence the induction of innate and acquired immune responses in chickens depending on the virulence of the infecting infectious bursal disease virus (IBDV) strain.

PubMed

Aricibasi, Merve; Jung, Arne; Heller, E Dan; Rautenschlein, Silke

2010-05-15

Previous studies and field observations have suggested that genetic background influences infectious bursal disease virus (IBDV) pathogenesis. However, the influence of the virulence of the infecting IBDV strain and the mechanisms underlying the differences in susceptibility are not known. In the present study IBDV pathogenesis was compared between specific-pathogen-free layer-type (LT) chickens, which are the most susceptible chicken for IBDV and have been used as the model for pathogenesis studies, and broiler-type (BT) chickens, which are known to be less susceptible to clinical infectious bursal disease (IBD). The innate and acquired immune responses were investigated after inoculation of an intermediate (i), virulent (v) or very virulent (vv) strain of IBDV. IBDV pathogenesis was comparable among genetic backgrounds after infection with iIBDV. After infection with vIBDV and vvIBDV, LT birds showed severe clinical disease and mortality, higher bursal lesion scores and IBDV-antigen load relative to BT birds. Circulating cytokine induction varied significantly in both timing and quantity between LT and BT birds and among virus strains (P<0.05). Evaluation of different immune cell populations by flow-cytometric analysis in the bursa of Fabricius provided circumstantial evidence of a stronger local T cell response in BT birds vs. LT birds after infection with the virulent strain. On the other hand, LT birds showed a more significant increase in circulating macrophage-derived immune mediators such as total interferon (IFN) and serum nitrite than BT birds on days 2 and 3 post-vIBDV infection (P<0.05). Stronger stimulation of innate immune reactions especially after vIBDV infection in the early phase may lead to faster and more severe lesion development accompanied by clinical disease and death in LT chickens relative to BT chickens. Interestingly, no significant differences were seen between genetic backgrounds in induction of the IBDV-specific humoral response

Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line

PubMed Central

Krentz, Anthony D.; Murphy, Mark W.; Zhang, Teng; Sarver, Aaron L.; Jain, Sanjay; Griswold, Michael D.; Bardwell, Vivian J.; Zarkower, David

2013-01-01

Dmrt1(doublesex and mab-3 related transcription factor 1) is a regulator of testis development in vertebrates that has been implicated in testicular germ cell tumors of mouse and human. In the fetal mouse testis Dmrt1 regulates germ cell pluripotency in a strain-dependent manner. Loss of Dmrt1 in 129Sv strain mice results in a >90% incidence of testicular teratomas, tumors consisting cells of multiple germ layers; by contrast, these tumors have never been observed in Dmrt1 mutants of C57BL/6J (B6) or mixed genetic backgrounds. To further investigate the interaction between Dmrt1 and genetic background we compared mRNA expression in wild type and Dmrt1 mutant fetal testes of 129Sv and B6 mice at embryonic day 15.5 (E15.5), prior to overt tumorigenesis. Loss of Dmrt1 caused misexpression of overlapping but distinct sets of mRNAs in the two strains. The mRNAs that were selectively affected included some that changed expression only in one strain or the other and some that changed in both strains but to a greater degree in one versus the other. In particular, loss of Dmrt1 in 129Sv testes caused a more severe failure to silence regulators of pluripotency than in B6 testes. A number of genes misregulated in 129Sv mutant testes also are misregulated in human testicular germ cell tumors (TGCTs), suggesting similar etiology between germ cell tumors in mouse and man. Expression profiling showed that DMRT1 also regulates pluripotency genes in the fetal ovary, although Dmrt1 mutant females do not develop teratomas. Pathway analysis indicated disruption of several signaling pathways in Dmrt1 mutant fetal testes, including Nodal, Notch, and GDNF. We used a Nanos3-cre knock-in allele to perform conditional gene targeting, testing the GDNF coreceptors Gfra1 and Ret for effects on teratoma susceptibility. Conditional deletion of Gfra1 but not Ret in fetal germ cells of animals outcrossed to 129Sv caused a modest but significant elevation in tumor incidence. Despite some

PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.

PubMed

Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

2014-06-17

Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

Using Interactive 3D PDF for Exploring Complex Biomedical Data: Experiences and Solutions.

PubMed

Newe, Axel; Becker, Linda

2016-01-01

The Portable Document Format (PDF) is the most commonly used file format for the exchange of electronic documents. A lesser-known feature of PDF is the possibility to embed three-dimensional models and to display these models interactively with a qualified reader. This technology is well suited to present, to explore and to communicate complex biomedical data. This applies in particular for data which would suffer from a loss of information if it was reduced to a static two-dimensional projection. In this article, we present applications of 3D PDF for selected scholarly and clinical use cases in the biomedical domain. Furthermore, we present a sophisticated tool for the generation of respective PDF documents.

ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

EPA Science Inventory

Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF.
Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

Genetic background in partitioning of metabolizable energy efficiency in dairy cows.

PubMed

Mehtiö, T; Negussie, E; Mäntysaari, P; Mäntysaari, E A; Lidauer, M H

2018-05-01

The main objective of this study was to assess the genetic differences in metabolizable energy efficiency and efficiency in partitioning metabolizable energy in different pathways: maintenance, milk production, and growth in primiparous dairy cows. Repeatability models for residual energy intake (REI) and metabolizable energy intake (MEI) were compared and the genetic and permanent environmental variations in MEI were partitioned into its energy sinks using random regression models. We proposed 2 new feed efficiency traits: metabolizable energy efficiency (MEE), which is formed by modeling MEI fitting regressions on energy sinks [metabolic body weight (BW 0.75 ), energy-corrected milk, body weight gain, and body weight loss] directly; and partial MEE (pMEE), where the model for MEE is extended with regressions on energy sinks nested within additive genetic and permanent environmental effects. The data used were collected from Luke's experimental farms Rehtijärvi and Minkiö between 1998 and 2014. There were altogether 12,350 weekly MEI records on 495 primiparous Nordic Red dairy cows from wk 2 to 40 of lactation. Heritability estimates for REI and MEE were moderate, 0.33 and 0.26, respectively. The estimate of the residual variance was smaller for MEE than for REI, indicating that analyzing weekly MEI observations simultaneously with energy sinks is preferable. Model validation based on Akaike's information criterion showed that pMEE models fitted the data even better and also resulted in smaller residual variance estimates. However, models that included random regression on BW 0.75 converged slowly. The resulting genetic standard deviation estimate from the pMEE coefficient for milk production was 0.75 MJ of MEI/kg of energy-corrected milk. The derived partial heritabilities for energy efficiency in maintenance, milk production, and growth were 0.02, 0.06, and 0.04, respectively, indicating that some genetic variation may exist in the efficiency of using

Galaxy clustering with photometric surveys using PDF redshift information

DOE PAGES

Asorey, J.; Carrasco Kind, M.; Sevilla-Noarbe, I.; ...

2016-03-28

Here, photometric surveys produce large-area maps of the galaxy distribution, but with less accurate redshift information than is obtained from spectroscopic methods. Modern photometric redshift (photo-z) algorithms use galaxy magnitudes, or colors, that are obtained through multi-band imaging to produce a probability density function (PDF) for each galaxy in the map. We used simulated data to study the effect of using different photo-z estimators to assign galaxies to redshift bins in order to compare their effects on angular clustering and galaxy bias measurements. We found that if we use the entire PDF, rather than a single-point (mean or mode) estimate, the deviations are less biased, especially when using narrow redshift bins. When the redshift bin widths aremore » $$\\Delta z=0.1$$, the use of the entire PDF reduces the typical measurement bias from 5%, when using single point estimates, to 3%.« less

Non-Gaussian PDF Modeling of Turbulent Boundary Layer Fluctuating Pressure Excitation

NASA Technical Reports Server (NTRS)

Steinwolf, Alexander; Rizzi, Stephen A.

2003-01-01

The purpose of the study is to investigate properties of the probability density function (PDF) of turbulent boundary layer fluctuating pressures measured on the exterior of a supersonic transport aircraft. It is shown that fluctuating pressure PDFs differ from the Gaussian distribution even for surface conditions having no significant discontinuities. The PDF tails are wider and longer than those of the Gaussian model. For pressure fluctuations upstream of forward-facing step discontinuities and downstream of aft-facing step discontinuities, deviations from the Gaussian model are more significant and the PDFs become asymmetrical. Various analytical PDF distributions are used and further developed to model this behavior.

Progress in the development of PDF turbulence models for combustion

NASA Technical Reports Server (NTRS)

Hsu, Andrew T.

1991-01-01

A combined Monte Carlo-computational fluid dynamic (CFD) algorithm was developed recently at Lewis Research Center (LeRC) for turbulent reacting flows. In this algorithm, conventional CFD schemes are employed to obtain the velocity field and other velocity related turbulent quantities, and a Monte Carlo scheme is used to solve the evolution equation for the probability density function (pdf) of species mass fraction and temperature. In combustion computations, the predictions of chemical reaction rates (the source terms in the species conservation equation) are poor if conventional turbulence modles are used. The main difficulty lies in the fact that the reaction rate is highly nonlinear, and the use of averaged temperature produces excessively large errors. Moment closure models for the source terms have attained only limited success. The probability density function (pdf) method seems to be the only alternative at the present time that uses local instantaneous values of the temperature, density, etc., in predicting chemical reaction rates, and thus may be the only viable approach for more accurate turbulent combustion calculations. Assumed pdf's are useful in simple problems; however, for more general combustion problems, the solution of an evolution equation for the pdf is necessary.

The Physiological Effects of Deleting the Mouse Slc30a8 Gene Encoding Zinc Transporter-8 Are Influenced by Gender and Genetic Background

PubMed Central

Pound, Lynley D.; Sarkar, Suparna A.; Ustione, Alessandro; Dadi, Prasanna K.; Shadoan, Melanie K.; Lee, Catherine E.; Walters, Jay A.; Shiota, Masakazu; McGuinness, Owen P.; Jacobson, David A.; Piston, David W.; Hutton, John C.; Powell, David R.; O’Brien, Richard M.

2012-01-01

Objective The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes. Methods The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background. Results Male C57BL/6J Slc30a8 knockout (KO) mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS) from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20%) fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG), or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance. Conclusions Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology. PMID:22829903

Handling a Collection of PDF Documents

EPA Pesticide Factsheets

You have several options for making a large collection of PDF documents more accessible to your audience: avoid uploading altogether, use multiple document pages, and use document IDs as anchors for direct links within a document page.

Shared Genetic Background for Regulation of Mood and Sleep: Association of GRIA3 with Sleep Duration in Healthy Finnish Women

PubMed Central

Utge, Siddheshwar; Kronholm, Erkki; Partonen, Timo; Soronen, Pia; Ollila, Hanna M.; Loukola, Anu; Perola, Markus; Salomaa, Veikko; Porkka-Heiskanen, Tarja; Paunio, Tiina

2011-01-01

Study Objectives: Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder. Design: Population-based molecular genetic study. Setting: Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals. Participants: Three thousand, one hundred, forty-seven individuals (25–75 y) from population-based Health 2000 and FINRISK 2007 samples. Measurements and Results: We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P = 0.00001, β = 0.27; Bonferroni corrected P = 0.0052; f = 0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P = 0.0003, OR = 1.81). Conclusions: The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission. Citation: Utge S; Kronholm E; Partonen T; Soronen P; Ollila HM; Loukola A; Perola M; Salomaa V; Porkka-Heiskanen T; Paunio T. Shared genetic background for

Analytical Plug-In Method for Kernel Density Estimator Applied to Genetic Neutrality Study

NASA Astrophysics Data System (ADS)

Troudi, Molka; Alimi, Adel M.; Saoudi, Samir

2008-12-01

The plug-in method enables optimization of the bandwidth of the kernel density estimator in order to estimate probability density functions (pdfs). Here, a faster procedure than that of the common plug-in method is proposed. The mean integrated square error (MISE) depends directly upon [InlineEquation not available: see fulltext.] which is linked to the second-order derivative of the pdf. As we intend to introduce an analytical approximation of [InlineEquation not available: see fulltext.], the pdf is estimated only once, at the end of iterations. These two kinds of algorithm are tested on different random variables having distributions known for their difficult estimation. Finally, they are applied to genetic data in order to provide a better characterisation in the mean of neutrality of Tunisian Berber populations.

Modeling Interactions Among Turbulence, Gas-Phase Chemistry, Soot and Radiation Using Transported PDF Methods

NASA Astrophysics Data System (ADS)

Haworth, Daniel

2013-11-01

The importance of explicitly accounting for the effects of unresolved turbulent fluctuations in Reynolds-averaged and large-eddy simulations of chemically reacting turbulent flows is increasingly recognized. Transported probability density function (PDF) methods have emerged as one of the most promising modeling approaches for this purpose. In particular, PDF methods provide an elegant and effective resolution to the closure problems that arise from averaging or filtering terms that correspond to nonlinear point processes, including chemical reaction source terms and radiative emission. PDF methods traditionally have been associated with studies of turbulence-chemistry interactions in laboratory-scale, atmospheric-pressure, nonluminous, statistically stationary nonpremixed turbulent flames; and Lagrangian particle-based Monte Carlo numerical algorithms have been the predominant method for solving modeled PDF transport equations. Recent advances and trends in PDF methods are reviewed and discussed. These include advances in particle-based algorithms, alternatives to particle-based algorithms (e.g., Eulerian field methods), treatment of combustion regimes beyond low-to-moderate-Damköhler-number nonpremixed systems (e.g., premixed flamelets), extensions to include radiation heat transfer and multiphase systems (e.g., soot and fuel sprays), and the use of PDF methods as the basis for subfilter-scale modeling in large-eddy simulation. Examples are provided that illustrate the utility and effectiveness of PDF methods for physics discovery and for applications to practical combustion systems. These include comparisons of results obtained using the PDF method with those from models that neglect unresolved turbulent fluctuations in composition and temperature in the averaged or filtered chemical source terms and/or the radiation heat transfer source terms. In this way, the effects of turbulence-chemistry-radiation interactions can be isolated and quantified.

How to Create a Web-Ready PDF

EPA Pesticide Factsheets

Making EPA's PDF documents accessible (by Section 508 standards) and user-friendly includes steps such as adding bookmarks, using electronic conversion rather than scanning pages, and adding metadata.

Drosophila GPCR Han is a receptor for the circadian clock neuropeptide PDF.

PubMed

Hyun, Seogang; Lee, Youngseok; Hong, Sung-Tae; Bang, Sunhoe; Paik, Donggi; Kang, Jongkyun; Shin, Jinwhan; Lee, Jaejung; Jeon, Keunhye; Hwang, Seungyoon; Bae, Eunkyung; Kim, Jaeseob

2005-10-20

The pigment-dispersing factor (PDF) is a neuropeptide controlling circadian behavioral rhythms in Drosophila, but its receptor is not yet known. From a large-scale temperature preference behavior screen in Drosophila, we isolated a P insertion mutant that preferred different temperatures during the day and night. This mutation, which we named han, reduced the transcript level of CG13758. We found that Han was expressed specifically in 13 pairs of circadian clock neurons in the adult brain. han null flies showed arrhythmic circadian behavior in constant darkness. The behavioral characteristics of han null mutants were similar to those of pdf null mutants. We also found that PDF binds specifically to S2 cells expressing Han, which results in the elevation of cAMP synthesis. Therefore, we herein propose that Han is a PDF receptor regulating circadian behavioral rhythm through coordination of activities of clock neurons.

Sparse PDF Volumes for Consistent Multi-Resolution Volume Rendering.

PubMed

Sicat, Ronell; Krüger, Jens; Möller, Torsten; Hadwiger, Markus

2014-12-01

This paper presents a new multi-resolution volume representation called sparse pdf volumes, which enables consistent multi-resolution volume rendering based on probability density functions (pdfs) of voxel neighborhoods. These pdfs are defined in the 4D domain jointly comprising the 3D volume and its 1D intensity range. Crucially, the computation of sparse pdf volumes exploits data coherence in 4D, resulting in a sparse representation with surprisingly low storage requirements. At run time, we dynamically apply transfer functions to the pdfs using simple and fast convolutions. Whereas standard low-pass filtering and down-sampling incur visible differences between resolution levels, the use of pdfs facilitates consistent results independent of the resolution level used. We describe the efficient out-of-core computation of large-scale sparse pdf volumes, using a novel iterative simplification procedure of a mixture of 4D Gaussians. Finally, our data structure is optimized to facilitate interactive multi-resolution volume rendering on GPUs.

Sparse PDF Volumes for Consistent Multi-Resolution Volume Rendering

PubMed Central

Sicat, Ronell; Krüger, Jens; Möller, Torsten; Hadwiger, Markus

2015-01-01

This paper presents a new multi-resolution volume representation called sparse pdf volumes, which enables consistent multi-resolution volume rendering based on probability density functions (pdfs) of voxel neighborhoods. These pdfs are defined in the 4D domain jointly comprising the 3D volume and its 1D intensity range. Crucially, the computation of sparse pdf volumes exploits data coherence in 4D, resulting in a sparse representation with surprisingly low storage requirements. At run time, we dynamically apply transfer functions to the pdfs using simple and fast convolutions. Whereas standard low-pass filtering and down-sampling incur visible differences between resolution levels, the use of pdfs facilitates consistent results independent of the resolution level used. We describe the efficient out-of-core computation of large-scale sparse pdf volumes, using a novel iterative simplification procedure of a mixture of 4D Gaussians. Finally, our data structure is optimized to facilitate interactive multi-resolution volume rendering on GPUs. PMID:26146475

PDF neuron firing phase-shifts key circadian activity neurons in Drosophila

PubMed Central

Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

2014-01-01

Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY. DOI: http://dx.doi.org/10.7554/eLife.02780.001 PMID:24939987

SU-F-T-94: Plan2pdf - a Software Tool for Automatic Plan Report for Philips Pinnacle TPS

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

Wu, C

Purpose: To implement an automatic electronic PDF plan reporting tool for Philips Pinnacle treatment planning system (TPS) Methods: An electronic treatment plan reporting software is developed by us to enable fully automatic PDF report from Pinnacle TPS to external EMR programs such as MOSAIQ. The tool is named “plan2pdf”. plan2pdf is implemented using Pinnacle scripts, Java and UNIX shell scripts, without any external program needed. plan2pdf supports full auto-mode and manual mode reporting. In full auto-mode, with a single mouse click, plan2pdf will generate a detailed Pinnacle plan report in PDF format, which includes customizable cover page, Pinnacle plan summary,more » orthogonal views through each plan POI and maximum dose point, DRR for each beam, serial transverse views captured throughout the dose grid at a user specified interval, DVH and scorecard windows. The final PDF report is also automatically bookmarked for each section above for convenient plan review. The final PDF report can either be saved on a user specified folder on Pinnacle, or it can be automatically exported to an EMR import folder via a user configured FTP service. In manual capture mode, plan2pdf allows users to capture any Pinnacle plan by full screen, individual window or rectangular ROI drawn on screen. Furthermore, to avoid possible patients’ plan mix-up during auto-mode reporting, a user conflict check feature is included in plan2pdf: it prompts user to wait if another patient is being exported by plan2pdf by another user. Results: plan2pdf is tested extensively and successfully at our institution consists of 5 centers, 15 dosimetrists and 10 physicists, running Pinnacle version 9.10 on Enterprise servers. Conclusion: plan2pdf provides a highly efficient, user friendly and clinical proven platform for all Philips Pinnacle users, to generate a detailed plan report in PDF format for external EMR systems.« less

Layout-aware text extraction from full-text PDF of scientific articles.

PubMed

Ramakrishnan, Cartic; Patnia, Abhishek; Hovy, Eduard; Burns, Gully Apc

2012-05-28

The Portable Document Format (PDF) is the most commonly used file format for online scientific publications. The absence of effective means to extract text from these PDF files in a layout-aware manner presents a significant challenge for developers of biomedical text mining or biocuration informatics systems that use published literature as an information source. In this paper we introduce the 'Layout-Aware PDF Text Extraction' (LA-PDFText) system to facilitate accurate extraction of text from PDF files of research articles for use in text mining applications. Our paper describes the construction and performance of an open source system that extracts text blocks from PDF-formatted full-text research articles and classifies them into logical units based on rules that characterize specific sections. The LA-PDFText system focuses only on the textual content of the research articles and is meant as a baseline for further experiments into more advanced extraction methods that handle multi-modal content, such as images and graphs. The system works in a three-stage process: (1) Detecting contiguous text blocks using spatial layout processing to locate and identify blocks of contiguous text, (2) Classifying text blocks into rhetorical categories using a rule-based method and (3) Stitching classified text blocks together in the correct order resulting in the extraction of text from section-wise grouped blocks. We show that our system can identify text blocks and classify them into rhetorical categories with Precision1 = 0.96% Recall = 0.89% and F1 = 0.91%. We also present an evaluation of the accuracy of the block detection algorithm used in step 2. Additionally, we have compared the accuracy of the text extracted by LA-PDFText to the text from the Open Access subset of PubMed Central. We then compared this accuracy with that of the text extracted by the PDF2Text system, 2commonly used to extract text from PDF. Finally, we discuss preliminary error analysis for

PDF methods for combustion in high-speed turbulent flows

NASA Technical Reports Server (NTRS)

Pope, Stephen B.

1995-01-01

This report describes the research performed during the second year of this three-year project. The ultimate objective of the project is extend the applicability of probability density function (pdf) methods from incompressible to compressible turbulent reactive flows. As described in subsequent sections, progress has been made on: (1) formulation and modelling of pdf equations for compressible turbulence, in both homogeneous and inhomogeneous inert flows; and (2) implementation of the compressible model in various flow configurations, namely decaying isotropic turbulence, homogeneous shear flow and plane mixing layer.

PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator.

PubMed

Mezan, Shaul; Feuz, Jean Daniel; Deplancke, Bart; Kadener, Sebastian

2016-10-11

Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

PubMed

Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

2014-01-01

Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

Anatomical characterization of PDF-tri neurons and peptidergic neurons associated with eclosion behavior in Drosophila.

PubMed

Selcho, Mareike; Mühlbauer, Barbara; Hensgen, Ronja; Shiga, Sakiko; Wegener, Christian; Yasuyama, Kouji

2018-06-01

The peptidergic Pigment-dispersing factor (PDF)-Tri neurons are a group of non-clock neurons that appear transiently around the time of adult ecdysis (=eclosion) in the fruit fly Drosophila melanogaster. This specific developmental pattern points to a function of these neurons in eclosion or other processes that are active around pupal-adult transition. As a first step to understand the role of these neurons, we here characterize the anatomy of the PDF-Tri neurons. In addition, we describe a further set of peptidergic neurons that have been associated with eclosion behavior, eclosion hormone (EH), and crustacean cardioactive peptide (CCAP) neurons, to single cell level in the pharate adult brain. PDF-Tri neurons as well as CCAP neurons co-express a classical transmitter indicated by the occurrence of small clear vesicles in addition to dense-core vesicles containing the peptides. In the tritocerebrum, gnathal ganglion and the superior protocerebrum PDF-Tri neurites contain peptidergic varicosities and both pre- and postsynaptic sites, suggesting that the PDF-Tri neurons represent modulatory rather than pure interneurons that connect the subesophageal zone with the superior protocerebrum. The extensive overlap of PDF-Tri arborizations with neurites of CCAP- and EH-expressing neurons in distinct brain regions provides anatomical evidence for a possible function of the PDF-Tri neurons in eclosion behavior. © 2018 Wiley Periodicals, Inc.

DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila.

PubMed

Zhang, Luoying; Chung, Brian Y; Lear, Bridget C; Kilman, Valerie L; Liu, Yixiao; Mahesh, Guruswamy; Meissner, Rose-Anne; Hardin, Paul E; Allada, Ravi

2010-04-13

Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for approximately 16-20 circadian pacemaker neurons, a subset of the posterior dorsal neurons 1 (DN1(p)s), in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) are especially important for morning anticipation and free-running rhythms and send projections to the DN1(p)s. We also demonstrate that DN1(p)Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms, including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting that they are direct targets. Taking these results together, we demonstrate that the DN1(p)s lie at the nexus of PDF and photic signaling to produce appropriate daily behavior.

An easy and effective approach to manage radiologic portable document format (PDF) files using iTunes.

PubMed

Qian, Li Jun; Zhou, Mi; Xu, Jian Rong

2008-07-01

The objective of this article is to explain an easy and effective approach for managing radiologic files in portable document format (PDF) using iTunes. PDF files are widely used as a standard file format for electronic publications as well as for medical online documents. Unfortunately, there is a lack of powerful software to manage numerous PDF documents. In this article, we explain how to use the hidden function of iTunes (Apple Computer) to manage PDF documents as easily as managing music files.

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

DOE PAGES

Tang, Jonathan; Huang, Yurong; Nguyen, David H.; ...

2015-02-04

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

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

Tang, Jonathan; Huang, Yurong; Nguyen, David H.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

A circadian neuropeptide PDF in the honeybee, Apis mellifera: cDNA cloning and expression of mRNA.

PubMed

Sumiyoshi, Miho; Sato, Seiji; Takeda, Yukimasa; Sumida, Kazunori; Koga, Keita; Itoh, Tsunao; Nakagawa, Hiroyuki; Shimohigashi, Yasuyuki; Shimohigashi, Miki

2011-12-01

Pigment-dispersing factor (PDF) is a pacemaker hormone regulating the locomotor rhythm in insects. In the present study, we cloned the cDNAs encoding the Apis PDF precursor protein, and found that there are at least seven different pdf mRNAs yielded by an alternative splicing site and five alternative polyadenylation sites in the 5'UTR and 3'UTR regions. The amino acid sequence of Apis PDF peptide has a characteristic novel amino acid residue, aspargine (Asn), at position 17. Quantitative real-time PCR of total and 5'UTR insertion-type pdf mRNAs revealed, for the first time, that the expression levels change in a circadian manner with a distinct trough at the beginning of night in LD conditions, and at the subjective night under DD conditions. In contrast, the expression level of 5'UTR deletion-type pdf mRNAs was about half of that of the insertion type, and the expression profile failed to show a circadian rhythm. As the expression profile of the total pdf mRNA exhibited a circadian rhythm, transcription regulated at the promoter region was supposed to be controlled by some of the clock components. Whole mount in situ hybridization revealed that 14 lateral neurons at the frontal margin of the optic lobe express these mRNA isoforms. PDF expressing cells examined with a newly produced antibody raised against Apis PDF were also found to have a dense supply of axon terminals in the optic lobes and the central brain.

Crystal structure of an EfPDF complex with Met-Ala-Ser based on crystallographic packing.

PubMed

Nam, Ki Hyun; Kim, Kook-Han; Kim, Eunice Eun Kyeong; Hwang, Kwang Yeon

2009-04-17

PDF (peptide deformylase) plays a critical role in the production of mature proteins by removing the N-formyl polypeptide of nascent proteins in the prokaryote cell system. This protein is essential for bacterial growth, making it an attractive target for the design of new antibiotics. Accordingly, PDF has been evaluated as a drug target; however, architectural mechanism studies of PDF have not yet fully elucidated its molecular function. We recently reported the crystal structure of PDF produced by Enterococcus faecium [K.H. Nam, J.I. Ham, A. Priyadarshi, E.E. Kim, N. Chung, K.Y. Hwang, "Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure", Proteins 74 (2009) 261-265]. Here, we present the crystal structure of the EfPDF complex with MAS (Met-Ser-Ala), thereby not only delineating the architectural mechanism for the recognition of mimic-peptides by N-terminal cleaved expression peptide, but also suggesting possible targets for rational design of antibacterial drugs. In addition to their implications for drug design, these structural studies will facilitate elucidation of the architectural mechanism responsible for the peptide recognition of PDF.

Pigment-dispersing factor (PDF) has different effects on Drosophila's circadian clocks in the accessory medulla and in the dorsal brain.

PubMed

Wülbeck, Corinna; Grieshaber, Eva; Helfrich-Förster, Charlotte

2008-10-01

The neuropeptide pigment-dispersing factor (PDF) is a key transmitter in the circadian clock of Drosophila melanogaster. Here we studied the rhythmic behavior of neural mutants with modified arborizations of the large PDF neurons. In sine oculis(1) (so(1)) mutants we found a higher density of PDF fibers in the fly's pacemaker center, the accessory medulla. These flies exhibited a significantly longer period (24.6 h) than control flies. When PDF levels were elevated to very high levels in the dorsal brain as true for so(mda) mutants and small optic lobes;so(1) double mutants (sol(1);so( 1)), a short-period component split off the long period in behavioral rhythmicity. The short period became shorter the higher the amount of PDF in this brain region and reached a value of approximately 21 h. The period alterations were clearly dependent on PDF, because so(1);Pdf 01 and so(mda);Pdf 01 double mutants showed a single free-running component with a period similar to Pdf 01 mutants (approximately 22.5 h) and significantly longer than the short period of so(mda) mutants. These observations indicate that PDF feeds back on the clock neurons and changes their period. Obviously, PDF lengthens the period of some clock neurons and shortens that of others.

Multi-location wheat stripe rust QTL analysis: genetic background and epistatic interactions.

PubMed

Vazquez, M Dolores; Zemetra, Robert; Peterson, C James; Chen, Xianming M; Heesacker, Adam; Mundt, Christopher C

2015-07-01

Epistasis and genetic background were important influences on expression of stripe rust resistance in two wheat RIL populations, one with resistance conditioned by two major genes and the other conditioned by several minor QTL. Stripe rust is a foliar disease of wheat (Triticum aestivum L.) caused by the air-borne fungus Puccinia striiformis f. sp. tritici and is present in most regions around the world where commercial wheat is grown. Breeding for durable resistance to stripe rust continues to be a priority, but also is a challenge due to the complexity of interactions among resistance genes and to the wide diversity and continuous evolution of the pathogen races. The goal of this study was to detect chromosomal regions for resistance to stripe rust in two winter wheat populations, 'Tubbs'/'NSA-98-0995' (T/N) and 'Einstein'/'Tubbs' (E/T), evaluated across seven environments and mapped with diversity array technology and simple sequence repeat markers covering polymorphic regions of ≈1480 and 1117 cM, respectively. Analysis of variance for phenotypic data revealed significant (P < 0.01) genotypic differentiation for stripe rust among the recombinant inbred lines. Results for quantitative trait loci/locus (QTL) analysis in the E/T population indicated that two major QTL located in chromosomes 2AS and 6AL, with epistatic interaction between them, were responsible for the main phenotypic response. For the T/N population, eight QTL were identified, with those in chromosomes 2AL and 2BL accounting for the largest percentage of the phenotypic variance.

Effect of urban traffic, individual habits, and genetic polymorphisms on background urinary 1-hydroxypyrene excretion.

PubMed

Cocco, Pierluigi; Moore, Patrick S; Ennas, Maria G; Tocco, Maria G; Ibba, Antonio; Mattuzzi, Silvia; Meloni, Michele; Monne, Maria; Piras, Giovanna; Collu, Stefania; Satta, Giannina; Zucca, Mariagrazia; Scarpa, Aldo; Flore, Costantino

2007-01-01

Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C-->T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.

The impact of the photon PDF and electroweak corrections on [Formula: see text] distributions.

PubMed

Pagani, D; Tsinikos, I; Zaro, M

2016-01-01

We discuss the impact of EW corrections on differential distributions in top-quark pair production at the LHC and future hadron colliders, focussing on the effects of initial-state photons. Performing a calculation at Next-to-Leading Order QCD+EW accuracy, we investigate in detail the impact of photon-initiated channels on central values as well as PDF and scale uncertainties, both at order [Formula: see text] and [Formula: see text]. We present predictions at 13 and 100 TeV, and provide results for the 8 TeV differential measurements performed by ATLAS and CMS. A thorough comparison of results obtained with the NNPDF2.3QED and CT14QED PDF sets is performed. While contributions due to the photon PDF are negligible with CT14QED, this is not the case for NNPDF2.3QED, where such contributions are sizeable and show large PDF uncertainties. On the one hand, we show that differential observables in top-pair production, in particular top-quark and [Formula: see text] rapidities, can be used to improve the determination of the photon PDF within the NNPDF approach. On the other hand, with current PDF sets, we demonstrate the necessity of including EW corrections and photon-induced contributions for a correct determination of both the central value and the uncertainties of theoretical predictions.

The PDF method for turbulent combustion

NASA Technical Reports Server (NTRS)

Pope, S. B.

1991-01-01

Probability Density Function (PDF) methods provide a means of calculating the properties of turbulent reacting flows. They have been successfully applied to many turbulent flames, including some with finite rate kinetic effects. Here the methods are reviewed with an emphasis on computational issues and their application to turbulent combustion.

High-pressure pair distribution function (PDF) measurement using high-energy focused x-ray beam

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

Hong, Xinguo, E-mail: xhong@bnl.gov; Weidner, Donald J.; Ehm, Lars

In this paper, we report recent development of the high-pressure pair distribution function (HP-PDF) measurement technique using a focused high-energy X-ray beam coupled with a diamond anvil cell (DAC). The focusing optics consist of a sagittally bent Laue monochromator and Kirkpatrick-Baez (K–B) mirrors. This combination provides a clean high-energy X-ray beam suitable for HP-PDF research. Demonstration of the HP-PDF technique for nanocrystalline platinum under quasi-hydrostatic condition above 30 GPa is presented.

Background field removal technique using regularization enabled sophisticated harmonic artifact reduction for phase data with varying kernel sizes.

PubMed

Kan, Hirohito; Kasai, Harumasa; Arai, Nobuyuki; Kunitomo, Hiroshi; Hirose, Yasujiro; Shibamoto, Yuta

2016-09-01

An effective background field removal technique is desired for more accurate quantitative susceptibility mapping (QSM) prior to dipole inversion. The aim of this study was to evaluate the accuracy of regularization enabled sophisticated harmonic artifact reduction for phase data with varying spherical kernel sizes (REV-SHARP) method using a three-dimensional head phantom and human brain data. The proposed REV-SHARP method used the spherical mean value operation and Tikhonov regularization in the deconvolution process, with varying 2-14mm kernel sizes. The kernel sizes were gradually reduced, similar to the SHARP with varying spherical kernel (VSHARP) method. We determined the relative errors and relationships between the true local field and estimated local field in REV-SHARP, VSHARP, projection onto dipole fields (PDF), and regularization enabled SHARP (RESHARP). Human experiment was also conducted using REV-SHARP, VSHARP, PDF, and RESHARP. The relative errors in the numerical phantom study were 0.386, 0.448, 0.838, and 0.452 for REV-SHARP, VSHARP, PDF, and RESHARP. REV-SHARP result exhibited the highest correlation between the true local field and estimated local field. The linear regression slopes were 1.005, 1.124, 0.988, and 0.536 for REV-SHARP, VSHARP, PDF, and RESHARP in regions of interest on the three-dimensional head phantom. In human experiments, no obvious errors due to artifacts were present in REV-SHARP. The proposed REV-SHARP is a new method combined with variable spherical kernel size and Tikhonov regularization. This technique might make it possible to be more accurate backgroud field removal and help to achive better accuracy of QSM. Copyright © 2016 Elsevier Inc. All rights reserved.

77 FR 38831 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-3D PDF Consortium...

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2012-06-29

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PDF cycling in the dorsal protocerebrum of the Drosophila brain is not necessary for circadian clock function.

PubMed

Kula, Elzbieta; Levitan, Edwin S; Pyza, Elzbieta; Rosbash, Michael

2006-04-01

In Drosophila, the neuropeptide pigment-dispersing factor (PDF) is a likely circadian molecule, secreted by central pacemaker neurons (LNvs). PDF is expressed in both small and large LNvs (sLNvs and lLNvs), and there are striking circadian oscillations of PDF staining intensity in the small cell termini, which require a functional molecular clock. This cycling may be relevant to the proposed role of PDF as a synchronizer of the clock system or as an output signal connecting pacemaker cells to locomotor activity centers. In this study, the authors use a generic neuropeptide fusion protein (atrial natriuretic factor-green fluorescent protein [ANF-GFP]) and show that it can be expressed in the same neurons as PDF itself. Yet, ANF-GFP as well as PDF itself does not manifest any cyclical accumulation in sLNv termini in adult transgenic flies. Surprisingly, the absence of detectable PDF cycling is not accompanied by any detectable behavioral pheno-type, since these transgenic flies have normal morning and evening anticipation in a light-dark cycle (LD) and are fully rhythmic in constant darkness (DD). The molecular clock is also not compromised. The results suggest that robust PDF cycling in sLNv termini plays no more than a minor role in the Drosophila circadian system and is apparently not even necessary for clock output function.

Handling a Large Collection of PDF Documents

EPA Pesticide Factsheets

You have several options for making a large collection of PDF documents more accessible to your audience: avoid uploading altogether, use multiple document pages, and use document IDs as anchors for direct links within a document page.

Exact PDF equations and closure approximations for advective-reactive transport

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

Venturi, D.; Tartakovsky, Daniel M.; Tartakovsky, Alexandre M.

2013-06-01

Mathematical models of advection–reaction phenomena rely on advective flow velocity and (bio) chemical reaction rates that are notoriously random. By using functional integral methods, we derive exact evolution equations for the probability density function (PDF) of the state variables of the advection–reaction system in the presence of random transport velocity and random reaction rates with rather arbitrary distributions. These PDF equations are solved analytically for transport with deterministic flow velocity and a linear reaction rate represented mathematically by a heterog eneous and strongly-correlated random field. Our analytical solution is then used to investigate the accuracy and robustness of the recentlymore » proposed large-eddy diffusivity (LED) closure approximation [1]. We find that the solution to the LED-based PDF equation, which is exact for uncorrelated reaction rates, is accurate even in the presence of strong correlations and it provides an upper bound of predictive uncertainty.« less

A compound scattering pdf for the ultrasonic echo envelope and its relationship to K and Nakagami distributions.

PubMed

Shankar, P Mohana

2003-03-01

A compound probability density function (pdf) is presented to describe the envelope of the backscattered echo from tissue. This pdf allows local and global variation in scattering cross sections in tissue. The ultrasonic backscattering cross sections are assumed to be gamma distributed. The gamma distribution also is used to model the randomness in the average cross sections. This gamma-gamma model results in the compound scattering pdf for the envelope. The relationship of this compound pdf to the Rayleigh, K, and Nakagami distributions is explored through an analysis of the signal-to-noise ratio of the envelopes and random number simulations. The three parameter compound pdf appears to be flexible enough to represent envelope statistics giving rise to Rayleigh, K, and Nakagami distributions.

Selected Readings in Genetic Engineering

ERIC Educational Resources Information Center

Mertens, Thomas R.; Robinson, Sandra K.

1973-01-01

Describes different sources of readings for understanding issues and concepts of genetic engineering. Broad categories of reading materials are: concerns about genetic engineering; its background; procedures; and social, ethical and legal issues. References are listed. (PS)

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

PubMed

Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

2015-12-01

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. Copyright © 2015 by the American Society of Nephrology.

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization

PubMed Central

Randles, Michael J.; Woolf, Adrian S.; Huang, Jennifer L.; Byron, Adam; Humphries, Jonathan D.; Price, Karen L.; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J.; Long, David A.

2015-01-01

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein–protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. PMID:25896609

New Tools to Convert PDF Math Contents into Accessible e-Books Efficiently.

PubMed

Suzuki, Masakazu; Terada, Yugo; Kanahori, Toshihiro; Yamaguchi, Katsuhito

2015-01-01

New features in our math-OCR software to convert PDF math contents into accessible e-books are shown. A method for recognizing PDF is thoroughly improved. In addition, contents in any selected area including math formulas in a PDF file can be cut and pasted into a document in various accessible formats, which is automatically recognized and converted into texts and accessible math formulas through this process. Combining it with our authoring tool for a technical document, one can easily produce accessible e-books in various formats such as DAISY, accessible EPUB3, DAISY-like HTML5, Microsoft Word with math objects and so on. Those contents are useful for various print-disabled students ranging from the blind to the dyslexic.

PDF-ECG in clinical practice: A model for long-term preservation of digital 12-lead ECG data.

PubMed

Sassi, Roberto; Bond, Raymond R; Cairns, Andrew; Finlay, Dewar D; Guldenring, Daniel; Libretti, Guido; Isola, Lamberto; Vaglio, Martino; Poeta, Roberto; Campana, Marco; Cuccia, Claudio; Badilini, Fabio

In clinical practice, data archiving of resting 12-lead electrocardiograms (ECGs) is mainly achieved by storing a PDF report in the hospital electronic health record (EHR). When available, digital ECG source data (raw samples) are only retained within the ECG management system. The widespread availability of the ECG source data would undoubtedly permit successive analysis and facilitate longitudinal studies, with both scientific and diagnostic benefits. PDF-ECG is a hybrid archival format which allows to store in the same file both the standard graphical report of an ECG together with its source ECG data (waveforms). Using PDF-ECG as a model to address the challenge of ECG data portability, long-term archiving and documentation, a real-world proof-of-concept test was conducted in a northern Italy hospital. A set of volunteers undertook a basic ECG using routine hospital equipment and the source data captured. Using dedicated web services, PDF-ECG documents were then generated and seamlessly uploaded in the hospital EHR, replacing the standard PDF reports automatically generated at the time of acquisition. Finally, the PDF-ECG files could be successfully retrieved and re-analyzed. Adding PDF-ECG to an existing EHR had a minimal impact on the hospital's workflow, while preserving the ECG digital data. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of PDF-immunoreactive neurons in the optic lobe and cerebral lobe of the cricket, Gryllus bimaculatus.

PubMed

Abdelsalam, Salaheldin; Uemura, Hiroyuki; Umezaki, Yujiro; Saifullah, A S M; Shimohigashi, Miki; Tomioka, Kenji

2008-07-01

Pigment-dispersing factor (PDF) is a neuropeptide playing important roles in insect circadian systems. In this study, we morphologically and physiologically characterized PDF-immunoreactive neurons in the optic lobe and the brain of the cricket Gryllus bimaculatus. PDF-immunoreactivity was detected in cells located in the proximal medulla (PDFMe cells) and those in the dorsal and ventral regions of the outer chiasma (PDFLa cells). The PDFMe cells had varicose processes spread over the frontal surface of the medulla and the PDFLa cells had varicose mesh-like innervations in almost whole lamina, suggesting their modulatory role in the optic lobe. Some of PDFMe cells had a hairpin-shaped axonal process running toward the lamina then turning back to project into the brain where they terminated at various protocerebral areas. The PDFMe cells had a low frequency spontaneous spike activity that was higher during the night and was often slightly increased by light pulses. Six pairs of PDF-immunoreactive neurons were also found in the frontal ganglion. Competitive ELISA with anti-PDF antibodies revealed daily cycling of PDF both in the optic lobe and cerebral lobe with an increase during the night that persisted in constant darkness. The physiological role of PDF is discussed based on these results.

AzTEC Survey of the Central Molecular Zone: Modeling Dust SEDs and N-PDF with Hierarchical Bayesian Analysis

NASA Astrophysics Data System (ADS)

Tang, Yuping; Wang, Daniel; Wilson, Grant; Gutermuth, Robert; Heyer, Mark

2018-01-01

We present the AzTEC/LMT survey of dust continuum at 1.1mm on the central ˜ 200pc (CMZ) of our Galaxy. A joint SED analysis of all existing dust continuum surveys on the CMZ is performed, from 160µm to 1.1mm. Our analysis follows a MCMC sampling strategy incorporating the knowledge of PSFs in different maps, which provides unprecedented spacial resolution on distributions of dust temperature, column density and emissivity index. The dense clumps in the CMZ typically show low dust temperature ( 20K), with no significant sign of buried star formation, and a weak evolution of higher emissivity index toward dense peak. A new model is proposed, allowing for varying dust temperature inside a cloud and self-shielding of dust emission, which leads to similar conclusions on dust temperature and grain properties. We further apply a hierarchical Bayesian analysis to infer the column density probability distribution function (N-PDF), while simultaneously removing the Galactic foreground and background emission. The N-PDF shows a steep power-law profile with α > 3, indicating that formation of dense structures are suppressed.

Genetic background and embryonic temperature affect DNA methylation and expression of myogenin and muscle development in Atlantic salmon (Salmo salar).

PubMed

Burgerhout, Erik; Mommens, Maren; Johnsen, Hanne; Aunsmo, Arnfinn; Santi, Nina; Andersen, Øivind

2017-01-01

The development of ectothermic embryos is strongly affected by incubation temperature, and thermal imprinting of body growth and muscle phenotype has been reported in various teleost fishes. The complex epigenetic regulation of muscle development in vertebrates involves DNA methylation of the myogenin promoter. Body growth is a heritable and highly variable trait among fish populations that allows for local adaptations, but also for selective breeding. Here we studied the epigenetic effects of embryonic temperature and genetic background on body growth, muscle cellularity and myogenin expression in farmed Atlantic salmon (Salmo salar). Eggs from salmon families with either high or low estimated breeding values for body growth, referred to as Fast and Slow genotypes, were incubated at 8°C or 4°C until the embryonic 'eyed-stage' followed by rearing at the production temperature of 8°C. Rearing temperature strongly affected the growth rates, and the 8°C fish were about twice as heavy as the 4°C fish in the order Fast8>Slow8>Fast4>Slow4 prior to seawater transfer. Fast8 was the largest fish also at harvest despite strong growth compensation in the low temperature groups. Larval myogenin expression was approximately 4-6 fold higher in the Fast8 group than in the other groups and was associated with relative low DNA methylation levels, but was positively correlated with the expression levels of the DNA methyltransferase genes dnmt1, dnmt3a and dnmt3b. Juvenile Fast8 fish displayed thicker white muscle fibres than Fast4 fish, while Slow 8 and Slow 4 showed no difference in muscle cellularity. The impact of genetic background on the thermal imprinting of body growth and muscle development in Atlantic salmon suggests that epigenetic variation might play a significant role in the local adaptation to fluctuating temperatures over short evolutionary time.

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

PubMed

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

2012-02-01

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

APFEL: A PDF evolution library with QED corrections

NASA Astrophysics Data System (ADS)

Bertone, Valerio; Carrazza, Stefano; Rojo, Juan

2014-06-01

Quantum electrodynamics and electroweak corrections are important ingredients for many theoretical predictions at the LHC. This paper documents APFEL, a new PDF evolution package that allows for the first time to perform DGLAP evolution up to NNLO in QCD and to LO in QED, in the variable-flavor-number scheme and with either pole or MS bar heavy quark masses. APFEL consistently accounts for the QED corrections to the evolution of quark and gluon PDFs and for the contribution from the photon PDF in the proton. The coupled QCD ⊗ QED equations are solved in x-space by means of higher order interpolation, followed by Runge-Kutta solution of the resulting discretized evolution equations. APFEL is based on an innovative and flexible methodology for the sequential solution of the QCD and QED evolution equations and their combination. In addition to PDF evolution, APFEL provides a module that computes Deep-Inelastic Scattering structure functions in the FONLL general-mass variable-flavor-number scheme up to O(αs2) . All the functionalities of APFEL can be accessed via a Graphical User Interface, supplemented with a variety of plotting tools for PDFs, parton luminosities and structure functions. Written in FORTRAN 77, APFEL can also be used via the C/C++ and Python interfaces, and is publicly available from the HepForge repository.

Disk diffusion quality control guidelines for NVP-PDF 713: a novel peptide deformylase inhibitor.

PubMed

Anderegg, Tamara R; Jones, Ronald N

2004-01-01

NVP-PDF713 is a peptide deformylase inhibitor that has emerged as a candidate for treating Gram-positive infections and selected Gram-negative species that commonly cause community-acquired respiratory tract infections. This report summarizes the results of a multi-center (seven participants) disk diffusion quality control (QC) investigation for NVP PDF-713 using guidelines of the National Committee for Clinical Laboratory Standards and the standardized disk diffusion method. A total of 420 NVP-PDF 713 zone diameter values were generated for each QC organism. The proposed zone diameter ranges contained 97.6-99.8% of the reported participant results and were: Staphylococcus aureus ATCC 25923 (25-35 mm), Streptococcus pneumoniae ATCC 49619 (30-37 mm), and Haemophilus influenzae ATCC 49247 (24-32 mm). These QC criteria for the disk diffusion method should be applied during the NVP-PDF 713 clinical trials to maximize test accuracy.

Evaluation of a Consistent LES/PDF Method Using a Series of Experimental Spray Flames

NASA Astrophysics Data System (ADS)

Heye, Colin; Raman, Venkat

2012-11-01

A consistent method for the evolution of the joint-scalar probability density function (PDF) transport equation is proposed for application to large eddy simulation (LES) of turbulent reacting flows containing evaporating spray droplets. PDF transport equations provide the benefit of including the chemical source term in closed form, however, additional terms describing LES subfilter mixing must be modeled. The recent availability of detailed experimental measurements provide model validation data for a wide range of evaporation rates and combustion regimes, as is well-known to occur in spray flames. In this work, the experimental data will used to investigate the impact of droplet mass loading and evaporation rates on the subfilter scalar PDF shape in comparison with conventional flamelet models. In addition, existing model term closures in the PDF transport equations are evaluated with a focus on their validity in the presence of regime changes.

New Powder Diffraction File (PDF-4) in relational database format: advantages and data-mining capabilities.

PubMed

Kabekkodu, Soorya N; Faber, John; Fawcett, Tim

2002-06-01

The International Centre for Diffraction Data (ICDD) is responding to the changing needs in powder diffraction and materials analysis by developing the Powder Diffraction File (PDF) in a very flexible relational database (RDB) format. The PDF now contains 136,895 powder diffraction patterns. In this paper, an attempt is made to give an overview of the PDF-4, search/match methods and the advantages of having the PDF-4 in RDB format. Some case studies have been carried out to search for crystallization trends, properties, frequencies of space groups and prototype structures. These studies give a good understanding of the basic structural aspects of classes of compounds present in the database. The present paper also reports data-mining techniques and demonstrates the power of a relational database over the traditional (flat-file) database structures.

PDF investigations of turbulent non-premixed jet flames with thin reaction zones

NASA Astrophysics Data System (ADS)

Wang, Haifeng; Pope, Stephen

2012-11-01

PDF (probability density function) modeling studies are carried out for the Sydney piloted jet flames. These Sydney flames feature much thinner reaction zones in the mixture fraction space compared to those in the well-studied Sandia piloted jet flames. The performance of the different turbulent combustion models in the Sydney flames with thin reaction zones has not been examined extensively before, and this work aims at evaluating the capability of the PDF method to represent the thin turbulent flame structures in the Sydney piloted flames. Parametric and sensitivity PDF studies are performed with respect to the different models and model parameters. A global error parameter is defined to quantify the departure of the simulation results from the experimental data, and is used to assess the performance of the different set of models and model parameters.

Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF.

PubMed

Chen, Jiangtian; Reiher, Wencke; Hermann-Luibl, Christiane; Sellami, Azza; Cognigni, Paola; Kondo, Shu; Helfrich-Förster, Charlotte; Veenstra, Jan A; Wegener, Christian

2016-09-01

Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF.

Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF

PubMed Central

Reiher, Wencke; Hermann-Luibl, Christiane; Sellami, Azza; Cognigni, Paola; Helfrich-Förster, Charlotte; Veenstra, Jan A.

2016-01-01

Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF. PMID:27689358

The pdf approach to turbulent polydispersed two-phase flows

NASA Astrophysics Data System (ADS)

Minier, Jean-Pierre; Peirano, Eric

2001-10-01

The purpose of this paper is to develop a probabilistic approach to turbulent polydispersed two-phase flows. The two-phase flows considered are composed of a continuous phase, which is a turbulent fluid, and a dispersed phase, which represents an ensemble of discrete particles (solid particles, droplets or bubbles). Gathering the difficulties of turbulent flows and of particle motion, the challenge is to work out a general modelling approach that meets three requirements: to treat accurately the physically relevant phenomena, to provide enough information to address issues of complex physics (combustion, polydispersed particle flows, …) and to remain tractable for general non-homogeneous flows. The present probabilistic approach models the statistical dynamics of the system and consists in simulating the joint probability density function (pdf) of a number of fluid and discrete particle properties. A new point is that both the fluid and the particles are included in the pdf description. The derivation of the joint pdf model for the fluid and for the discrete particles is worked out in several steps. The mathematical properties of stochastic processes are first recalled. The various hierarchies of pdf descriptions are detailed and the physical principles that are used in the construction of the models are explained. The Lagrangian one-particle probabilistic description is developed first for the fluid alone, then for the discrete particles and finally for the joint fluid and particle turbulent systems. In the case of the probabilistic description for the fluid alone or for the discrete particles alone, numerical computations are presented and discussed to illustrate how the method works in practice and the kind of information that can be extracted from it. Comments on the current modelling state and propositions for future investigations which try to link the present work with other ideas in physics are made at the end of the paper.

Serotonin and the Neuropeptide PDF Initiate and Extend Opposing Behavioral States in C. elegans

PubMed Central

Flavell, Steven W.; Pokala, Navin; Macosko, Evan Z.; Albrecht, Dirk R.; Larsch, Johannes; Bargmann, Cornelia I.

2013-01-01

SUMMARY Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete behavioral states. Here we characterize a neuromodulatory circuit that generates long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes roaming states through a Gαs-coupled PDF receptor; optogenetic activation of cAMP production in PDF receptor-expressing cells induces prolonged roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of this neuromodulatory circuit supplement fast motor circuits to organize long-lasting behavioral states. PMID:23972393

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

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

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

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

Combined PDF and Rietveld studies of ADORable zeolites and the disordered intermediate IPC-1P.

PubMed

Morris, Samuel A; Wheatley, Paul S; Položij, Miroslav; Nachtigall, Petr; Eliášová, Pavla; Čejka, Jiří; Lucas, Tim C; Hriljac, Joseph A; Pinar, Ana B; Morris, Russell E

2016-09-28

The disordered intermediate of the ADORable zeolite UTL has been structurally confirmed using the pair distribution function (PDF) technique. The intermediate, IPC-1P, is a disordered layered compound formed by the hydrolysis of UTL in 0.1 M hydrochloric acid solution. Its structure is unsolvable by traditional X-ray diffraction techniques. The PDF technique was first benchmarked against high-quality synchrotron Rietveld refinements of IPC-2 (OKO) and IPC-4 (PCR) - two end products of IPC-1P condensation that share very similar structural features. An IPC-1P starting model derived from density functional theory was used for the PDF refinement, which yielded a final fit of Rw = 18% and a geometrically reasonable structure. This confirms the layers do stay intact throughout the ADOR process and shows PDF is a viable technique for layered zeolite structure determination.

Structural reconstruction of the catalytic center of LiPDF through multiple scattering calculation with MXAN

NASA Astrophysics Data System (ADS)

Guo, Xiaoyun; Chu, Wangsheng; Ma, Sixuan; Gong, Weimin; Benfatto, Maurizio; Hu, Tiandou; Xie, Yaning; Wu, ZiYu

2006-11-01

Peptide deformylase (PDF, EC 3.5.1.27) is essential for the normal growth of eubacterium but not for mammalians. Recently, PDF has been studied as a target for new antibiotics. In this paper, X-ray absorption spectroscopy was employed to determine the local structure around the zinc ion of PDF from Leptospira Interrogans in dry powder, because it is very difficult to obtain the crystallized sample of LiPDF. We performed X-ray absorption near edge structure (XANES) calculation and reconstructed successfully the local geometry of the active center, and the results from calculations show that a water molecule (Wat1) has moved towards the zinc ion and lies in the distance range to coordinate with the zinc ion weakly. In addition, the sensitivity of theoretical spectra to the different ligand bodies was evaluated in terms of goodness-of-fit.

Application and evaluation of interactive 3D PDF for presenting and sharing planning results for liver surgery in clinical routine.

PubMed

Newe, Axel; Becker, Linda; Schenk, Andrea

2014-01-01

The Portable Document Format (PDF) is the de-facto standard for the exchange of electronic documents. It is platform-independent, suitable for the exchange of medical data, and allows for the embedding of three-dimensional (3D) surface mesh models. In this article, we present the first clinical routine application of interactive 3D surface mesh models which have been integrated into PDF files for the presentation and the exchange of Computer Assisted Surgery Planning (CASP) results in liver surgery. We aimed to prove the feasibility of applying 3D PDF in medical reporting and investigated the user experience with this new technology. We developed an interactive 3D PDF report document format and implemented a software tool to create these reports automatically. After more than 1000 liver CASP cases that have been reported in clinical routine using our 3D PDF report, an international user survey was carried out online to evaluate the user experience. Our solution enables the user to interactively explore the anatomical configuration and to have different analyses and various resection proposals displayed within a 3D PDF document covering only a single page that acts more like a software application than like a typical PDF file ("PDF App"). The new 3D PDF report offers many advantages over the previous solutions. According to the results of the online survey, the users have assessed the pragmatic quality (functionality, usability, perspicuity, efficiency) as well as the hedonic quality (attractiveness, novelty) very positively. The usage of 3D PDF for reporting and sharing CASP results is feasible and well accepted by the target audience. Using interactive PDF with embedded 3D models is an enabler for presenting and exchanging complex medical information in an easy and platform-independent way. Medical staff as well as patients can benefit from the possibilities provided by 3D PDF. Our results open the door for a wider use of this new technology, since the basic idea

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background.

PubMed

Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio

2015-01-01

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

EUPDF: An Eulerian-Based Monte Carlo Probability Density Function (PDF) Solver. User's Manual

NASA Technical Reports Server (NTRS)

Raju, M. S.

1998-01-01

EUPDF is an Eulerian-based Monte Carlo PDF solver developed for application with sprays, combustion, parallel computing and unstructured grids. It is designed to be massively parallel and could easily be coupled with any existing gas-phase flow and spray solvers. The solver accommodates the use of an unstructured mesh with mixed elements of either triangular, quadrilateral, and/or tetrahedral type. The manual provides the user with the coding required to couple the PDF code to any given flow code and a basic understanding of the EUPDF code structure as well as the models involved in the PDF formulation. The source code of EUPDF will be available with the release of the National Combustion Code (NCC) as a complete package.

The study of PDF turbulence models in combustion

NASA Technical Reports Server (NTRS)

Hsu, Andrew T.

1991-01-01

In combustion computations, it is known that the predictions of chemical reaction rates are poor if conventional turbulence models are used. The probability density function (pdf) method seems to be the only alternative that uses local instantaneous values of the temperature, density, etc., in predicting chemical reaction rates, and thus is the only viable approach for more accurate turbulent combustion calculations. The fact that the pdf equation has a very large dimensionality renders finite difference schemes extremely demanding on computer memories and thus impractical. A logical alternative is the Monte Carlo scheme. Since CFD has a certain maturity as well as acceptance, it seems that the use of a combined CFD and Monte Carlo scheme is more beneficial. Therefore, a scheme is chosen that uses a conventional CFD flow solver in calculating the flow field properties such as velocity, pressure, etc., while the chemical reaction part is solved using a Monte Carlo scheme. The discharge of a heated turbulent plane jet into quiescent air was studied. Experimental data for this problem shows that when the temperature difference between the jet and the surrounding air is small, buoyancy effect can be neglected and the temperature can be treated as a passive scalar. The fact that jet flows have a self-similar solution lends convenience in the modeling study. Futhermore, the existence of experimental data for turbulent shear stress and temperature variance make the case ideal for the testing of pdf models wherein these values can be directly evaluated.

Genetics Home Reference: Fabry disease

MedlinePlus

... Sheet (PDF) Disease InfoSearch: Fabry Disease Emory University School of Medicine (PDF) International Center for Fabry Disease, Mount Sinai School of Medicine MalaCards: fabry disease Merck Manual Consumer ...

Difference in suitable mechanical properties of three-dimensional, synthetic scaffolds for self-renewing mouse embryonic stem cells of different genetic backgrounds.

PubMed

Lee, Myungook; Ahn, Jong Il; Ahn, Ji Yeon; Yang, Woo Sub; Hubbell, Jeffrey A; Lim, Jeong Mook; Lee, Seung Tae

2017-11-01

We evaluated whether the genetic background of embryonic stem cells (ESCs) affects the properties suitable for three-dimensional (3D) synthetic scaffolds for cell self-renewal. Inbred R1 and hybrid B6D2F1 mouse ESC lines were cultured for 7 days in hydrogel scaffolds with different properties derived from conjugating 7.5, 10, 12.5, or 15% (wt/vol) vinylsulfone-functionalized three-, four-, or eight-arm polyethylene glycol (PEG) with dicysteine-containing crosslinkers with an intervening matrix metalloproteinase-specific cleavage sites. Cell proliferation and expression of self-renewal-related genes and proteins by ESCs cultured in feeder-free or containing 2D culture plate or 3D hydrogel were monitored. As a preliminary experiment, the E14 ESC-customized synthetic 3D microenvironment did not maintain self-renewal of either the R1 or B6D2F1 ESCs. The best R1 cell proliferation (10.04 vs. 0.16-4.39; p < 0.0001) was observed in the four-arm 7.5% PEG-based hydrogels than those with other properties, whereas the F1 ESCs showed better proliferation when they were embedded in the three-arm 10% hydrogels. Self-renewal-related gene and protein expression by ESCs after feeder-free 3D culture was generally maintained compared with the feeder-containing 2D culture, but expression patterns and quantities differed. However, the feeder-free 3D culture yielded better expression than the feeder-free 2D culture. In conclusion, genetic background determined the suitability of hydrogel scaffolds for self-renewal of ESCs, which requires customization for the mechanical properties of each cell line. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2261-2268, 2017. © 2016 Wiley Periodicals, Inc.

The PDF4LHC report on PDFs and LHC data: Results from Run I and preparation for Run II

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

Rojo, Juan; Accardi, Alberto; Ball, Richard D.

2015-09-16

The accurate determination of Parton Distribution Functions (PDFs) of the proton is an essential ingredient of the Large Hadron Collider (LHC) program. PDF uncertainties impact a wide range of processes, from Higgs boson characterization and precision Standard Model measurements to New Physics searches. A major recent development in modern PDF analyses has been to exploit the wealth of new information contained in precision measurements from the LHC Run I, as well as progress in tools and methods to include these data in PDF fits. In this report we summarize the information that PDF-sensitive measurements at the LHC have provided somore » far, and review the prospects for further constraining PDFs with data from the recently started Run II. As a result, this document aims to provide useful input to the LHC collaborations to prioritize their PDF-sensitive measurements at Run II, as well as a comprehensive reference for the PDF-fitting collaborations.« less

Assessment of PDF Micromixing Models Using DNS Data for a Two-Step Reaction

NASA Astrophysics Data System (ADS)

Tsai, Kuochen; Chakrabarti, Mitali; Fox, Rodney O.; Hill, James C.

1996-11-01

Although the probability density function (PDF) method is known to treat the chemical reaction terms exactly, its application to turbulent reacting flows have been overshadowed by the ability to model the molecular mixing terms satisfactorily. In this study, two PDF molecular mixing models, the linear-mean-square-estimation (LMSE or IEM) model and the generalized interaction-by-exchange-with-the-mean (GIEM) model, are compared with the DNS data in decaying turbulence with a two-step parallel-consecutive reaction and two segregated initial conditions: ``slabs" and ``blobs". Since the molecular mixing model is expected to have a strong effect on the mean values of chemical species under such initial conditions, the model evaluation is intended to answer the following questions: Can the PDF models predict the mean values of chemical species correctly with completely segregated initial conditions? (2) Is a single molecular mixing timescale sufficient for the PDF models to predict the mean values with different initial conditions? (3) Will the chemical reactions change the molecular mixing timescales of the reacting species enough to affect the accuracy of the model's prediction for the mean values of chemical species?

PDF modeling of turbulent flows on unstructured grids

NASA Astrophysics Data System (ADS)

Bakosi, Jozsef

In probability density function (PDF) methods of turbulent flows, the joint PDF of several flow variables is computed by numerically integrating a system of stochastic differential equations for Lagrangian particles. Because the technique solves a transport equation for the PDF of the velocity and scalars, a mathematically exact treatment of advection, viscous effects and arbitrarily complex chemical reactions is possible; these processes are treated without closure assumptions. A set of algorithms is proposed to provide an efficient solution of the PDF transport equation modeling the joint PDF of turbulent velocity, frequency and concentration of a passive scalar in geometrically complex configurations. An unstructured Eulerian grid is employed to extract Eulerian statistics, to solve for quantities represented at fixed locations of the domain and to track particles. All three aspects regarding the grid make use of the finite element method. Compared to hybrid methods, the current methodology is stand-alone, therefore it is consistent both numerically and at the level of turbulence closure without the use of consistency conditions. Since both the turbulent velocity and scalar concentration fields are represented in a stochastic way, the method allows for a direct and close interaction between these fields, which is beneficial in computing accurate scalar statistics. Boundary conditions implemented along solid bodies are of the free-slip and no-slip type without the need for ghost elements. Boundary layers at no-slip boundaries are either fully resolved down to the viscous sublayer, explicitly modeling the high anisotropy and inhomogeneity of the low-Reynolds-number wall region without damping or wall-functions or specified via logarithmic wall-functions. As in moment closures and large eddy simulation, these wall-treatments provide the usual trade-off between resolution and computational cost as required by the given application. Particular attention is focused on

A study of hydrogen diffusion flames using PDF turbulence model

NASA Technical Reports Server (NTRS)

Hsu, Andrew T.

1991-01-01

The application of probability density function (pdf) turbulence models is addressed. For the purpose of accurate prediction of turbulent combustion, an algorithm that combines a conventional computational fluid dynamic (CFD) flow solver with the Monte Carlo simulation of the pdf evolution equation was developed. The algorithm was validated using experimental data for a heated turbulent plane jet. The study of H2-F2 diffusion flames was carried out using this algorithm. Numerical results compared favorably with experimental data. The computations show that the flame center shifts as the equivalence ratio changes, and that for the same equivalence ratio, similarity solutions for flames exist.

A study of hydrogen diffusion flames using PDF turbulence model

NASA Technical Reports Server (NTRS)

Hsu, Andrew T.

1991-01-01

The application of probability density function (pdf) turbulence models is addressed in this work. For the purpose of accurate prediction of turbulent combustion, an algorithm that combines a conventional CFD flow solver with the Monte Carlo simulation of the pdf evolution equation has been developed. The algorithm has been validated using experimental data for a heated turbulent plane jet. The study of H2-F2 diffusion flames has been carried out using this algorithm. Numerical results compared favorably with experimental data. The computuations show that the flame center shifts as the equivalence ratio changes, and that for the same equivalence ratio, similarity solutions for flames exist.

Publications - PDF 88-8 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 88-8 Publication Details Title: Alaska's mineral industry 1987: Executive summary Authors , Alaska's mineral industry 1987: Executive summary: Alaska Division of Geological & Geophysical Surveys

Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis.

PubMed

Sisay, Sofia; Pryce, Gareth; Jackson, Samuel J; Tanner, Carolyn; Ross, Ruth A; Michael, Gregory J; Selwood, David L; Giovannoni, Gavin; Baker, David

2013-01-01

Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim)) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen)) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim) mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some

Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C. elegans.

PubMed

Flavell, Steven W; Pokala, Navin; Macosko, Evan Z; Albrecht, Dirk R; Larsch, Johannes; Bargmann, Cornelia I

2013-08-29

Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete behavioral states. Here, we characterize a neuromodulatory circuit that generates long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes roaming states through a Gαs-coupled PDF receptor; optogenetic activation of cAMP production in PDF receptor-expressing cells induces prolonged roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of this neuromodulatory circuit supplement fast motor circuits to organize long-lasting behavioral states. Copyright © 2013 Elsevier Inc. All rights reserved.

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Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility

PubMed Central

Dale, Matthew A.; Ruhlman, Melissa K.; Zhao, Shijia; Meisinger, Trevor; Gu, Linxia; Swier, Vicki J.; Agrawal, Devendra K.; Greiner, Timothy C.; Carson, Jeffrey S.; Baxter, B. Timothy; Xiong, Wanfen

2015-01-01

Objective Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. Methods Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. Results Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. Conclusions These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA. PMID:26546710

Enriching a document collection by integrating information extraction and PDF annotation

NASA Astrophysics Data System (ADS)

Powley, Brett; Dale, Robert; Anisimoff, Ilya

2009-01-01

Modern digital libraries offer all the hyperlinking possibilities of the World Wide Web: when a reader finds a citation of interest, in many cases she can now click on a link to be taken to the cited work. This paper presents work aimed at providing the same ease of navigation for legacy PDF document collections that were created before the possibility of integrating hyperlinks into documents was ever considered. To achieve our goal, we need to carry out two tasks: first, we need to identify and link citations and references in the text with high reliability; and second, we need the ability to determine physical PDF page locations for these elements. We demonstrate the use of a high-accuracy citation extraction algorithm which significantly improves on earlier reported techniques, and a technique for integrating PDF processing with a conventional text-stream based information extraction pipeline. We demonstrate these techniques in the context of a particular document collection, this being the ACL Anthology; but the same approach can be applied to other document sets.

Genetic background and embryonic temperature affect DNA methylation and expression of myogenin and muscle development in Atlantic salmon (Salmo salar)

PubMed Central

Burgerhout, Erik; Mommens, Maren; Johnsen, Hanne; Aunsmo, Arnfinn; Santi, Nina

2017-01-01

The development of ectothermic embryos is strongly affected by incubation temperature, and thermal imprinting of body growth and muscle phenotype has been reported in various teleost fishes. The complex epigenetic regulation of muscle development in vertebrates involves DNA methylation of the myogenin promoter. Body growth is a heritable and highly variable trait among fish populations that allows for local adaptations, but also for selective breeding. Here we studied the epigenetic effects of embryonic temperature and genetic background on body growth, muscle cellularity and myogenin expression in farmed Atlantic salmon (Salmo salar). Eggs from salmon families with either high or low estimated breeding values for body growth, referred to as Fast and Slow genotypes, were incubated at 8°C or 4°C until the embryonic ‘eyed-stage’ followed by rearing at the production temperature of 8°C. Rearing temperature strongly affected the growth rates, and the 8°C fish were about twice as heavy as the 4°C fish in the order Fast8>Slow8>Fast4>Slow4 prior to seawater transfer. Fast8 was the largest fish also at harvest despite strong growth compensation in the low temperature groups. Larval myogenin expression was approximately 4–6 fold higher in the Fast8 group than in the other groups and was associated with relative low DNA methylation levels, but was positively correlated with the expression levels of the DNA methyltransferase genes dnmt1, dnmt3a and dnmt3b. Juvenile Fast8 fish displayed thicker white muscle fibres than Fast4 fish, while Slow 8 and Slow 4 showed no difference in muscle cellularity. The impact of genetic background on the thermal imprinting of body growth and muscle development in Atlantic salmon suggests that epigenetic variation might play a significant role in the local adaptation to fluctuating temperatures over short evolutionary time. PMID:28662198

Extraction and labeling high-resolution images from PDF documents

NASA Astrophysics Data System (ADS)

Chachra, Suchet K.; Xue, Zhiyun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.

2013-12-01

Accuracy of content-based image retrieval is affected by image resolution among other factors. Higher resolution images enable extraction of image features that more accurately represent the image content. In order to improve the relevance of search results for our biomedical image search engine, Open-I, we have developed techniques to extract and label high-resolution versions of figures from biomedical articles supplied in the PDF format. Open-I uses the open-access subset of biomedical articles from the PubMed Central repository hosted by the National Library of Medicine. Articles are available in XML and in publisher supplied PDF formats. As these PDF documents contain little or no meta-data to identify the embedded images, the task includes labeling images according to their figure number in the article after they have been successfully extracted. For this purpose we use the labeled small size images provided with the XML web version of the article. This paper describes the image extraction process and two alternative approaches to perform image labeling that measure the similarity between two images based upon the image intensity projection on the coordinate axes and similarity based upon the normalized cross-correlation between the intensities of two images. Using image identification based on image intensity projection, we were able to achieve a precision of 92.84% and a recall of 82.18% in labeling of the extracted images.

An Enterobacter plasmid as a new genetic background for the transposon Tn1331

PubMed Central

Alavi, Mohammad R; Antonic, Vlado; Ravizee, Adrien; Weina, Peter J; Izadjoo, Mina; Stojadinovic, Alexander

2011-01-01

Background Genus Enterobacter includes important opportunistic nosocomial pathogens that could infect complex wounds. The presence of antibiotic resistance genes in these microorganisms represents a challenging clinical problem in the treatment of these wounds. In the authors’ screening of antibiotic-resistant bacteria from complex wounds, an Enterobacter species was isolated that harbors antibiotic-resistant plasmids conferring resistance to Escherichia coli. The aim of this study was to identify the resistance genes carried by one of these plasmids. Methods The plasmids from the Enterobacter isolate were propagated in E. coli and one of the plasmids, designated as pR23, was sequenced by the Sanger method using fluorescent dyeterminator chemistry on a genetic analyzer. The assembled sequence was annotated by search of the GenBank database. Results Plasmid pR23 is composed of the transposon Tn1331 and a backbone plasmid that is identical to the plasmid pPIGDM1 from Enterobacter agglomerans. The multidrug-resistance transposon Tn1331, which confers resistance to aminoglycoside and beta lactam antibiotics, has been previously isolated only from Klebsiella. The Enterobacter plasmid pPIGDM1, which carries a ColE1-like origin of replication and has no apparent selective marker, appears to provide a backbone for propagation of Tn1331 in Enterobacter. The recognition sequence of Tn1331 transposase for insertion into pPIGDM1 is the pentanucleotide TATTA, which occurs only once throughout the length of this plasmid. Conclusion Transposition of Tn1331 into the Enterobacter plasmid pPIGDM1 enables this transposon to propagate in this Enterobacter. Since Tn1331 was previously isolated only from Klebsiella, this report suggests horizontal transfer of this transposon between the two bacterial genera. PMID:22259249

Genetic Distinctiveness of Rye In situ Accessions from Portugal Unveils a New Hotspot of Unexplored Genetic Resources

PubMed Central

Monteiro, Filipa; Vidigal, Patrícia; Barros, André B.; Monteiro, Ana; Oliveira, Hugo R.; Viegas, Wanda

2016-01-01

Rye (Secale cereale L.) is a cereal crop of major importance in many parts of Europe and rye breeders are presently very concerned with the restrict pool of rye genetic resources available. Such narrowing of rye genetic diversity results from the presence of “Petkus” pool in most modern rye varieties as well as “Petkus” × “Carsten” heterotic pool in hybrid rye breeding programs. Previous studies on rye's genetic diversity revealed moreover a common genetic background on landraces (ex situ) and cultivars, regardless of breeding level or geographical origin. Thus evaluation of in situ populations is of utmost importance to unveil “on farm” diversity, which is largely undervalued. Here, we perform the first comprehensive assessment of rye's genetic diversity and population structuring using cultivars, ex situ landraces along a comprehensive sampling of in situ accessions from Portugal, through a molecular-directed analysis using SSRs markers. Rye genetic diversity and population structure analysis does not present any geographical trend but disclosed marked differences between genetic backgrounds of in situ accessions and those of cultivars/ex situ collections. Such genetic distinctiveness of in situ accessions highlights their unexplored potential as new genetic resources, which can be used to boost rye breeding strategies and the production of new varieties. Overall, our study successfully demonstrates the high prospective impact of comparing genetic diversity and structure of cultivars, ex situ, and in situ samples in ascertaining the status of plant genetic resources (PGR). PMID:27630658

Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds

PubMed Central

Makhanova, Natalia; Morgan, Andrew P.; Kayashima, Yukako; Makhanov, Andrei; Hiller, Sylvia; Zhilicheva, Svetlana; Xu, Longquan; Pardo-Manuel de Villena, Fernando; Maeda, Nobuyo

2017-01-01

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of

Publications - PDF 89-7 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 89-7 Publication Details Title: Summary of Alaska's mineral industry in 1988 Authors , Summary of Alaska's mineral industry in 1988: Alaska Division of Geological & Geophysical Surveys

Publications - PDF 90-10 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 90-10 Publication Details Title: Summary of Alaska's mineral industry in 1989 Authors , Summary of Alaska's mineral industry in 1989: Alaska Division of Geological & Geophysical Surveys

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PDF Lecture Materials for Online and ``Flipped'' Format Astronomy Courses

NASA Astrophysics Data System (ADS)

Kary, D. M.; Eisberg, J.

2013-04-01

Online astronomy courses typically rely on students reading the textbook and/or a set of text-based lecture notes to replace the “lecture” material. However, many of our students report that this is much less engaging than in-person lectures, especially given the amount of interactive work such as “think-pair-share” problems done in many astronomy classes. Students have similarly criticized direct lecture-capture. To address this, we have developed a set of PowerPoint-style presentations with embedded lecture audio combined with prompts for student interaction including think-pair-share questions. These are formatted PDF packages that can be used on a range of different computers using free software. The presentations are first developed using Microsoft PowerPoint software. Audio recordings of scripted lectures are then synchronized with the presentations and the entire package is converted to PDF using Adobe Presenter. This approach combines the ease of editing that PowerPoint provides along with the platform-independence of PDF. It's easy to add, remove, or edit individual slides as needed, and PowerPoint supports internal links so that think-pair-share questions can be inserted with links to feedback based on the answers selected. Modern PDF files support animated visuals with synchronized audio and they can be read using widely available free software. Using these files students in an online course can get many of the benefits of seeing and hearing the course material presented in an in-person lecture format. Students needing extra help in traditional lecture classes can use these presentations to help review the materials covered in lecture. Finally, the presentations can be used in a “flipped” format in which students work through the presentations outside of class time while spending the “lecture” time on in-class interaction.

Modeling error PDF optimization based wavelet neural network modeling of dynamic system and its application in blast furnace ironmaking

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

Zhou, Ping; Wang, Chenyu; Li, Mingjie

In general, the modeling errors of dynamic system model are a set of random variables. The traditional performance index of modeling such as means square error (MSE) and root means square error (RMSE) can not fully express the connotation of modeling errors with stochastic characteristics both in the dimension of time domain and space domain. Therefore, the probability density function (PDF) is introduced to completely describe the modeling errors in both time scales and space scales. Based on it, a novel wavelet neural network (WNN) modeling method is proposed by minimizing the two-dimensional (2D) PDF shaping of modeling errors. First,more » the modeling error PDF by the tradional WNN is estimated using data-driven kernel density estimation (KDE) technique. Then, the quadratic sum of 2D deviation between the modeling error PDF and the target PDF is utilized as performance index to optimize the WNN model parameters by gradient descent method. Since the WNN has strong nonlinear approximation and adaptive capability, and all the parameters are well optimized by the proposed method, the developed WNN model can make the modeling error PDF track the target PDF, eventually. Simulation example and application in a blast furnace ironmaking process show that the proposed method has a higher modeling precision and better generalization ability compared with the conventional WNN modeling based on MSE criteria. Furthermore, the proposed method has more desirable estimation for modeling error PDF that approximates to a Gaussian distribution whose shape is high and narrow.« less

Modeling error PDF optimization based wavelet neural network modeling of dynamic system and its application in blast furnace ironmaking

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

Zhou, Ping; Wang, Chenyu; Li, Mingjie

In general, the modeling errors of dynamic system model are a set of random variables. The traditional performance index of modeling such as means square error (MSE) and root means square error (RMSE) cannot fully express the connotation of modeling errors with stochastic characteristics both in the dimension of time domain and space domain. Therefore, the probability density function (PDF) is introduced to completely describe the modeling errors in both time scales and space scales. Based on it, a novel wavelet neural network (WNN) modeling method is proposed by minimizing the two-dimensional (2D) PDF shaping of modeling errors. First, themore » modeling error PDF by the traditional WNN is estimated using data-driven kernel density estimation (KDE) technique. Then, the quadratic sum of 2D deviation between the modeling error PDF and the target PDF is utilized as performance index to optimize the WNN model parameters by gradient descent method. Since the WNN has strong nonlinear approximation and adaptive capability, and all the parameters are well optimized by the proposed method, the developed WNN model can make the modeling error PDF track the target PDF, eventually. Simulation example and application in a blast furnace ironmaking process show that the proposed method has a higher modeling precision and better generalization ability compared with the conventional WNN modeling based on MSE criteria. However, the proposed method has more desirable estimation for modeling error PDF that approximates to a Gaussian distribution whose shape is high and narrow.« less

Modeling error PDF optimization based wavelet neural network modeling of dynamic system and its application in blast furnace ironmaking

DOE PAGES

Zhou, Ping; Wang, Chenyu; Li, Mingjie; ...

2018-01-31

In general, the modeling errors of dynamic system model are a set of random variables. The traditional performance index of modeling such as means square error (MSE) and root means square error (RMSE) cannot fully express the connotation of modeling errors with stochastic characteristics both in the dimension of time domain and space domain. Therefore, the probability density function (PDF) is introduced to completely describe the modeling errors in both time scales and space scales. Based on it, a novel wavelet neural network (WNN) modeling method is proposed by minimizing the two-dimensional (2D) PDF shaping of modeling errors. First, themore » modeling error PDF by the traditional WNN is estimated using data-driven kernel density estimation (KDE) technique. Then, the quadratic sum of 2D deviation between the modeling error PDF and the target PDF is utilized as performance index to optimize the WNN model parameters by gradient descent method. Since the WNN has strong nonlinear approximation and adaptive capability, and all the parameters are well optimized by the proposed method, the developed WNN model can make the modeling error PDF track the target PDF, eventually. Simulation example and application in a blast furnace ironmaking process show that the proposed method has a higher modeling precision and better generalization ability compared with the conventional WNN modeling based on MSE criteria. However, the proposed method has more desirable estimation for modeling error PDF that approximates to a Gaussian distribution whose shape is high and narrow.« less

Hybrid finite-volume/transported PDF method for the simulation of turbulent reactive flows

NASA Astrophysics Data System (ADS)

Raman, Venkatramanan

A novel computational scheme is formulated for simulating turbulent reactive flows in complex geometries with detailed chemical kinetics. A Probability Density Function (PDF) based method that handles the scalar transport equation is coupled with an existing Finite Volume (FV) Reynolds-Averaged Navier-Stokes (RANS) flow solver. The PDF formulation leads to closed chemical source terms and facilitates the use of detailed chemical mechanisms without approximations. The particle-based PDF scheme is modified to handle complex geometries and grid structures. Grid-independent particle evolution schemes that scale linearly with the problem size are implemented in the Monte-Carlo PDF solver. A novel algorithm, in situ adaptive tabulation (ISAT) is employed to ensure tractability of complex chemistry involving a multitude of species. Several non-reacting test cases are performed to ascertain the efficiency and accuracy of the method. Simulation results from a turbulent jet-diffusion flame case are compared against experimental data. The effect of micromixing model, turbulence model and reaction scheme on flame predictions are discussed extensively. Finally, the method is used to analyze the Dow Chlorination Reactor. Detailed kinetics involving 37 species and 158 reactions as well as a reduced form with 16 species and 21 reactions are used. The effect of inlet configuration on reactor behavior and product distribution is analyzed. Plant-scale reactors exhibit quenching phenomena that cannot be reproduced by conventional simulation methods. The FV-PDF method predicts quenching accurately and provides insight into the dynamics of the reactor near extinction. The accuracy of the fractional time-stepping technique in discussed in the context of apparent multiple-steady states observed in a non-premixed feed configuration of the chlorination reactor.

The orbital PDF: general inference of the gravitational potential from steady-state tracers

NASA Astrophysics Data System (ADS)

Han, Jiaxin; Wang, Wenting; Cole, Shaun; Frenk, Carlos S.

2016-02-01

We develop two general methods to infer the gravitational potential of a system using steady-state tracers, I.e. tracers with a time-independent phase-space distribution. Combined with the phase-space continuity equation, the time independence implies a universal orbital probability density function (oPDF) dP(λ|orbit) ∝ dt, where λ is the coordinate of the particle along the orbit. The oPDF is equivalent to Jeans theorem, and is the key physical ingredient behind most dynamical modelling of steady-state tracers. In the case of a spherical potential, we develop a likelihood estimator that fits analytical potentials to the system and a non-parametric method (`phase-mark') that reconstructs the potential profile, both assuming only the oPDF. The methods involve no extra assumptions about the tracer distribution function and can be applied to tracers with any arbitrary distribution of orbits, with possible extension to non-spherical potentials. The methods are tested on Monte Carlo samples of steady-state tracers in dark matter haloes to show that they are unbiased as well as efficient. A fully documented C/PYTHON code implementing our method is freely available at a GitHub repository linked from http://icc.dur.ac.uk/data/#oPDF.

Modeling of turbulent supersonic H2-air combustion with an improved joint beta PDF

NASA Technical Reports Server (NTRS)

Baurle, R. A.; Hassan, H. A.

1991-01-01

Attempts at modeling recent experiments of Cheng et al. indicated that discrepancies between theory and experiment can be a result of the form of assumed probability density function (PDF) and/or the turbulence model employed. Improvements in both the form of the assumed PDF and the turbulence model are presented. The results are again used to compare with measurements. Initial comparisons are encouraging.

Research on Optimization of Encoding Algorithm of PDF417 Barcodes

NASA Astrophysics Data System (ADS)

Sun, Ming; Fu, Longsheng; Han, Shuqing

The purpose of this research is to develop software to optimize the data compression of a PDF417 barcode using VC++6.0. According to the different compression mode and the particularities of Chinese, the relevant approaches which optimize the encoding algorithm of data compression such as spillage and the Chinese characters encoding are proposed, a simple approach to compute complex polynomial is introduced. After the whole data compression is finished, the number of the codeword is reduced and then the encoding algorithm is optimized. The developed encoding system of PDF 417 barcodes will be applied in the logistics management of fruits, therefore also will promote the fast development of the two-dimensional bar codes.

Publications - PDF 87-2 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 87-2 Publication Details Title: Alaska's mineral industry 1986: Executive summary Authors : Executive summary: Alaska Division of Geological & Geophysical Surveys Public Data File 87-2, 5 p. http

Host Genetic Background Strongly Affects Pulmonary microRNA Expression before and during Influenza A Virus Infection.

PubMed

Preusse, Matthias; Schughart, Klaus; Pessler, Frank

2017-01-01

Expression of host microRNAs (miRNAs) changes markedly during influenza A virus (IAV) infection of natural and adaptive hosts, but their role in genetically determined host susceptibility to IAV infection has not been explored. We, therefore, compared pulmonary miRNA expression during IAV infection in two inbred mouse strains with differential susceptibility to IAV infection. miRNA expression profiles were determined in lungs of the more susceptible strain DBA/2J and the less susceptible strain C57BL/6J within 120 h post infection (hpi) with IAV (H1N1) PR8. Even the miRNomes of uninfected lungs differed substantially between the two strains. After a period of relative quiescence, major miRNome reprogramming was detected in both strains by 48 hpi and increased through 120 hpi. Distinct groups of miRNAs regulated by IAV infection could be defined: (1) miRNAs ( n  = 39) whose expression correlated with hemagglutinin (HA) mRNA expression and represented the general response to IAV infection independent of host genetic background; (2) miRNAs ( n  = 20) whose expression correlated with HA mRNA expression but differed between the two strains; and (3) remarkably, miR-147-3p, miR-208b-3p, miR-3096a-5p, miR-3069b-3p, and the miR-467 family, whose abundance even in uninfected lungs differentiated nearly perfectly (area under the ROC curve > 0.99) between the two strains throughout the time course, suggesting a particularly strong association with the differential susceptibility of the two mouse strains. Expression of subsets of miRNAs correlated significantly with peripheral blood granulocyte and monocyte numbers, particularly in DBA/2J mice; miR-223-3p, miR-142-3p, and miR-20b-5p correlated most positively with these cell types in both mouse strains. Higher abundance of antiapoptotic (e.g., miR-467 family) and lower abundance of proapoptotic miRNAs (e.g., miR-34 family) and those regulating the PI3K-Akt pathway (e.g., miR-31-5p) were associated with the

Blocking synaptic transmission with tetanus toxin light chain reveals modes of neurotransmission in the PDF-positive circadian clock neurons of Drosophila melanogaster.

PubMed

Umezaki, Yujiro; Yasuyama, Kouji; Nakagoshi, Hideki; Tomioka, Kenji

2011-09-01

Circadian locomotor rhythms of Drosophila melanogaster are controlled by a neuronal circuit composed of approximately 150 clock neurons that are roughly classified into seven groups. In the circuit, a group of neurons expressing pigment-dispersing factor (PDF) play an important role in organizing the pacemaking system. Recent studies imply that unknown chemical neurotransmitter(s) (UNT) other than PDF is also expressed in the PDF-positive neurons. To explore its role in the circadian pacemaker, we examined the circadian locomotor rhythms of pdf-Gal4/UAS-TNT transgenic flies in which chemical synaptic transmission in PDF-positive neurons was blocked by expressed tetanus toxin light chain (TNT). In constant darkness (DD), the flies showed a free-running rhythm, which was similar to that of wild-type flies but significantly different from pdf null mutants. Under constant light conditions (LL), however, they often showed complex rhythms with a short period and a long period component. The UNT is thus likely involved in the synaptic transmission in the clock network and its release caused by LL leads to arrhythmicity. Immunocytochemistry revealed that LL induced phase separation in TIMELESS (TIM) cycling among some of the PDF-positive and PDF-negative clock neurons in the transgenic flies. These results suggest that both PDF and UNT play important roles in the Drosophila circadian clock, and activation of PDF pathway alone by LL leads to the complex locomotor rhythm through desynchronized oscillation among some of the clock neurons. Copyright © 2011 Elsevier Ltd. All rights reserved.

PDF turbulence modeling and DNS

NASA Technical Reports Server (NTRS)

Hsu, A. T.

1992-01-01

The problem of time discontinuity (or jump condition) in the coalescence/dispersion (C/D) mixing model is addressed in probability density function (pdf). A C/D mixing model continuous in time is introduced. With the continuous mixing model, the process of chemical reaction can be fully coupled with mixing. In the case of homogeneous turbulence decay, the new model predicts a pdf very close to a Gaussian distribution, with finite higher moments also close to that of a Gaussian distribution. Results from the continuous mixing model are compared with both experimental data and numerical results from conventional C/D models. The effect of Coriolis forces on compressible homogeneous turbulence is studied using direct numerical simulation (DNS). The numerical method used in this study is an eight order compact difference scheme. Contrary to the conclusions reached by previous DNS studies on incompressible isotropic turbulence, the present results show that the Coriolis force increases the dissipation rate of turbulent kinetic energy, and that anisotropy develops as the Coriolis force increases. The Taylor-Proudman theory does apply since the derivatives in the direction of the rotation axis vanishes rapidly. A closer analysis reveals that the dissipation rate of the incompressible component of the turbulent kinetic energy indeed decreases with a higher rotation rate, consistent with incompressible flow simulations (Bardina), while the dissipation rate of the compressible part increases; the net gain is positive. Inertial waves are observed in the simulation results.

Nuclear PDF for neutrino and charged lepton data

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

Kovarik, K.

2011-10-06

Neutrino Deep Inelastic Scattering (DIS) on nuclei is an essential process to constrain the strange quark parton distribution functions (PDF) in the proton. The critical component on the way to using the neutrino DIS data in a proton PDF analysis is understanding the nuclear effects in parton distribution functions. We parametrize these effects by nuclear parton distribution functions (NPDF). Here we compare results from two analysis of NPDF both done at next-to-leading order in QCD. The first uses neutral current charged-lepton (l{sup {+-}A}) Deeply Inelastic Scattering (DIS) and Drell-Yan data for several nuclear targets and the second uses neutrino-nucleon DISmore » data. We compare the nuclear corrections factors (F{sub 2}{sup Fe}/F{sub 2}{sup D}) for the charged-lepton data with other results from the literature. In particular, we compare and contrast fits based upon the charged-lepton DIS data with those using neutrino-nucleon DIS data.« less

Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

DOE PAGES

Jensen, K. M.Ø.; Blichfeld, A. B.; Bauers, S. R.; ...

2015-07-05

By means of normal incidence, high flux and high energy x-rays, we have obtained total scattering data for Pair Distribution Function (PDF) analysis from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. We illustrate the ‘tfPDF’ method through studies of as depositedmore » (i.e. amorphous) and crystalline FeSb 3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb 3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb 3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb 6 octahedra with motifs highly resembling the local structure in crystalline FeSb 3. Analysis of the amorphous structure allows predicting whether the final crystalline product will form the FeSb 3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films.« less

A Comparative Study of PDF Generation Methods: Measuring Loss of Fidelity When Converting Arabic and Persian MS Word Files to PDF

DTIC Science & Technology

2011-02-17

document objects, on one or more electronic document pages. These commands have their roots in typography , so, to understand the PDF Language, one...must have at least a rudimentary understanding of typography . Only a few of the typographic commands, called text showing operators, can hold strings

The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

PubMed

Cossa-Moiane, I L; Mendes, T; Ferreira, T M; Mauricio, I; Calado, M; Afonso, A; Belo, S

2015-11-01

Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (Jα18- / - and TGFβRIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGFβRIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations.

Extra dimensions: 3d and time in pdf documentation

NASA Astrophysics Data System (ADS)

Graf, N. A.

2008-07-01

High energy physics is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide audience. In this talk, we present examples of HEP applications which take advantage of this functionality. We demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input. Using this technique, higher dimensional data, such as LEGO plots or time-dependent information can be included in PDF files. In principle, a complete event display, with full interactivity, can be incorporated into a PDF file. This would allow the end user not only to customize the view and representation of the data, but to access the underlying data itself.

[Genetic information and future medicine].

PubMed

Sakurai, Akihiro

2012-11-01

Rapid technological advances in genetic analysis have revealed the genetic background of various diseases. Elucidation of the genes responsible for a disease enables better clinical management of the disease and helps to develop targeted drugs. Also, early diagnosis and management of at-risk family members can be made by identification of a genetic disease in the proband. On the other hand, genetic issues often cause psychological distress to the family. To perform genetic testing appropriately and to protect patients and family members from any harm, guidelines for genetic testing were released from the alliance of Japanese genetics-related academic societies in 2003. As genetic testing is becoming incorporated into clinical practice more broadly, the guideline was revised and released by the Japanese Society of Medical Sciences in 2011. All medical professionals in Japan are expected to follow this guideline.

Publications - PDF 91-6 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 91-6 Publication Details Title: Summary of Alaska's mineral industry for 1990 Authors ., Bundtzen, T.K., and Wood, J.E., 1991, Summary of Alaska's mineral industry for 1990: Alaska Division of

Publications - PDF 98-39 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 98-39 Publication Details Title: Rock geochemistry from the Manley mining district ., Bundtzen, T.K., Newberry, R.J., Dover, J.H., and Blodgett, R.B., 1998, Rock geochemistry from the Manley

STP 4-06 Model-Based Technical Data in Procurement, 3D PDF Technology Data Demonstration Project. Phase 1 Summary

DTIC Science & Technology

2015-07-01

O R G STP 4-06 MODEL-BASED TECHNICAL DATA IN PROCUREMENT 3D PDF TECHNOLOGY DATA DEMONSTRATION PROJECT PHASE 1 SUMMARY REPORT DL309T2...LMI’s ISO- certified quality management procedures. J U L Y 2 0 1 5 STP 4-06 MODEL-BASED TECHNICAL DATA IN PROCUREMENT 3D PDF TECHNICAL DATA...Based Technical Data ..................................................................................... 5 3D PDF Demonstration Team

Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

PubMed

Kitao, Kyoko; Mutai, Hideki; Namba, Kazunori; Morimoto, Noriko; Nakano, Atsuko; Arimoto, Yukiko; Sugiuchi, Tomoko; Masuda, Sawako; Okamoto, Yasuhide; Morita, Noriko; Sakamoto, Hirokazu; Shintani, Tomoko; Fukuda, Satoshi; Kaga, Kimitaka; Matsunaga, Tatsuo

2018-04-23

Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs

What Use Is Population Genetics?

PubMed

Charlesworth, Brian

2015-07-01

The Genetic Society of America's Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth's research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation. Copyright © 2015 by the Genetics Society of America.

Probing Genetic Control of Swine Responses to PRRSV Infection: Current Progress of the PRRS Host Genetics Consortium

USDA-ARS?s Scientific Manuscript database

Background: Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC). Methods: The project uses a nursery pig model ...

MSL: Facilitating automatic and physical analysis of published scientific literature in PDF format.

PubMed

Ahmed, Zeeshan; Dandekar, Thomas

2015-01-01

Published scientific literature contains millions of figures, including information about the results obtained from different scientific experiments e.g. PCR-ELISA data, microarray analysis, gel electrophoresis, mass spectrometry data, DNA/RNA sequencing, diagnostic imaging (CT/MRI and ultrasound scans), and medicinal imaging like electroencephalography (EEG), magnetoencephalography (MEG), echocardiography  (ECG), positron-emission tomography (PET) images. The importance of biomedical figures has been widely recognized in scientific and medicine communities, as they play a vital role in providing major original data, experimental and computational results in concise form. One major challenge for implementing a system for scientific literature analysis is extracting and analyzing text and figures from published PDF files by physical and logical document analysis. Here we present a product line architecture based bioinformatics tool 'Mining Scientific Literature (MSL)', which supports the extraction of text and images by interpreting all kinds of published PDF files using advanced data mining and image processing techniques. It provides modules for the marginalization of extracted text based on different coordinates and keywords, visualization of extracted figures and extraction of embedded text from all kinds of biological and biomedical figures using applied Optimal Character Recognition (OCR). Moreover, for further analysis and usage, it generates the system's output in different formats including text, PDF, XML and images files. Hence, MSL is an easy to install and use analysis tool to interpret published scientific literature in PDF format.

Synaptic connections of PDF-immunoreactive lateral neurons projecting to the dorsal protocerebrum of Drosophila melanogaster.

PubMed

Yasuyama, Kouji; Meinertzhagen, Ian A

2010-02-01

Recent studies in Drosophila melanogaster indicate that the neuropeptide pigment-dispersing factor (PDF) is an important output signal from a set of major clock neurons, s-LN(v)s (small ventral lateral neurons), which transmit the circadian phase to subsets of other clock neurons, DNs (dorsal neurons). Both s-LN(v)s and DNs have fiber projections to the dorsal protocerebrum of the brain, so that this area is a conspicuous locus for coupling between different subsets of clock neurons. To unravel the neural circuits underlying the fly's circadian rhythms, we examined the detailed subcellular morphology of the PDF-positive fibers of the s-LN(v)s in the dorsal protocerebrum, focusing on their synaptic connections, using preembedding immunoelectron microscopy. To examine the distribution of synapses, we also reconstructed the three-dimensional morphology of PDF-positive varicosities from fiber profiles in the dorsal protocerebrum. The varicosities contained large dense-core vesicles (DCVs), and also numerous small clear vesicles, forming divergent output synapses onto unlabeled neurites. The DCVs apparently dock at nonsynaptic sites, suggesting their nonsynaptic release. In addition, a 3D reconstruction revealed the presence of input synapses onto the PDF-positive fibers. These were detected less frequently than output sites. These observations suggest that the PDF-positive clock neurons receive neural inputs directly through synaptic connections in the dorsal protocerebrum, in addition to supplying dual outputs, either synaptic or via paracrine release of the DCV contents, to unidentified target neurons.

A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating.

PubMed

Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

2013-12-04

A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced Longer-Mating-Duration (LMD). Here, we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. Copyright © 2013 Elsevier Inc. All rights reserved.

A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating

PubMed Central

Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

2013-01-01

SUMMARY A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced longer mating duration (LMD). Here we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. PMID:24314729

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PubMed Central

Jackson, Samuel J.; Tanner, Carolyn; Ross, Ruth A.; Michael, Gregory J.; Selwood, David L.; Giovannoni, Gavin; Baker, David

2013-01-01

Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2 tm1Zim) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 Dgen) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some

On Variations in the Level of PER in Glial Clocks of Drosophila Optic Lobe and Its Negative Regulation by PDF Signaling.

PubMed

Górska-Andrzejak, Jolanta; Chwastek, Elżbieta M; Walkowicz, Lucyna; Witek, Kacper

2018-01-01

We show that the level of the core protein of the circadian clock Period (PER) expressed by glial peripheral oscillators depends on their location in the Drosophila optic lobe. It appears to be controlled by the ventral lateral neurons (LNvs) that release the circadian neurotransmitter Pigment Dispersing Factor (PDF). We demonstrate that glial cells of the distal medulla neuropil (dMnGl) that lie in the vicinity of the PDF-releasing terminals of the LNvs possess receptors for PDF (PDFRs) and express PER at significantly higher level than other types of glia. Surprisingly, the amplitude of PER molecular oscillations in dMnGl is increased twofold in PDF-free environment, that is in Pdf 0 mutants. The Pdf 0 mutants also reveal an increased level of glia-specific protein REPO in dMnGl. The photoreceptors of the compound eye (R-cells) of the PDF-null flies, on the other hand, exhibit de-synchrony of PER molecular oscillations, which manifests itself as increased variability of PER-specific immunofluorescence among the R-cells. Moreover, the daily pattern of expression of the presynaptic protein Bruchpilot (BRP) in the lamina terminals of the R-cells is changed in Pdf 0 mutant. Considering that PDFRs are also expressed by the marginal glia of the lamina that surround the R-cell terminals, the LNv pacemakers appear to be the likely modulators of molecular cycling in the peripheral clocks of both the glial cells and the photoreceptors of the compound eye. Consequently, some form of PDF-based coupling of the glial clocks and the photoreceptors of the eye with the central LNv pacemakers must be operational.

On Variations in the Level of PER in Glial Clocks of Drosophila Optic Lobe and Its Negative Regulation by PDF Signaling

PubMed Central

Górska-Andrzejak, Jolanta; Chwastek, Elżbieta M.; Walkowicz, Lucyna; Witek, Kacper

2018-01-01

We show that the level of the core protein of the circadian clock Period (PER) expressed by glial peripheral oscillators depends on their location in the Drosophila optic lobe. It appears to be controlled by the ventral lateral neurons (LNvs) that release the circadian neurotransmitter Pigment Dispersing Factor (PDF). We demonstrate that glial cells of the distal medulla neuropil (dMnGl) that lie in the vicinity of the PDF-releasing terminals of the LNvs possess receptors for PDF (PDFRs) and express PER at significantly higher level than other types of glia. Surprisingly, the amplitude of PER molecular oscillations in dMnGl is increased twofold in PDF-free environment, that is in Pdf0 mutants. The Pdf0 mutants also reveal an increased level of glia-specific protein REPO in dMnGl. The photoreceptors of the compound eye (R-cells) of the PDF-null flies, on the other hand, exhibit de-synchrony of PER molecular oscillations, which manifests itself as increased variability of PER-specific immunofluorescence among the R-cells. Moreover, the daily pattern of expression of the presynaptic protein Bruchpilot (BRP) in the lamina terminals of the R-cells is changed in Pdf0 mutant. Considering that PDFRs are also expressed by the marginal glia of the lamina that surround the R-cell terminals, the LNv pacemakers appear to be the likely modulators of molecular cycling in the peripheral clocks of both the glial cells and the photoreceptors of the compound eye. Consequently, some form of PDF-based coupling of the glial clocks and the photoreceptors of the eye with the central LNv pacemakers must be operational. PMID:29615925

Source Fingerprinting in Adobe PDF Files

DTIC Science & Technology

2013-12-01

targeted, opportunistic attacks [2]. Figures from F -Secure for 2008–2010 indicate that anywhere from 28–61% of targeted attacks involved PDF exploits...digit byte offset into the file, a five-digit generation number, and either the character ‘ f ’ or ‘n’, indicating whether the object defined on that line...Walk through a path, extracting n-grams from files and associating # them with the directory that contains them. E.g., the file # ./my_docs/ foo

Structural isoforms of the circadian neuropeptide PDF expressed in the optic lobes of the cricket Gryllus bimaculatus: immunocytochemical evidence from specific monoclonal antibodies.

PubMed

Honda, Takeshi; Matsushima, Ayami; Sumida, Kazunori; Chuman, Yoshiro; Sakaguchi, Kazuyasu; Onoue, Hitoshi; Meinertzhagen, Ian A; Shimohigashi, Yasuyuki; Shimohigashi, Miki

2006-11-20

Pigment-dispersing factor (PDF) is an 18-mer peptide that acts as a principal neurotransmitter of the insect circadian clock. Our previous study, utilizing anti-Uca beta-PDH polyclonal antibody (pAb) to immunolabel the optic lobe of the cricket Gryllus bimaculatus, suggested the existence of an alternative PDF-like peptide in the outer cells of the first neuropile, or lamina (La), which were much less immunoreactive than the inner cells of the second neuropile, the medulla (Me). To obtain structural information about such a PDF-like peptide, we prepared 10 anti-Gryllus PDF monoclonal (mAb) and pAb antibodies and analyzed their detailed epitope specificities. The PDFMe and PDFLa inner cells and their axonal projections were clearly immunoreactive to all these antibodies, revealing the widespread immunocytochemical organization of the PDF system in the optic lobe, as seen previously with anti-Uca beta-PDH pAb and anti-Gryllus PDF mAb, the epitope structures of which were also clarified in this study. The lamina outer cells, which we found lacked a target pdf mRNA, displayed specific immunoreactivities, indicating that the cells contain a distinct PDF-like peptide possessing both N- and C-terminal structures. These cells were not immunolabeled by some other monoclonal antibodies, however, implying that the PDFLa outer cells have a PDF isoform peptide devoid of Asn at positions 6 and 16. This isoform was also identified in a varicose arborization in the lamina. These results suggest not only the structure of the peptide, but also the possibility of additional functions of this novel PDF isoform.

Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

PubMed Central

Jensen, Kirsten M. Ø.; Blichfeld, Anders B.; Bauers, Sage R.; Wood, Suzannah R.; Dooryhée, Eric; Johnson, David C.; Iversen, Bo B.; Billinge, Simon J. L.

2015-01-01

By means of normal-incidence, high-flux and high-energy X-rays, total scattering data for pair distribution function (PDF) analysis have been obtained from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. The ‘tfPDF’ method is illustrated through studies of as-deposited (i.e. amorphous) and crystalline FeSb3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb6 octahedra with motifs highly resembling the local structure in crystalline FeSb3. Analysis of the amorphous structure allows the prediction of whether the final crystalline product will form the FeSb3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films. PMID:26306190

A new subgrid-scale representation of hydrometeor fields using a multivariate PDF

DOE PAGES

Griffin, Brian M.; Larson, Vincent E.

2016-06-03

The subgrid-scale representation of hydrometeor fields is important for calculating microphysical process rates. In order to represent subgrid-scale variability, the Cloud Layers Unified By Binormals (CLUBB) parameterization uses a multivariate probability density function (PDF). In addition to vertical velocity, temperature, and moisture fields, the PDF includes hydrometeor fields. Previously, hydrometeor fields were assumed to follow a multivariate single lognormal distribution. Now, in order to better represent the distribution of hydrometeors, two new multivariate PDFs are formulated and introduced.The new PDFs represent hydrometeors using either a delta-lognormal or a delta-double-lognormal shape. The two new PDF distributions, plus the previous single lognormalmore » shape, are compared to histograms of data taken from large-eddy simulations (LESs) of a precipitating cumulus case, a drizzling stratocumulus case, and a deep convective case. In conclusion, the warm microphysical process rates produced by the different hydrometeor PDFs are compared to the same process rates produced by the LES.« less

Comparison of PDF and Moment Closure Methods in the Modeling of Turbulent Reacting Flows

NASA Technical Reports Server (NTRS)

Norris, Andrew T.; Hsu, Andrew T.

1994-01-01

In modeling turbulent reactive flows, Probability Density Function (PDF) methods have an advantage over the more traditional moment closure schemes in that the PDF formulation treats the chemical reaction source terms exactly, while moment closure methods are required to model the mean reaction rate. The common model used is the laminar chemistry approximation, where the effects of turbulence on the reaction are assumed negligible. For flows with low turbulence levels and fast chemistry, the difference between the two methods can be expected to be small. However for flows with finite rate chemistry and high turbulence levels, significant errors can be expected in the moment closure method. In this paper, the ability of the PDF method and the moment closure scheme to accurately model a turbulent reacting flow is tested. To accomplish this, both schemes were used to model a CO/H2/N2- air piloted diffusion flame near extinction. Identical thermochemistry, turbulence models, initial conditions and boundary conditions are employed to ensure a consistent comparison can be made. The results of the two methods are compared to experimental data as well as to each other. The comparison reveals that the PDF method provides good agreement with the experimental data, while the moment closure scheme incorrectly shows a broad, laminar-like flame structure.

The mathematical limits of genetic prediction for complex chronic disease.

PubMed

Keyes, Katherine M; Smith, George Davey; Koenen, Karestan C; Galea, Sandro

2015-06-01

Attempts at predicting individual risk of disease based on common germline genetic variation have largely been disappointing. The present paper formalises why genetic prediction at the individual level is and will continue to have limited utility given the aetiological architecture of most common complex diseases. Data were simulated on one million populations with 10 000 individuals in each populations with varying prevalences of a genetic risk factor, an interacting environmental factor and the background rate of disease. The determinant risk ratio and risk difference magnitude for the association between a gene variant and disease is a function of the prevalence of the interacting factors that activate the gene, and the background rate of disease. The risk ratio and total excess cases due to the genetic factor increase as the prevalence of interacting factors increase, and decrease as the background rate of disease increases. Germline genetic variations have high predictive capacity for individual disease only under conditions of high heritability of particular genetic sequences, plausible only under rare variant hypotheses. Under a model of common germline genetic variants that interact with other genes and/or environmental factors in order to cause disease, the predictive capacity of common genetic variants is determined by the prevalence of the factors that interact with the variant and the background rate. A focus on estimating genetic associations for the purpose of prediction without explicitly grounding such work in an understanding of modifiable (including environmentally influenced) factors will be limited in its ability to yield important insights about the risk of disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetic Knowledge Among Participants in the Coriell Personalized Medicine Collaborative.

PubMed

Schmidlen, Tara J; Scheinfeldt, Laura; Zhaoyang, Ruixue; Kasper, Rachel; Sweet, Kevin; Gordon, Erynn S; Keller, Margaret; Stack, Cathy; Gharani, Neda; Daly, Mary B; Jarvis, Joseph; Christman, Michael F

2016-04-01

Genetic literacy is essential for the effective integration of genomic information into healthcare; yet few recent studies have been conducted to assess the current state of this knowledge base. Participants in the Coriell Personalized Medicine Collaborative (CPMC), a prospective study assessing the impact of personalized genetic risk reports for complex diseases and drug response on behavior and health outcomes, completed genetic knowledge questionnaires and other surveys through an online portal. To assess the association between genetic knowledge and genetic education background, multivariate linear regression was performed. 4 062 participants completed a genetic knowledge and genetic education background questionnaire. Most were older (mean age: 50), Caucasian (90 %), female (59 %), highly educated (69 % bachelor's or higher), with annual household income over $100 000 (49 %). Mean percent correct was 76 %. Controlling for demographics revealed that health care providers, participants previously exposed to genetics, and participants with 'better than most' self-rated knowledge were significantly more likely to have a higher knowledge score (p < 0.001). Overall, genetic knowledge was high with previous genetic education experience predictive of higher genetic knowledge score. Education is likely to improve genetic literacy, an important component to expanded use of genomics in personalized medicine.

Extra Dimensions: 3D and Time in PDF Documentation

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

Graf, Norman A.; /SLAC

2011-11-10

High energy physics is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standardmore » Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide audience. In this talk, we present examples of HEP applications which take advantage of this functionality. We demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input. Using this technique, higher dimensional data, such as LEGO plots or time-dependent information can be included in PDF files. In principle, a complete event display, with full interactivity, can be incorporated into a PDF file. This would allow the end user not only to customize the view and representation of the data, but to access the underlying data itself.« less

Full-Genome Sequencing Identifies in the Genetic Background Several Determinants That Modulate the Resistance Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Carrying the Novel mecC Gene

PubMed Central

de Lencastre, Hermínia; Tomasz, Alexander

2017-01-01

ABSTRACT Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant. PMID:28069659

Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila.

PubMed

Choi, Charles; Cao, Guan; Tanenhaus, Anne K; McCarthy, Ellena V; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C P; Nitabach, Michael N

2012-08-30

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LN(v)s) that secrete the neuropeptide PDF (pigment dispersing factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. Although LN(v)s also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1) PDFR activation in LN(v)s shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2) this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LN(v)s. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

MSL: Facilitating automatic and physical analysis of published scientific literature in PDF format

PubMed Central

Ahmed, Zeeshan; Dandekar, Thomas

2018-01-01

Published scientific literature contains millions of figures, including information about the results obtained from different scientific experiments e.g. PCR-ELISA data, microarray analysis, gel electrophoresis, mass spectrometry data, DNA/RNA sequencing, diagnostic imaging (CT/MRI and ultrasound scans), and medicinal imaging like electroencephalography (EEG), magnetoencephalography (MEG), echocardiography  (ECG), positron-emission tomography (PET) images. The importance of biomedical figures has been widely recognized in scientific and medicine communities, as they play a vital role in providing major original data, experimental and computational results in concise form. One major challenge for implementing a system for scientific literature analysis is extracting and analyzing text and figures from published PDF files by physical and logical document analysis. Here we present a product line architecture based bioinformatics tool ‘Mining Scientific Literature (MSL)’, which supports the extraction of text and images by interpreting all kinds of published PDF files using advanced data mining and image processing techniques. It provides modules for the marginalization of extracted text based on different coordinates and keywords, visualization of extracted figures and extraction of embedded text from all kinds of biological and biomedical figures using applied Optimal Character Recognition (OCR). Moreover, for further analysis and usage, it generates the system’s output in different formats including text, PDF, XML and images files. Hence, MSL is an easy to install and use analysis tool to interpret published scientific literature in PDF format. PMID:29721305

Autoreceptor Modulation of Peptide/Neurotransmitter Co-release from PDF Neurons Determines Allocation of Circadian Activity in Drosophila

PubMed Central

Choi, Charles; Cao, Guan; Tanenhaus, Anne K.; McCarthy, Ellena v.; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C.P.; Nitabach, Michael N.

2012-01-01

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral ventral pacemaker neurons (LNvs) that secrete the neuropeptide PDF (Pigment Dispersing Factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. While LNvs also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here we show that (1) PDFR activation in LNvs shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions and (2) this shift is mediated by stimulation of the Ga,s-cAMP pathway and a consequent change in PDF/neurotransmitter co-release from the LNvs. These results suggest a novel mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. PMID:22938867

Genes and personality characteristics: Possible association of the genetic background with intelligence and decision making in 830 Caucasian Greek subjects

PubMed Central

Marinos, Georgios; Naziris, Nikolaos; Limnaios, Stefanos A.; Drakoulis, Nikolaos

2014-01-01

It is well known that intelligence consists of a variety of interactional and cognitive skills and abilities (e.g. tradecraft; critical and divergent thinking; perception of foreign information). Decision making is defined as the conscious choice between given options, relating to a problem. Both genetic background and environment comprise key elements for personality characteristics of the human being. The aim of this study is to determine the frequency distribution of rs324420, rs1800497, rs363050, rs6265, rs1328674 polymorphisms known to be involved in individual personality characteristics, in 830 Greek Subjects. The study is independent from direct clinical measurements (e.g. IQ measurements; physiological tests). The population of the volunteers is described, based on genotype, sex, with the respective gene frequencies, including the Minor Allele Frequency (MAF). A potential influence of the volunteer gender with the above characteristics (based on genotypes and alleles) is examined and finally, volunteers are classified as follows: A volunteer receives + 1, for each genotype/allele, which enhances his intelligence or his decision-making. In contrast, he receives − 1, for each genotype/allele, which relegates the individual characteristic. No statistically significant gender-characteristics correlation is observed. According to their genetic profile, a rate of 92.5%, of the volunteers may be characterized by prudence and temperance of thought, with only a small proportion of them (7.5%) may be classified as genetically spontaneous and adventurous. Regarding intelligence, the study population may lay around average and a little above it, at a rate of 96.3%, while the edges of the scale suggest only a 0.5% of the volunteers, who, although the “smartest”, somehow seem to lack prudence. In conclusion, individuals with low cognitive ability may be more prudent than others and vice versa, while the “smartest” ones tend to be more risky, in decision

Female Mecp2+/− mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies

PubMed Central

Samaco, Rodney C.; McGraw, Christopher M.; Ward, Christopher S.; Sun, Yaling; Neul, Jeffrey L.; Zoghbi, Huda Y.

2013-01-01

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the gene encoding the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2). Typical RTT primarily affects girls and is characterized by a brief period of apparently normal development followed by the loss of purposeful hand skills and language, the onset of anxiety, hand stereotypies, autistic features, seizures and autonomic dysfunction. Mecp2 mouse models have extensively been studied to demonstrate the functional link between MeCP2 dysfunction and RTT pathogenesis. However, the majority of studies have focused primarily on the molecular and behavioral consequences of the complete absence of MeCP2 in male mice. Studies of female Mecp2+/− mice have been limited because of potential phenotypic variability due to X chromosome inactivation effects. To determine whether reproducible and reliable phenotypes can be detected Mecp2+/− mice, we analyzed Mecp2+/− mice of two different F1 hybrid isogenic backgrounds and at young and old ages using several neurobehavioral and physiological assays. Here, we report a multitude of phenotypes in female Mecp2+/− mice, some presenting as early as 5 weeks of life. We demonstrate that Mecp2+/− mice recapitulate several aspects of typical RTT and show that mosaic expression of MeCP2 does not preclude the use of female mice in behavioral and molecular studies. Importantly, we uncover several behavioral abnormalities that are present in two genetic backgrounds and report on phenotypes that are unique to one background. These findings provide a framework for pre-clinical studies aimed at improving the constellation of phenotypes in a mouse model of RTT. PMID:23026749

Constraints on the Profiles of Total Water PDF in AGCMs from AIRS and a High-Resolution Model

NASA Technical Reports Server (NTRS)

Molod, Andrea

2012-01-01

Atmospheric general circulation model (AGCM) cloud parameterizations generally include an assumption about the subgrid-scale probability distribution function (PDF) of total water and its vertical profile. In the present study, the Atmospheric Infrared Sounder (AIRS) monthly-mean cloud amount and relative humidity fields are used to compute a proxy for the second moment of an AGCM total water PDF called the RH01 diagnostic, which is the AIRS mean relative humidity for cloud fractions of 0.1 or less. The dependence of the second moment on horizontal grid resolution is analyzed using results from a high-resolution global model simulation.The AIRS-derived RH01 diagnostic is generally larger near the surface than aloft, indicating a narrower PDF near the surface, and varies with the type of underlying surface. High-resolution model results show that the vertical structure of profiles of the AGCM PDF second moment is unchanged as the grid resolution changes from 200 to 100 to 50 km, and that the second-moment profiles shift toward higher values with decreasing grid spacing.Several Goddard Earth Observing System, version 5 (GEOS-5), AGCM simulations were performed with several choices for the profile of the PDF second moment. The resulting cloud and relative humidity fields were shown to be quite sensitive to the prescribed profile, and the use of a profile based on the AIRS-derived proxy results in improvements relative to observational estimates. The AIRS-guided total water PDF profiles, including their dependence on underlying surface type and on horizontal resolution, have been implemented in the version of the GEOS-5 AGCM used for publicly released simulations.

Identification of QTLs for rice grain size using a novel set of chromosomal segment substitution lines derived from Yamadanishiki in the genetic background of Koshihikari

PubMed Central

Okada, Satoshi; Onogi, Akio; Iijima, Ken; Hori, Kiyosumi; Iwata, Hiroyoshi; Yokoyama, Wakana; Suehiro, Miki; Yamasaki, Masanori

2018-01-01

Grain size is important for brewing-rice cultivars, but the genetic basis for this trait is still unclear. This paper aims to identify QTLs for grain size using novel chromosomal segment substitution lines (CSSLs) harboring chromosomal segments from Yamadanishiki, an excellent sake-brewing rice, in the genetic background of Koshihikari, a cooking cultivar. We developed a set of 49 CSSLs. Grain length (GL), grain width (GWh), grain thickness (GT), 100-grain weight (GWt) and days to heading (DTH) were evaluated, and a CSSL-QTL analysis was conducted. Eighteen QTLs for grain size and DTH were identified. Seven (qGL11, qGWh5, qGWh10, qGWt6-2, qGWt10-2, qDTH3, and qDTH6) that were detected in F2 and recombinant inbred lines (RILs) from Koshihikari/Yamadanishiki were validated, suggesting that they are important for large grain size and heading date in Yamadanishiki. Additionally, QTL reanalysis for GWt showed that qGWt10-2 was only detected in early-flowering RILs, while qGWt5 (in the same region as qGWh5) was only detected in late-flowering RILs, suggesting that these QTLs show different responses to the environment. Our study revealed that grain size in the Yamadanishiki cultivar is determined by a complex genetic mechanism. These findings could be useful for the breeding of both cooking and brewing rice. PMID:29875604

PDF added value of a high resolution climate simulation for precipitation

NASA Astrophysics Data System (ADS)

Soares, Pedro M. M.; Cardoso, Rita M.

2015-04-01

General Circulation Models (GCMs) are models suitable to study the global atmospheric system, its evolution and response to changes in external forcing, namely to increasing emissions of CO2. However, the resolution of GCMs, of the order of 1o, is not sufficient to reproduce finer scale features of the atmospheric flow related to complex topography, coastal processes and boundary layer processes, and higher resolution models are needed to describe observed weather and climate. The latter are known as Regional Climate Models (RCMs) and are widely used to downscale GCMs results for many regions of the globe and are able to capture physically consistent regional and local circulations. Most of the RCMs evaluations rely on the comparison of its results with observations, either from weather stations networks or regular gridded datasets, revealing the ability of RCMs to describe local climatic properties, and assuming most of the times its higher performance in comparison with the forcing GCMs. The additional climatic details given by RCMs when compared with the results of the driving models is usually named as added value, and it's evaluation is still scarce and controversial in the literuature. Recently, some studies have proposed different methodologies to different applications and processes to characterize the added value of specific RCMs. A number of examples reveal that some RCMs do add value to GCMs in some properties or regions, and also the opposite, elighnening that RCMs may add value to GCM resuls, but improvements depend basically on the type of application, model setup, atmospheric property and location. The precipitation can be characterized by histograms of daily precipitation, or also known as probability density functions (PDFs). There are different strategies to evaluate the quality of both GCMs and RCMs in describing the precipitation PDFs when compared to observations. Here, we present a new method to measure the PDF added value obtained from

Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

PubMed

Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

2013-10-15

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories.

PubMed

Reding, Dawn M; Addis, Elizabeth A; Palacios, Maria G; Schwartz, Tonia S; Bronikowski, Anne M

2016-07-01

The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs. Copyright © 2016 Elsevier Inc. All rights reserved.

Obtaining genetic testing in pediatric epilepsy.

PubMed

Ream, Margie A; Patel, Anup D

2015-10-01

The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

External intermittency prediction using AMR solutions of RANS turbulence and transported PDF models

NASA Astrophysics Data System (ADS)

Olivieri, D. A.; Fairweather, M.; Falle, S. A. E. G.

2011-12-01

External intermittency in turbulent round jets is predicted using a Reynolds-averaged Navier-Stokes modelling approach coupled to solutions of the transported probability density function (pdf) equation for scalar variables. Solutions to the descriptive equations are obtained using a finite-volume method, combined with an adaptive mesh refinement algorithm, applied in both physical and compositional space. This method contrasts with conventional approaches to solving the transported pdf equation which generally employ Monte Carlo techniques. Intermittency-modified eddy viscosity and second-moment turbulence closures are used to accommodate the effects of intermittency on the flow field, with the influence of intermittency also included, through modifications to the mixing model, in the transported pdf equation. Predictions of the overall model are compared with experimental data on the velocity and scalar fields in a round jet, as well as against measurements of intermittency profiles and scalar pdfs in a number of flows, with good agreement obtained. For the cases considered, predictions based on the second-moment turbulence closure are clearly superior, although both turbulence models give realistic predictions of the bimodal scalar pdfs observed experimentally.

Publications - PDF 97-29G | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 97-29G Publication Details Title: Rock geochemistry from the Rampart mining district , K.H., Bundtzen, T.K., Newberry, R.J., Dover, J.H., and Blodgett, R.B., 1997, Rock geochemistry from

Alcoholism: recent advances in epidemiology, biochemistry and genetics.

PubMed

Ginter, E; Simko, V

2009-01-01

Countries traditionally consuming beer and wine have high alcohol consumption as compared to East Asia, where the fact of low alcoholism prevalence can be attributed to a defect in metabolic degradation of ethanol. Dependence on alcohol is multifactorial and is related to a complex interplay of metabolic, genetic, social and environmental factors. Repetitive alcohol ingestion and its resulting dependence is associated with false euphoria triggered by an inhibition of glutamate receptors and other brain neurotransmitters, namely dopamine and serotonine. Genetic polymorphisms of genes encoding the alcohol metabolism enzymes and neurotransmitter signaling molecules in dopamine, gamma aminobutyric acid, opioid and serotonin systems, are involved in individual variations for susceptibility to alcohol dependence. Prominent progress has been achieved toward identification of genes related to alcoholism. Six genes were described on chromosomes 4, 7, 8, 11, 15 and 20, which are known to have influence on neuronal signal transfer and generation of dopamine receptors. It is suggested that such genes carry the risk for alcoholism. In the last years, the role of (GABA) receptors in the development of alcoholism is studied in detail. In future it may be possible to separate the genetic, enzymatic and environmental factors that are responsible for increased vulnerability of some individuals to alcohol abuse (Fig. 2, Tab. 1, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.

PubMed

Parisky, Katherine M; Agosto, Jose; Pulver, Stefan R; Shang, Yuhua; Kuklin, Elena; Hodge, James J L; Kang, Kyeongjin; Kang, Keongjin; Liu, Xu; Garrity, Paul A; Rosbash, Michael; Griffith, Leslie C

2008-11-26

Daily sleep cycles in humans are driven by a complex circuit within which GABAergic sleep-promoting neurons oppose arousal. Drosophila sleep has recently been shown to be controlled by GABA, which acts on unknown cells expressing the Rdl GABAA receptor. We identify here the relevant Rdl-containing cells as PDF-expressing small and large ventral lateral neurons (LNvs) of the circadian clock. LNv activity regulates total sleep as well as the rate of sleep onset; both large and small LNvs are part of the sleep circuit. Flies mutant for pdf or its receptor are hypersomnolent, and PDF acts on the LNvs themselves to control sleep. These features of the Drosophila sleep circuit, GABAergic control of onset and maintenance as well as peptidergic control of arousal, support the idea that features of sleep-circuit architecture as well as the mechanisms governing the behavioral transitions between sleep and wake are conserved between mammals and insects.

ChemEngine: harvesting 3D chemical structures of supplementary data from PDF files.

PubMed

Karthikeyan, Muthukumarasamy; Vyas, Renu

2016-01-01

Digital access to chemical journals resulted in a vast array of molecular information that is now available in the supplementary material files in PDF format. However, extracting this molecular information, generally from a PDF document format is a daunting task. Here we present an approach to harvest 3D molecular data from the supporting information of scientific research articles that are normally available from publisher's resources. In order to demonstrate the feasibility of extracting truly computable molecules from PDF file formats in a fast and efficient manner, we have developed a Java based application, namely ChemEngine. This program recognizes textual patterns from the supplementary data and generates standard molecular structure data (bond matrix, atomic coordinates) that can be subjected to a multitude of computational processes automatically. The methodology has been demonstrated via several case studies on different formats of coordinates data stored in supplementary information files, wherein ChemEngine selectively harvested the atomic coordinates and interpreted them as molecules with high accuracy. The reusability of extracted molecular coordinate data was demonstrated by computing Single Point Energies that were in close agreement with the original computed data provided with the articles. It is envisaged that the methodology will enable large scale conversion of molecular information from supplementary files available in the PDF format into a collection of ready- to- compute molecular data to create an automated workflow for advanced computational processes. Software along with source codes and instructions available at https://sourceforge.net/projects/chemengine/files/?source=navbar.Graphical abstract.

Identification of a new peptide deformylase gene from enterococcus faecium and establishment of a new screening model targeted on PDF for novel antibiotics.

PubMed

Tang, Xian-Bing; Si, Shu-Yi; Zhang, Yue-Qin

2004-09-01

To identify a new peptide deformylase (PDF) gene (Genebank Accession AY238515) from Enterococcus faecium and to establish a new screening model targeted on PDF. A new PDF gene was identified by BLAST analysis and PCR and was subsequently over-expressed in the prokaryotic expression host E. coli B121(DE3). Over-expressed protein was purified for enzymatic assay by metal affinity chromatography and a new screening model was established for novel antibiotics. A new PDF gene of Enterococcus faecium was identified successfully. Ten positive samples were picked up from 8000 compound library and the microbial fermentation broth samples. A new PDF of gene Enterococcus faecium was first identified and the model had a high efficacy. Positive samples screened may be antibacterial agents of broad spectrum.

Genetic and Environmental Influences on Adolescent Attachment

ERIC Educational Resources Information Center

Fearon, Pasco; Shmueli-Goetz, Yael; Viding, Essi; Fonagy, Peter; Plomin, Robert

2014-01-01

Background: Twin studies consistently point to limited genetic influence on attachment security in the infancy period, but no study has examined whether this remains the case in later development. This study presents the findings from a twin study examining the relative importance of genetic and environmental influences on attachment in…

Monte Carlo PDF method for turbulent reacting flow in a jet-stirred reactor

NASA Astrophysics Data System (ADS)

Roekaerts, D.

1992-01-01

A stochastic algorithm for the solution of the modeled scalar probability density function (PDF) transport equation for single-phase turbulent reacting flow is described. Cylindrical symmetry is assumed. The PDF is represented by ensembles of N representative values of the thermochemical variables in each cell of a nonuniform finite-difference grid and operations on these elements representing convection, diffusion, mixing and reaction are derived. A simplified model and solution algorithm which neglects the influence of turbulent fluctuations on mean reaction rates is also described. Both algorithms are applied to a selectivity problem in a real reactor.

Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background.

PubMed

Siuciak, Judith A; McCarthy, Sheryl A; Chapin, Douglas S; Martin, Ashley N; Harms, John F; Schmidt, Christopher J

2008-02-01

The phenotype of genetically modified animals is strongly influenced by both the genetic background of the animal as well as environmental factors. We have previously reported the behavioral and neurochemical characterization of PDE10A knockout mice maintained on a DBA1LacJ (PDE10A(DBA)) genetic background. The aim of the present studies was to assess the behavioral and neurochemical phenotype of PDE10A knockout mice on an alternative congenic C57BL/6N (PDE10A(C57)) genetic background. Consistent with our previous results, PDE10A(C57) knockout mice showed a decrease in exploratory locomotor activity and a delay in the acquisition of conditioned avoidance responding. Also consistent with previous studies, the elimination of PDE10A did not alter basal levels of striatal cGMP or cAMP or affect behavior in several other well-characterized behavioral assays. PDE10A(C57) knockout mice showed a blunted response to MK-801, although to a lesser degree than previously observed in the PDE10A(DBA) knockout mice, and no differences were observed following a PCP challenge. PDE10A(C57) knockout mice showed a significant change in striatal dopamine turnover, which was accompanied by an enhanced locomotor response to AMPH, These studies demonstrate that while many of the behavioral effects of the PDE10A gene deletion appear to be independent of genetic background, the impact of the deletion on behavior can vary in magnitude. Furthermore, the effects on the dopaminergic system appear to be background-dependent, with significant effects observed only in knockout mice on the C57BL6N genetic background.

Explanatory Models of Genetics and Genetic Risk among a Selected Group of Students.

PubMed

Goltz, Heather Honoré; Bergman, Margo; Goodson, Patricia

2016-01-01

This exploratory qualitative study focuses on how college students conceptualize genetics and genetic risk, concepts essential for genetic literacy (GL) and genetic numeracy (GN), components of overall health literacy (HL). HL is dependent on both the background knowledge and culture of a patient, and lower HL is linked to increased morbidity and mortality for a number of chronic health conditions (e.g., diabetes and cancer). A purposive sample of 86 students from three Southwestern universities participated in eight focus groups. The sample ranged in age from 18 to 54 years, and comprised primarily of female (67.4%), single (74.4%), and non-White (57%) participants, none of whom were genetics/biology majors. A holistic-content approach revealed broad categories concerning participants' explanatory models (EMs) of genetics and genetic risk. Participants' EMs were grounded in highly contextualized narratives that only partially overlapped with biomedical models. While higher education levels should be associated with predominately knowledge-based EM of genetic risk, this study shows that even in well-educated populations cultural factors can dominate. Study findings reveal gaps in how this sample of young adults obtains, processes, and understands genetic/genomic concepts. Future studies should assess how individuals with low GL and GN obtain and process genetics and genetic risk information and incorporate this information into health decision making. Future work should also address the interaction of communication between health educators, providers, and genetic counselors, to increase patient understanding of genetic risk.

Genetic progression of malignant melanoma.

PubMed

Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

2016-03-01

Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

Multiple effects of genetic background on variegated transgene expression in mice.

PubMed Central

Opsahl, Margaret L; McClenaghan, Margaret; Springbett, Anthea; Reid, Sarah; Lathe, Richard; Colman, Alan; Whitelaw, C Bruce A

2002-01-01

BLG/7 transgenic mice express an ovine beta-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression. PMID:11901126

Multiple effects of genetic background on variegated transgene expression in mice.

PubMed

Opsahl, Margaret L; McClenaghan, Margaret; Springbett, Anthea; Reid, Sarah; Lathe, Richard; Colman, Alan; Whitelaw, C Bruce A

2002-03-01

BLG/7 transgenic mice express an ovine beta-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression.

PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans.

PubMed

Barrios, Arantza; Ghosh, Rajarshi; Fang, Chunhui; Emmons, Scott W; Barr, Maureen M

2012-12-01

Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non-sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

Offline modeling for product quality prediction of mineral processing using modeling error PDF shaping and entropy minimization.

PubMed

Ding, Jinliang; Chai, Tianyou; Wang, Hong

2011-03-01

This paper presents a novel offline modeling for product quality prediction of mineral processing which consists of a number of unit processes in series. The prediction of the product quality of the whole mineral process (i.e., the mixed concentrate grade) plays an important role and the establishment of its predictive model is a key issue for the plantwide optimization. For this purpose, a hybrid modeling approach of the mixed concentrate grade prediction is proposed, which consists of a linear model and a nonlinear model. The least-squares support vector machine is adopted to establish the nonlinear model. The inputs of the predictive model are the performance indices of each unit process, while the output is the mixed concentrate grade. In this paper, the model parameter selection is transformed into the shape control of the probability density function (PDF) of the modeling error. In this context, both the PDF-control-based and minimum-entropy-based model parameter selection approaches are proposed. Indeed, this is the first time that the PDF shape control idea is used to deal with system modeling, where the key idea is to turn model parameters so that either the modeling error PDF is controlled to follow a target PDF or the modeling error entropy is minimized. The experimental results using the real plant data and the comparison of the two approaches are discussed. The results show the effectiveness of the proposed approaches.

Computations of steady-state and transient premixed turbulent flames using pdf methods

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

Hulek, T.; Lindstedt, R.P.

1996-03-01

Premixed propagating turbulent flames are modeled using a one-point, single time, joint velocity-composition probability density function (pdf) closure. The pdf evolution equation is solved using a Monte Carlo method. The unclosed terms in the pdf equation are modeled using a modified version of the binomial Langevin model for scalar mixing of Valino and Dopazo, and the Haworth and Pope (HP) and Lagrangian Speziale-Sarkar-Gatski (LSSG) models for the viscous dissipation of velocity and the fluctuating pressure gradient. The source terms for the presumed one-step chemical reaction are extracted from the rate of fuel consumption in laminar premixed hydrocarbon flames, computed usingmore » a detailed chemical kinetic mechanism. Steady-state and transient solutions are obtained for planar turbulent methane-air and propane-air flames. The transient solution method features a coupling with a Finite Volume (FV) code to obtain the mean pressure field. The results are compared with the burning velocity measurements of Abdel-Gayed et al. and with velocity measurements obtained in freely propagating propane-air flames by Videto and Santavicca. The effects of different upstream turbulence fields, chemical source terms (different fuels and strained/unstrained laminar flames) and the influence of the velocity statistics models (HP and LSSG) are assessed.« less

The C-terminal residue of phage Vp16 PDF, the smallest peptide deformylase, acts as an offset element locking the active conformation.

PubMed

Grzela, Renata; Nusbaum, Julien; Fieulaine, Sonia; Lavecchia, Francesco; Bienvenut, Willy V; Dian, Cyril; Meinnel, Thierry; Giglione, Carmela

2017-09-08

Prokaryotic proteins must be deformylated before the removal of their first methionine. Peptide deformylase (PDF) is indispensable and guarantees this mechanism. Recent metagenomics studies revealed new idiosyncratic PDF forms as the most abundant family of viral sequences. Little is known regarding these viral PDFs, including the capacity of the corresponding encoded proteins to ensure deformylase activity. We provide here the first evidence that viral PDFs, including the shortest PDF identified to date, Vp16 PDF, display deformylase activity in vivo, despite the absence of the key ribosome-interacting C-terminal region. Moreover, characterization of phage Vp16 PDF underscores unexpected structural and molecular features with the C-terminal Isoleucine residue significantly contributing to deformylase activity both in vitro and in vivo. This residue fully compensates for the absence of the usual long C-domain. Taken together, these data elucidate an unexpected mechanism of enzyme natural evolution and adaptation within viral sequences.

American Society of Human Genetics

MedlinePlus

... and Background Risk October 20, 2017 Personal Omics Data Informative for Precision Health and Preventive Care October 20, 2017 Physical Inactivity and Restless Sleep Exacerbate Genetic Risk of Obesity October 20, 2017 ASHG 2018 ...

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

PubMed Central

2011-01-01

Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

Genetic Doping and Health Damages

PubMed Central

Fallahi, AA; Ravasi, AA; Farhud, DD

2011-01-01

Background: Use of genetic doping or gene transfer technology will be the newest and the lethal method of doping in future and have some unpleasant consequences for sports, athletes, and outcomes of competitions. The World Anti-Doping Agency (WADA) defines genetic doping as “the non-therapeutic use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance ”. The purpose of this review is to consider genetic doping, health damages and risks of new genes if delivered in athletes. Methods: This review, which is carried out by reviewing relevant publications, is primarily based on the journals available in GOOGLE, ELSEVIER, PUBMED in fields of genetic technology, and health using a combination of keywords (e.g., genetic doping, genes, exercise, performance, athletes) until July 2010. Conclusion: There are several genes related to sport performance and if they are used, they will have health risks and sever damages such as cancer, autoimmunization, and heart attack. PMID:23113049

Introgression of two chromosome regions for leaf photosynthesis from an indica rice into the genetic background of a japonica rice

PubMed Central

Hirasawa, Tadashi

2014-01-01

Increases in rates of individual leaf photosynthesis (P n) are critical for future increases of rice yields. A previous study, using introgression lines derived from a cross between indica cultivar Habataki, with one of the highest recorded values of P n, and the Japanese elite cultivar Koshihikari, identified four QTLs (qCAR4, qCAR5, qCAR8, and qCAR11) that affect P n. The present study examined the combined effect of qCAR4 and qCAR8 on P n in the genetic background of Koshihikari. The pyramided near-isogenic line NIL(qCAR4+qCAR8) showed higher P n than both NIL(qCAR4) and NIL(qCAR8), equivalent to that of Habataki despite being due to only two out of the four QTLs. The high P n of NIL(qCAR4+qCAR8) may be attributable to the high leaf nitrogen content, which may have been inherited from NIL(qCAR4), to the large hydraulic conductance due to the large root surface area from NIL(qCAR4), and to the high hydraulic conductivity from NIL(qCAR8). It might be also attributable to high mesophyll conductance, which may have been inherited from NIL(qCAR4). The induction of mesophyll conductance and the high leaf nitrogen content and high hydraulic conductivity could not be explained in isolation from the Koshihikari background. These results suggest that QTL pyramiding is a useful approach in rice breeding aimed at increasing P n. PMID:24591053

PDF as a coupling mediator between the light-entrainable and temperature-entrainable clocks in Drosophila melanogaster.

PubMed

Tomioka, K; Miyasako, Y; Umezaki, Y

2008-01-01

Drosophila shows bimodal circadian locomotor rhythms with peaks around light-on (morning peak) and before light-off (evening peak). The rhythm synchronizes to light and temperature cycles and the synchronization is achieved by two sets of clocks: one entrains to light cycles and the other to temperature cycles. The light-entrainable clock consists of the clock neurons located in the lateral protocerebrum (LNs) and the temperature-entrainable clock involves those located in the dorsal protocerebrum (DNs) and the cells located in the posterior lateral protocerebrum (LPNs). To understand the interaction between the light-entrainable and the temperature-entrainable clock neurons, locomotor rhythms of the mutant flies lacking PDF or PDF-positive clock neurons were examined. Under the light cycles, they showed altered phase of the evening peak. When exposed to temperature cycles of lower temperature levels, the onset of evening peak showed larger advance in contrast to those of wild-type flies. The termination of the peak also advanced while that of wild-type flies remained almost at the same phase as in the constant temperature. These results support our hypothesis that the PDF-positive light entrainable cells regulate the phase of the temperature entrainable cells to be synchronized to their own phase using PDF as a coupling mediator.

Comparisons of Lagrangian and Eulerian PDF methods in simulations of non-premixed turbulent jet flames with moderate-to-strong turbulence-chemistry interactions

NASA Astrophysics Data System (ADS)

Jaishree, J.; Haworth, D. C.

2012-06-01

Transported probability density function (PDF) methods have been applied widely and effectively for modelling turbulent reacting flows. In most applications of PDF methods to date, Lagrangian particle Monte Carlo algorithms have been used to solve a modelled PDF transport equation. However, Lagrangian particle PDF methods are computationally intensive and are not readily integrated into conventional Eulerian computational fluid dynamics (CFD) codes. Eulerian field PDF methods have been proposed as an alternative. Here a systematic comparison is performed among three methods for solving the same underlying modelled composition PDF transport equation: a consistent hybrid Lagrangian particle/Eulerian mesh (LPEM) method, a stochastic Eulerian field (SEF) method and a deterministic Eulerian field method with a direct-quadrature-method-of-moments closure (a multi-environment PDF-MEPDF method). The comparisons have been made in simulations of a series of three non-premixed, piloted methane-air turbulent jet flames that exhibit progressively increasing levels of local extinction and turbulence-chemistry interactions: Sandia/TUD flames D, E and F. The three PDF methods have been implemented using the same underlying CFD solver, and results obtained using the three methods have been compared using (to the extent possible) equivalent physical models and numerical parameters. Reasonably converged mean and rms scalar profiles are obtained using 40 particles per cell for the LPEM method or 40 Eulerian fields for the SEF method. Results from these stochastic methods are compared with results obtained using two- and three-environment MEPDF methods. The relative advantages and disadvantages of each method in terms of accuracy and computational requirements are explored and identified. In general, the results obtained from the two stochastic methods (LPEM and SEF) are very similar, and are in closer agreement with experimental measurements than those obtained using the MEPDF method

Development and characterization of two cell lines PDF and PDH from Puntius denisonii (Day 1865).

PubMed

Lakra, Wazir S; Goswami, M; Yadav, Kamalendra; Gopalakrishnan, A; Patiyal, R S; Singh, M

2011-02-01

The Puntius denisonii colloquially and more popularly referred to as Miss Kerala is a subtropical fish belonging to the genus Puntius (Barb) and family Cyprinidae. Two cell lines PDF and PDH were developed from the caudal fin and heart of P. denisonii, respectively. The cell lines were optimally maintained at 26°C in Leibovitz-15 medium supplemented with 10% fetal bovine serum. A diploid count of 50 chromosomes at passage 50 was observed in both the cell lines. The high growth potential of the cell lines was reflected from the cell doubling time of 28 and 30 h of PDF and PDH cell lines, respectively. The viability of the PDF and PDH cell lines was 70% and 76%, respectively, after 4 mo of storage in liquid nitrogen (-196°C). The origin of the cell lines was confirmed by the amplification of 653 bp fragments of cytochrome oxidase subunit I of mitochondrial DNA genes.

A consistent transported PDF model for treating differential molecular diffusion

NASA Astrophysics Data System (ADS)

Wang, Haifeng; Zhang, Pei

2016-11-01

Differential molecular diffusion is a fundamentally significant phenomenon in all multi-component turbulent reacting or non-reacting flows caused by the different rates of molecular diffusion of energy and species concentrations. In the transported probability density function (PDF) method, the differential molecular diffusion can be treated by using a mean drift model developed by McDermott and Pope. This model correctly accounts for the differential molecular diffusion in the scalar mean transport and yields a correct DNS limit of the scalar variance production. The model, however, misses the molecular diffusion term in the scalar variance transport equation, which yields an inconsistent prediction of the scalar variance in the transported PDF method. In this work, a new model is introduced to remedy this problem that can yield a consistent scalar variance prediction. The model formulation along with its numerical implementation is discussed, and the model validation is conducted in a turbulent mixing layer problem.

Maximum entropy PDF projection: A review

NASA Astrophysics Data System (ADS)

Baggenstoss, Paul M.

2017-06-01

We review maximum entropy (MaxEnt) PDF projection, a method with wide potential applications in statistical inference. The method constructs a sampling distribution for a high-dimensional vector x based on knowing the sampling distribution p(z) of a lower-dimensional feature z = T (x). Under mild conditions, the distribution p(x) having highest possible entropy among all distributions consistent with p(z) may be readily found. Furthermore, the MaxEnt p(x) may be sampled, making the approach useful in Monte Carlo methods. We review the theorem and present a case study in model order selection and classification for handwritten character recognition.

A Electronic Map Data Model Based on PDF

NASA Astrophysics Data System (ADS)

Zhou, Xiaodong; Yang, Chuncheng; Meng, Nina; Peng, Peng

2018-05-01

In this paper, we proposed the PDFEMAP (PDF electronic map) that is a kind of new electronic map products aiming at the current situation and demand of the use of electronic map products. Firstly gives the definition and characteristics of PDFEMAP, followed by a detailed description of the data model and method for generating PDFEMAP, and finally expounds application modes of the PDFEMAP which feasibility and effectiveness are verified.

Large variations in ocular dimensions in a multiethnic population with similar genetic background.

PubMed

Niu, Zhiqiang; Li, Jun; Zhong, Hua; Yuan, Zhonghua; Zhou, Hua; Zhang, Yang; Yuan, Yuansheng; Chen, Qin; Pan, Chen-Wei

2016-03-07

We aimed to describe the ethnic variations in ocular dimensions among three ethnic groups with similar genetic ancestry from mainland of China. We included 2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han adults aged 50 years or older in the study. Ocular dimensions including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD) and lens thickness (LT) were measured using A-scan ultrasonography. Bai Chinese had longer ALs (P < 0.001), deeper ACDs (P < 0.001) but shallower VCDs (P < 0.001) compared with the other two ethnic groups. There were no ethnic variations in LTs. Diabetes was associated with shallower ACDs and this association was stronger in Bai Chinese compared with Yi or Han Chinese (P for interaction = 0.02). Thicker lenses were associated with younger age (P = 0.04), male gender (P < 0.001), smoking history (P = 0.01), alcohol intake (P = 0.03), the presence of cataract (P < 0.001), and the presence of diabetes (P < 0.001). There were significant differences in ocular dimensions among different ethnic groups with small differences in genetics but large variations in cultures and lifestyles.

Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds

PubMed Central

Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa

2015-01-01

Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates. PMID:25809972

An LES-PBE-PDF approach for modeling particle formation in turbulent reacting flows

NASA Astrophysics Data System (ADS)

Sewerin, Fabian; Rigopoulos, Stelios

2017-10-01

Many chemical and environmental processes involve the formation of a polydispersed particulate phase in a turbulent carrier flow. Frequently, the immersed particles are characterized by an intrinsic property such as the particle size, and the distribution of this property across a sample population is taken as an indicator for the quality of the particulate product or its environmental impact. In the present article, we propose a comprehensive model and an efficient numerical solution scheme for predicting the evolution of the property distribution associated with a polydispersed particulate phase forming in a turbulent reacting flow. Here, the particulate phase is described in terms of the particle number density whose evolution in both physical and particle property space is governed by the population balance equation (PBE). Based on the concept of large eddy simulation (LES), we augment the existing LES-transported probability density function (PDF) approach for fluid phase scalars by the particle number density and obtain a modeled evolution equation for the filtered PDF associated with the instantaneous fluid composition and particle property distribution. This LES-PBE-PDF approach allows us to predict the LES-filtered fluid composition and particle property distribution at each spatial location and point in time without any restriction on the chemical or particle formation kinetics. In view of a numerical solution, we apply the method of Eulerian stochastic fields, invoking an explicit adaptive grid technique in order to discretize the stochastic field equation for the number density in particle property space. In this way, sharp moving features of the particle property distribution can be accurately resolved at a significantly reduced computational cost. As a test case, we consider the condensation of an aerosol in a developed turbulent mixing layer. Our investigation not only demonstrates the predictive capabilities of the LES-PBE-PDF model but also

Grandmothers as gems of genetic wisdom: exploring South African traditional beliefs about the causes of childhood genetic disorders.

PubMed

Penn, Claire; Watermeyer, Jennifer; MacDonald, Carol; Moabelo, Colleen

2010-02-01

With its diverse cultural and linguistic profile, South Africa provides a unique context to explore contextual influences on the process of genetic counseling. Prior research suggests intergenerational differences regarding models of causation which influence treatment-seeking paths. This pilot study therefore aimed to explore South African traditional beliefs regarding common childhood genetic disorders. Three focus groups were conducted with fifteen grandmothers from different cultural backgrounds in an urban community. Questions pertained to the role of the grandmother, traditional beliefs regarding causes of genetic disorders, explanations of heredity, and prevention and management of genetic disorders. Results indicate a variety of cultural explanations for causes of childhood genetic disorders. These causes can be classified into categories related to lifestyle, behavior, social issues, culture, religion, genetic, and familial causes. Prevention and treatment issues are also highlighted. These findings have implications for genetic counseling practice, which needs to include a greater focus on cultural issues.

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness.

PubMed

Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

2017-01-01

In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation.

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness

PubMed Central

Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

2017-01-01

In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation. PMID:28558035

Association of Recurrent Furunculosis with Panton-Valentine Leukocidin and the Genetic Background of Staphylococcus aureus▿ †

PubMed Central

Masiuk, Helena; Kopron, Katarzyna; Grumann, Dorothee; Goerke, Christiane; Kolata, Julia; Jursa-Kulesza, Joanna; Giedrys-Kalemba, Stefania; Bröker, Barbara M.; Holtfreter, Silva

2010-01-01

Staphylococcus aureus is a major cause of skin and soft tissue infections, such as furuncles, carbuncles, and abscesses, but it also frequently colonizes the human skin and mucosa without causing clinical symptoms. Panton-Valentine leukocidin (PVL) is a pore-forming toxin that has been associated with soft tissue infections and necrotizing pneumonia. We have compared the genotypes, virulence gene repertoires, and phage patterns of 74 furunculosis isolates with those of 108 control strains from healthy nasal carriers. The large majority of furunculosis strains were methicillin sensitive. Clonal cluster (CC) 121 (CC121) and CC22 accounted for 70% of the furunculosis strains but for only 8% of the nasal isolates. The PVL-encoding genes luk-PV were detected in 85% of furunculosis strains, while their prevalence among colonizing S. aureus strains was below 1%. luk-PV genes were distributed over several lineages (CCs 5, 8, 22, 30, and 121 and sequence type 59). Even within the same lineages, luk-PV-positive phages characterized furunculosis strains, while their luk-PV-negative variants were frequent among nasal strains. The very tight epidemiological linkage between luk-PV and furunculosis, which could be separated from the genetic background of the S. aureus strain as well as from the gene makeup of the luk-PV-transducing phage, lends support to the notion of an important role for PVL in human furunculosis. These results make a case for the determination of luk-PV in recurrent soft tissue infections with methicillin-sensitive as well as methicillin-resistant S. aureus. PMID:20200289

Interactions between genetic background, insulin resistance and β-cell function.

PubMed

Kahn, S E; Suvag, S; Wright, L A; Utzschneider, K M

2012-10-01

An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the β-cell, including the identification of molecules involved in β-cell function that were not previously recognized as playing a role in this critical cell. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

EUPDF-II: An Eulerian Joint Scalar Monte Carlo PDF Module : User's Manual

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, Nan-Suey (Technical Monitor)

2004-01-01

EUPDF-II provides the solution for the species and temperature fields based on an evolution equation for PDF (Probability Density Function) and it is developed mainly for application with sprays, combustion, parallel computing, and unstructured grids. It is designed to be massively parallel and could easily be coupled with any existing gas-phase CFD and spray solvers. The solver accommodates the use of an unstructured mesh with mixed elements of either triangular, quadrilateral, and/or tetrahedral type. The manual provides the user with an understanding of the various models involved in the PDF formulation, its code structure and solution algorithm, and various other issues related to parallelization and its coupling with other solvers. The source code of EUPDF-II will be available with National Combustion Code (NCC) as a complete package.

[Difficulties of genetic counselling in rare, mainly neurogenetic disorders].

PubMed

Horváth, Emese; Nagy, Nikoletta; Széll, Márta

2014-08-03

In recent decades methods used for the investigation of the genetic background of rare diseases showed a great improvement. The aim of the authors was to demonstrate difficulties of genetic counselling and investigations in case of five rare, mainly neurogenetic diseases. During pre-test genetic counselling, the disease suspected from the clinical symptoms and the available genetic tests were considered. During post-test genetic counselling, the results of the genetic tests were discussed. In three of the five cases genetic tests identified the disease-causing genetic abnormalities, while in two cases the causative abnormalities were not identified. Despite a great improvement of the available genetic methods, the causative genetic abnormalities cannot be identified in some cases. The genetic counsellor has a key role in the assessment and interpretation of the results and in helping the family planning.

Pdf prediction of supersonic hydrogen flames

NASA Technical Reports Server (NTRS)

Eifler, P.; Kollmann, W.

1993-01-01

A hybrid method for the prediction of supersonic turbulent flows with combustion is developed consisting of a second order closure for the velocity field and a multi-scalar pdf method for the local thermodynamic state. It is shown that for non-premixed flames and chemical equilibrium mixture fraction, the logarithm of the (dimensionless) density, internal energy per unit mass and the divergence of the velocity have several advantages over other sets of scalars. The closure model is applied to a supersonic non-premixed flame burning hydrogen with air supplied by a supersonic coflow and the results are compared with a limited set of experimental data.

Multiresolution MAP despeckling of SAR images based on locally adaptive generalized Gaussian pdf modeling.

PubMed

Argenti, Fabrizio; Bianchi, Tiziano; Alparone, Luciano

2006-11-01

In this paper, a new despeckling method based on undecimated wavelet decomposition and maximum a posteriori MIAP) estimation is proposed. Such a method relies on the assumption that the probability density function (pdf) of each wavelet coefficient is generalized Gaussian (GG). The major novelty of the proposed approach is that the parameters of the GG pdf are taken to be space-varying within each wavelet frame. Thus, they may be adjusted to spatial image context, not only to scale and orientation. Since the MAP equation to be solved is a function of the parameters of the assumed pdf model, the variance and shape factor of the GG function are derived from the theoretical moments, which depend on the moments and joint moments of the observed noisy signal and on the statistics of speckle. The solution of the MAP equation yields the MAP estimate of the wavelet coefficients of the noise-free image. The restored SAR image is synthesized from such coefficients. Experimental results, carried out on both synthetic speckled images and true SAR images, demonstrate that MAP filtering can be successfully applied to SAR images represented in the shift-invariant wavelet domain, without resorting to a logarithmic transformation.

Embedding and Publishing Interactive, 3-Dimensional, Scientific Figures in Portable Document Format (PDF) Files

PubMed Central

Barnes, David G.; Vidiassov, Michail; Ruthensteiner, Bernhard; Fluke, Christopher J.; Quayle, Michelle R.; McHenry, Colin R.

2013-01-01

With the latest release of the S2PLOT graphics library, embedding interactive, 3-dimensional (3-d) scientific figures in Adobe Portable Document Format (PDF) files is simple, and can be accomplished without commercial software. In this paper, we motivate the need for embedding 3-d figures in scholarly articles. We explain how 3-d figures can be created using the S2PLOT graphics library, exported to Product Representation Compact (PRC) format, and included as fully interactive, 3-d figures in PDF files using the movie15 LaTeX package. We present new examples of 3-d PDF figures, explain how they have been made, validate them, and comment on their advantages over traditional, static 2-dimensional (2-d) figures. With the judicious use of 3-d rather than 2-d figures, scientists can now publish, share and archive more useful, flexible and faithful representations of their study outcomes. The article you are reading does not have embedded 3-d figures. The full paper, with embedded 3-d figures, is recommended and is available as a supplementary download from PLoS ONE (File S2). PMID:24086243

Embedding and publishing interactive, 3-dimensional, scientific figures in Portable Document Format (PDF) files.

PubMed

Barnes, David G; Vidiassov, Michail; Ruthensteiner, Bernhard; Fluke, Christopher J; Quayle, Michelle R; McHenry, Colin R

2013-01-01

With the latest release of the S2PLOT graphics library, embedding interactive, 3-dimensional (3-d) scientific figures in Adobe Portable Document Format (PDF) files is simple, and can be accomplished without commercial software. In this paper, we motivate the need for embedding 3-d figures in scholarly articles. We explain how 3-d figures can be created using the S2PLOT graphics library, exported to Product Representation Compact (PRC) format, and included as fully interactive, 3-d figures in PDF files using the movie15 LaTeX package. We present new examples of 3-d PDF figures, explain how they have been made, validate them, and comment on their advantages over traditional, static 2-dimensional (2-d) figures. With the judicious use of 3-d rather than 2-d figures, scientists can now publish, share and archive more useful, flexible and faithful representations of their study outcomes. The article you are reading does not have embedded 3-d figures. The full paper, with embedded 3-d figures, is recommended and is available as a supplementary download from PLoS ONE (File S2).

Arabidopsis research requires a critical re-evaluation of genetic tools.

PubMed

Nikonorova, Natalia; Yue, Kun; Beeckman, Tom; De Smet, Ive

2018-06-27

An increasing number of reports question conclusions based on loss-of-function lines that have unexpected genetic backgrounds. In this opinion paper, we urge researchers to meticulously (re)investigate phenotypes retrieved from various genetic backgrounds and be critical regarding some previously drawn conclusions. As an example, we provide new evidence that acr4-2 mutant phenotypes with respect to columella stem cells are due to the lack of ACR4 and not - at least not as a major contributor - to a mutation in QRT1. In addition, we take the opportunity to alert the scientific community about the qrt1-2 background of a large number of Syngenta Arabidopsis Insertion Library (SAIL) T-DNA lines, a feature that is not commonly recognized by Arabidopsis researchers. This qrt1-2 background might have an important impact on the interpretation of the results obtained using these research tools, now and in the past. In conclusion, as a community, we should continuously assess and - if necessary - correct our conclusions based on the large number of (genetic) tools our work is built on. In addition, the positive or negative results of this self-criticism should be made available to the scientific community.

Genetic Modifiers and Oligogenic Inheritance

PubMed Central

Kousi, Maria; Katsanis, Nicholas

2015-01-01

Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptual and technological tools used to overcome some of the challenges inherent in modifier mapping and cloning. Finally, we discuss how the identification of these modifiers has facilitated the elucidation of biological pathways and holds the potential to improve the clinical predictive value of primary causal mutations and to develop novel drug targets. PMID:26033081

Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus

PubMed Central

Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L.; Whiteman, David C.; MacGregor, Stuart

2016-01-01

Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3–11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA. PMID:26704365

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

PubMed Central

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

The genetic architecture of maize (Zea mays L.) kernel weight determination.

PubMed

Alvarez Prado, Santiago; López, César G; Senior, M Lynn; Borrás, Lucas

2014-09-18

Individual kernel weight is an important trait for maize yield determination. We have identified genomic regions controlling this trait by using the B73xMo17 population; however, the effect of genetic background on control of this complex trait and its physiological components is not yet known. The objective of this study was to understand how genetic background affected our previous results. Two nested stable recombinant inbred line populations (N209xMo17 and R18xMo17) were designed for this purpose. A total of 408 recombinant inbred lines were genotyped and phenotyped at two environments for kernel weight and five other traits related to kernel growth and development. All traits showed very high and significant (P < 0.001) phenotypic variability and medium-to-high heritability (0.60-0.90). When N209xMo17 and R18xMo17 were analyzed separately, a total of 23 environmentally stable quantitative trait loci (QTL) and five epistatic interactions were detected for N209xMo17. For R18xMo17, 59 environmentally stable QTL and 17 epistatic interactions were detected. A joint analysis detected 14 stable QTL regardless of the genetic background. Between 57 and 83% of detected QTL were population specific, denoting medium-to-high genetic background effects. This percentage was dependent on the trait. A meta-analysis including our previous B73xMo17 results identified five relevant genomic regions deserving further characterization. In summary, our grain filling traits were dominated by small additive QTL with several epistatic and few environmental interactions and medium-to-high genetic background effects. This study demonstrates that the number of detected QTL and additive effects for different physiologically related grain filling traits need to be understood relative to the specific germplasm. Copyright © 2014 Alvarez Prado et al.

Revised estimates for continuous shoreline fumigation: a PDF approach.

PubMed

Nazir, Muddassir; Khan, Faisal I; Husain, Tahir

2005-02-14

A probability density function (PDF) fumigation model is presented here to study the dispersion of air pollutants emitted from a tall stack on the shoreline. This work considers dispersion of the pollutants in the stable layer and within the thermal internal boundary layer (TIBL) proceeds independently. The growth of TIBL is considered parabolic with distance inland. Turbulence is taken as homogeneous and stationary. Dispersion of particles (contaminant) in lateral and vertical directions is assumed independent of each other. This assumption allows us to consider the position of particles in both directions as independent random variables. The lateral dispersion distribution within the TIBL is considered as Gaussian and independent of height. A skewed bi-Gaussian vertical velocity PDF is used to account for the physics of dispersion due to different characteristics of updrafts and downdrafts within the TIBL. We have used Weil (J.C. Weil, A diagnosis of the asymmetry in top-down and bottom-up diffusion using a Lagrangian stochastic model, J. Atmos. Sci., 47 (1990) 501-515) solutions to find out the parameters of this PDF. Incorporating finite Lagrangian integral time scale for the vertical velocity component, it is observed that it reduces the vertical dispersion in the beginning and moves the point of maximum concentration further downwind. Due to little dispersion in the beginning, there is more plume to be dispersed causing higher concentrations at large distances. The model has considered Weil and Brower's (J.C. Weil, P.R. Brower, Estimating convective boundary layer parameters for diffusion applications, Maryland Power Plant Siting Program Rep. PPSP-MP-48, Department of Natural Resources, Annapolis, MD, 1985, 37 pp.) convective limit to analyze dispersion characteristics within TIBL. The revised model discussed here is evaluated with the data available from the Nanticoke field experiment on fumigation conducted in summer of 1978 in Ontario, Canada. The results

The genetic architecture of long QT syndrome: A critical reappraisal.

PubMed

Giudicessi, John R; Wilde, Arthur A M; Ackerman, Michael J

2018-03-30

Collectively, the completion of the Human Genome Project and subsequent development of high-throughput next-generation sequencing methodologies have revolutionized genomic research. However, the rapid sequencing and analysis of thousands upon thousands of human exomes and genomes has taught us that most genes, including those known to cause heritable cardiovascular disorders such as long QT syndrome, harbor an unexpected background rate of rare, and presumably innocuous, non-synonymous genetic variation. In this Review, we aim to reappraise the genetic architecture underlying both the acquired and congenital forms of long QT syndrome by examining how the clinical phenotype associated with and background genetic variation in long QT syndrome-susceptibility genes impacts the clinical validity of existing gene-disease associations and the variant classification and reporting strategies that serve as the foundation for diagnostic long QT syndrome genetic testing. Copyright © 2018 Elsevier Inc. All rights reserved.

A PDF projection method: A pressure algorithm for stand-alone transported PDFs

NASA Astrophysics Data System (ADS)

Ghorbani, Asghar; Steinhilber, Gerd; Markus, Detlev; Maas, Ulrich

2015-03-01

In this paper, a new formulation of the projection approach is introduced for stand-alone probability density function (PDF) methods. The method is suitable for applications in low-Mach number transient turbulent reacting flows. The method is based on a fractional step method in which first the advection-diffusion-reaction equations are modelled and solved within a particle-based PDF method to predict an intermediate velocity field. Then the mean velocity field is projected onto a space where the continuity for the mean velocity is satisfied. In this approach, a Poisson equation is solved on the Eulerian grid to obtain the mean pressure field. Then the mean pressure is interpolated at the location of each stochastic Lagrangian particle. The formulation of the Poisson equation avoids the time derivatives of the density (due to convection) as well as second-order spatial derivatives. This in turn eliminates the major sources of instability in the presence of stochastic noise that are inherent in particle-based PDF methods. The convergence of the algorithm (in the non-turbulent case) is investigated first by the method of manufactured solutions. Then the algorithm is applied to a one-dimensional turbulent premixed flame in order to assess the accuracy and convergence of the method in the case of turbulent combustion. As a part of this work, we also apply the algorithm to a more realistic flow, namely a transient turbulent reacting jet, in order to assess the performance of the method.

Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

PubMed Central

Seppälä, Otto; Langeloh, Laura

2016-01-01

Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

aMC fast: automation of fast NLO computations for PDF fits

NASA Astrophysics Data System (ADS)

Bertone, Valerio; Frederix, Rikkert; Frixione, Stefano; Rojo, Juan; Sutton, Mark

2014-08-01

We present the interface between M adG raph5_ aMC@NLO, a self-contained program that calculates cross sections up to next-to-leading order accuracy in an automated manner, and APPL grid, a code that parametrises such cross sections in the form of look-up tables which can be used for the fast computations needed in the context of PDF fits. The main characteristic of this interface, which we dub aMC fast, is its being fully automated as well, which removes the need to extract manually the process-specific information for additional physics processes, as is the case with other matrix-element calculators, and renders it straightforward to include any new process in the PDF fits. We demonstrate this by studying several cases which are easily measured at the LHC, have a good constraining power on PDFs, and some of which were previously unavailable in the form of a fast interface.

Charm and beauty quark masses in the MMHT2014 global PDF analysis.

PubMed

Harland-Lang, L A; Martin, A D; Motylinski, P; Thorne, R S

We investigate the variation in the MMHT2014 PDFs when we allow the heavy-quark masses [Formula: see text] and [Formula: see text] to vary away from their default values. We make PDF sets available in steps of [Formula: see text] and [Formula: see text], and present the variation in the PDFs and in the predictions. We examine the comparison to the HERA data on charm and beauty structure functions and note that in each case the heavy-quark data, and the inclusive data, have a slight preference for lower masses than our default values. We provide PDF sets with three and four active quark flavours, as well as the standard value of five flavours. We use the pole mass definition of the quark masses, as in the default MMHT2014 analysis, but briefly comment on the [Formula: see text] definition.

Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs

PubMed Central

Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

2016-01-01

With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS–LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds.

PubMed

Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa; Hirai, Itaru

2015-06-01

Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Israel: Background and U.S. Relations in Brief

DTIC Science & Technology

2016-09-16

above and below the $500 million mark from year to year. 32 Barbara Opall -Rome, “Israel Claims...at page 119-A, available at http://docs.house.gov/meetings/RU/RU00/20151216/104298/HMTG-114-RU00-20151216-SD004.pdf. 34 Barbara Opall -Rome, “Israel

Preservation of Eumelanin Hair Pigmentation in Proopiomelanocortin-Deficient Mice on a Nonagouti (a/a) Genetic Background

PubMed Central

Slominski, Andrzej; Plonka, Przemyslaw M.; Pisarchik, Alexander; Smart, James L.; Tolle, Virginie; Wortsman, Jacobo; Low, Malcolm J.

2005-01-01

The original strain of proopiomelanocortin (POMC)-deficient mice (Pomc−/− ) was generated by homologous recombination in 129X1/SvJ (Aw/Aw)-derived embryonic stem cells using a targeting construct that deleted exon 3, encoding all the known functional POMC-derived peptides including αMSH, from the Pomc gene. Although these Pomc−/− mice exhibited adrenal hypoplasia and obesity similar to the syndrome of POMC deficiency in children, their agouti coat color was only subtly altered. To further investigate the mechanism of hair pigmentation in the absence of POMC peptides, we studied wild-type (Pomc+/+), heterozygous (Pomc+/−), and homozygous (Pomc−/−) mice on a nonagouti (a/a) 129;B6 hybrid genetic background. All three genotypes had similar black fur pigmentation with yellow hairs behind the ears, around the nipples, and in the perianal area characteristic of inbred C57BL/6 mice. Histologic and electron paramagnetic resonance spectrometry examination demonstrated that hair follicles in back skin of Pomc−/− mice developed with normal structure and eumelanin pigmentation; corresponding molecular analyses, however, excluded local production of αMSH and ACTH because neither Pomc nor putative Pomc pseudogene mRNAs were detected in the skin. Thus, 129;B6 Pomc null mutant mice produce abundant eumelanin hair pigmentation despite their congenital absence of melanocortin ligands. These results suggest that either the mouse melanocortin receptor 1 has sufficient basal activity to trigger and sustain eumelanogenesis in vivo or that redundant nonmelanocortin pathway(s) compensate for the melanocortin deficiency. Whereas the latter implies feedback control of melanogenesis, it is also possible that the two mechanisms operate jointly in hair follicles. PMID:15564334

Transported PDF Modeling of Nonpremixed Turbulent CO/H-2/N-2 Jet Flames

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

Zhao, xinyu; Haworth, D. C.; Huckaby, E. David

2012-01-01

Turbulent CO/H{sub 2}/N{sub 2} (“syngas”) flames are simulated using a transported composition probability density function (PDF) method. A consistent hybrid Lagrangian particle/Eulerian mesh algorithm is used to solve the modeled PDF transport equation. The model includes standard k–ϵ turbulence, gradient transport for scalars, and Euclidean minimum spanning tree (EMST) mixing. Sensitivities of model results to variations in the turbulence model, the treatment of radiation heat transfer, the choice of chemical mechanism, and the PDF mixing model are explored. A baseline model reproduces the measured mean and rms temperature, major species, and minor species profiles reasonably well, and captures the scalingmore » that is observed in the experiments. Both our results and the literature suggest that further improvements can be realized with adjustments in the turbulence model, the radiation heat transfer model, and the chemical mechanism. Although radiation effects are relatively small in these flames, consideration of radiation is important for accurate NO prediction. Chemical mechanisms that have been developed specifically for fuels with high concentrations of CO and H{sub 2} perform better than a methane mechanism that was not designed for this purpose. It is important to account explicitly for turbulence–chemistry interactions, although the details of the mixing model do not make a large difference in the results, within reasonable limits.« less

The background puzzle: how identical mutations in the same gene lead to different disease symptoms.

PubMed

Kammenga, Jan E

2017-10-01

Identical disease-causing mutations can lead to different symptoms in different people. The reason for this has been a puzzling problem for geneticists. Differential penetrance and expressivity of mutations has been observed within individuals with different and similar genetic backgrounds. Attempts have been made to uncover the underlying mechanisms that determine differential phenotypic effects of identical mutations through studies of model organisms. From these studies evidence is accumulating that to understand disease mechanism or predict disease prevalence, an understanding of the influence of genetic background is as important as the putative disease-causing mutations of relatively large effect. This review highlights current insights into phenotypic variation due to gene interactions, epigenetics and stochasticity in model organisms, and discusses their importance for understanding the mutational effect on disease symptoms. © 2017 Federation of European Biochemical Societies.

Senegal: Background and U.S. Relations

DTIC Science & Technology

2012-04-11

Politique et Révolution Passive. ‘Sopi’ or not ‘Sopi’?” Politique Africaine, December 2004. 12 See, for example, Abdou Latif Coulibaly, Contes et ...regional presence of violent extremist groups. Al Qaeda in the Islamic Maghreb (AQIM), an criminal- terrorist network with ties to Al Qaeda and roots...FTF_2010_Implementation_Plan_Senegal.pdf. 27 U.N. Development Program and Government of Senegal, Changement Climatique, Sécurité Alimentaire et Développement Humain

Endogenous enzyme activities and polyamine levels in diverse rice cultivars depend on the genetic background and are not affected by the presence of the hygromycin phosphotransferase selectable marker.

PubMed

Lepri, O.; Bassie, L.; Thu-Hang, P.; Christou, P.; Capell, T.

2002-09-01

We used the polyamine biosynthetic pathway and rice as a relevant model to understand the genetic basis of variation in endogenous levels of metabolites and key enzymes involved in the pathway. Wild-type tissues and also tissues containing a commonly used selectable marker gene were employed. We detected a wide variation in levels of arginine decarboxylase activity and in the three polyamines, putrescine, spermidine and spermine, in different tissues and varieties, but this was not dependent on the presence of the selectable marker. A more-extensive profile of enzyme activities (ADC, ODC, SAMDC, DAO and PAO) and polyamine levels in different tissues was generated in two different varieties. Our results indicate that genetic background is important in terms of the basal levels of metabolites and enzyme activity, particularly in situations in which we aim to engineer metabolic pathways that are also encoded by homologous endogenous genes. We did not find any evidence that the presence of a selectable marker in any way influences enzyme activity or metabolite levels.

Genetics Home Reference: aspartylglucosaminuria

MedlinePlus

... PDF) Disease InfoSearch: Aspartylglucosaminuria KidsHealth: Delayed Speech or Language Development MalaCards: aspartylglucosaminuria Orphanet: Aspartylglucosaminuria Patient Support and Advocacy ...

Evolution of the concentration PDF in random environments modeled by global random walk

NASA Astrophysics Data System (ADS)

Suciu, Nicolae; Vamos, Calin; Attinger, Sabine; Knabner, Peter

2013-04-01

The evolution of the probability density function (PDF) of concentrations of chemical species transported in random environments is often modeled by ensembles of notional particles. The particles move in physical space along stochastic-Lagrangian trajectories governed by Ito equations, with drift coefficients given by the local values of the resolved velocity field and diffusion coefficients obtained by stochastic or space-filtering upscaling procedures. A general model for the sub-grid mixing also can be formulated as a system of Ito equations solving for trajectories in the composition space. The PDF is finally estimated by the number of particles in space-concentration control volumes. In spite of their efficiency, Lagrangian approaches suffer from two severe limitations. Since the particle trajectories are constructed sequentially, the demanded computing resources increase linearly with the number of particles. Moreover, the need to gather particles at the center of computational cells to perform the mixing step and to estimate statistical parameters, as well as the interpolation of various terms to particle positions, inevitably produce numerical diffusion in either particle-mesh or grid-free particle methods. To overcome these limitations, we introduce a global random walk method to solve the system of Ito equations in physical and composition spaces, which models the evolution of the random concentration's PDF. The algorithm consists of a superposition on a regular lattice of many weak Euler schemes for the set of Ito equations. Since all particles starting from a site of the space-concentration lattice are spread in a single numerical procedure, one obtains PDF estimates at the lattice sites at computational costs comparable with those for solving the system of Ito equations associated to a single particle. The new method avoids the limitations concerning the number of particles in Lagrangian approaches, completely removes the numerical diffusion, and

Genetic characterization and fine mapping of S25, a hybrid male sterility gene, on rice chromosome 12.

PubMed

Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori

2018-02-10

Hybrid male sterility genes are important factors in creating postzygotic reproductive isolation barriers in plants. One such gene, S25, is known to cause severe transmission ratio distortion in inter-subspecific progeny of cultivated rice Oryza sativa ssp. indica and japonica. To further characterize the S25 gene, we fine-mapped and genetically characterized the S25 gene using near-isogenic lines with reciprocal genetic backgrounds. We mapped the S25 locus within the 0.67-1.02 Mb region on rice chromosome 12. Further genetic analyses revealed that S25 substantially reduced male fertility in the japonica background, but not in the indica background. In first-generation hybrid progeny, S25 had a milder effect than it had in the japonica background. These results suggest that the expression of S25 is epistatically regulated by at least one partially dominant gene present in the indica genome. This finding supports our previous studies showing that hybrid male sterility due to pollen killer genes results from epistatic interaction with other genes that are hidden in the genetic background.

[Genetic diversity analysis of Andrographis paniculata in China based on SRAP and SNP].

PubMed

Chen, Rong; Wang, Xiao-Yun; Song, Yu-Ning; Zhu, Yun-feng; Wang, Peng-liang; Li, Min; Zhong, Guo-Yue

2014-12-01

In order to reveal genetic diversity of domestic Andrographis paniculata and its impact on quality, genetic backgrounds of 103 samples from 7 provinces in China were analyzed using SRAP marker and SNP marker. Genetic structures of the A. paniculata populations were estimated with Powermarker V 3.25 and Mega 6.0 software, and polymorphic SNPs were identified with CodonCode Aligner software. The results showed that the genetic distances of domestic A. paniculata germplasm ranged from 0. 01 to 0.09, and no polymorphic SNPs were discovered in coding sequence fragments of ent-copalyl diphosphate synthase. A. paniculata germplasm from various regions in China had poor genetic diversity. This phenomenon was closely related to strict self-fertilization and earlier introduction from the same origin. Therefore, genetic background had little impact on variable qualities of A. paniculata in domestic market. Mutation breeding, polyploid breeding and molecular breeding were proposed as promising strategies in germplasm innovation.

Elucidation of Genetic Backgrounds Necessary for Chlorophyll a Biosynthesis Toward Artificial Creation of Oxygenic Photosynthesis

NASA Astrophysics Data System (ADS)

Tsukatani, Yusuke; Masuda, Shinji

2015-09-01

We succeeded to create the genetically modified purple photosynthetic bacterium capable of synthesizing chlorophyll a. The results indicate that not only chlorophyll synthase, but also an enzyme for galactolipid synthesis and reaction center proteins are required for accumulating chlorophyll a.

Genetic Testing: Understanding the Personal Stories.

PubMed

DuBois, James M

2015-01-01

Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.

Understanding of research, genetics and genetic research in a rapid ethical assessment in north west Cameroon

PubMed Central

Kengne-Ouafo, Jonas A.; Millard, James D.; Nji, Theobald M.; Tantoh, William F.; Nyoh, Doris N.; Tendongfor, Nicholas; Enyong, Peter A.; Newport, Melanie J.; Davey, Gail; Wanji, Samuel

2016-01-01

Background There is limited assessment of whether research participants in low-income settings are afforded a full understanding of the meaning of medical research. There may also be particular issues with the understanding of genetic research. We used a rapid ethical assessment methodology to explore perceptions surrounding the meaning of research, genetics and genetic research in north west Cameroon. Methods Eleven focus group discussions (including 107 adults) and 72 in-depth interviews were conducted with various stakeholders in two health districts in north west Cameroon between February and April 2012. Results Most participants appreciated the role of research in generating knowledge and identified a difference between research and healthcare but gave varied explanations as to this difference. Most participants' understanding of genetics was limited to concepts of hereditary, with potential benefits limited to the level of the individual or family. Explanations based on supernatural beliefs were identified as a special issue but participants tended not to identify any other special risks with genetic research. Conclusion We demonstrated a variable level of understanding of research, genetics and genetic research, with implications for those carrying out genetic research in this and other low resource settings. Our study highlights the utility of rapid ethical assessment prior to complex or sensitive research. PMID:25969503

Genetic counselling in the era of genomic medicine

PubMed Central

Middleton, Anna

2018-01-01

Abstract Background Genomic technology can now deliver cost effective, targeted diagnosis and treatment for patients. Genetic counselling is a communication process empowering patients and families to make autonomous decisions and effectively use new genetic information. The skills of genetic counselling and expertise of genetic counsellors are integral to the effective implementation of genomic medicine. Sources of data Original papers, reviews, guidelines, policy papers and web-resources. Areas of agreement An international consensus on the definition of genetic counselling. Genetic counselling is necessary for implementation of genomic medicine. Areas of controversy Models of genetic counselling. Growing points Genomic medicine is a growing and strategic priority for many health care systems. Genetic counselling is part of this. Areas timely for developing research An evidence base is necessary, incorporating implementation and outcome research, to enable health care systems, practitioners, patients and families to maximize the utility (medically and psychologically) of the new genomic possibilities. PMID:29617718

Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain

PubMed Central

Shimada, Naoto; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro; Sakai, Takaomi

2016-01-01

Apterous (Ap), the best studied LIM-homeodomain transcription factor in Drosophila, cooperates with the cofactor Chip (Chi) to regulate transcription of specific target genes. Although Ap regulates various developmental processes, its function in the adult brain remains unclear. Here, we report that Ap and Chi in the neurons expressing PDF, a neuropeptide, play important roles in proper sleep/wake regulation in adult flies. PDF-expressing neurons consist of two neuronal clusters: small ventral-lateral neurons (s-LNvs) acting as the circadian pacemaker and large ventral-lateral neurons (l-LNvs) regulating light-driven arousal. We identified that Ap localizes to the nuclei of s-LNvs and l-LNvs. In light-dark (LD) cycles, RNAi knockdown or the targeted expression of dominant-negative forms of Ap or Chi in PDF-expressing neurons or l-LNvs promoted arousal. In contrast, in constant darkness, knockdown of Ap in PDF-expressing neurons did not promote arousal, indicating that a reduced Ap function in PDF-expressing neurons promotes light-driven arousal. Furthermore, Ap expression in l-LNvs showed daily rhythms (peaking at midnight), which are generated by a direct light-dependent mechanism rather than by the endogenous clock. These results raise the possibility that the daily oscillation of Ap expression in l-LNvs may contribute to the buffering of light-driven arousal in wild-type flies. PMID:27853240

Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain.

PubMed

Shimada, Naoto; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro; Sakai, Takaomi

2016-11-17

Apterous (Ap), the best studied LIM-homeodomain transcription factor in Drosophila, cooperates with the cofactor Chip (Chi) to regulate transcription of specific target genes. Although Ap regulates various developmental processes, its function in the adult brain remains unclear. Here, we report that Ap and Chi in the neurons expressing PDF, a neuropeptide, play important roles in proper sleep/wake regulation in adult flies. PDF-expressing neurons consist of two neuronal clusters: small ventral-lateral neurons (s-LNvs) acting as the circadian pacemaker and large ventral-lateral neurons (l-LNvs) regulating light-driven arousal. We identified that Ap localizes to the nuclei of s-LNvs and l-LNvs. In light-dark (LD) cycles, RNAi knockdown or the targeted expression of dominant-negative forms of Ap or Chi in PDF-expressing neurons or l-LNvs promoted arousal. In contrast, in constant darkness, knockdown of Ap in PDF-expressing neurons did not promote arousal, indicating that a reduced Ap function in PDF-expressing neurons promotes light-driven arousal. Furthermore, Ap expression in l-LNvs showed daily rhythms (peaking at midnight), which are generated by a direct light-dependent mechanism rather than by the endogenous clock. These results raise the possibility that the daily oscillation of Ap expression in l-LNvs may contribute to the buffering of light-driven arousal in wild-type flies.

Publications - PDF 94-40 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 94-40 Publication Details Title: Geology of the Gagaryah River area, Lime Hills C-5 and C ., Clautice, K.H., and Harris, E.E., 1994, Geology of the Gagaryah River area, Lime Hills C-5 and C-6 Sheet 1 Geologic map of the Gagaryah River Area, Lime Hills C-5 and C-6 quadrangles, Southwestern Alaska

Interactive 3D-PDF Presentations for the Simulation and Quantification of Extended Endoscopic Endonasal Surgical Approaches.

PubMed

Mavar-Haramija, Marija; Prats-Galino, Alberto; Méndez, Juan A Juanes; Puigdelívoll-Sánchez, Anna; de Notaris, Matteo

2015-10-01

A three-dimensional (3D) model of the skull base was reconstructed from the pre- and post-dissection head CT images and embedded in a Portable Document Format (PDF) file, which can be opened by freely available software and used offline. The CT images were segmented using a specific 3D software platform for biomedical data, and the resulting 3D geometrical models of anatomical structures were used for dual purpose: to simulate the extended endoscopic endonasal transsphenoidal approaches and to perform the quantitative analysis of the procedures. The analysis consisted of bone removal quantification and the calculation of quantitative parameters (surgical freedom and exposure area) of each procedure. The results are presented in three PDF documents containing JavaScript-based functions. The 3D-PDF files include reconstructions of the nasal structures (nasal septum, vomer, middle turbinates), the bony structures of the anterior skull base and maxillofacial region and partial reconstructions of the optic nerve, the hypoglossal and vidian canals and the internal carotid arteries. Alongside the anatomical model, axial, sagittal and coronal CT images are shown. Interactive 3D presentations were created to explain the surgery and the associated quantification methods step-by-step. The resulting 3D-PDF files allow the user to interact with the model through easily available software, free of charge and in an intuitive manner. The files are available for offline use on a personal computer and no previous specialized knowledge in informatics is required. The documents can be downloaded at http://hdl.handle.net/2445/55224 .

Forensic and population genetic characteristics of 62 X chromosome SNPs revealed by multiplex PCR and MALDI-TOF mass spectrometry genotyping in 4 North Eurasian populations.

PubMed

Stepanov, Vadim; Vagaitseva, Ksenyia; Kharkov, Vladimir; Cherednichenko, Anastasia; Bocharova, Anna; Berezina, Galina; Svyatova, Gulnara

2016-01-01

X chromosome genetic markers are widely used in basic population genetic research as well as in forensic genetics. In this paper we analyze the genetic diversity of 62 X chromosome SNPs in 4 populations using multiplex genotyping based on multi-locus PCR and MALDI-TOF mass spectrometry, and report forensic and population genetic features of the panel of X-linked SNPs (XSNPid). Studied populations represent Siberian (Buryat and Khakas), North Asian (Khanty) and Central Asian (Kazakh) native people. Khanty, Khakas and Kazakh population demonstrate average gene diversity over 0.45. Only East Siberian Buryat population is characterized by lower average heterozygosity (0.436). AMOVA analysis of genetic structure reveals a relatively low but significant level of genetic differentiation in a group of 4 population studied (FST=0.023, p=0.0000). The XSNPid panel provides a very high discriminating power in each population. The combined probability of discrimination in females (PDf) for XSNPid panel ranged between populations from 0.99999999999999999999999982 in Khakas to 0.9999999999999999999999963 in Buryats. The combined discriminating power in males (PDm) varies from 0.999999999999999792 to 0.9999999999999999819. The developed multiplex set of X chromosome SNPs can be a useful tool for population genetic studies and for forensic identity and kinship testing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Calibration and data collection protocols for reliable lattice parameter values in electron pair distribution function (ePDF) studies

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

Abeykoon, A. M. Milinda; Hu, Hefei; Wu, Lijun

2015-02-01

We explore and describe different protocols for calibrating electron pair distribution function (ePDF) measurements for quantitative studies on nano-materials. We find the most accurate approach to determine the camera-length is to use a standard calibration sample of Au nanoparticles from National Institute of Standards and Technology. Different protocols for data collection are also explored, as are possible operational errors, to find the best approaches for accurate data collection for quantitative ePDF studies.

Advantages of using molecular coancestry in the removal of introgressed genetic material

PubMed Central

2013-01-01

Background When introgression of undesired exogenous genetic material occurs in a population intended to remain pure, actions are necessary to recover the original background. It has been shown that genome-wide information can replace pedigree information for different objectives and is a valuable tool in the fields of genetic conservation and breeding. In this simulation study, molecular information provided by 50 000 SNP was used to minimise the molecular coancestry between individuals of an admixed population and the foreign individuals that originally introgressed a native population in order to remove the exogenous DNA. Results This management method, which detects the ‘purest’ individuals to be used as parents for the next generation, allowed recovery of the native genetic background to a great extent in all simulated scenarios. However, it also caused an increase in inbreeding larger than expected because of the lower number of individuals selected as parents and the higher coancestry between them. In scenarios involving several introgression events the method was more efficient than in those involving a single introgression event because part of the genetic information was mixed with the native genetic material for a shorter period. Conclusions Genome-wide information can be used to identify the purest individuals via the minimisation of molecular coancestry between individuals of the admixed and exogenous populations. Removal of the undesired genetic material is more efficient with a molecular-based approach than with a pedigree-based approach. PMID:23634969

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity.

PubMed

Boyce, Walter M; Weisenberger, Mara E; Penedo, M Cecilia T; Johnson, Christine K

2011-02-01

A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

Defining and redefining the scope and goals of genetic counseling.

PubMed

Resta, Robert G

2006-11-15

Many definitions of genetic counseling have been proposed since Sheldon Reed first defined the term in 1947. This study reviews selected definitions of genetic counseling including the most recent definition proposed by a committee of the National Society of Genetic Counselors. The analysis focuses on the professional background of who was formulating the definition; the reasons why the definition was created; medical, historical, and social factors; and the definer's implicit or explicit goals of genetic counseling. No definition of genetic counseling is ideal, and any definition can only reflect the values, ethics, goals, and medical practices of the person or group defining the practice of genetic counseling. (c) 2006 Wiley-Liss, Inc.

Genetic Susceptibility to Lymphoma

PubMed Central

Skibola, Christine F.; Curry, John D.; Nieters, Alexandra

2010-01-01

BACKGROUND Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. METHODS This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. RESULTS Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol assessments are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis, but will need replication in larger populations. CONCLUSIONS Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations. PMID:17606447

Elucidation of structure and nature of the PdO-Pd transformation using in situ PDF and XAS techniques.

PubMed

Keating, Jonathan; Sankar, Gopinathan; Hyde, Timothy I; Kohara, Shinji; Ohara, Koji

2013-06-14

The PdO-Pd phase transformation in a 4 wt% Pd/Al2O3 catalyst has been investigated using in situ X-ray absorption spectroscopy (XAS) and in situ X-ray total scattering (also known as high-energy X-ray diffraction) techniques. Both the partial and total pair distribution functions (PDF) from these respective techniques have been analysed in depth. New information from PDF analysis of total scattering data has been garnered using the differential PDF (d-PDF) approach where only correlations orginating from PdO and metallic Pd are extracted. This method circumvents problems encountered in characerising the catalytically active components due to the diffuse scattering from the disordered γ-Al2O3 support phase. Quantitative analysis of the palladium components within the catalyst allowed for the phase composition to be established at various temperatures. Above 850 °C it was found that PdO had converted to metallic Pd, however, the extent of reduction was of the order ca. 70% Pd metal and 30% PdO. Complementary in situ XANES and EXAFS were performed, with heating to high temperature and subsequent cooling in air, and the results of the analyses support the observations, that residual PdO is detected at elevated temperatures. Hysteresis in the transformation upon cooling is confirmed from XAS studies where reoxidation occurs below 680 °C.

Asymptotic stability of spectral-based PDF modeling for homogeneous turbulent flows

NASA Astrophysics Data System (ADS)

Campos, Alejandro; Duraisamy, Karthik; Iaccarino, Gianluca

2015-11-01

Engineering models of turbulence, based on one-point statistics, neglect spectral information inherent in a turbulence field. It is well known, however, that the evolution of turbulence is dictated by a complex interplay between the spectral modes of velocity. For example, for homogeneous turbulence, the pressure-rate-of-strain depends on the integrated energy spectrum weighted by components of the wave vectors. The Interacting Particle Representation Model (IPRM) (Kassinos & Reynolds, 1996) and the Velocity/Wave-Vector PDF model (Van Slooten & Pope, 1997) emulate spectral information in an attempt to improve the modeling of turbulence. We investigate the evolution and asymptotic stability of the IPRM using three different approaches. The first approach considers the Lagrangian evolution of individual realizations (idealized as particles) of the stochastic process defined by the IPRM. The second solves Lagrangian evolution equations for clusters of realizations conditional on a given wave vector. The third evolves the solution of the Eulerian conditional PDF corresponding to the aforementioned clusters. This last method avoids issues related to discrete particle noise and slow convergence associated with Lagrangian particle-based simulations.

Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates.

PubMed

Jones, Ronald N; Moet, Gary J; Sader, Helio S; Fritsche, Thomas R

2004-05-01

To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin. A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target. NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation. NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.

[Practical guidelines for genetic testing in cardiovascular diseases].

PubMed

Reinhard, W; Trenkwalder, T; Schunkert, H

2017-08-01

In the last decade, genetic testing for cardiovascular disorders has become more and more relevant. Progress in molecular genetics has led to new opportunities for diagnostics, improved risk prediction and could lead to novel therapeutic approaches. Genetic diagnostic testing is relevant for both confirming a diagnosis as well as deciding on therapeutic consequences, if applicable. Furthermore, predictive testing in family members for specific cardiovascular diseases is now a standard procedure in holistic patient management. The process of genetic testing as well as documentation requirements and discussion of test results with patients are subject to legal regulations. These regulations might be confusing for clinical practitioners/cardiologists. The aim of this article is to provide a clinical framework for genetic testing. First, we explain the legal and ethical background. Second, we illustrate the process of genetic testing step by step and present updates on remuneration. Finally, we discuss the significance of genetic testing and specific disease indications in cardiology.

The photon PDF from high-mass Drell-Yan data at the LHC.

PubMed

Giuli, F

2017-01-01

Achieving the highest precision for theoretical predictions at the LHC requires the calculation of hard-scattering cross sections that include perturbative QCD corrections up to (N)NNLO and electroweak (EW) corrections up to NLO. Parton distribution functions (PDFs) need to be provided with matching accuracy, which in the case of QED effects involves introducing the photon parton distribution of the proton, [Formula: see text]. In this work a determination of the photon PDF from fits to recent ATLAS measurements of high-mass Drell-Yan dilepton production at [Formula: see text] TeV is presented. This analysis is based on the xFitter framework, and has required improvements both in the APFEL program, to account for NLO QED effects, and in the aMCfast interface to account for the photon-initiated contributions in the EW calculations within MadGraph5_aMC@NLO. The results are compared with other recent QED fits and determinations of the photon PDF, consistent results are found.

Refinement of the Pion PDF implementing Drell-Yan and Deep Inelastic Scattering Experimental Data

NASA Astrophysics Data System (ADS)

Barry, Patrick; Sato, Nobuo; Melnitchouk, Wally; Ji, Chueng-Ryong

2017-09-01

We realize that an abundance of ``sea'' quarks and gluons (as opposed to three valence quarks) is crucial to understanding the mass and internal structure of the proton. An effective pion cloud exists around the core valence structure. In the Drell-Yan (DY) process, two hadrons collide, one donating a quark and the other donating an antiquark. The quark-antiquark pair annihilate, forming a virtual photon, which creates a lepton-antilepton pair. By measuring their cross-sections, we obtain information about the parton distribution function (PDF) of the hadrons. The PDF is the probability of finding a parton at a momentum fraction of the hadron, x, between 0 and 1. Complementary to the DY process is deep inelastic scattering (DIS). Here, a target nucleon is probed by a lepton, and we investigate the pion cloud of the nucleon. The experiments H1 and ZEUS done at HERA at DESY collect DIS data by detecting a leading neutron (LN). By using nested sampling to generate sets of parameters, we present some preliminary fits of pion PDFs to DY (Fermilab-E615 and CERN-NA10) and LN (H1 and ZEUS) datasets. We aim to perform a full NLO QCD global analysis to determine pion PDFs accurately for all x. There have been no attempts to fit the pion PDF using both low and high x data until now.

The Neuropeptides FLP-2 and PDF-1 Act in Concert To Arouse Caenorhabditis elegans Locomotion

PubMed Central

Chen, Didi; Taylor, Kelsey P.; Hall, Qi; Kaplan, Joshua M.

2016-01-01

During larval molts, Caenorhabditis elegans exhibits a sleep-like state (termed lethargus) that is characterized by the absence of feeding and profound locomotion quiescence. The rhythmic pattern of locomotion quiescence and arousal linked to the molting cycle is mediated by reciprocal changes in sensory responsiveness, whereby arousal is associated with increased responsiveness. Sensory neurons arouse locomotion via release of a neuropeptide (PDF-1) and glutamate. Here we identify a second arousing neuropeptide (FLP-2). We show that FLP-2 acts via an orexin-like receptor (FRPR-18), and that FLP-2 and PDF-1 secretion are regulated by reciprocal positive feedback. These results suggest that the aroused behavioral state is stabilized by positive feedback between two neuropeptides. PMID:27585848

Signs of atopic dermatitis and contact dermatitis affected by distinct H2-haplotype in the NC/Nga genetic background.

PubMed

Ohkusu-Tsukada, Kozo; Ito, Daiki; Okuno, Yuki; Tsukada, Teruyo; Takahashi, Kimimasa

2018-02-07

We recently advocated in favour of naming a novel H2-haplotype consisting of K d , D/L dm7 , I-A k and I-E k in the atopic dermatitis (AD) mouse model NC/Nga as "H-2 nc ." The role of the H2-haplotype in AD development was investigated in H2 b -congenic NC/Nga mice (NC.h2 b/b and NC.h2 b/nc ) established by backcrossing. A severe 2,4-dinitrofluorobenzene (DNFB)-induced dermatitis in NC/Nga was alleviated partially in NC.h2 b/nc and significantly in NC.h2 b/b . The AD phenotype was correlated with thymic stromal lymphopoietin (TSLP)-epidermal expression levels and serum levels of total IgE and IL-18/IL-33. Histologically, allergic contact dermatitis (ACD) was accompanied by lymphocytes and plasma cells-infiltrating perivasculitis in NC.h2 b/nc and NC.h2 b/b and clearly differed from AD accompanied by neutrophils, eosinophils and macrophages-infiltrating diffuse suppurative dermatitis in NC/Nga. Interestingly, IFN-γ/IL-17 production from autoreactive CD4 + T-cells remarkably increased in DNFB-sensitised NC.h2 b/b but not in NC/Nga. Our findings suggest that AD or ACD may depend on haplotype H-2 nc or H-2 b , respectively, in addition to the NC/Nga genetic background.

The heterogeneous HLA genetic makeup of the Swiss population.

PubMed

Buhler, Stéphane; Nunes, José Manuel; Nicoloso, Grazia; Tiercy, Jean-Marie; Sanchez-Mazas, Alicia

2012-01-01

This study aims at investigating the HLA molecular variation across Switzerland in order to determine possible regional differences, which would be highly relevant to several purposes: optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT), providing reliable reference data in HLA and disease association studies, and understanding the population genetic background(s) of this culturally heterogeneous country. HLA molecular data of more than 20,000 HSCT donors from 9-13 recruitment centers of the whole country were analyzed. Allele and haplotype frequencies were estimated by using new computer tools adapted to the heterogeneity and ambiguity of the data. Non-parametric and resampling statistical tests were performed to assess Hardy-Weinberg equilibrium, selective neutrality and linkage disequilibrium among different loci, both in each recruitment center and in the whole national registry. Genetic variation was explored through genetic distance and hierarchical analysis of variance taking into account both geographic and linguistic subdivisions in Switzerland. The results indicate a heterogeneous genetic makeup of the Swiss population: first, allele frequencies estimated on the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by contrast with the results obtained for individual centers; second, a pronounced differentiation is observed for Ticino, Graubünden, and, to a lesser extent, Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally, although cultural (linguistic) boundaries do not represent a main genetic differentiation factor in Switzerland, the genetic relatedness between population from south-eastern Switzerland and Italy agrees with historical and linguistic data. Overall, this study justifies the maintenance of a decentralized donor recruitment structure in Switzerland allowing increasing the genetic diversity of the national--and hence global--donor registry. It also

The Heterogeneous HLA Genetic Makeup of the Swiss Population

PubMed Central

Buhler, Stéphane; Nunes, José Manuel; Nicoloso, Grazia; Tiercy, Jean-Marie; Sanchez-Mazas, Alicia

2012-01-01

This study aims at investigating the HLA molecular variation across Switzerland in order to determine possible regional differences, which would be highly relevant to several purposes: optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT), providing reliable reference data in HLA and disease association studies, and understanding the population genetic background(s) of this culturally heterogeneous country. HLA molecular data of more than 20,000 HSCT donors from 9–13 recruitment centers of the whole country were analyzed. Allele and haplotype frequencies were estimated by using new computer tools adapted to the heterogeneity and ambiguity of the data. Non-parametric and resampling statistical tests were performed to assess Hardy-Weinberg equilibrium, selective neutrality and linkage disequilibrium among different loci, both in each recruitment center and in the whole national registry. Genetic variation was explored through genetic distance and hierarchical analysis of variance taking into account both geographic and linguistic subdivisions in Switzerland. The results indicate a heterogeneous genetic makeup of the Swiss population: first, allele frequencies estimated on the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by contrast with the results obtained for individual centers; second, a pronounced differentiation is observed for Ticino, Graubünden, and, to a lesser extent, Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally, although cultural (linguistic) boundaries do not represent a main genetic differentiation factor in Switzerland, the genetic relatedness between population from south-eastern Switzerland and Italy agrees with historical and linguistic data. Overall, this study justifies the maintenance of a decentralized donor recruitment structure in Switzerland allowing increasing the genetic diversity of the national—and hence global—donor registry. It also

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Modeling the Bergeron-Findeisen Process Using PDF Methods With an Explicit Representation of Mixing

NASA Astrophysics Data System (ADS)

Jeffery, C.; Reisner, J.

2005-12-01

Currently, the accurate prediction of cloud droplet and ice crystal number concentration in cloud resolving, numerical weather prediction and climate models is a formidable challenge. The Bergeron-Findeisen process in which ice crystals grow by vapor deposition at the expense of super-cooled droplets is expected to be inhomogeneous in nature--some droplets will evaporate completely in centimeter-scale filaments of sub-saturated air during turbulent mixing while others remain unchanged [Baker et al., QJRMS, 1980]--and is unresolved at even cloud-resolving scales. Despite the large body of observational evidence in support of the inhomogeneous mixing process affecting cloud droplet number [most recently, Brenguier et al., JAS, 2000], it is poorly understood and has yet to be parameterized and incorporated into a numerical model. In this talk, we investigate the Bergeron-Findeisen process using a new approach based on simulations of the probability density function (PDF) of relative humidity during turbulent mixing. PDF methods offer a key advantage over Eulerian (spatial) models of cloud mixing and evaporation: the low probability (cm-scale) filaments of entrained air are explicitly resolved (in probability space) during the mixing event even though their spatial shape, size and location remain unknown. Our PDF approach reveals the following features of the inhomogeneous mixing process during the isobaric turbulent mixing of two parcels containing super-cooled water and ice, respectively: (1) The scavenging of super-cooled droplets is inhomogeneous in nature; some droplets evaporate completely at early times while others remain unchanged. (2) The degree of total droplet evaporation during the initial mixing period depends linearly on the mixing fractions of the two parcels and logarithmically on Damköhler number (Da)---the ratio of turbulent to evaporative time-scales. (3) Our simulations predict that the PDF of Lagrangian (time-integrated) subsaturation (S) goes as

Resolving the Conflict Between Associative Overdominance and Background Selection

PubMed Central

Zhao, Lei; Charlesworth, Brian

2016-01-01

In small populations, genetic linkage between a polymorphic neutral locus and loci subject to selection, either against partially recessive mutations or in favor of heterozygotes, may result in an apparent selective advantage to heterozygotes at the neutral locus (associative overdominance) and a retardation of the rate of loss of variability by genetic drift at this locus. In large populations, selection against deleterious mutations has previously been shown to reduce variability at linked neutral loci (background selection). We describe analytical, numerical, and simulation studies that shed light on the conditions under which retardation vs. acceleration of loss of variability occurs at a neutral locus linked to a locus under selection. We consider a finite, randomly mating population initiated from an infinite population in equilibrium at a locus under selection. With mutation and selection, retardation occurs only when S, the product of twice the effective population size and the selection coefficient, is of order 1. With S >> 1, background selection always causes an acceleration of loss of variability. Apparent heterozygote advantage at the neutral locus is, however, always observed when mutations are partially recessive, even if there is an accelerated rate of loss of variability. With heterozygote advantage at the selected locus, loss of variability is nearly always retarded. The results shed light on experiments on the loss of variability at marker loci in laboratory populations and on the results of computer simulations of the effects of multiple selected loci on neutral variability. PMID:27182952

Publications - PDF 95-33C | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 95-33C Publication Details Title: Surficial geologic map of the Charley River D-1, C-1 , and part of the B-1 quadrangles, east-central Alaska Authors: Pinney, D.S., Clough, J.G., and Liss ., 1995, Surficial geologic map of the Charley River D-1, C-1, and part of the B-1 quadrangles, east

Drosophila DH31 Neuropeptide and PDF Receptor Regulate Night-Onset Temperature Preference

PubMed Central

Goda, Tadahiro; Tang, Xin; Umezaki, Yujiro; Chu, Michelle L.

2016-01-01

Body temperature exhibits rhythmic fluctuations over a 24 h period (Refinetti and Menaker, 1992) and decreases during the night, which is associated with sleep initiation (Gilbert et al., 2004; Kräuchi, 2007a,b). However, the underlying mechanism of this temperature decrease is largely unknown. We have previously shown that Drosophila exhibit a daily temperature preference rhythm (TPR), in which their preferred temperatures increase during the daytime and then decrease at the transition from day to night (night-onset) (Kaneko et al., 2012). Because Drosophila are small ectotherms, their body temperature is very close to that of the ambient temperature (Stevenson, 1985), suggesting that their TPR generates their body temperature rhythm. Here, we demonstrate that the neuropeptide diuretic hormone 31 (DH31) and pigment-dispersing factor receptor (PDFR) contribute to regulate the preferred temperature decrease at night-onset. We show that PDFR and tethered-DH31 expression in dorsal neurons 2 (DN2s) restore the preferred temperature decrease at night-onset, suggesting that DH31 acts on PDFR in DN2s. Notably, we previously showed that the molecular clock in DN2s is important for TPR. Although PDF (another ligand of PDFR) is a critical factor for locomotor activity rhythms, Pdf mutants exhibit normal preferred temperature decreases at night-onset. This suggests that DH31-PDFR signaling specifically regulates a preferred temperature decrease at night-onset. Thus, we propose that night-onset TPR and locomotor activity rhythms are differentially controlled not only by clock neurons but also by neuropeptide signaling in the brain. SIGNIFICANCE STATEMENT Body temperature rhythm (BTR) is fundamental for the maintenance of functions essential for homeostasis, such as generating metabolic energy and sleep. One major unsolved question is how body temperature decreases dramatically during the night. Previously, we demonstrated that a BTR-like mechanism, referred to as temperature

Publications - PDF 93-47 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 93-47 Publication Details Title: Geologic map of the Sleetmute C-7, D-7, C-8, and D-8 ., Harris, E.E., Kline, J.T., and Miller, M.L., 1993, Geologic map of the Sleetmute C-7, D-7, C-8, and D-8 Sleetmute C-7, C-8, D-7 and D-8 quadrangles, Horn Mountain Area, southwest Alaska, scale 1:63,360 (34.0 M

Congenital heart disease and genetic syndromes: new insights into molecular mechanisms.

PubMed

Calcagni, Giulio; Unolt, Marta; Digilio, Maria Cristina; Baban, Anwar; Versacci, Paolo; Tartaglia, Marco; Baldini, Antonio; Marino, Bruno

2017-09-01

Advances in genetics allowed a better definition of the role of specific genetic background in the etiology of syndromic congenital heart defects (CHDs). The identification of a number of disease genes responsible for different syndromes have led to the identification of several transcriptional regulators and signaling transducers and modulators that are critical for heart morphogenesis. Understanding the genetic background of syndromic CHDs allowed a better characterization of the genetic basis of non-syndromic CHDs. In this sense, the well-known association of typical CHDs in Down syndrome, 22q11.2 microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy, chromosomal microdeletion and intragenic mutation, respectively. Area covered: For each syndrome the anatomical features, distinctive cardiac phenotype and molecular mechanisms are discussed. Moreover, the authors include recent genetic findings that may shed light on some aspects of still unclear molecular mechanisms of these syndromes. Expert commentary: Further investigations are needed to enhance the translational approach in the field of genetics of CHDs. When there is a well-established definition of genotype-phenotype (reverse medicine) and genotype-prognosis (predictive and personalized medicine) correlations, hopefully preventive medicine will make its way in this field. Subsequently a reduction will be achieved in the morbidity and mortality of children with CHDs.

A Role for the GCC-Box in Jasmonate-Mediated Activation of the PDF1.2 Gene of Arabidopsis1

PubMed Central

Brown, Rebecca L.; Kazan, Kemal; McGrath, Ken C.; Maclean, Don J.; Manners, John M.

2003-01-01

The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a marker for characterization of the jasmonate-dependent defense responses. Here, using PDF1.2 promoter-deletion lines linked to the β-glucoronidase-reporter gene, we examined putative promoter elements associated with jasmonate-responsive expression of this gene. Using stably transformed plants, we first characterized the extended promoter region that positively regulates basal expression from the PDF1.2 promoter. Second, using promoter deletion constructs including one from which the GCC-box region was deleted, we observed a substantially lower response to jasmonate than lines carrying this motif. In addition, point mutations introduced into the core GCC-box sequence substantially reduced jasmonate responsiveness, whereas addition of a 20-nucleotide-long promoter element carrying the core GCC-box and flanking nucleotides provided jasmonate responsiveness to a 35S minimal promoter. Taken together, these results indicated that the GCC-box plays a key role in conferring jasmonate responsiveness to the PDF1.2 promoter. However, deletion or specific mutations introduced into the core GCC-box did not completely abolish the jasmonate responsiveness of the promoter, suggesting that the other promoter elements lying downstream from the GCC-box region may also contribute to jasmonate responsiveness. In other experiments, we identified a jasmonate- and pathogen-responsive ethylene response factor transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase) genes, all of which contain a GCC-box sequence in their promoters. Our results suggest that in addition to their roles in regulating ethylene-mediated gene expression, ethylene response factors also appear to play important roles in regulating jasmonate-responsive gene expression, possibly via interaction with the GCC-box. PMID:12805630

Genetics Home Reference: non-alcoholic fatty liver disease

MedlinePlus

... different populations of microorganisms in the intestines (gut microbiota) on the breakdown and absorption of nutrients are ... Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterol Res Pract. 2016;2016: ...

Diagnosis of cystic fibrosis in a patient of Egyptian background.

PubMed

Yoshida, Rie; Ruge, Bobby

2016-10-20

Cystic fibrosis (CF) is the most common genetically inherited condition in European-derived populations. However, it is being increasingly recognised in other populations, including people of Asian, Black African and Caribbean descent. We present a case detailing the diagnosis of CF in a 12-year-old patient of Egyptian background who had been treated for difficult asthma. In doing so, we aim to highlight the importance of considering CF in all patients, regardless of ethnicity. 2016 BMJ Publishing Group Ltd.

Genetic and Environmental Influences on the Growth of Early Reading Skills

ERIC Educational Resources Information Center

Petrill, Stephen A.; Hart, Sara A.; Harlaar, Nicole; Logan, Jessica; Justice, Laura M.; Schatschneider, Christopher; Thompson, Lee; DeThorne, Laura S.; Deater-Deckard, Kirby; Cutting, Laurie

2010-01-01

Background: Studies have suggested genetic and environmental influences on overall level of early reading whereas the larger reading literature has shown environmental influences on the rate of growth of early reading skills. This study is the first to examine the genetic and environmental influences on both initial level of performance and rate…

[Genetic and epigenetic aspects of celiac disease].

PubMed

Kocsis, Dorottya; Béres, Nóra; Veres, Gábor; Szabó, Dolóresz; Müller, Katalin Eszter; Arató, András; Juhász, Márk

2014-01-19

Genetic background of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications.

Publications - PDF 95-33E | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS PDF 95-33E Publication Details Title: Geologic hazards map of the Charley River D-1, C-1, and part of the B-1 quadrangles, east-central Alaska Authors: Pinney, D.S., Clough, J.G., Reifenstuhl, R.R ., Reifenstuhl, R.R., and Liss, S.A., 1995, Geologic hazards map of the Charley River D-1, C-1, and part of the B

Chemically reacting supersonic flow calculation using an assumed PDF model

NASA Technical Reports Server (NTRS)

Farshchi, M.

1990-01-01

This work is motivated by the need to develop accurate models for chemically reacting compressible turbulent flow fields that are present in a typical supersonic combustion ramjet (SCRAMJET) engine. In this paper the development of a new assumed probability density function (PDF) reaction model for supersonic turbulent diffusion flames and its implementation into an efficient Navier-Stokes solver are discussed. The application of this model to a supersonic hydrogen-air flame will be considered.