Callosal Influence on Visual Receptive Fields Has an Ocular, an Orientation-and Direction Bias

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Sergio A. Conde-Ocazionez

2018-04-01

Full Text Available One leading hypothesis on the nature of visual callosal connections (CC is that they replicate features of intrahemispheric lateral connections. However, CC act also in the central part of the binocular visual field. In agreement, early experiments in cats indicated that they provide the ipsilateral eye part of binocular receptive fields (RFs at the vertical midline (Berlucchi and Rizzolatti, 1968, and play a key role in stereoscopic function. But until today callosal inputs to receptive fields activated by one or both eyes were never compared simultaneously, because callosal function has been often studied by cutting or lesioning either corpus callosum or optic chiasm not allowing such a comparison. To investigate the functional contribution of CC in the intact cat visual system we recorded both monocular and binocular neuronal spiking responses and receptive fields in the 17/18 transition zone during reversible deactivation of the contralateral hemisphere. Unexpectedly from many of the previous reports, we observe no change in ocular dominance during CC deactivation. Throughout the transition zone, a majority of RFs shrink, but several also increase in size. RFs are significantly more affected for ipsi- as opposed to contralateral stimulation, but changes are also observed with binocular stimulation. Noteworthy, RF shrinkages are tiny and not correlated to the profound decreases of monocular and binocular firing rates. They depend more on orientation and direction preference than on eccentricity or ocular dominance of the receiving neuron's RF. Our findings confirm that in binocularly viewing mammals, binocular RFs near the midline are constructed via the direct geniculo-cortical pathway. They also support the idea that input from the two eyes complement each other through CC: Rather than linking parts of RFs separated by the vertical meridian, CC convey a modulatory influence, reflecting the feature selectivity of lateral circuits, with a

Callosal involvement in a lateralized stroop task in alcoholic and healthy subjects.

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Schulte, T; Müller-Oehring, E M; Salo, R; Pfefferbaum, A; Sullivan, E V

2006-11-01

To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

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Arya Bagus Boedi Iswanto

2017-04-01

Full Text Available Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD, which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs is highly controlled by plasmodesmata callose (PDC, which is synthesized by callose synthases (CalS and degraded by β-1,3-glucanases (BGs. In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft–processed PDC.

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

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Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

2017-04-03

A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

The plasmodesmal protein PDLP1 localises to haustoria-associated membranes during downy mildew infection and regulates callose deposition.

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Marie-Cécile Caillaud

2014-10-01

Full Text Available The downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa is a filamentous oomycete that invades plant cells via sophisticated but poorly understood structures called haustoria. Haustoria are separated from the host cell cytoplasm and surrounded by an extrahaustorial membrane (EHM of unknown origin. In some interactions, including Hpa-Arabidopsis, haustoria are progressively encased by host-derived, callose-rich materials but the molecular mechanisms by which callose accumulates around haustoria remain unclear. Here, we report that PLASMODESMATA-LOCATED PROTEIN 1 (PDLP1 is expressed at high levels in Hpa infected cells. Unlike other plasma membrane proteins, which are often excluded from the EHM, PDLP1 is located at the EHM in Hpa-infected cells prior to encasement. The transmembrane domain and cytoplasmic tail of PDLP1 are sufficient to convey this localization. PDLP1 also associates with the developing encasement but this association is lost when encasements are fully mature. We found that the pdlp1,2,3 triple mutant is more susceptible to Hpa while overexpression of PDLP1 enhances plant resistance, suggesting that PDLPs enhance basal immunity against Hpa. Haustorial encasements are depleted in callose in pdlp1,2,3 mutant plants whereas PDLP1 over-expression elevates callose deposition around haustoria and across the cell surface. These data indicate that PDLPs contribute to callose encasement of Hpa haustoria and suggests that the deposition of callose at haustoria may involve similar mechanisms to callose deposition at plasmodesmata.

The enhanced callose deposition in barley with ml-o powdery mildew resistance genes

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Skou, Jens-Peder

1985-01-01

Carborundum treatment of barley leaves induced a callose deposition which was detected as diffuse blotches in the epidermal cells of susceptible barleys and as deeply stained tracks along the scratches in barleys with the ml-o powdery mildew resistance gene. Subsequent inoculation with powdery...... mildew resulted in appositions that enlarged inversely to their size in the respective varieties when inoculated without carborundum treatment. Aphids sucking the leaves resulted in rows of callose containing spots along the anticlinal cell walls. The spots were larger in the ml-o mutant than...... in the mother variety. Callose was deposited in connection with the pleiotropic necrotic spotting in barleys with the ml-o gene. Modification of the necrotic spotting by crossing the ml-o gene into other gene backgrounds did not result in any change in the size of appositions upon inoculation with powdery...

Developmental evolution of flowering plant pollen tube cell walls: callose synthase (CalS gene expression patterns

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Abercrombie Jason M

2011-07-01

Full Text Available Abstract Background A number of innovations underlie the origin of rapid reproductive cycles in angiosperms. A critical early step involved the modification of an ancestrally short and slow-growing pollen tube for faster and longer distance transport of sperm to egg. Associated with this shift are the predominantly callose (1,3-β-glucan walls and septae (callose plugs of angiosperm pollen tubes. Callose synthesis is mediated by callose synthase (CalS. Of 12 CalS gene family members in Arabidopsis, only one (CalS5 has been directly linked to pollen tube callose. CalS5 orthologues are present in several monocot and eudicot genomes, but little is known about the evolutionary origin of CalS5 or what its ancestral function may have been. Results We investigated expression of CalS in pollen and pollen tubes of selected non-flowering seed plants (gymnosperms and angiosperms within lineages that diverged below the monocot/eudicot node. First, we determined the nearly full length coding sequence of a CalS5 orthologue from Cabomba caroliniana (CcCalS5 (Nymphaeales. Semi-quantitative RT-PCR demonstrated low CcCalS5 expression within several vegetative tissues, but strong expression in mature pollen. CalS transcripts were detected in pollen tubes of several species within Nymphaeales and Austrobaileyales, and comparative analyses with a phylogenetically diverse group of sequenced genomes indicated homology to CalS5. We also report in silico evidence of a putative CalS5 orthologue from Amborella. Among gymnosperms, CalS5 transcripts were recovered from germinating pollen of Gnetum and Ginkgo, but a novel CalS paralog was instead amplified from germinating pollen of Pinus taeda. Conclusion The finding that CalS5 is the predominant callose synthase in pollen tubes of both early-diverging and model system angiosperms is an indicator of the homology of their novel callosic pollen tube walls and callose plugs. The data suggest that CalS5 had transient expression

The effect of intracellular calcium level regulators on the synthesis of pollen tube callose in Oenothera biennis L.

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Elżbieta Bednarska

2014-01-01

Full Text Available It is shown that callose synthesis in the Oenothera biennis pollen tube is regulated by the endogenous Ca2+ level. Calcium antagonists reduced the amount of callose in the wall above the tip of the pollen tube (Verapamil - calcium channels blocker and at the tube tip after stopping tube growth (La3+ - a Ca2+ substitute. Ruthenium red and ionophore A 23187, which raise the Ca 21 level in the cytoplasm, induced callose synthesis at the tip of pollen tube.

Relation of callosal structure to cognitive abilities in temporal lobe epilepsy

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Christine eSchneider

2014-02-01

Full Text Available The main objective of this paper is to analyse the influence of mesial temporal lobe epilepsy (TLE on the morphology of the corpus callosum (CC and its relation to cognitive abilities. More specifically, we investigated correlations between intellectual abilities and callosal morphology, while additionally exploring the modulating impact of (a side of seizure onset (b age of disease onset.For this reason a large representative sample of patients with hippocampal sclerosis (n=79; 35 males; 44 females; age: 18-63 years with disease onset ranging from 0 to 50 years of age, and consisting of 46 left and 33 right TLE patients was recruited. Intelligence was measured using the Wechsler Adult Intelligence Scale Revised (WAIS-R.To get localizations of correlations with high anatomic precision, callosal morphology was examined using computational mesh-based modeling methods, applied to anatomical brain MRI scans.Intellectual performance was positively associated with callosal thickness in anterior and midcallosal callosal regions, with anterior parts being slightly more affected by age of disease onset and side of seizure onset than posterior parts. Earlier age at onset of epilepsy was associated with lower thickness in anterior and midcallosal regions. In addition, laterality of seizure onset had a significant influence on anterior CC morphology, with left hemispheric origin having stronger effects.We found that in TLE, anterior and midcallosal CC morphology are related to cognitive performance. The findings support recent findings of detrimental effects of early onset mTLE on anterior brain regions and of a distinct effect particularly of left TLE on frontal lobe functioning and structure. The causal nature of the relationship remains an open question, i.e., whether CC morphology impacts IQ development or whether IQ development impacts CC morphology, or both.

Microsurgical anatomy of the ventral callosal radiations: new destination, correlations with diffusion tensor imaging fiber-tracking, and clinical relevance.

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Peltier, Johann; Verclytte, Sébastien; Delmaire, Christine; Deramond, Hervé; Pruvo, Jean-Pierre; Le Gars, Daniel; Godefroy, Olivier

2010-03-01

In the current literature, there is a lack of a detailed map of the origin, course, and connections of the ventral callosal radiations of the human brain. The authors used an older dissection technique based on a freezing process as well as diffusion tensor imaging to investigate this area of the human brain. The authors demonstrated interconnections between areas 11, 12, and 25 for the callosal radiations of the trunk and rostrum of the corpus callosum; between areas 9, 10, and 32 for the genu; and between areas 6, 8, and 9 for the ventral third of the body. The authors identified new ventral callosal connections crossing the rostrum between both temporal poles and coursing within the temporal stem, and they named these connections the "callosal radiations of Peltier." They found that the breadth of the callosal radiations slightly increases along their course from the rostrum to the first third of the body of the corpus callosum. The fiber dissection and diffusion tensor imaging techniques are complementary not only in their application to the study of the commissural system in the human brain, but also in their practical use for diagnosis and surgical planning. Further investigations, neurocognitive tests, and other contributions will permit elucidation of the functional relevance of the newly identified callosal radiations in patients with disease involving the ventral corpus callosum.

Agnosia, apraxia, callosal disconnection and other specific cognitive disorders.

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Acciarresi, Monica

2012-01-01

Cortical function deficits have long been studied by anatomoclinic correlations. Recent functional imaging studies have allowed scientists to better understand which cerebral areas and which networks are involved in cognitive function deficit. This chapter will review the current knowledge on agnosia, apraxia and callosal disconnection syndromes. Copyright © 2012 S. Karger AG, Basel.

The PTI1-like kinase ZmPti1a from maize (Zea mays L.) co-localizes with callose at the plasma membrane of pollen and facilitates a competitive advantage to the male gametophyte.

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Herrmann, Markus M; Pinto, Sheena; Kluth, Jantjeline; Wienand, Udo; Lorbiecke, René

2006-10-06

The tomato kinase Pto confers resistance to bacterial speck disease caused by Pseudomonas syringae pv. tomato in a gene for gene manner. Upon recognition of specific avirulence factors the Pto kinase activates multiple signal transduction pathways culminating in induction of pathogen defense. The soluble cytoplasmic serine/threonine kinase Pti1 is one target of Pto phosphorylation and is involved in the hypersensitive response (HR) reaction. However, a clear role of Pti1 in plant pathogen resistance is uncertain. So far, no Pti1 homologues from monocotyledonous species have been studied. Here we report the identification and molecular analysis of four Pti1-like kinases from maize (ZmPti1a, -b, -c, -d). These kinase genes showed tissue-specific expression and their corresponding proteins were targeted to different cellular compartments. Sequence similarity, expression pattern and cellular localization of ZmPti1b suggested that this gene is a putative orthologue of Pti1 from tomato. In contrast, ZmPti1a was specifically expressed in pollen and sequestered to the plasma membrane, evidently owing to N-terminal modification by myristoylation and/or S-acylation. The ZmPti1a:GFP fusion protein was not evenly distributed at the pollen plasma membrane but accumulated as an annulus-like structure which co-localized with callose (1,3-beta-glucan) deposition. In addition, co-localization of ZmPti1a and callose was observed during stages of pollen mitosis I and pollen tube germination. Maize plants in which ZmPti1a expression was silenced by RNA interference (RNAi) produced pollen with decreased competitive ability. Hence, our data provide evidence that ZmPti1a plays an important part in a signalling pathway that accelerates pollen performance and male fitness. ZmPti1a from maize is involved in pollen-specific processes during the progamic phase of reproduction, probably in crucial signalling processes associated with regions of callose deposition. Pollen

Evolutionary history of callose synthases in terrestrial plants with emphasis on proteins involved in male gametophyte development.

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Lenka Záveská Drábková

Full Text Available Callose is a plant-specific polysaccharide (β-1,3-glucan playing an important role in angiosperms in many developmental processes and responses to biotic and abiotic stresses. Callose is synthesised at the plasma membrane of plant cells by callose synthase (CalS and, among others, represents the main polysaccharide in the callose wall surrounding the tetrads of developing microspores and in the growing pollen tube wall. CalS proteins involvement in spore development is a plesiomorphic feature of terrestrial plants, but very little is known about their evolutionary origin and relationships amongst the members of this protein family. We performed thorough comparative analyses of callose synthase family proteins from major plant lineages to determine their evolutionary history across the plant kingdom. A total of 1211 candidate CalS sequences were identified and compared amongst diverse taxonomic groups of plants, from bryophytes to angiosperms. Phylogenetic analyses identified six main clades of CalS proteins and suggested duplications during the evolution of specialised functions. Twelve family members had previously been identified in Arabidopsis thaliana. We focused on five CalS subfamilies directly linked to pollen function and found that proteins expressed in pollen evolved twice. CalS9/10 and CalS11/12 formed well-defined clades, whereas pollen-specific CalS5 was found within subfamilies that mostly did not express in mature pollen vegetative cell, although were found in sperm cells. Expression of five out of seven mature pollen-expressed CalS genes was affected by mutations in bzip transcription factors. Only three subfamilies, CalS5, CalS10, and CalS11, however, formed monophyletic, mostly conserved clades. The pairs CalS9/CalS10, CalS11/CalS12 and CalS3 may have diverged after angiosperms diversified from lycophytes and bryophytes. Our analysis of fully sequenced plant proteins identified new evolutionary lineages of callose synthase

Why size matters: differences in brain volume account for apparent sex differences in callosal anatomy: the sexual dimorphism of the corpus callosum.

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Luders, Eileen; Toga, Arthur W; Thompson, Paul M

2014-01-01

Numerous studies have demonstrated a sexual dimorphism of the human corpus callosum. However, the question remains if sex differences in brain size, which typically is larger in men than in women, or biological sex per se account for the apparent sex differences in callosal morphology. Comparing callosal dimensions between men and women matched for overall brain size may clarify the true contribution of biological sex, as any observed group difference should indicate pure sex effects. We thus examined callosal morphology in 24 male and 24 female brains carefully matched for overall size. In addition, we selected 24 extremely large male brains and 24 extremely small female brains to explore if observed sex effects might vary depending on the degree to which male and female groups differed in brain size. Using the individual T1-weighted brain images (n=96), we delineated the corpus callosum at midline and applied a well-validated surface-based mesh-modeling approach to compare callosal thickness at 100 equidistant points between groups determined by brain size and sex. The corpus callosum was always thicker in men than in women. However, this callosal sex difference was strongly determined by the cerebral sex difference overall. That is, the larger the discrepancy in brain size between men and women, the more pronounced the sex difference in callosal thickness, with hardly any callosal differences remaining between brain-size matched men and women. Altogether, these findings suggest that individual differences in brain size account for apparent sex differences in the anatomy of the corpus callosum. © 2013.

Herbivore-induced callose deposition on the sieve plates of rice: an important mechanism for host resistance.

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Hao, Peiying; Liu, Caixiang; Wang, Yuanyuan; Chen, Rongzhi; Tang, Ming; Du, Bo; Zhu, Lili; He, Guangcun

2008-04-01

The brown planthopper (Nilaparvata lugens Stål; BPH) is a specialist herbivore on rice (Oryza sativa) that ingests phloem sap from the plant through its stylet mouthparts. Electronic penetration graphs revealed that BPH insects spent more time wandering over plants carrying the resistance genes Bph14 and Bph15, but less time ingesting phloem than they did on susceptible plants. They also showed that their feeding was frequently interrupted. Tests with [(14)C]sucrose showed that insects ingested much less phloem sap from the resistant than the susceptible plants. BPH feeding up-regulated callose synthase genes and induced callose deposition in the sieve tubes at the point where the stylet was inserted. The compact callose remained intact in the resistant plants, but genes encoding beta-1,3-glucanases were activated, causing unplugging of the sieve tube occlusions in susceptible plants. Continuing ingestion led to a remarkable reduction in the susceptible plants' sucrose content and activation of the RAmy3D gene, leading to starch hydrolysis and ultimately carbohydrate deprivation in the plants. Our results demonstrate that BPH feeding induces the deposition of callose on sieve plates in rice and that this is an important defense mechanism that prevents insects from ingesting phloem sap. In response, however, the BPH can unplug sieve tube occlusions by activating beta-1,3-glucanase genes in rice plants.

Generalized epilepsy syndromes and callosal thickness: Differential effects between patients with juvenile myoclonic epilepsy and those with generalized tonic-clonic seizures alone.

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Anastasopoulou, Stavroula; Kurth, Florian; Luders, Eileen; Savic, Ivanka

2017-01-01

The definition of two well-studied genetic generalized epilepsy syndromes (GGE) - juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) - suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. We studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. Significant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. The present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME. Copyright © 2016 Elsevier B.V. All rights reserved.

Research Project Evaluation-Learnings from the PATHWAYS Project Experience.

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Galas, Aleksander; Pilat, Aleksandra; Leonardi, Matilde; Tobiasz-Adamczyk, Beata

2018-05-25

Every research project faces challenges regarding how to achieve its goals in a timely and effective manner. The purpose of this paper is to present a project evaluation methodology gathered during the implementation of the Participation to Healthy Workplaces and Inclusive Strategies in the Work Sector (the EU PATHWAYS Project). The PATHWAYS project involved multiple countries and multi-cultural aspects of re/integrating chronically ill patients into labor markets in different countries. This paper describes key project's evaluation issues including: (1) purposes, (2) advisability, (3) tools, (4) implementation, and (5) possible benefits and presents the advantages of a continuous monitoring. Project evaluation tool to assess structure and resources, process, management and communication, achievements, and outcomes. The project used a mixed evaluation approach and included Strengths (S), Weaknesses (W), Opportunities (O), and Threats (SWOT) analysis. A methodology for longitudinal EU projects' evaluation is described. The evaluation process allowed to highlight strengths and weaknesses and highlighted good coordination and communication between project partners as well as some key issues such as: the need for a shared glossary covering areas investigated by the project, problematic issues related to the involvement of stakeholders from outside the project, and issues with timing. Numerical SWOT analysis showed improvement in project performance over time. The proportion of participating project partners in the evaluation varied from 100% to 83.3%. There is a need for the implementation of a structured evaluation process in multidisciplinary projects involving different stakeholders in diverse socio-environmental and political conditions. Based on the PATHWAYS experience, a clear monitoring methodology is suggested as essential in every multidisciplinary research projects.

The PTI1-like kinase ZmPti1a from maize (Zea mays L. co-localizes with callose at the plasma membrane of pollen and facilitates a competitive advantage to the male gametophyte

Directory of Open Access Journals (Sweden)

Wienand Udo

2006-10-01

Full Text Available Abstract Background The tomato kinase Pto confers resistance to bacterial speck disease caused by Pseudomonas syringae pv. tomato in a gene for gene manner. Upon recognition of specific avirulence factors the Pto kinase activates multiple signal transduction pathways culminating in induction of pathogen defense. The soluble cytoplasmic serine/threonine kinase Pti1 is one target of Pto phosphorylation and is involved in the hypersensitive response (HR reaction. However, a clear role of Pti1 in plant pathogen resistance is uncertain. So far, no Pti1 homologues from monocotyledonous species have been studied. Results Here we report the identification and molecular analysis of four Pti1-like kinases from maize (ZmPti1a, -b, -c, -d. These kinase genes showed tissue-specific expression and their corresponding proteins were targeted to different cellular compartments. Sequence similarity, expression pattern and cellular localization of ZmPti1b suggested that this gene is a putative orthologue of Pti1 from tomato. In contrast, ZmPti1a was specifically expressed in pollen and sequestered to the plasma membrane, evidently owing to N-terminal modification by myristoylation and/or S-acylation. The ZmPti1a:GFP fusion protein was not evenly distributed at the pollen plasma membrane but accumulated as an annulus-like structure which co-localized with callose (1,3-β-glucan deposition. In addition, co-localization of ZmPti1a and callose was observed during stages of pollen mitosis I and pollen tube germination. Maize plants in which ZmPti1a expression was silenced by RNA interference (RNAi produced pollen with decreased competitive ability. Hence, our data provide evidence that ZmPti1a plays an important part in a signalling pathway that accelerates pollen performance and male fitness. Conclusion ZmPti1a from maize is involved in pollen-specific processes during the progamic phase of reproduction, probably in crucial signalling processes associated with regions

Research Project Evaluation—Learnings from the PATHWAYS Project Experience

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Aleksander Galas

2018-05-01

Full Text Available Background: Every research project faces challenges regarding how to achieve its goals in a timely and effective manner. The purpose of this paper is to present a project evaluation methodology gathered during the implementation of the Participation to Healthy Workplaces and Inclusive Strategies in the Work Sector (the EU PATHWAYS Project. The PATHWAYS project involved multiple countries and multi-cultural aspects of re/integrating chronically ill patients into labor markets in different countries. This paper describes key project’s evaluation issues including: (1 purposes, (2 advisability, (3 tools, (4 implementation, and (5 possible benefits and presents the advantages of a continuous monitoring. Methods: Project evaluation tool to assess structure and resources, process, management and communication, achievements, and outcomes. The project used a mixed evaluation approach and included Strengths (S, Weaknesses (W, Opportunities (O, and Threats (SWOT analysis. Results: A methodology for longitudinal EU projects’ evaluation is described. The evaluation process allowed to highlight strengths and weaknesses and highlighted good coordination and communication between project partners as well as some key issues such as: the need for a shared glossary covering areas investigated by the project, problematic issues related to the involvement of stakeholders from outside the project, and issues with timing. Numerical SWOT analysis showed improvement in project performance over time. The proportion of participating project partners in the evaluation varied from 100% to 83.3%. Conclusions: There is a need for the implementation of a structured evaluation process in multidisciplinary projects involving different stakeholders in diverse socio-environmental and political conditions. Based on the PATHWAYS experience, a clear monitoring methodology is suggested as essential in every multidisciplinary research projects.

Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex.

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Fame, Ryann M; Dehay, Colette; Kennedy, Henry; Macklis, Jeffrey D

2017-03-01

Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex

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Emily K. Stephens

2018-01-01

Full Text Available Serotonin (5-HT selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current, or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs. However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation in commissural/callosal (COM projection neurons, a subpopulation of pyramidal neurons that exhibits 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%, rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances gated by 2A receptors. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50%, when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a non-specific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third

Effects of tissue-preparation-induced callose synthesis on estimates of plasmodesma size exclusion limits.

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Radford, J E; White, R G

2001-01-01

Plasmodesmata are often characterised by their size exclusion limit (SEL), which is the molecular weight of the largest dye, introduced by microinjection, that will move from cell to cell. In this study, we investigated whether commonly used techniques for isolation and manipulation of tissues, and microinjection of fluorescent dyes, affected the SEL, and whether any such effects could be ameliorated by inhibiting callose deposition. We examined young root epidermal cells of Arabidopsis thaliana and staminal hair cells of Tradescantia virginiana, two tissues often used in experiments on symplastic transport. Transport in root tips dissected from the main plant body and in stamen hairs removed from the base of the stamen filament was compared with transport in undissected roots and stamen hairs attached to the base of the filament, respectively. Tissues were microinjected with fluorescent dyes (457 Da to > 3 kDa) with or without prior incubation in the callose deposition inhibitors 2-deoxy-D-glucose or aniline blue fluorochrome. In both tissues, dissection reduced the SEL, which was largely prevented by prior incubation in 2-deoxy-D-glucose but not by incubation in aniline blue fluorochrome. Thus, standard methods for tissue preparation can cause sufficient callose deposition to reduce cell-to-cell transport, and this needs to be considered in studies employing microinjection. Introduction of the dyes by pressure injection rather than iontophoresis decreased the SEL in A. thaliana but increased it in T. virginiana, showing that these two injection techniques do not necessarily give identical results and that plasmodesmata in different tissues may respond differently to similar experimental procedures.

Callosal tracts and patterns of hemispheric dominance: a combined fMRI and DTI study.

Science.gov (United States)

Häberling, Isabelle S; Badzakova-Trajkov, Gjurgjica; Corballis, Michael C

2011-01-15

Left-hemispheric dominance for language and right-hemispheric dominance for spatial processing are distinctive characteristics of the human brain. However, variations of these hemispheric asymmetries have been observed, with a minority showing crowding of both functions to the same hemisphere or even a mirror reversal of the typical lateralization pattern. Here, we used diffusion tensor imaging and functional magnetic imaging to investigate the role of the corpus callosum in participants with atypical hemispheric dominance. The corpus callosum was segmented according to the projection site of the underlying fibre tracts. Analyses of the microstructure of the identified callosal segments revealed that atypical hemispheric dominance for language was associated with high anisotropic diffusion through the corpus callosum as a whole. This effect was most evident in participants with crowding of both functions to the right. The enhanced anisotropic diffusion in atypical hemispheric dominance implies that in these individuals the two hemispheres are more heavily interconnected. Copyright © 2010 Elsevier Inc. All rights reserved.

Deafferentation-Induced Plasticity of Visual Callosal Connections: Predicting Critical Periods and Analyzing Cortical Abnormalities Using Diffusion Tensor Imaging

Directory of Open Access Journals (Sweden)

Jaime F. Olavarria

2012-01-01

Full Text Available Callosal connections form elaborate patterns that bear close association with striate and extrastriate visual areas. Although it is known that retinal input is required for normal callosal development, there is little information regarding the period during which the retina is critically needed and whether this period correlates with the same developmental stage across species. Here we review the timing of this critical period, identified in rodents and ferrets by the effects that timed enucleations have on mature callosal connections, and compare it to other developmental milestones in these species. Subsequently, we compare these events to diffusion tensor imaging (DTI measurements of water diffusion anisotropy within developing cerebral cortex. We observed that the relationship between the timing of the critical period and the DTI-characterized developmental trajectory is strikingly similar in rodents and ferrets, which opens the possibility of using cortical DTI trajectories for predicting the critical period in species, such as humans, in which this period likely occurs prenatally. Last, we discuss the potential of utilizing DTI to distinguish normal from abnormal cerebral cortical development, both within the context of aberrant connectivity induced by early retinal deafferentation, and more generally as a potential tool for detecting abnormalities associated with neurodevelopmental disorders.

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance.

Science.gov (United States)

Innocenti, Giorgio M; Dyrby, Tim B; Andersen, Kasper Winther; Rouiller, Eric M; Caminiti, Roberto

2017-06-01

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Impact of Feet Callosities, Arm Posture, and Usage of Electrolyte Wipes on Body Composition by Bioelectrical Impedance Analysis in Morbidly Obese Adults.

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Roekenes, Jessica; Strømmen, Magnus; Kulseng, Bård; Martins, Catia

2015-01-01

This study evaluated the impact of feet callosities, arm posture, and use of electrolyte wipes on body composition measurements by bioelectrical impedance analysis (BIA) in morbidly obese adults. 36 morbidly obese patients (13 males, aged 28-70 years, BMI 41.6 ± 4.3 kg/m2) with moderate/severe feet callosities participated in this study. Body composition (percent body fat (%BF)) was measured while fasting using multi-frequency BIA (InBody 720®), before and after removal of callosities, with and without InBody® electrolyte wipes and custom-built auxiliary pads (to assess arm posture impact). Results from BIA were compared to air displacement plethysmography (ADP, BodPod®). Median %BF was significantly higher with auxiliary pads than without (50.1 (interquartile range 8.2) vs. 49.3 (interquartile range 9.1); p interquartile range 9.1) vs. 50.0 (interquartile range 7.9); NS) or use of wipes (49.6 (interquartile range 8.5) vs. 49.3 (interquartile range 9.1); NS). No differences in %BF were found between BIA and ADP (49.1 (IQR: 8.9) vs. 49.3 (IQR: 9.1); NS). Arm posture has a significant impact on %BF assessed by BIA, contrary to the presence of feet callosities and use of electrolyte wipes. Arm posture standardization during BIA for body composition assessment is, therefore, recommended. © 2015 S. Karger GmbH, Freiburg.

Selective elimination of intracortically projecting neurons of the rat neocortex by prenatal x-irradiation

International Nuclear Information System (INIS)

Jensen, K.F.

1981-01-01

The development of new racing methods has suggested that there are species differences in the extent of the contribution of the different layers of the neocortex to the callosal projection. The present investigation has utilized prenatal x-irradiation to selectively eliminate the late forming neurons of the supragranular layers of the rat neocortex. The reduction in the neuronal population of the supragranular layers closely parallels the reduction in the corpus callosum. These results indicate that the primary source of neurons of the callosal projection, are the late forming neurons of the supragranular layers. Thus, the current results suggest that low dose prenatal x-irradiation may be used to evaluate important developmental events in the formation of neocortical circuitry

Hexanoic Acid Treatment Prevents Systemic MNSV Movement in Cucumis melo Plants by Priming Callose Deposition Correlating SA and OPDA Accumulation

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Emma Fernández-Crespo

2017-10-01

Full Text Available Unlike fungal and bacterial diseases, no direct method is available to control viral diseases. The use of resistance-inducing compounds can be an alternative strategy for plant viruses. Here we studied the basal response of melon to Melon necrotic spot virus (MNSV and demonstrated the efficacy of hexanoic acid (Hx priming, which prevents the virus from systemically spreading. We analysed callose deposition and the hormonal profile and gene expression at the whole plant level. This allowed us to determine hormonal homeostasis in the melon roots, cotyledons, hypocotyls, stems and leaves involved in basal and hexanoic acid-induced resistance (Hx-IR to MNSV. Our data indicate important roles of salicylic acid (SA, 12-oxo-phytodienoic acid (OPDA, jasmonic-isoleucine, and ferulic acid in both responses to MNSV. The hormonal and metabolites balance, depending on the time and location associated with basal and Hx-IR, demonstrated the reprogramming of plant metabolism in MNSV-inoculated plants. The treatment with both SA and OPDA prior to virus infection significantly reduced MNSV systemic movement by inducing callose deposition. This demonstrates their relevance in Hx-IR against MNSV and a high correlation with callose deposition. Our data also provide valuable evidence to unravel priming mechanisms by natural compounds.

Characterization and partial purification of beta-1,3-D-glucan (callose) synthase from barley (Hordeum vulgare) leaves

DEFF Research Database (Denmark)

Pedersen, L.H.; Jacobsen, S.; Hejgaard, J.

1993-01-01

The plasma membrane bound beta-1,3-D-glucan (callose) synthase. assumed to be involved in the resistance to the powdery mildew fungus (Erysiphe graminis f.sp. hordei), was partially purified from a microsomal fraction of green barley leaves (Hordeum vulgare L.). Plasma membranes were enriched...

Callosal hyperintensities and gait speed gain from two types of mobility interventions in older adults.

Science.gov (United States)

Nadkarni, Neelesh K; Perera, Subashan; Studenski, Stephanie A; Rosano, Caterina; Aizenstein, Howard J; VanSwearingen, Jessie M

2015-06-01

To assess whether the volume of callosal hyperintensities in the genu and splenium of older adults with mobility impairment is differentially associated with the degree of gain in gait speed after 2 types of gait interventions. Single-blind randomized controlled trial of 2 types of gait exercises in older adults. Research center in an academic institution. Ambulatory adults (N=44) aged ≥65 years with a slow and variable gait. Twelve-week physical therapist-guided trial of a conventional walking, endurance, balance, and strength (WEBS) intervention (n=20) versus a timing and coordination of gait (TC) intervention (n=22). Gain in gait speed after the intervention and its relation to callosal hyperintensities in the genu and splenium of the corpus callosum. Gait speed improved in both the WEBS group (mean change, 0.16m/s) and the TC group (mean change, 0.21m/s; both PMobility impaired older adults with genual hyperintensities may benefit from a rehabilitation program focused on motor skill learning rather than on strength and endurance training. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Asymmetrical interhemispheric connections develop in cat visual cortex after early unilateral convergent strabismus: Anatomy, physiology and mechanisms

Directory of Open Access Journals (Sweden)

Emmanuel eBui Quoc

2012-01-01

Full Text Available In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When the latter is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, such data are sparse and incomplete. Thus, little is known about the consequences of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non deviated eye. Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute in succession to the development of the callosal maps in visual cortex.

Community-researcher liaisons: the Pathways to Resilience Project ...

African Journals Online (AJOL)

The Pathways to Resilience Project is an ongoing, community-based participatory research (CBPR) project. Its express focus is the exploration of how at-risk youths use formal services and/or informal, naturally occurring resources to beat the odds that have been stacked against them, with the intent of partnering with ...

the Pathways to Resilience Project Advisory Panel

African Journals Online (AJOL)

the South African Pathways to Resilience Project, between 2008 and the present, in order to ... vice versa, and divergent objectives (e.g. building community infrastructure versus ... inadequate time and resources and associated risks. A review ...

Tocopherol deficiency reduces sucrose export from salt-stressed potato leaves independently of oxidative stress and symplastic obstruction by callose

Science.gov (United States)

Asensi-Fabado, María Amparo; Ammon, Alexandra; Sonnewald, Uwe; Munné-Bosch, Sergi; Voll, Lars M.

2015-01-01

Tocopherol cyclase, encoded by the gene SUCROSE EXPORT DEFECTIVE1, catalyses the second step in the synthesis of the antioxidant tocopherol. Depletion of SXD1 activity in maize and potato leaves leads to tocopherol deficiency and a ‘sugar export block’ phenotype that comprises massive starch accumulation and obstruction of plasmodesmata in paraveinal tissue by callose. We grew two transgenic StSXD1:RNAi potato lines with severe tocopherol deficiency under moderate light conditions and subjected them to salt stress. After three weeks of salt exposure, we observed a strongly reduced sugar exudation rate and a lack of starch mobilization in leaves of salt-stressed transgenic plants, but not in wild-type plants. However, callose accumulation in the vasculature declined upon salt stress in all genotypes, indicating that callose plugging of plasmodesmata was not the sole cause of the sugar export block phenotype in tocopherol-deficient leaves. Based on comprehensive gene expression analyses, we propose that enhanced responsiveness of SnRK1 target genes in mesophyll cells and altered redox regulation of phloem loading by SUT1 contribute to the attenuation of sucrose export from salt-stressed SXD:RNAi source leaves. Furthermore, we could not find any indication that elevated oxidative stress may have served as a trigger for the salt-induced carbohydrate phenotype of SXD1:RNAi transgenic plants. In leaves of the SXD1:RNAi plants, sodium accumulation was diminished, while proline accumulation and pools of soluble antioxidants were increased. As supported by phytohormone contents, these differences seem to increase longevity and prevent senescence of SXD:RNAi leaves under salt stress. PMID:25428995

Plasmodesmata without callose and calreticulin in higher plants - open channels for fast symplastic transport?

Directory of Open Access Journals (Sweden)

Kirill N. Demchenko

2014-03-01

Full Text Available Plasmodesmata (PD represent membrane-lined channels that link adjacent plant cells across the cell wall. PD of higher plants contain a central tube of endoplasmic reticulum called desmotubule. Membrane and lumen proteins seem to be able to move through the desmotubule, but most transport processes through PD occur through the cytoplasmic annulus (Brunkard et al., 2013. Calreticulin (CRT, a highly conserved Ca2+-binding protein found in all multi-cellular eukaryotes, predominantly located in the ER, was shown to localize to PD, though not all PD accumulate CRT. In nitrogen fixing actinorhizal root nodules of the Australian tree Casuarina glauca, the primary walls of infected cells containing the microsymbiont become lignified upon infection. TEM analysis of these nodules showed that during the differentiation of infected cells, PD connecting infected cells, and connecting infected and adjacent uninfected cells, were reduced in number as well as diameter (Schubert et al., 2013. In contrast with PD connecting young infected cells, and most PD connecting mature infected and adjacent uninfected cells, PD connecting mature infected cells did not accumulate CRT. Furthermore, as shown here, these PD were not associated with callose, and based on their diameter, they probably had lost their desmotubules. We speculate that either this is a slow path to PD degradation, or that the loss of callose accumulation and presumably also desmotubules leads to the PD becoming open channels and improves metabolite exchange between cells.

the Pathways to Resilience Project Advisory Panel

African Journals Online (AJOL)

Its express focus is the exploration of how at-risk youths use formal services ... the South African Pathways to Resilience Project, between 2008 and the present, .... included daily, meaningful interaction with the local youth; and (iii) willingness to be ..... the theory of resilience that Khazimula advocated (see Theron, in press, ...

Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

Energy Technology Data Exchange (ETDEWEB)

Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

2014-04-15

Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

Attention to impact pathways in EISs of large dam projects

International Nuclear Information System (INIS)

Brismar, Anna

2004-01-01

The importance of addressing cumulative environmental impacts in Environmental Impact Statements (EISs) of large development projects is increasingly underlined. However, cumulative impacts are generated through complex impact pathways, involving multiple root causes and lower and higher order effects, interlinked by cause-effect relationships. Consideration to potential impact pathways may thus be difficult without appropriate analytical methods, expertise, and supportive Environmental Impact Assessment guidelines and terms-of-references (TOR). This paper presents the results of an analysis of six EISs prepared for large dam projects between 1994 and 2001. The objective was to analyze if, how, and to what extent potential impact pathways involved in the generation of dam-related cumulative impacts have been addressed in the analyzed material. For this purpose, a theoretical framework was developed, which identifies four key root causes, their potential effects, and associated cause-effect relationships. The analysis revealed various shortcomings. Important imbalances were found in the degree of attention given to effects of different categories. Lower order effects received greater attention than higher order, and the potential effects of reservoir filling were more extensively attended to than those of flow blockage, storage, and regulation. Most importantly, little effort was made to carefully explain the potential impact pathways involved; root causes were often referred to in general terms only, and potential pathways leading up to an anticipated higher order effect or following upon an expected lower order effect were often inadequately addressed or ignored. Probable reasons for the discovered shortcomings are discussed and recommendations are presented for improving the World Bank EIA guidelines for large dam projects

White matter pathways in persistent developmental stuttering: Lessons from tractography.

Science.gov (United States)

Kronfeld-Duenias, Vered; Civier, Oren; Amir, Ofer; Ezrati-Vinacour, Ruth; Ben-Shachar, Michal

2018-03-01

Fluent speech production relies on the coordinated processing of multiple brain regions. This highlights the role of neural pathways that connect distinct brain regions in producing fluent speech. Here, we aim to investigate the role of the white matter pathways in persistent developmental stuttering (PDS), where speech fluency is disrupted. We use diffusion weighted imaging and tractography to compare the white matter properties between adults who do and do not stutter. We compare the diffusion properties along 18 major cerebral white matter pathways. We complement the analysis with an overview of the methodology and a roadmap of the pathways implicated in PDS according to the existing literature. We report differences in the microstructural properties of the anterior callosum, the right inferior longitudinal fasciculus and the right cingulum in people who stutter compared with fluent controls. Persistent developmental stuttering is consistently associated with differences in bilateral distributed networks. We review evidence showing that PDS involves differences in bilateral dorsal fronto-temporal and fronto-parietal pathways, in callosal pathways, in several motor pathways and in basal ganglia connections. This entails an important role for long range white matter pathways in this disorder. Using a wide-lens analysis, we demonstrate differences in additional, right hemispheric pathways, which go beyond the replicable findings in the literature. This suggests that the affected circuits may extend beyond the known language and motor pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Mid-callosal plane determination using preferred directions from diffusion tensor images

Science.gov (United States)

Costa, André L.; Rittner, Letícia; Lotufo, Roberto A.; Appenzeller, Simone

2015-03-01

The corpus callosum is the major brain structure responsible for inter{hemispheric communication between neurons. Many studies seek to relate corpus callosum attributes to patient characteristics, cerebral diseases and psychological disorders. Most of those studies rely on 2D analysis of the corpus callosum in the mid-sagittal plane. However, it is common to find conflicting results among studies, once many ignore methodological issues and define the mid-sagittal plane based on precary or invalid criteria with respect to the corpus callosum. In this work we propose a novel method to determine the mid-callosal plane using the corpus callosum internal preferred diffusion directions obtained from diffusion tensor images. This plane is analogous to the mid-sagittal plane, but intended to serve exclusively as the corpus callosum reference. Our method elucidates the great potential the directional information of the corpus callosum fibers have to indicate its own referential. Results from experiments with five image pairs from distinct subjects, obtained under the same conditions, demonstrate the method effectiveness to find the corpus callosum symmetric axis relative to the axial plane.

Cortical Divergent Projections in Mice Originate from Two Sequentially Generated, Distinct Populations of Excitatory Cortical Neurons with Different Initial Axonal Outgrowth Characteristics.

Science.gov (United States)

Hatanaka, Yumiko; Namikawa, Tomohiro; Yamauchi, Kenta; Kawaguchi, Yasuo

2016-05-01

Excitatory cortical neurons project to various subcortical and intracortical regions, and exhibit diversity in their axonal connections. Although this diversity may develop from primary axons, how many types of axons initially occur remains unknown. Using a sparse-labeling in utero electroporation method, we investigated the axonal outgrowth of these neurons in mice and correlated the data with axonal projections in adults. Examination of lateral cortex neurons labeled during the main period of cortical neurogenesis (E11.5-E15.5) indicated that axonal outgrowth commonly occurs in the intermediate zone. Conversely, the axonal direction varied; neurons labeled before E12.5 and the earliest cortical plate neurons labeled at E12.5 projected laterally, whereas neurons labeled thereafter projected medially. The expression of Ctip2 and Satb2 and the layer destinations of these neurons support the view that lateral and medial projection neurons are groups of prospective subcortical and callosal projection neurons, respectively. Consistently, birthdating experiments demonstrated that presumptive lateral projection neurons were generated earlier than medial projection neurons, even within the same layer. These results suggest that the divergent axonal connections of excitatory cortical neurons begin from two types of primary axons, which originate from two sequentially generated distinct subpopulations: early-born lateral (subcortical) and later-born medial (callosal) projection neuron groups. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nurse Educator Pathway Project: a competency-based intersectoral curriculum.

Science.gov (United States)

Young, Lynne; Frost, Linda J; Bigl, Julie; Clauson, Marion; McRae, Cora; Scarborough, Kathy S; Murphy, Sue; Jillings, Carol; Gillespie, Frank

2010-01-01

In this paper, we begin by providing an overview of the Educator Pathway Project (EPP), an education infrastructure that was developed in response to emerging critical nursing workplace issues, and the related demand for enhanced workplace education. We then describe the EPP competency-based curriculum designed to prepare nurses as preceptors, mentors, and educators to lead learning with diverse learner groups. This competency-based curriculum was developed through a collaboration of nurse leaders across practice, academic, and union sectors and drew from a widely embraced curriculum development model (Iwasiw, Goldenberg, & Andrusyzyn, 2005). The goal of the curriculum was to prepare nurses through a four-level career pathway model that contextualized practice and education theory to various education-related roles and levels of experience within the practice setting. Over 1,100 nurses participated in this innovative intersectoral nursing initiative.

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

DEFF Research Database (Denmark)

Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

2017-01-01

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...... diameters and conduction distance are monkey and, by extrapolation,

Columbia River pathway report: phase I of the Hanford Environmental Dose Reconstruction Project

Energy Technology Data Exchange (ETDEWEB)

1991-07-01

This report summarizes the river-pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project is estimating radiation doses that could have been received by the public from the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the river-pathway dose reconstruction effort sought to determine whether dose estimates could be calculated for populations in the area from above the Hanford Site at Priest Rapids Dam to below the site at McNary Dam from January 1964 to December 1966. Of the potential sources of radionuclides from the river, fish consumption was the most important. Doses from drinking water were lower at Pasco than at Richland and lower at Kennewick than at Pasco. The median values of preliminary dose estimates calculated by HEDR are similar to independent, previously published estimates of average doses to Richland residents. Later phases of the HEDR Project will address dose estimates for periods other than 1964--1966 and for populations downstream of McNary Dam. 17 refs., 19 figs., 1 tab.

Pathway to Graduation: A Pilot Reading Project for Middle School Students during the Summer Months

Science.gov (United States)

Hilsmier, Amanda Strong; Wood, Patricia F.; Wirt, Susan; McTamney, Diane; Malone, Mary Beth; Milstead, Becky

2014-01-01

The purpose of this article is to outline the implementation of a summer reading project targeted at middle school students with identified reading deficits and behavioral concerns called Pathway to Graduation (PTG). The project was a collaborative process between a school district, local university, and department of mental health. The students…

Mechanisms of callose deposition in rice regulated by exogenous abscisic acid and its involvement in rice resistance to Nilaparvata lugens Stål (Hemiptera: Delphacidae).

Science.gov (United States)

Liu, Jinglan; Du, Haitao; Ding, Xu; Zhou, Yaodong; Xie, Pengfei; Wu, Jincai

2017-12-01

Callose is a plant cell wall polysaccharide controlled by β-1,3-glucanase and synthase. Abscisic acid (ABA) is an important plant hormone. Exogenous ABA promotes rice resistance to pests. Whether exogenous ABA could reduce the decline in rice yield after brown planthopper (Nilaparvata lugens Stål; BPH) feeding is an important question, however, the mechanisms behind rice resistance induced by ABA remain obscure. Electronic penetration graph (EPG) recording indicated a significant increase in rice resistance to BPH, and the number of BPH eggs decreased significantly upon application of exogenous ABA. As the concentration of ABA increased, the reduction in rice yield decreased significantly after BPH feeding. Further studies showed that β-1,3-glucanase activity was significantly lower, but synthase activity was higher after ABA treatment than in controls. Our results demonstrated that exogenous ABA suppressed β-1,3-glucanase and induced synthase activity, and promoted callose deposition. This is an important defense mechanism that prevents BPH from ingesting phloem sap. These studies provide support for an insect-resistance mechanism after ABA treatment and provide a reference for the integrated management of other piercing-sucking pests. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Building integrated pathways to independence for diverse biomedical researchers: Project Pathways, the BUILD program at Xavier University of Louisiana.

Science.gov (United States)

Foroozesh, Maryam; Giguette, Marguerite; Morgan, Kathleen; Johanson, Kelly; D'Amour, Gene; Coston, Tiera; Wilkins-Green, Clair

2017-01-01

Xavier University of Louisiana is a historically Black and Catholic university that is nationally recognized for its science, technology, engineering and mathematics (STEM) curricula. Approximately 73% of Xavier's students are African American, and about 77% major in the biomedical sciences. Xavier is a national leader in the number of STEM majors who go on to receive M.D. degrees and Ph.D. degrees in science and engineering. Despite Xavier's advances in this area, African Americans still earn about 7.5% of the Bachelor's degrees, less than 8% of the Master's degrees, and less than 5% of the doctoral degrees conferred in STEM disciplines in the United States. Additionally, although many well-prepared, highly-motivated students are attracted by Xavier's reputation in the sciences, many of these students, though bright and capable, come from underperforming public school systems and receive substandard preparation in STEM disciplines. The purpose of this article is to describe how Xavier works to overcome unequal education backgrounds and socioeconomic challenges to develop student talent through expanding biomedical training opportunities and build on an established reputation in science education. The National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS)-funded BUILD (Building Infrastructure Leading to Diversity) Program at Xavier University of Louisiana, Project Pathways , is a highly-innovative program designed to broaden the career interests of students early on, and to engage them in activities that entice them to continue their education towards biomedical research careers. Project strategies involve a transformation of Xavier's academic and non-academic programs through the redesign, supplementation and integration of academic advising, tutoring, career services, personal counseling, undergraduate research training, faculty research mentoring, and development of new biomedical and research skills courses. The Program also

Associations between mobility, cognition and callosal integrity in people with parkinsonism

Directory of Open Access Journals (Sweden)

Brett W. Fling

2016-01-01

Full Text Available Falls in people with parkinsonism are likely related to both motor and cognitive impairments. In addition to idiopathic Parkinson's disease (PD, some older adults have lower body parkinsonism (a frontal gait disorder, characterized by impaired lower extremity balance and gait as well as cognition, but without tremor or rigidity. Neuroimaging during virtual gait suggests that interhemispheric, prefrontal cortex communication may be involved in locomotion, but contributions of neuroanatomy connecting these regions to objective measures of gait in people with parkinsonism remains unknown. Our objectives were to compare the integrity of fiber tracts connecting prefrontal and sensorimotor cortical regions via the corpus callosum in people with two types of parkinsonism and an age-matched control group and to relate integrity of these callosal fibers with clinical and objective measures of mobility and cognition. We recruited 10 patients with frontal gait disorders, 10 patients with idiopathic PD and 10 age-matched healthy control participants. Participants underwent cognitive and mobility testing as well as diffusion weighted magnetic resonance imaging to quantify white matter microstructural integrity of interhemispheric fiber tracts. People with frontal gait disorders displayed poorer cognitive performance and a slower, wider-based gait compared to subjects with PD and age-matched control subjects. Despite a widespread network of reduced white matter integrity in people with frontal gait disorders, gait and cognitive deficits were solely related to interhemispheric circuitry employing the genu of the corpus callosum. Current results highlight the importance of prefrontal interhemispheric communication for lower extremity control in neurological patients with cognitive dysfunction.

Aims and first assessments of the French hydrogen pathways project HyFrance3

Energy Technology Data Exchange (ETDEWEB)

Le Duigou, Alain [CEA/DEN/DANS/I-Tese, Gif-sur-Yvette (France); Quemere, Marie-Marguerite [EDF R et D, Moret sur Loing (France). Dept. EPI; Marion, Pierre [IFP, Rueil Malmaison (FR)] (and others)

2010-07-01

The HyFrance Group was originally formed in France to support the European project HyWays, by providing (former projects HyFrance1 and HyFrance2) the French data and possible hydrogen pathways according to national specificities. HyFrance3 is a new project that focuses on the economic competitiveness of different steps of the hydrogen chain, from the production to end usage, at the time horizon of 2030 in France. The project is coordinated by CEA with the other partners being: ADEME (co-funding), AFH2, CNRS, IFP, Air Liquide, EdF, GdF Suez, TOTAL, ALPHEA. The project is divided into 4 sub-projects, that address present and future French hydrogen industrial markets for chemical and refinery uses, the analysis of the interplay between wind energy production and storage of hydrogen for different automotive requirements (refuelling stations, BtL plants, H2/NG mix), massive hydrogen storage to balance various offer and demand characteristics, and the supply network (pipeline option competitiveness vs. trucked in supply) to distribute hydrogen in a French region for automotive applications. Technical and economical issues, as well as GHG emissions, are addressed. (orig.)

Transparent national strategies for long-term decarbonization in compliance with the 2 deg. C goal: The Deep Decarbonization Pathways Project

International Nuclear Information System (INIS)

Colombier, Michel; Waisman, Henri

2015-01-01

Fifteen countries among the biggest emitters of greenhouse gases are involved in the Deep Decarbonization Pathways Project (DDPP), which is based on 'country teams' of climate experts. This international project seeks to draw the pathways for a transition toward national decarbonization in compliance with the goal of limiting global warming to 2 deg. C maximum by 2050. These pathways should serve to: a) foresee the economic, technical and behavioral 'ruptures' to be addressed in order to facilitate the transition; b) identify specifically national factors in pathways toward decarbonization; and c) analyze the effects over time of this transition and the sequencing of the measures that might cause them. A preliminary report was released in September 2014, and the final report is scheduled for mid-2015. In support of an international agreement during the Paris Climate Conference, it will focus on the implications of deep decarbonization and the conditions for achieving it

Draft Air Pathway Report: Phase 1 of the Hanford Environmental Dose Reconstruction Project

Energy Technology Data Exchange (ETDEWEB)

1990-07-20

This report summarizes the air pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project, conducted by Battelle staff at the Pacific Northwest Laboratory under the direction of an independent Technical Steering Panel. The HEDR Project is estimating historical radiation doses that could have been received by populations near the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the air-pathway dose reconstruction sought to determine whether dose estimates could be calculated for populations in the 10 counties nearest the Hanford Site from atmospheric releases of iodine-131 from the site from 1944--1947. Phase 1 demonstrated the following: HEDR-calculated source-term estimates of iodine-131 releases to the atmosphere were within 20% of previously published estimates; calculated vegetation concentrations of iodine-131 agree well with previously published measurements; the highest of the Phase 1 preliminary dose estimates to the thyroid are consistent with independent, previously published estimates of doses to maximally exposed individuals; and relatively crude, previously published measurements of thyroid burdens for Hanford workers are in the range of average burdens that the HEDR model estimated for similar reference individuals'' for the period 1944--1947. 4 refs., 10 figs., 9 tabs.

Projecting Drivers of Human Vulnerability under the Shared Socioeconomic Pathways.

Science.gov (United States)

Rohat, Guillaume

2018-03-19

The Shared Socioeconomic Pathways (SSPs) are the new set of alternative futures of societal development that inform global and regional climate change research. They have the potential to foster the integration of socioeconomic scenarios within assessments of future climate-related health impacts. To date, such assessments have primarily superimposed climate scenarios on current socioeconomic conditions only. Until now, the few assessments of future health risks that employed the SSPs have focused on future human exposure-i.e., mainly future population patterns-, neglecting future human vulnerability. This paper first explores the research gaps-mainly linked to the paucity of available projections-that explain such a lack of consideration of human vulnerability under the SSPs. It then highlights the need for projections of socioeconomic variables covering the wide range of determinants of human vulnerability, available at relevant spatial and temporal scales, and accounting for local specificities through sectoral and regional extended versions of the global SSPs. Finally, this paper presents two innovative methods of obtaining and computing such socioeconomic projections under the SSPs-namely the scenario matching approach and an approach based on experts' elicitation and correlation analyses-and applies them to the case of Europe. They offer a variety of possibilities for practical application, producing projections at sub-national level of various drivers of human vulnerability such as demographic and social characteristics, urbanization, state of the environment, infrastructure, health status, and living arrangements. Both the innovative approaches presented in this paper and existing methods-such as the spatial disaggregation of existing projections and the use of sectoral models-show great potential to enhance the availability of relevant projections of determinants of human vulnerability. Assessments of future climate-related health impacts should thus rely

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Science.gov (United States)

Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

2016-01-01

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

Retroambiguus projections to the cutaneus trunci motoneurons may form a pathway in the central control of mating

NARCIS (Netherlands)

Gerrits, Peter O.; Vodde, Chris; Holstege, Gert

Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system

Virginia Solar Pathways Project Final Technical Report

Energy Technology Data Exchange (ETDEWEB)

Bond, Katharine; Cosby, Sarah

2018-03-28

This Report provides a technical review of the final results of a funding award to Virginia Electric and Power Company (Dominion Energy Virginia (DEV) or the Company) for a project under the U.S. Department of Energy’s Solar Energy Technologies Office. The three-year project was formally known as the Virginia Solar Pathways Project (VSPP or the Project). The purpose of the VSPP was to develop a collaborative utility-administered solar strategy (Solar Strategy) for DEV’s service territory in the Commonwealth that could serve as a replicable model for other states with similar policy environments. The U.S. Department of Energy (DOE) funding award enabled DEV to take a focused approach to developing the Solar Strategy for its Virginia service territory. The structure and funding from the DOE award also facilitated valuable input from a formal stakeholder team convened to serve as advisors (Advisory Team) to the VSPP and contribute their perspectives and expertise to both the analysis and strategy development aspects of the Project. The development of the Solar Strategy involved three main goals: • Establish a policy and program framework that would integrate existing solar programs with new options appropriate for the Commonwealth’s policy environment and broader economic development objectives; • Promote wider deployment of solar within a low retail electric rate environment; and • Serve as a sustainable, utility-administered solar model that could be replicated in other states with similar policy environments, including, but not limited to, the entire Southeast region. In support of the VSPP goals, the Project Team commissioned four studies to support the Solar Strategy development. Two studies, completed by Navigant Consulting, focused on the integration of solar into the electric grid. The first solar integration study focused on integration of solar into the distribution grid where the utility system directly connects to and serves end-use customers

The “CROMa” Project: A Care Pathway for Clinical Management of Patients with Bisphosphonate Exposure

Directory of Open Access Journals (Sweden)

Mauro Capocci

2014-01-01

Full Text Available Aim. To describe 7 years of activity of “CROMa” (Coordination of Research on Osteonecrosis of the Jaws project of “Sapienza” University of Rome. Materials and Methods. A preventive and therapeutic care pathway was created for patients with bisphosphonates (BPs exposure. Demographic, social, behavioural, pharmacological, and clinical variables were registered in a dedicated database. Results. In the project, 502 patients, 403 females and 99 males, were observed. Bone pathologies were 79% osteometabolic diseases (OMD and 21% metastatic cancer (CA. Females were 90% in OMD group and 41% in CA. BP administration was 54% oral, 31% IV, and 11% IM; 89% of BPs were amino-BP and 11% non-amino-BP. Consistently with bone pathology (OMD/CA, alendronate appears to be prevalent for OMD (40% relative, while zoledronate was indicated in 92% of CA patients. Out of 502 cases collected, 28 BRONJ were detected: 17 of them were related to IV BP treatment. Preventive oral assessment was required for 50% of CA patients and by 4% of OMD patients. Conclusions. The proposed care pathway protocols for BP exposed patients appeared to be useful to meet treatment and preventive needs, in both oncological and osteometabolic diseases patients. Patients’ and physicians’ prevention awareness can be the starting point of a multilevel prevention system.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

Science.gov (United States)

Lord, J; Willis, S; Eatock, J; Tappenden, P; Trapero-Bertran, M; Miners, A; Crossan, C; Westby, M; Anagnostou, A; Taylor, S; Mavranezouli, I; Wonderling, D; Alderson, P; Ruiz, F

2013-12-01

National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from

Genetic effects in callose content in root apex of inbred resistant and susceptible corn lines to acid soils Efectos genéticos de la formación de calosa en ápices radicales de líneas de maíz resistentes y susceptibles a suelos ácidos

Directory of Open Access Journals (Sweden)

Arcos Alba Lucía

2007-12-01

Full Text Available

The main objective of this work was to identify genetic parameters that are related to callose accumulation using tropical inbreeds corn. Fourteen inbreed lines selected for different levels of tolerance to acid soils were chosen and a diallel among them was generated. The seeds were grown under controlled environmental conditions in a growth chamber and transferred to a nutrient solution at pH 4.3. After 12 hours of 25 µM Al (AlCl3 treatment was applied, callose contents of 1 cm root apex were determined with fluorescence spectrophotometer. Significant differences were found for parents, crosses and parents vs crosses. Average callose content varied from 0.746 to 2.035 (µg PE/cm root apex. Heterosis varied from –21.2% to 276.3%. General combining ability (GCA and specific combining ability (SCA were highly significant indicating that both, additive and non–additive gene effects were important for callose inheritance. SCA and GCA sum of squares accounted for 54% and 46%, respectively of crosses of squares sum. Correlation coefficient between callose content and corn grain yield in the field was negative but not significant (r = –0.38.

Key words: Zea mays; callose; inheritance; diallel; heterosis; acid soils.

El objetivo de este trabajo fue estudiar la herencia de la producción de calosa utilizando líneas endogámicas de maíz. Seleccionando 14 líneas (7 tolerantes y 7 susceptibles a suelos ácidos se formó un dialelo que fue probado en campo y en invernadero. Se determinó el contenido de calosa en los 91 cruzamientos resultantes y los 14 progenitores. Para ello se colocaron las semillas en cámara de crecimiento en condiciones controladas. Después de 4–5 días las plántulas fueron transferidas a cubetas que contenían solución nutritiva con aireación constante. Luego de 48 horas se adicionaron 25 µM de aluminio (AlCl3 a cada una de las cubetas y se mantuvieron por 12 horas. Se cortaron tres ápices radicales de

Automated measurement of the human corpus callosum using MRI

Directory of Open Access Journals (Sweden)

Timothy J Herron

2012-09-01

Full Text Available The corpus callosum includes the majority of fibers that connect the two cortical hemispheres. Studies of cross-sectional callosal morphometry and area have revealed developmental, gender, and hemispheric differences in healthy populations and callosal deficits associated with neurodegenerative disease and brain injury. However, accurate quantification of the callosum using magnetic resonance imaging is complicated by intersubject variability in callosal size, shape, and location and often requires manual outlining of the callosum in order to achieve adequate performance. Here we describe an objective, fully automated protocol that utilizes voxel-based image to quantify the area and thickness both of the entire callosum and of different callosal compartments. We verify the method’s accuracy, reliability, robustness and multisite consistency and make comparisons with manual measurements using public brain-image databases. An analysis of age-related changes in the callosum showed increases in length and reductions in thickness and area with age. A comparison of older subjects with and without mild dementia revealed that reductions in anterior callosal area independently predicted poorer cognitive performance after factoring out Mini-Mental Status Examination scores and normalized whole brain volume. Open-source software implementing the algorithm is available at www.nitrc.org/projects/c8c8.

Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging

International Nuclear Information System (INIS)

Ding, Xiao-Qi; Sun, Yimeng; Illies, Till; Zeumer, Hermann; Fiehler, Jens; Kruse, Bernd; Lanfermann, Heinrich

2009-01-01

Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay. (orig.)

Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease dementia.

Science.gov (United States)

Wang, Pei-Ning; Chou, Kun-Hsien; Chang, Ni-Jung; Lin, Ker-Neng; Chen, Wei-Ta; Lan, Gong-Yau; Lin, Ching-Po; Lirng, Jiing-Feng

2014-04-01

Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single-domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Copyright © 2013 Wiley Periodicals, Inc.

The role of Δ¹-pyrroline-5-carboxylate dehydrogenase in proline degradation

DEFF Research Database (Denmark)

Deuschle, Karen; Funck, Dietmar; Forlani, Giuseppe

2004-01-01

growth. External Pro application caused programmed cell death, with callose deposition, reactive oxygen species production, and DNA laddering, involving a salicylic acid signal transduction pathway. p5cdh mutants were hypersensitive toward Pro and other molecules producing P5C, such as Arg and Orn. Pro...

In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee.

Science.gov (United States)

Kropf, Jan; Rössler, Wolfgang

2018-01-01

The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.

Future Projection of Droughts over South Korea Using Representative Concentration Pathways (RCPs

Directory of Open Access Journals (Sweden)

Byung Sik Kim

2014-01-01

Full Text Available The Standardized Precipitation Index (SPI, a method widely used to analyze droughts related to climate change, does not consider variables related to temperature and is limited because it cannot consider changes in hydrological balance, such as evapotranspiration from climate change. If we were to consider only the future increase in precipitation from climate change, droughts may decrease. However, because usable water can diminish from an increase in evapotranspiration, it is important to research on projected droughts considering the amount of evapotranspiration along with projecting and evaluating potential droughts considering the impact of climate change. As such, this study evaluated the occurrence of droughts using the Standardized Precipitation Evapotranspiration Index (SPEI as a newly conceptualized drought index that is similar to SPI but includes the temperature variability. We extracted simulated future precipitation and temperature data (2011 - 2099 from the Representative Concentration Pathway (RCP climate change scenario of IPCC AR5 to evaluate the impact of future climate change on the occurrence of droughts of South Korea. We analyzed the ratio of evapotranspiration to precipitation of meteorological observatories nationwide. In addition, we calculated the SPEI related to drought in the process to evaluate the future occurrence of droughts of South Korea. To confirm validity of SPEI results, extreme indices were analyzed. This resulted in the notion that as we go further into the future, the precipitation increases. But because of an increase in evapotranspiration also from a rise in temperature and continued dryness, the severity of droughts is projected to exacerbate.

The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a.

Science.gov (United States)

Cánovas, José; Berndt, F Andrés; Sepúlveda, Hugo; Aguilar, Rodrigo; Veloso, Felipe A; Montecino, Martín; Oliva, Carlos; Maass, Juan C; Sierralta, Jimena; Kukuljan, Manuel

2015-05-13

The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities. Copyright © 2015 the authors 0270-6474/15/357552-13$15.00/0.

In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee.

Directory of Open Access Journals (Sweden)

Jan Kropf

Full Text Available The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN convey olfactory information on ~900 projection neurons (PN in the antennal lobe (AL. To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB. This pathway comprises the medial (m-ALT and the lateral antennal lobe tract (l-ALT. PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.

[Acute disseminated encephalomyelitis following influenza vaccination: report of a case with callosal disconnection syndrome].

Science.gov (United States)

Arai, Motomi; Takagi, Daisuke; Nagao, Ryosuke

2014-01-01

We present a case of callosal disconnection syndrome as a rare manifestation of acute disseminated encephalomyelitis (ADEM). A dextral 48-year-old Japanese woman received trivalent inactivated influenza vaccine in mid-November 2011. Twenty days later, she was found to be in a daze. Subsequently, she developed abnormal behavior and gait disturbance, and she was disoriented regarding time and place. Nystagmus and abnormal ocular movements were absent. Upper limb power was normal, whereas her lower limbs were mildly weak. Tendon reflexes were normally evoked without pathological reflexes. There was no sensory impairment. Serum CRP levels were slightly elevated; other routine laboratory tests, thyroid functions, and vitamin B1 levels were within the normal range. Cerebrospinal fluid examination revealed that it was acellular with a protein level of 54 mg/dl and high myelin basic protein level. Fluid-attenuated inversion recovery MR images revealed a large hyperintense lesion in the corpus callosum, but the lower part of the splenium was spared. Flow voids were observed in the pericallosal arteries. She was diagnosed with post-vaccination ADEM and vigorously treated with an intravenous infusion of methylprednisolone (1 g/day for 6 days) and immunoglobulin (1.2 g/kg). Gait disturbance and disorientation rapidly improved; however, tactile anomia, ideomotor apraxia, ideational apraxia, and agraphia of the left hand were present one month after onset. She had no aphasia or alexia.Interestingly, the patient's left unilateral agraphia was more prominent in kana than kanji (an article in Japanese text) for polysyllabic words, whereas she could write kana characters to dictation. Changes in the sequential order of kana characters within a word were observed. These findings were similar to those observed in pure agraphia associated with lesions in the posterior part of the left middle frontal gyrus. Thus, an interhemispheric mechanism is probably involved in the selection and

Glutamate and GABA in vestibulo-sympathetic pathway neurons

Directory of Open Access Journals (Sweden)

Gay R Holstein

2016-02-01

Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

Analysis of culture media screening data by projection to latent pathways: The case of Pichia pastoris X-33.

Science.gov (United States)

Isidro, Inês A; Ferreira, Ana R; Clemente, João J; Cunha, António E; Oliveira, Rui

2016-01-10

Cell culture media formulations contain hundreds of individual components in water solutions which have complex interactions with metabolic pathways. The currently used statistical design methods are empirical and very limited to explore such a large design space. In a previous work we developed a computational method called projection to latent pathways (PLP), which was conceived to maximize covariance between envirome and fluxome data under the constraint of metabolic network elementary flux modes (EFM). More specifically, PLP identifies a minimal set of EFMs (i.e., pathways) with the highest possible correlation with envirome and fluxome measurements. In this paper we extend the concept for the analysis of culture media screening data to investigate how culture medium components up-regulate or down-regulate key metabolic pathways. A Pichia pastoris X-33 strain was cultivated in 26 shake flask experiments with variations in trace elements concentrations and basal medium dilution, based on the standard BSM+PTM1 medium. PLP identified 3 EFMs (growth, maintenance and by-product formation) describing 98.8% of the variance in observed fluxes. Furthermore, PLP presented an overall predictive power comparable to that of PLS regression. Our results show iron and manganese at concentrations close to the PTM1 standard inhibit overall metabolic activity, while the main salts concentration (BSM) affected mainly energy expenditures for cellular maintenance. Copyright © 2015 Elsevier B.V. All rights reserved.

Infarction of the entire corpus callosum as a complication in subarachnoid hemorrhage: A case report

Directory of Open Access Journals (Sweden)

Satoru Takahashi, M.D.

2017-03-01

Full Text Available The corpus callosum is the major commissural pathway connecting the cerebral hemispheres. This pathway receives its blood supply from anterior communicating artery, pericallosal artery, and posterior pericallosal artery. However, in some cases, the entire corpus callosum is supplied by median callosal artery; thus, occlusion of this artery can lead to infarction of the entire corpus callosum. Few reports have described this type of infarction, and no reports after subarachnoid hemorrhage (SAH exist. Here, we report on a 42-year-old female who was diagnosed with SAH after two aneurysms were discovered in bifurcation of left anterior cerebral artery (A1-A2. After successful clipping was performed, the patient was alert and had no neurological deficits; moreover, the computed tomography images that were acquired after the operation showed no evidence of infarction. Nine days after admittance to the hospital, drowsiness and weakness of the left limbs with brain swelling appeared and decompressive hemi-craniectomy was performed. Diagnostic cerebral angiography revealed vasospasms in both anterior and middle cerebral arteries, thus fasudil hydrochloride was administered intra-arterially. While blood flow in all arteries improved, diffusion-weighted magnetic resonance imaging detected infarction along the entire length of the corpus callosum and in the medial region of the right frontal lobe. We believe this infarction was due to secondary ischemia of median callosal artery. This case reminded us of the anatomical variation wherein median callosal artery is the sole blood supply line for the corpus callosum and demonstrated that infarction of the entire corpus callosum is possible.

Extending the Pathway: Building on a National Science Foundation Workforce Development Project for Underserved k-12 Students

Science.gov (United States)

Slattery, W.; Smith, T.

2014-12-01

With new career openings in the geosciences expected and a large number of presently employed geoscientists retiring in the next decade there is a critical need for a new cadre of geoscientists to fill these positions. A project funded by the National Science Foundation titled K-12 Students, Teachers, Parents, Administrators and Higher Education Faculty: Partners Helping Rural Disadvantaged Students Stay on the Pathway to a Geoscience Career involving Wright State University and the Ripley, Lewis, Union, Huntington k-12 school district in Appalachian Ohio took led to dozens of seventh and eighth grade students traveling to Sandy Hook, New Jersey for a one week field experience to study oceanography with staff of the New Jersey Sea Grant Consortium. Teachers, parent chaperones, administrators and university faculty accompanied the students in the field. Teachers worked alongside their students in targeted professional development during the weeklong field experience. During the two academic years of the project, both middle school and high school teachers received professional development in Earth system science so that all students, not just those that were on the summer field experience could receive enhanced science learning. All ninth grade high school students were given the opportunity to take a high school/college dual credit Earth system science course. Community outreach provided widespread knowledge of the project and interest among parents to have their children participate. In addition, ninth grade students raised money themselves to fund a trip to the International Field Studies Forfar Field Station on Andros Island, Bahamas to study a tropical aquatic system. Students who before this project had never traveled outside of Ohio are currently discussing ways that they can continue on the pathway to a geoscience career by applying for internships for the summer between their junior and senior years. These are positive steps towards taking charge of their

Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

Science.gov (United States)

Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

2017-08-16

Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

Science.gov (United States)

Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

2017-10-11

Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

Pathways for Emotions: Specializations in the Amygdalar, Mediodorsal Thalamic, and Posterior Orbitofrontal Network.

Science.gov (United States)

Timbie, Clare; Barbas, Helen

2015-08-26

The primate amygdala projects to posterior orbitofrontal cortex (pOFC) directly and possibly indirectly through a pathway to the magnocellular mediodorsal thalamic nucleus (MDmc), which may convey signals about the significance of stimuli. However, because MDmc receives input from structures in addition to the amygdala and MDmc projects to areas in addition to pOFC, it is unknown whether amygdalar pathways in MDmc innervate pOFC-bound neurons. We addressed this issue using double- or triple-labeling approaches to identify pathways and key cellular and molecular features in rhesus monkeys. We found that amygdalar terminations innervated labeled neurons in MDmc that project to pOFC. Projection neurons in MDmc directed to pOFC included comparatively fewer "core" parvalbumin neurons that project focally to the middle cortical layers and more "matrix" calbindin neurons that project expansively to the upper cortical layers. In addition, a small and hitherto unknown pathway originated from MDmc calretinin neurons and projected to pOFC. Further, whereas projection neurons directed to MDmc and to pOFC were intermingled in the amygdala, none projected to both structures. Larger amygdalar neurons projected to MDmc and expressed the vesicular glutamate transporter 2 (VGLUT2), which is found in highly efficient "driver" pathways. In contrast, smaller amygdalar neurons directed to pOFC expressed VGLUT1 found in modulatory pathways. The indirect pathway from the amygdala to pOFC via MDmc may provide information about the emotional significance of events and, along with a parallel direct pathway, ensures transfer of signals to all layers of pOFC. The amygdala-the brain's center for emotions-is strongly linked with the orbital cortex, a region associated with social interactions. This study provides evidence that a robust pathway from the amygdala reaches neurons in the thalamus that link directly with the orbital cortex, forming a tight tripartite network. The dual pathways from

Columbia River pathway report

International Nuclear Information System (INIS)

1991-07-01

This report summarizes the river-pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project is estimating radiation doses that could have been received by the public from the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the river-pathway dose reconstruction effort sought to determine whether dose estimates could be calculated for populations in the area from above the Hanford Site at Priest Rapids Dam to below the site at McNary Dam from January 1964 to December 1966. Of the potential sources of radionuclides from the river, fish consumption was the most important. Doses from drinking water were lower at Pasco than at Richland and lower at Kennewick than at Pasco. The median values of preliminary dose estimates calculated by HEDR are similar to independent, previously published estimates of average doses to Richland residents. Later phases of the HEDR Project will address dose estimates for periods other than 1964--1966 and for populations downstream of McNary Dam. 17 refs., 19 figs., 1 tab

Regional variation of white matter development in the cat brain revealed by ex vivo diffusion MR tractography.

Science.gov (United States)

Dai, Guangping; Das, Avilash; Hayashi, Emiko; Chen, Qin; Takahashi, Emi

2016-11-01

Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Virginia Solar Pathways Project: Economic Study of Utility-Administered Solar Programs: Soft Costs, Community Solar, and Tax Normalization Considerations

Energy Technology Data Exchange (ETDEWEB)

Reiter, Emerson [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lowder, Travis [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mathur, Shivani [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mercer, Megan [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-06-23

This report presents economic considerations for solar development in support of the Virginia Solar Pathways Project (VSPP), an effort funded by the U.S. Department of Energy (DOE) SunShot Initiative that seeks to develop a collaborative utility-administered solar strategy for the Commonwealth of Virginia. The results presented are intended to be considered alongside the results of other studies conducted under the VSPP that evaluate the impacts of solar energy on the electric distribution, transmission, and generation systems in Virginia.

Different corticostriatal integration in spiny projection neurons from direct and indirect pathways

Directory of Open Access Journals (Sweden)

Edén Flores-Barrera

2010-06-01

Full Text Available The striatum is the principal input structure of the basal ganglia (BG. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs and interneurons. Despite differences in axonal projections, dopamine receptors expression and differences in excitability between MSNs from “direct” and “indirect” BG pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with BAC transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P>0.9, in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA-depletion in 6-hydroxy-dopamine (6-OHDA lesioned animals: a response reduction was seen in SP+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.

The quest for predicting sustained shunt response in normal pressure hydrocephalus: an analysis of the callosal angle's utility.

Science.gov (United States)

Grahnke, Kurt; Jusue-Torres, Ignacio; Szujewski, Caroline; Joyce, Cara; Schneck, Michael; Prabhu, Vikram; Anderson, Douglas

2018-04-30

Diagnosing normal pressure hydrocephalus (NPH) and selecting patients who will experience a sustained benefit from fluid diversion surgery remains challenging. This study seeks to evaluate the association between the callosal angle (CA) and the long-term post-operative response to ventriculoperitoneal shunt (VPS) surgery in a different subgroup population than previously studied to assess its generalizability. We studied 73 patients with idiopathic NPH who underwent VPS surgery and had at least 18 months of follow-up between 2000-2016. We recorded their pre and postoperative symptoms according to the NPH Eide scale and their comorbidities with the Kiefer index. Their CA, as well as Evan's Index, ventricular height, and transependymal signal were measured. Multivariable statistical models were used to determine which factors were associated with postoperative improvement, while controlling for the presence of the NPH triad. Fifty-nine patients (82%) demonstrated a successful response to surgery at their first postoperative follow-up. However, this declined to 54 patients (75%) at one year and 45 (62.5%) patients at their last follow-up. When controlling for the presence of the triad of symptoms, the CA significantly predicted a good, sustained response to surgery; for every degree decrease in the CA, a patient is 4% more likely to experience benefit from surgery. The CA is a useful preoperative prognostic tool for predicting which patients will experience a sustained benefit from surgery. Further studies are required to clarify this disease in the context of old age, comorbidity, and possible concomitant neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Pathways to deep decarbonization - 2015 report

International Nuclear Information System (INIS)

Ribera, Teresa; Colombier, Michel; Waisman, Henri; Bataille, Chris; Pierfederici, Roberta; Sachs, Jeffrey; Schmidt-Traub, Guido; Williams, Jim; Segafredo, Laura; Hamburg Coplan, Jill; Pharabod, Ivan; Oury, Christian

2015-12-01

In September 2015, the Deep Decarbonization Pathways Project published the Executive Summary of the Pathways to Deep Decarbonization: 2015 Synthesis Report. The full 2015 Synthesis Report was launched in Paris on December 3, 2015, at a technical workshop with the Mitigation Action Plans and Scenarios (MAPS) program. The Deep Decarbonization Pathways Project (DDPP) is a collaborative initiative to understand and show how individual countries can transition to a low-carbon economy and how the world can meet the internationally agreed target of limiting the increase in global mean surface temperature to less than 2 degrees Celsius (deg. C). Achieving the 2 deg. C limit will require that global net emissions of greenhouse gases (GHG) approach zero by the second half of the century. In turn, this will require a profound transformation of energy systems by mid-century through steep declines in carbon intensity in all sectors of the economy, a transition we call 'deep decarbonization'

A reliability assessment of constrained spherical deconvolution-based diffusion-weighted magnetic resonance imaging in individuals with chronic stroke.

Science.gov (United States)

Snow, Nicholas J; Peters, Sue; Borich, Michael R; Shirzad, Navid; Auriat, Angela M; Hayward, Kathryn S; Boyd, Lara A

2016-01-15

Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter properties after stroke. Novel work is utilizing constrained spherical deconvolution (CSD) to estimate complex intra-voxel fiber architecture unaccounted for with tensor-based fiber tractography. However, the reliability of CSD-based tractography has not been established in people with chronic stroke. Establishing the reliability of CSD-based DW-MRI in chronic stroke. High-resolution DW-MRI was performed in ten adults with chronic stroke during two separate sessions. Deterministic region of interest-based fiber tractography using CSD was performed by two raters. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract number, and tract volume were extracted from reconstructed fiber pathways in the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). Callosal fiber pathways connecting the primary motor cortices were also evaluated. Inter-rater and test-retest reliability were determined by intra-class correlation coefficients (ICCs). ICCs revealed excellent reliability for FA and ADC in ipsilesional (0.86-1.00; preliability for all metrics in callosal fibers (0.85-1.00; preliable approach to evaluate FA and ADC in major white matter pathways, in chronic stroke. Future work should address the reproducibility and utility of CSD-based metrics of tract number and tract volume. Copyright © 2015 Elsevier B.V. All rights reserved.

Businesses Partner with Schools, Community to Create Alternative Career Pathways

Science.gov (United States)

Overman, Stephenie

2012-01-01

Business, education and community leaders are working together to create alternative career pathways for young people who are not profiting from the four-year college track. The new Pathways to Prosperity Network brings together the Pathways to Prosperity Project at Harvard Graduate School of Education (HGSE), Jobs for the Future (JFF) and six…

Anatomical study of the final common pathway for vocalization in the cat

Science.gov (United States)

Holstege, Gert

1989-01-01

Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway. Hanford Environmental Dose Reconstruction Project

Energy Technology Data Exchange (ETDEWEB)

Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

1992-09-01

This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides.

DESCENDING PATHWAYS AND THE HOPPING RESPONSE IN THE RABBIT

NARCIS (Netherlands)

HOBBELEN, JF; GRAMSBERGEN, A; VANHOF, MW

1992-01-01

Descending pathways were studied in 5 adult rabbits by means of HRP, injected in the cervical spinal cord (in C2 and C3) at the right side. Results indicate the existence of pathways from the contralateral motor cortex, bilateral projections from the red nuclei, from the vestibular nuclei and from

D-[3H]aspartate retrograde labelling of callosal and association neurons of somatosensory areas I and II of cats

International Nuclear Information System (INIS)

Barbaresi, P.; Fabri, M.; Conti, F.; Manzoni, T.

1987-01-01

Experiments were carried out on cats to ascertain whether corticocortical neurons of somatosensory areas I (SI) and II (SII) could be labelled by retrograde axonal transport of D-[ 3 H]aspartate (D-[ 3 H]Asp). This tritiated enantiomer of the amino acid aspartate is (1) taken up selectively by axon terminals of neurons releasing aspartate and/or glutamate as excitatory neurotransmitter, (2) retrogradely transported and accumulated in perikarya, (3) not metabolized, and (4) visualized by autoradiography. A solution of D-[ 3 H]Asp was injected in eight cats in the trunk and forelimb zones of SI (two cats) or in the forelimb zone of SII (six cats). In order to compare the labelling patterns obtained with D-[ 3 H]Asp with those resulting after injection of a nonselective neuronal tracer, horseradish peroxidase (HRP) was delivered mixed with the radioactive tracer in seven of the eight cats. Furthermore, six additional animals received HRP injections in SI (three cats; trunk and forelimb zones) or SII (three cats; forelimb zone). D-[ 3 H]Asp retrograde labelling of perikarya was absent from the ipsilateral thalamus of all cats injected with the radioactive tracer but a dense terminal plexus of anterogradely labelled corticothalamic fibers from SI and SII was observed, overlapping the distribution area of thalamocortical neurons retrogradely labelled with HRP from the same areas. D-[ 3 H]Asp-labelled neurones were present in ipsilateral SII (SII-SI association neurones) in cats injected in SI. In these animals a bundle of radioactive fibres was observed in the rostral portion of the corpus callosum entering the contralateral hemisphere. There, neurones retrogradely labelled with silver grains were present in SI (SI-SI callosal neurons)

Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

Science.gov (United States)

Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

2015-11-01

The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Signal Transduction Pathways that Regulate CAB Gene Expression

Energy Technology Data Exchange (ETDEWEB)

Chory, Joanne

2004-12-31

The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

Signal Transduction Pathways that Regulate CAB Gene Expression

Energy Technology Data Exchange (ETDEWEB)

Chory, Joanne

2006-01-16

The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

The extracellular matrix of plants: Molecular, cellular and developmental biology

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

Mutant Allele-Specific Uncoupling of PENETRATION3 Functions Reveals Engagement of the ATP-Binding Cassette Transporter in Distinct Tryptophan Metabolic Pathways1[OPEN

Science.gov (United States)

Lu, Xunli; Dittgen, Jan; Piślewska-Bednarek, Mariola; Molina, Antonio; Schneider, Bernd; Doubský, Jan; Schneeberger, Korbinian; Schulze-Lefert, Paul

2015-01-01

Arabidopsis (Arabidopsis thaliana) PENETRATION (PEN) genes quantitatively contribute to the execution of different forms of plant immunity upon challenge with diverse leaf pathogens. PEN3 encodes a plasma membrane-resident pleiotropic drug resistance-type ATP-binding cassette transporter and is thought to act in a pathogen-inducible and PEN2 myrosinase-dependent metabolic pathway in extracellular defense. This metabolic pathway directs the intracellular biosynthesis and activation of tryptophan-derived indole glucosinolates for subsequent PEN3-mediated efflux across the plasma membrane at pathogen contact sites. However, PEN3 also functions in abiotic stress responses to cadmium and indole-3-butyric acid (IBA)-mediated auxin homeostasis in roots, raising the possibility that PEN3 exports multiple functionally unrelated substrates. Here, we describe the isolation of a pen3 allele, designated pen3-5, that encodes a dysfunctional protein that accumulates in planta like wild-type PEN3. The specific mutation in pen3-5 uncouples PEN3 functions in IBA-stimulated root growth modulation, callose deposition induced with a conserved peptide epitope of bacterial flagellin (flg22), and pathogen-inducible salicylic acid accumulation from PEN3 activity in extracellular defense, indicating the engagement of multiple PEN3 substrates in different PEN3-dependent biological processes. We identified 4-O-β-d-glucosyl-indol-3-yl formamide (4OGlcI3F) as a pathogen-inducible, tryptophan-derived compound that overaccumulates in pen3 leaf tissue and has biosynthesis that is dependent on an intact PEN2 metabolic pathway. We propose that a precursor of 4OGlcI3F is the PEN3 substrate in extracellular pathogen defense. These precursors, the shared indole core present in IBA and 4OGlcI3F, and allele-specific uncoupling of a subset of PEN3 functions suggest that PEN3 transports distinct indole-type metabolites in distinct biological processes. PMID:26023163

Career pathways in research: support and management.

Science.gov (United States)

Kenkre, J E; Foxcroft, D R

This article, the third in the series on career pathways, highlights support and management careers open to nurses working in the NHS and research and development, or people working for funding bodies or charitable organisations. These roles involve ensuring that the right infrastructure is in place to support research projects, and the correct decisions are made about which research projects should be supported and commissioned.

Branching points for transition pathways: assessing responses of actors to challenges on pathways to a low carbon future

International Nuclear Information System (INIS)

Foxon, Timothy J.; Pearson, Peter J.G.; Arapostathis, Stathis; Carlsson-Hyslop, Anna; Thornton, Judith

2013-01-01

This paper describes initial analysis of branching points on a set of transition pathways to a UK low carbon electricity future by 2050. As described in other papers in this special issue, we are exploring and analysing a set of core transition pathways, based on alternative governance patterns in which the ‘logics’ of market actors, government actors and civil society actors, respectively dominate. This core pathway analysis is enhanced by analyses of branching points within and across the pathways, which informs how competition between different logics plays out at key decision points. Branching points are defined as key decision points at which choices made by actors, in response to internal or external stresses or triggers, determine whether and in what ways the pathway is followed. A set of initial branching points for our three core transition pathways is identified through project and stakeholder workshops, and drawing on analysis of actors’ choices and responses at past branching points in energy system transitions. The potential responses of the actors are identified at these branching points, and risk mitigation strategies are formulated for the dominant actors to reinforce that pathway, as well as opportunities for actors to move away from the pathway. - Highlights: Transition Pathways is analysing three potential pathways to a low carbon future. ► Stresses lead to branching points, where actors make choices, creating pathways. ► These choices may lead to path-dependency. ► Differences in governance logics within transition pathways are also analysed. ► Studying branching points adds theoretical understanding and policy relevance to TP.

Central neural pathways for thermoregulation

Science.gov (United States)

Morrison, Shaun F.; Nakamura, Kazuhiro

2010-01-01

Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

Pathways to deep decarbonization in India

DEFF Research Database (Denmark)

Shukla, P.; Dhar, Subash; Pathak, Minal

This report is a part of the global Deep Decarbonisation Pathways (DDP) Project. The analysis consider two development scenarios for India and assess alternate roadmaps for transiting to a low carbon economy consistent with the globally agreed 2°C stabilization target. The report does not conside...

Segmentation of the Canine Corpus Callosum using Diffusion Tensor Imaging Tractography

Science.gov (United States)

Pierce, T.T.; Calabrese, E.; White, L.E.; Chen, S.D.; Platt, S.R.; Provenzale, J.M.

2014-01-01

Background We set out to determine functional white matter (WM) connections passing through the canine corpus callosum useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex while progressively posterior segments would send projections to more posterior cortex. Methods A post mortem canine brain was imaged using a 7T MRI producing 100 micron isotropic resolution DTI analyzed by tractography. Using ROIs within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified 6 important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) in tracts passing through the genu and splenium. Results Callosal fibers were organized based upon cortical destination, i.e. fibers from the genu project to the frontal cortex. Histologic results identified the motor cortex based on cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, RD and AD values were all higher in posterior corpus callosum fiber tracts. Conclusions Using 6 cortical ROIs, we identified 6 major white matter tracts that reflect major functional divisions of the cerebral hemispheres and we derived quantitative values that can be used for study of canine models of human WM pathological states. PMID:24370161

Segmentation of the canine corpus callosum using diffusion-tensor imaging tractography.

Science.gov (United States)

Pierce, Theodore T; Calabrese, Evan; White, Leonard E; Chen, Steven D; Platt, Simon R; Provenzale, James M

2014-01-01

We set out to determine functional white matter (WM) connections passing through the canine corpus callosum; these WM connections would be useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex whereas progressively posterior segments would send projections to more posterior cortex. A postmortem canine brain was imaged using a 7-T MRI system producing 100-μm-isotropic-resolution diffusion-tensor imaging analyzed by tractography. Using regions of interest (ROIs) within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified six important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity, and axial diffusivity in tracts passing through the genu and splenium. Callosal fibers were organized on the basis of cortical destination (e.g., fibers from the genu project to the frontal cortex). Histologic results identified the motor cortex on the basis of cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, radial diffusivity, and axial diffusivity values were all higher in posterior corpus callosum fiber tracts. Using six cortical ROIs, we identified six major WM tracts that reflect major functional divisions of the cerebral hemispheres, and we derived quantitative values that can be used for study of canine models of human WM pathologic states.

Phase II Final Project Report SBIR Project: "A High Efficiency PV to Hydrogen Energy System"

Energy Technology Data Exchange (ETDEWEB)

Slade, A; Turner, J; Stone, K; McConnell, R

2008-09-02

The innovative research conducted for this project contributed greatly to the understanding of generating low-cost hydrogen from solar energy. The project’s research identified two highly leveraging and complementary pathways. The first pathway is to dramatically increase the efficiency of converting sunlight into electricity. Improving solar electric conversion efficiency directly increases hydrogen production. This project produced a world record efficiency for silicon solar cells and contributed to another world record efficiency for a solar concentrator module using multijunction solar cells. The project’s literature review identified a second pathway in which wasted heat from the solar concentration process augments the electrolysis process generating hydrogen. One way to do this is to use a “heat mirror” that reflects the heat-producing infrared and transmits the visible spectrum to the solar cells; this also increases solar cell conversion efficiency. An economic analysis of this concept confirms that, if long-term concentrator photovoltaic (CPV) and solid-oxide electrolyzer cost goals can be achieved, hydrogen will be produced from solar energy cheaper than the cost of gasoline. The potential public benefits from this project are significant. The project has identified a potential energy source for the nation’s future electricity and transportation needs that is entirely “home grown” and carbon free. As CPV enter the nation’s utility markets, the opportunity for this approach to be successful is greatly increased. Amonix strongly recommends further exploration of this project’s findings.

Pathways to Sustainability: 8-year follow-up from the PROSPER Project

Science.gov (United States)

Welsh, Janet A.; Chilenski, Sarah M.; Johnson, Lesley; Greenberg, Mark T.; Spoth, Richard L.

2016-01-01

The large-scale dissemination of evidence-based practices (EBPs) is often hindered by problems with sustaining initiatives past a period of initial grant funding. Communities often have difficulty generating resources needed to sustain and grow their initiatives, resulting in limited public health impact. The PROSPER project, initiated in 2001, provided community coalitions with intensive technical assistance around marketing, communications, and revenue generating strategies. Past reports from PROSPER have indicated that these coalitions were successful with sustaining their programming, and that sustainability could be predicted by early aspects of team functioning and leadership. The current study examines financial sustainability eight years following the discontinuation of grant funding, with an emphasis on sources of revenue and the relationships between revenue generation, team functioning, and EBP participation. This study used four waves of data related to resource generation collected between 2004-2010 by PROSPER teams in Iowa and Pennsylvania. Teams reported annually on the amount and sources of funding procured, as well as annual reports of team functioning and leadership and annual reports of EBP participation by youth and parents. Data revealed that teams' overall revenue generation increased over time. There was significant variation in success with revenue generation at both the community level and across the two states. Teams accessed a variety of sources. Cash revenue generation was positively and predictively associated with EBP participation, but relationships with team functioning and leadership ratings varied significantly by state. State level differences in in-kind support were also apparent. The results indicated that there are different pathways to sustainability, and that no one method works for all teams. The presence of state level infrastructures available to support prevention appeared to account for significant differences in

Advanced Instrumentation, Information, and Control Systems Technologies Pathway: FY 2016 External Review

Energy Technology Data Exchange (ETDEWEB)

Thomas, Kenneth David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hallbert, Bruce Perry [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-11-01

This report describes an External Review conducted by the LWRS Program Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway to solicit feedback on the topics and results of the ongoing II&C research program. This review was held in conjunction with the Nuclear Energy Institute (NEI) Digital I&C Working Group meeting that was held at Idaho National Laboratory (INL) on August 9-10, 2016. Given the opportunity to visit INL and see the pathway research projects, NEI agreed that the Working Group would serve as the External Review panel for the purpose of obtaining expert input on the value and timing of the research projects. This consisted of demonstrations in the Human Systems Simulation Laboratory followed by presentations on the II&C research program in general as well as the five technology development areas. Following the meeting, the presentations were sent to each of the attendees so they could review them in more detail and refer to them in completing the feedback form. Follow-up activities were conducted with the attendees following the meeting to obtain the completed feedback forms. A total of 13 forms were returned. The feedback forms were reviewed by the pathway to compile the data and comments received, which are documented in the report. In all, the feedback provided by the External Review participants is taken to be a strong endorsement of the types of projects being conducted by the pathway, the value they hold for the nuclear plants, and the general timing of need. The feedback aligns well with the priorities, levels of efforts allocated for the research projects, and project schedules. The feedback also represents realistic observations on the practicality of some aspects of implementing these technologies. In some cases, the participants provided thoughtful challenges to certain assumptions in the formulation of the technologies or in deployment plans. These deserve further review and revision of plans if warranted

Advanced Instrumentation, Information, and Control Systems Technologies Pathway: FY 2016 External Review

International Nuclear Information System (INIS)

Thomas, Kenneth David; Hallbert, Bruce Perry

2016-01-01

This report describes an External Review conducted by the LWRS Program Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway to solicit feedback on the topics and results of the ongoing II&C research program. This review was held in conjunction with the Nuclear Energy Institute (NEI) Digital I&C Working Group meeting that was held at Idaho National Laboratory (INL) on August 9-10, 2016. Given the opportunity to visit INL and see the pathway research projects, NEI agreed that the Working Group would serve as the External Review panel for the purpose of obtaining expert input on the value and timing of the research projects. This consisted of demonstrations in the Human Systems Simulation Laboratory followed by presentations on the II&C research program in general as well as the five technology development areas. Following the meeting, the presentations were sent to each of the attendees so they could review them in more detail and refer to them in completing the feedback form. Follow-up activities were conducted with the attendees following the meeting to obtain the completed feedback forms. A total of 13 forms were returned. The feedback forms were reviewed by the pathway to compile the data and comments received, which are documented in the report. In all, the feedback provided by the External Review participants is taken to be a strong endorsement of the types of projects being conducted by the pathway, the value they hold for the nuclear plants, and the general timing of need. The feedback aligns well with the priorities, levels of efforts allocated for the research projects, and project schedules. The feedback also represents realistic observations on the practicality of some aspects of implementing these technologies. In some cases, the participants provided thoughtful challenges to certain assumptions in the formulation of the technologies or in deployment plans. These deserve further review and revision of plans if warranted

Pathways to Energy from Inertial Fusion. An Integrated Approach. Report of a Coordinated Research Project 2006-2010

International Nuclear Information System (INIS)

2013-04-01

The IAEA has continuously demonstrated its commitment to supporting the development of safe and environmentally clean nuclear fusion energy. Statistics show that at the current rate of energy consumption, fusion energy would remain an inexhaustible energy source for humankind for millions of years. Furthermore, some of the existing and foreseen risks - such as nuclear waste disposal and rising greenhouse gas emissions from the use of fossil fuels - can also be reduced. In the quest for fusion energy, two main lines of research and development are currently being pursued worldwide, namely the inertial and the magnetic confinement fusion concepts. For both approaches, the IAEA has conducted coordinated research activities focusing on specific physics and technological issues relevant the establishment of the knowledge base and foundation for the design and construction of fusion power plants. This report describes the recent research and technological developments and challenges in inertial fusion energy within the framework of such a coordinated research effort. The coordinated research project on Pathways to Energy from Inertial Fusion: An Integrated Approach was initiated in 2006 and concluded in 2010. The project involved experts and institutions from 16 Member States, addressing issues relevant to advancing inertial fusion energy research and development in its practical applications. The key topics addressed include: (i) high repetition rate, low cost, high efficiency ignition drivers; (ii) beam-matter/beam-plasma interaction related to inertial fusion target physics; (iii) target fusion chamber coupling and interface; and (iv) integrated inertial fusion power plant design. Participants in this coordinated research project have contributed 17 detailed research and technology progress reports of work performed at national and international levels. This report compiles all these reports while highlighting the various achievements.

Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

McMakin, A.H.; Cannon, S.D.; Finch, S.M.

1992-07-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The TSP consists of experts in environmental pathways, epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering, radiation dosimetry, and cultural anthropology. Included are appointed technical members representing the states of Oregon, Washington, and Idaho, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): Source terms, environmental transport, environmental monitoring data, demography, food consumption, and agriculture, and environmental pathways and dose estimates. Progress is discussed

Pathway Distiller - multisource biological pathway consolidation.

Science.gov (United States)

Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

2012-01-01

One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

Pathways to deep decarbonization - Interim 2014 Report

International Nuclear Information System (INIS)

2014-01-01

The interim 2014 report by the Deep Decarbonization Pathways Project (DDPP), coordinated and published by IDDRI and the Sustainable Development Solutions Network (SDSN), presents preliminary findings of the pathways developed by the DDPP Country Research Teams with the objective of achieving emission reductions consistent with limiting global warming to less than 2 deg. C. The DDPP is a knowledge network comprising 15 Country Research Teams and several Partner Organizations who develop and share methods, assumptions, and findings related to deep decarbonization. Each DDPP Country Research Team has developed an illustrative road-map for the transition to a low-carbon economy, with the intent of taking into account national socio-economic conditions, development aspirations, infrastructure stocks, resource endowments, and other relevant factors. The interim 2014 report focuses on technically feasible pathways to deep decarbonization

Advanced Energy Projects: FY 1993, Research summaries

Energy Technology Data Exchange (ETDEWEB)

1993-09-01

AEP has been supporting research on novel materials for energy technology, renewable and biodegradable materials, new uses for scientific discoveries, alternate pathways to energy efficiency, alternative energy sources, innovative approaches to waste treatment and reduction, etc. The summaries are grouped according to projects active in FY 1993, Phase I SBIR projects, and Phase II SBIR projects. Investigator and institutional indexes are included.

Advanced Energy Projects: FY 1993, Research summaries

International Nuclear Information System (INIS)

1993-09-01

AEP has been supporting research on novel materials for energy technology, renewable and biodegradable materials, new uses for scientific discoveries, alternate pathways to energy efficiency, alternative energy sources, innovative approaches to waste treatment and reduction, etc. The summaries are grouped according to projects active in FY 1993, Phase I SBIR projects, and Phase II SBIR projects. Investigator and institutional indexes are included

Prevention of Alcohol-Related Crime and Trauma (PACT: brief interventions in routine care pathway – a study protocol

Directory of Open Access Journals (Sweden)

Jayaraj Rama

2013-01-01

Full Text Available Abstract Background Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. Methods Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG and an Expert Reference Group (ERG. Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. Implementation: The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. Evaluation: File audits, post workshop questionnaires and semi-structured interviews are administered. Discussion This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies.

All projects related to Canada | Page 2 | IDRC - International ...

International Development Research Centre (IDRC) Digital Library (Canada)

The Bolivian public justice performance research study. Project ... A functioning immune system is critical for successful treatment of cancer. Region: ... Regulation of stem-cell mediated host immunity by the sphingolipid pathway. Project.

Electronic SSKIN pathway: reducing device-related pressure ulcers.

Science.gov (United States)

Campbell, Natalie

2016-08-11

This article describes how an interprofessional project in a London NHS Foundation Trust was undertaken to develop an intranet-based medical device-related pressure ulcer prevention and management pathway for clinical staff working across an adult critical care directorate, where life-threatening events require interventions using medical devices. The aim of this project was to improve working policies and processes to define key prevention strategies and provide clinicians with a clear, standardised approach to risk and skin assessment, equipment use, documentation and reporting clinical data using the Trust's CareVue (electronic medical records), Datix (incident reporting and risk-management tool) and eTRACE (online clinical protocol ordering) systems. The process included the development, trial and local implementation of the pathway using collaborative teamwork and the SSKIN care bundle tool. The experience of identifying issues, overcoming challenges, defining best practice and cascading SSKIN awareness training is shared.

Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Finch, S.M.; McMakin, A.H.

1991-04-01

The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from released to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; and, environmental pathways and dose estimates

Final report on the Pathway Analysis Task

International Nuclear Information System (INIS)

Whicker, F.W.; Kirchner, T.B.

1993-04-01

The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University's Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere

Final report on the Pathway Analysis Task

Energy Technology Data Exchange (ETDEWEB)

Whicker, F.W.; Kirchner, T.B. [Colorado State Univ., Fort Collins, CO (United States)

1993-04-01

The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

Connectome imaging for mapping human brain pathways.

Science.gov (United States)

Shi, Y; Toga, A W

2017-09-01

With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research.

Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants

Science.gov (United States)

Davenport, K. D.; Williams, K. E.; Ullmann, B. D.; Gustin, M. C.; McIntire, L. V. (Principal Investigator)

1999-01-01

Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

Science.gov (United States)

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

Parameters used in the environmental pathways and radiological dose modules of the Phase I air pathway code

International Nuclear Information System (INIS)

Shindle, S.F.; Ikenberry, T.A.; Napier, B.A.

1992-05-01

This report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944, when facilities there first began operating. An independent Technical Steering Panel directs the project, which is conducted by Battelle staff from the Pacific Northwest Laboratory. The objective of Phase 1 of the HEDR Project was to demonstrate through calculation that adequate models and support data existed or could be developed to allow estimation of realistic doses to individuals from historical Hanford Site radionuclide releases. The HEDR Phase 1 computer code was used to model the transport of iodine-131 released to the atmosphere from the Hanford Site facilities, through environmental pathways to points of human exposure. Output from the code was preliminary estimates of doses received by members of the public living in the vicinity of the Hanford Site. Later project work continues to build upon Phase 1 progress in order to refine dose estimates

A pathway for hospital librarians: why is it vital?

Science.gov (United States)

Tooey, Mary Joan M J

2009-10-01

By the mid 2000s, reports of hospital librarians losing jobs and hospital libraries closing were rife. In 2005, Vital Pathways: The Hospital Libraries Project was established by 2005/06 MLA President M.J. Tooey, AHIP, FMLA, to assess the truth of these reports and to study and develop strategies to support hospital librarians. Throughout this long-term project, opportunities were sought to understand the issues more clearly. A steering committee, along with three task forces, was established to carry out the work of the project. The steering committee provided oversight and had responsibility for promoting and marketing the project. The three task forces were responsible for conducting a survey on the status of hospital librarians, determining the involvement of librarians in medical education and accreditation, and researching and writing a document reviewing current and future roles for hospital librarians. Along the way, these responsibilities grew and evolved. After a little more than three years, the Task Force on Vital Pathways for Hospital Librarians Steering Committee presented a final report regarding its accomplishments to the MLA Board of Directors. A sampling of these accomplishments includes the status of hospital librarians survey, a website, a position document with an accompanying executive summary, a short promotional brochure, and a final culminating activity, this symposium. Although these are difficult times for all libraries, hospital librarians and libraries seem particularly affected. In a competitive health care environment that is driven by the bottom line, influenced by real estate hunger, and affected by the belief of hospital administrators that access to health information comes from the Internet and is free, the hospital librarian seems doomed. However, even in these difficult times, there are hospital librarians who are not only surviving, but thriving. Is it because they are entrepreneurial? Opportunistic? Innovative? Flexible? All

New insight into silica deposition in horsetail (Equisetum arvense

Directory of Open Access Journals (Sweden)

Exley Christopher

2011-07-01

Full Text Available Abstract Background The horsetails (Equisetum sp are known biosilicifiers though the mechanism underlying silica deposition in these plants remains largely unknown. Tissue extracts from horsetails grown hydroponically and also collected from the wild were acid-digested in a microwave oven and their silica 'skeletons' visualised using the fluor, PDMPO, and fluorescence microscopy. Results Silica deposits were observed in all plant regions from the rhizome through to the stem, leaf and spores. Numerous structures were silicified including cell walls, cell plates, plasmodesmata, and guard cells and stomata at varying stages of differentiation. All of the major sites of silica deposition in horsetail mimicked sites and structures where the hemicellulose, callose is known to be found and these serendipitous observations of the coincidence of silica and callose raised the possibility that callose might be templating silica deposition in horsetail. Hydroponic culture of horsetail in the absence of silicic acid resulted in normal healthy plants which, following acid digestion, showed no deposition of silica anywhere in their tissues. To test the hypothesis that callose might be templating silica deposition in horsetail commercially available callose was mixed with undersaturated and saturated solutions of silicic acid and the formation of silica was demonstrated by fluorimetry and fluorescence microscopy. Conclusions The initiation of silica formation by callose is the first example whereby any biomolecule has been shown to induce, as compared to catalyse, the formation of silica in an undersaturated solution of silicic acid. This novel discovery allowed us to speculate that callose and its associated biochemical machinery could be a missing link in our understanding of biosilicification.

Glycinergic Pathways of the Central Auditory System and Adjacent Reticular Formation of the Rat.

Science.gov (United States)

Hunter, Chyren

The development of techniques to visualize and identify specific transmitters of neuronal circuits has stimulated work on the characterization of pathways in the rat central nervous system that utilize the inhibitory amino acid glycine as its neurotransmitter. Glycine is a major inhibitory transmitter in the spinal cord and brainstem of vertebrates where it satisfies the major criteria for neurotransmitter action. Some of these characteristics are: uneven distribution in brain, high affinity reuptake mechanisms, inhibitory neurophysiological actions on certain neuronal populations, uneven receptor distribution and the specific antagonism of its actions by the convulsant alkaloid strychnine. Behaviorally, antagonism of glycinergic neurotransmission in the medullary reticular formation is linked to the development of myoclonus and seizures which may be initiated by auditory as well as other stimuli. In the present study, decreases in the concentration of glycine as well as the density of glycine receptors in the medulla with aging were found and may be responsible for the lowered threshold for strychnine seizures observed in older rats. Neuroanatomical pathways in the central auditory system and medullary and pontine reticular formation (RF) were investigated using retrograde transport of tritiated glycine to identify glycinergic pathways; immunohistochemical techniques were used to corroborate the location of glycine neurons. Within the central auditory system, retrograde transport studies using tritiated glycine demonstrated an ipsilateral glycinergic pathway linking nuclei of the ascending auditory system. This pathway has its cell bodies in the medial nucleus of the trapezoid body (MNTB) and projects to the ventrocaudal division of the ventral nucleus of the lateral lemniscus (VLL). Collaterals of this glycinergic projection terminate in the ipsilateral lateral superior olive (LSO). Other glycinergic pathways found were afferent to the VLL and have their origin

Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval.

Science.gov (United States)

Xu, Chun; Krabbe, Sabine; Gründemann, Jan; Botta, Paolo; Fadok, Jonathan P; Osakada, Fumitaka; Saur, Dieter; Grewe, Benjamin F; Schnitzer, Mark J; Callaway, Edward M; Lüthi, Andreas

2016-11-03

Memories about sensory experiences are tightly linked to the context in which they were formed. Memory contextualization is fundamental for the selection of appropriate behavioral reactions needed for survival, yet the underlying neuronal circuits are poorly understood. By combining trans-synaptic viral tracing and optogenetic manipulation, we found that the ventral hippocampus (vHC) and the amygdala, two key brain structures encoding context and emotional experiences, interact via multiple parallel pathways. A projection from the vHC to the basal amygdala mediates fear behavior elicited by a conditioned context, whereas a parallel projection from a distinct subset of vHC neurons onto midbrain-projecting neurons in the central amygdala is necessary for context-dependent retrieval of cued fear memories. Our findings demonstrate that two fundamentally distinct roles of context in fear memory retrieval are processed by distinct vHC output pathways, thereby allowing for the formation of robust contextual fear memories while preserving context-dependent behavioral flexibility. Copyright © 2016 Elsevier Inc. All rights reserved.

An overview of bioinformatics methods for modeling biological pathways in yeast.

Science.gov (United States)

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

2016-03-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Three pectin methylesterase inhibitors protect cell wall integrity for arabidopsis immunity to Botrytis

DEFF Research Database (Denmark)

Lionetti, Vincenzo; Fabri, Eleonora; Caroli, Monica De

2017-01-01

to the control plants. A higher stimulation of the fungal oxalic acid biosynthetic pathway also can contribute to the higher susceptibility of pmei mutants. The lack of PMEI expression does not affect hemicellulose strengthening, callose deposition, and the synthesis of structural defense proteins, proposed...... is posttranscriptionally regulated by endogenous protein inhibitors (PMEIs). Here, AtPMEI10, AtPMEI11, and AtPMEI12 are identified as functional PMEIs induced in Arabidopsis (Arabidopsis thaliana) during B. cinerea infection. AtPMEI expression is strictly regulated by jasmonic acid and ethylene signaling, while only At...

Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Finch, S.M.; McMakin, A.H.

1992-06-01

The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Battelle Pacific Northwest Laboratories under contract with the Centers for Disease Control. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates

PathwayAccess: CellDesigner plugins for pathway databases.

Science.gov (United States)

Van Hemert, John L; Dickerson, Julie A

2010-09-15

CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

IT-supported integrated care pathways for diabetes: A compilation and review of good practices.

Science.gov (United States)

Vrijhoef, Hubertus Jm; de Belvis, Antonio Giulio; de la Calle, Matias; de Sabata, Maria Stella; Hauck, Bastian; Montante, Sabrina; Moritz, Annette; Pelizzola, Dario; Saraheimo, Markku; Guldemond, Nick A

2017-06-01

Integrated Care Pathways (ICPs) are a method for the mutual decision-making and organization of care for a well-defined group of patients during a well-defined period. The aim of a care pathway is to enhance the quality of care by improving patient outcomes, promoting patient safety, increasing patient satisfaction, and optimizing the use of resources. To describe this concept, different names are used, e.g. care pathways and integrated care pathways. Modern information technologies (IT) can support ICPs by enabling patient empowerment, better management, and the monitoring of care provided by multidisciplinary teams. This study analyses ICPs across Europe, identifying commonalities and success factors to establish good practices for IT-supported ICPs in diabetes care. A mixed-method approach was applied, combining desk research on 24 projects from the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) with follow-up interviews of project participants, and a non-systematic literature review. We applied a Delphi technique to select process and outcome indicators, derived from different literature sources which were compiled and applied for the identification of successful good practices. Desk research identified sixteen projects featuring IT-supported ICPs, mostly derived from the EIP on AHA, as good practices based on our criteria. Follow-up interviews were then conducted with representatives from 9 of the 16 projects to gather information not publicly available and understand how these projects were meeting the identified criteria. In parallel, the non-systematic literature review of 434 PubMed search results revealed a total of eight relevant projects. On the basis of the selected EIP on AHA project data and non-systematic literature review, no commonalities with regard to defined process or outcome indicators could be identified through our approach. Conversely, the research produced a heterogeneous picture in all aspects of the projects

Hanford Environmental Dose Reconstruction Project monthly report

International Nuclear Information System (INIS)

McMakin, A.H., Cannon, S.D.; Finch, S.M.

1992-09-01

The objective of the Hanford Environmental Dose Reconstruction MDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The TSP consists of experts in envirorunental pathways. epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering. radiation dosimetry. and cultural anthropology. Included are appointed members representing the states of Oregon, Washington, and Idaho, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): Source Terms; Environmental Transport; Environmental Monitoring Data Demography, Food Consumption, and Agriculture; and Environmental Pathways and Dose Estimates

Policy Pathways: Modernising Building Energy Codes

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-01

Buildings are the largest consumers of energy worldwide and will continue to be a source of increasing energy demand in the future. Globally, the sector’s final energy consumption doubled between 1971 and 2010 to reach 2 794 million tonnes of oil equivalent (Mtoe), driven primarily by population increase and economic growth. Under current policies, the global energy demand of buildings is projected by the IEA experts to grow by an additional 838 Mtoe by 2035 compared to 2010. The challenges of the projected increase of energy consumption due to the built environment vary by country. In IEA member countries, much of the future buildings stock is already in place, and so the main challenge is to renovate existing buildings stock. In non-IEA countries, more than half of the buildings stock needed by 2050 has yet to be built. The IEA and the UNDP partnered to analyse current practices in the design and implementation of building energy codes. The aim is to consolidate existing efforts and to encourage more attention to the role of the built environment in a low-carbon and climate-resilient world. This joint IEA-UNDP Policy Pathway aims to share lessons learned between IEA member countries and non-IEA countries. The objective is to spread best practices, limit pressures on global energy supply, improve energy security, and contribute to environmental sustainability. Part of the IEA Policy Pathway series, Modernising building energy codes to secure our global energy future sets out key steps in planning, implementation, monitoring and evaluation. The Policy Pathway series aims to help policy makers implement the IEA 25 Energy Efficiency Policy Recommendations endorsed by IEA Ministers (2011).

Interhemispheric Transfer in Down’s Syndrome

Directory of Open Access Journals (Sweden)

C. M. J. Braun

1992-01-01

Full Text Available Callosal agenesics and callosotomized epileptics manifest markedly increasing simple visual reaction time (SVRT from conditions of ipsilateral to contralateral stimulus-response relation (SRR. In the contralateral SRR, a response is presumed possible because of presence of other commissures (anterior, intercollicular. The SRR effect is prolonged presumably because the remaining commissures are less efficient than the corpus callosum in relaying necessary visual or motor information. Consequently, the SRR effect is believed to correspond to callosal relay time (CRT in the normal subject. However, both callosal agenesics and callosotomy patients manifest general slowing of SVRT in addition to a prolonged SRR effect. These patients have massive extra-callosal damage which could plausibly cause both the SVRT and the CUD prolongation. If such were the case, the CRT inference would be in jeopardy. A test of the CRT inference is therefore required where patients with massive diffuse extra-callosal brain damage and normal callosi would show marked general SVRT prolongation and a normal SRR effect. Four trisomy-21 (T21 males were compared to age and sex-matched normal controls. General SVRT was highly significantly prolonged in T21, but the CUD was nearly identical in both groups.

Sensitivity of projected long-term CO 2 emissions across the Shared Socioeconomic Pathways

NARCIS (Netherlands)

Marangoni, G.; Tavoni, M.; Bosetti, V.; Borgonovo, E.; Capros, P.; Fricko, O.; Gernaat, D. E H J|info:eu-repo/dai/nl/372664636; Guivarch, C.; Havlik, P.; Huppmann, D.; Johnson, N.; Karkatsoulis, P.; Keppo, I.; Krey, V.; Ó Broin, E.; Price, J.; van Vuuren, Detlef|info:eu-repo/dai/nl/11522016X

2017-01-01

Scenarios showing future greenhouse gas emissions are needed to estimate climate impacts and the mitigation efforts required for climate stabilization. Recently, the Shared Socioeconomic Pathways (SSPs) have been introduced to describe alternative social, economic and technical narratives, spanning

Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Cannon, S.D.; Finch, S.M.

1992-10-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates

20180311 - High Throughput Transcriptomics: From screening to pathways (SOT 2018)

Science.gov (United States)

The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

Curation and Computational Design of Bioenergy-Related Metabolic Pathways

Energy Technology Data Exchange (ETDEWEB)

Karp, Peter D. [SRI International, Menlo Park, CA (United States)

2014-09-12

Pathway Tools is a systems-biology software package written by SRI International (SRI) that produces Pathway/Genome Databases (PGDBs) for organisms with a sequenced genome. Pathway Tools also provides a wide range of capabilities for analyzing predicted metabolic networks and user-generated omics data. More than 5,000 academic, industrial, and government groups have licensed Pathway Tools. This user community includes researchers at all three DOE bioenergy centers, as well as academic and industrial metabolic engineering (ME) groups. An integral part of the Pathway Tools software is MetaCyc, a large, multiorganism database of metabolic pathways and enzymes that SRI and its academic collaborators manually curate. This project included two main goals: I. Enhance the MetaCyc content of bioenergy-related enzymes and pathways. II. Develop computational tools for engineering metabolic pathways that satisfy specified design goals, in particular for bioenergy-related pathways. In part I, SRI proposed to significantly expand the coverage of bioenergy-related metabolic information in MetaCyc, followed by the generation of organism-specific PGDBs for all energy-relevant organisms sequenced at the DOE Joint Genome Institute (JGI). Part I objectives included: 1: Expand the content of MetaCyc to include bioenergy-related enzymes and pathways. 2: Enhance the Pathway Tools software to enable display of complex polymer degradation processes. 3: Create new PGDBs for the energy-related organisms sequenced by JGI, update existing PGDBs with new MetaCyc content, and make these data available to JBEI via the BioCyc website. In part II, SRI proposed to develop an efficient computational tool for the engineering of metabolic pathways. Part II objectives included: 4: Develop computational tools for generating metabolic pathways that satisfy specified design goals, enabling users to specify parameters such as starting and ending compounds, and preferred or disallowed intermediate compounds

Deterioration of the Gαo vomeronasal pathway in sexually dimorphic mammals.

Directory of Open Access Journals (Sweden)

Rodrigo Suárez

Full Text Available In mammals, social and sexual behaviours are largely mediated by the vomeronasal system (VNS. The accessory olfactory bulb (AOB is the first synaptic locus of the VNS and ranges from very large in Caviomorph rodents, small in carnivores and ungulates, to its complete absence in apes, elephants, most bats and aquatic species. Two pathways have been described in the VNS of mammals. In mice, vomeronasal neurons expressing Gαi2 protein project to the rostral portion of the AOB and respond mostly to small volatile molecules, whereas neurons expressing Gαo project to the caudal AOB and respond mostly to large non-volatile molecules. However, the Gαo-expressing pathway is absent in several species (horses, dogs, musk shrews, goats and marmosets but no hypotheses have been proposed to date to explain the loss of that pathway. We noted that the species that lost the Gαo pathway belong to Laurasiatheria and Primates lineages, both clades with ubiquitous sexual dimorphisms across species. To assess whether similar events of Gαo pathway loss could have occurred convergently in dimorphic species we studied G-protein expression in the AOB of two species that independently evolved sexually dimorphic traits: the California ground squirrel Spermophilus beecheyi (Rodentia; Sciurognathi and the cape hyrax Procavia capensis (Afrotheria; Hyracoidea. We found that both species show uniform expression of Gαi2-protein throughout AOB glomeruli, while Gαo expression is restricted to main olfactory glomeruli only. Our results suggest that the degeneration of the Gαo-expressing vomeronasal pathway has occurred independently at least four times in Eutheria, possibly related to the emergence of sexual dimorphisms and the ability of detecting the gender of conspecifics at distance.

Glucosinolate metabolites required for an Arabidopsis innate immune response.

Science.gov (United States)

Clay, Nicole K; Adio, Adewale M; Denoux, Carine; Jander, Georg; Ausubel, Frederick M

2009-01-02

The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity and is defined partly by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen-triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen-triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens.

Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

Science.gov (United States)

Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

2017-04-01

Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested ( n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function. NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not

Disruption of Ethylene Responses by Turnip mosaic virus Mediates Suppression of Plant Defense against the Green Peach Aphid Vector.

Science.gov (United States)

Casteel, Clare L; De Alwis, Manori; Bak, Aurélie; Dong, Haili; Whitham, Steven A; Jander, Georg

2015-09-01

Plants employ diverse responses mediated by phytohormones to defend themselves against pathogens and herbivores. Adapted pathogens and herbivores often manipulate these responses to their benefit. Previously, we demonstrated that Turnip mosaic virus (TuMV) infection suppresses callose deposition, an important plant defense induced in response to feeding by its aphid vector, the green peach aphid (Myzus persicae), and increases aphid fecundity compared with uninfected control plants. Further, we determined that production of a single TuMV protein, Nuclear Inclusion a-Protease (NIa-Pro) domain, was responsible for changes in host plant physiology and increased green peach aphid reproduction. To characterize the underlying molecular mechanisms of this phenomenon, we examined the role of three phytohormone signaling pathways, jasmonic acid, salicylic acid, and ethylene (ET), in TuMV-infected Arabidopsis (Arabidopsis thaliana), with or without aphid herbivory. Experiments with Arabidopsis mutants ethylene insensitive2 and ethylene response1, and chemical inhibitors of ET synthesis and perception (aminoethoxyvinyl-glycine and 1-methylcyclopropene, respectively), show that the ET signaling pathway is required for TuMV-mediated suppression of Arabidopsis resistance to the green peach aphid. Additionally, transgenic expression of NIa-Pro in Arabidopsis alters ET responses and suppresses aphid-induced callose formation in an ET-dependent manner. Thus, disruption of ET responses in plants is an additional function of NIa-Pro, a highly conserved potyvirus protein. Virus-induced changes in ET responses may mediate vector-plant interactions more broadly and thus represent a conserved mechanism for increasing transmission by insect vectors across generations. © 2015 American Society of Plant Biologists. All Rights Reserved.

Cortical involvement of marchiafava-bignami disease: a case report

Energy Technology Data Exchange (ETDEWEB)

Jang, Han Won [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

2007-03-15

Marchiafava-Bignami disease is a rare complication of chronic alcoholism and this malady typically manifests as callosal lesion. I report here on one patient with Marchiafava-bignami disease (MBD) who has symmetric restricted diffusion in both lateral-frontal cortices, in addition to the callosal lesion.

Hanford Environmental Dose Reconstruction Project monthly report

International Nuclear Information System (INIS)

Finch, S.M.

1991-10-01

The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doeses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; environmental pathways and dose estimates

PathScore: a web tool for identifying altered pathways in cancer data.

Science.gov (United States)

Gaffney, Stephen G; Townsend, Jeffrey P

2016-12-01

PathScore quantifies the level of enrichment of somatic mutations within curated pathways, applying a novel approach that identifies pathways enriched across patients. The application provides several user-friendly, interactive graphic interfaces for data exploration, including tools for comparing pathway effect sizes, significance, gene-set overlap and enrichment differences between projects. Web application available at pathscore.publichealth.yale.edu. Site implemented in Python and MySQL, with all major browsers supported. Source code available at: github.com/sggaffney/pathscore with a GPLv3 license. stephen.gaffney@yale.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse

Science.gov (United States)

Radulovic, Jelena

2016-01-01

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. SIGNIFICANCE STATEMENT Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we

Care pathways as boundary objects between primary and secondary care: Experiences from Norwegian home care services.

Science.gov (United States)

Håland, Erna; Røsstad, Tove; Osmundsen, Tonje C

2015-11-01

The need for integration of healthcare services and collaboration across organisational boundaries is highlighted as a major challenge within healthcare in many countries. Care pathways are often presented as a solution to this challenge. In this article, we study a project of developing, introducing and using a care pathway across healthcare levels focusing on older home-dwelling patients in need of home care services after hospital discharge. In so doing, we use the concept of boundary object, as described by Star and Griesemer, to explore how care pathways can act as tools for translation between specialist healthcare services and home care services. Based on interviews with participants in the project, we find that response to existing needs, local tailoring, involvement and commitment are all crucial for the care pathway to function as a boundary object in this setting. Furthermore, the care pathway, as we argue, can be used to push boundaries just as much as it can be used as a tool for bridging across them, thus potentially contributing to a more equal relationship between specialist healthcare services and home care services. © The Author(s) 2015.

pathways to deep decarbonization - 2014 report

International Nuclear Information System (INIS)

Sachs, Jeffrey; Guerin, Emmanuel; Mas, Carl; Schmidt-Traub, Guido; Tubiana, Laurence; Waisman, Henri; Colombier, Michel; Bulger, Claire; Sulakshana, Elana; Zhang, Kathy; Barthelemy, Pierre; Spinazze, Lena; Pharabod, Ivan

2014-09-01

The Deep Decarbonization Pathways Project (DDPP) is a collaborative initiative to understand and show how individual countries can transition to a low-carbon economy and how the world can meet the internationally agreed target of limiting the increase in global mean surface temperature to less than 2 degrees Celsius (deg. C). Achieving the 2 deg. C limit will require that global net emissions of greenhouse gases (GHG) approach zero by the second half of the century. This will require a profound transformation of energy systems by mid-century through steep declines in carbon intensity in all sectors of the economy, a transition we call 'deep decarbonization.' Successfully transition to a low-carbon economy will require unprecedented global cooperation, including a global cooperative effort to accelerate the development and diffusion of some key low carbon technologies. As underscored throughout this report, the results of the DDPP analyses remain preliminary and incomplete. The DDPP proceeds in two phases. This 2014 report describes the DDPP's approach to deep decarbonization at the country level and presents preliminary findings on technically feasible pathways to deep decarbonization, utilizing technology assumptions and timelines provided by the DDPP Secretariat. At this stage we have not yet considered the economic and social costs and benefits of deep decarbonization, which will be the topic for the next report. The DDPP is issuing this 2014 report to the UN Secretary-General Ban Ki-moon in support of the Climate Leaders' Summit at the United Nations on September 23, 2014. This 2014 report by the Deep Decarbonization Pathway Project (DDPP) summarizes preliminary findings of the technical pathways developed by the DDPP Country Research Partners with the objective of achieving emission reductions consistent with limiting global warming to less than 2 deg. C., without, at this stage, consideration of economic and social costs and benefits. The DDPP is a knowledge

Does the projected pathway to global warming targets matter?

Science.gov (United States)

Bärring, Lars; Strandberg, Gustav

2018-02-01

Since the ‘Paris agreement’ in 2015 there has been much focus on what a +1.5 °C or +2 °C warmer world would look like. Since the focus lies on policy relevant global warming targets, or specific warming levels (SWLs), rather than a specific point in time, projections are pooled together to form SWL ensembles based on the target temperature rather than emission scenario. This study uses an ensemble of CMIP5 global model projections to analyse how well SWL ensembles represent the stabilized climate of global warming targets. The results show that the SWL ensembles exhibit significant trends that reflect the transient nature of the RCP scenarios. These trends have clear effect on the timing and clustering of monthly cold and hot extremes, even though the effect on the temperature of the extreme months is less visible. In many regions there is a link between choice of RCP scenario used in the SWL ensemble and climate change signal in the highest monthly temperatures. In other regions there is no such clear-cut link. From this we conclude that comprehensive analyses of what prospects the different global warming targets bring about will require stabilization scenarios. Awaiting such targeted scenarios we suggest that prudent use of SWL scenarios, taking their characteristics and limitations into account, may serve as reasonable proxies in many situations.

New Pathways to Resilience: Interactive report on CCAA program ...

International Development Research Centre (IDRC) Digital Library (Canada)

2012-11-08

Nov 8, 2012 ... Throughout the report, you will find links to program and project resources, and directions for delving further into its scientific findings. Read the interactive report, New Pathways to Resilience (PDF, 2.96MB). A recent version of Adobe Reader is required to read the PDF. You can download the most recent ...

Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response*

Science.gov (United States)

Clay, Nicole K.; Adio, Adewale M.; Denoux, Carine; Jander, Georg; Ausubel, Frederick M.

2008-01-01

Summary The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity, and is defined in part by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens. PMID:19095898

Chemically different non-thermal plasmas target distinct cell death pathways

Czech Academy of Sciences Publication Activity Database

Lunov, O.; Zablotskyy, V.; Chrupina, O.; Lunova, M.; Jirsa, M.; Dejneka, A.; Kubinová, Šárka

2017-01-01

Roč. 7, apr (2017), s. 600 ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : chemically different * non-thermal plasmas * target distinct cell death pathways Subject RIV: FP - Other Medical Disciplines OBOR OECD: Biophysics Impact factor: 4.259, year: 2016

Linking fungal secondary metabolites and pathways to their genes in Aspergillus

DEFF Research Database (Denmark)

Petersen, Lene Maj

. oryzae metabolites, however, revealed the chemical link between the two species. In two parallel projects, involving A. niger and A. aculeatus respectively, the polyketide 6-methyl salicylic acid (6-MSA), and corresponding biosynthetic pathways, were investigated. In A. niger, 6-MSA was converted...

Fear extinction requires infralimbic cortex projections to the basolateral amygdala.

Science.gov (United States)

Bloodgood, Daniel W; Sugam, Jonathan A; Holmes, Andrew; Kash, Thomas L

2018-03-06

Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

Crossing frontiers in tackling pathways of biological invasions

Czech Academy of Sciences Publication Activity Database

Essl, F.; Bacher, S.; Blackburn, T. M.; Booy, O.; Brundu, G.; Brunel, S.; Cardoso, A.-C.; Eschen, R.; Gallardo, B.; Galil, B.; García-Berthou, E.; Genovesi, P.; Groom, Q.; Harrower, C.; Hulme, P. E.; Katsanevakis, S.; Kenis, M.; Kühn, I.; Kumschick, S.; Martinou, A. F.; Nentwig, W.; O´Flynn, C.; Pagad, S.; Pergl, Jan; Pyšek, Petr; Rabitsch, W.; Richardson, D. M.; Roques, A.; Roy, H. E.; Sclarea, R.; Schindler, S.; Seebens, H.; Vanderhoeven, S.; Vila, M.; Wilson, J. R. U.; Zenetos, A.; Jeschke, J.M.

2015-01-01

Roč. 65, č. 8 (2015), s. 769-782 ISSN 0006-3568 R&D Projects: GA ČR GB14-36079G; GA ČR(CZ) GAP504/11/1028 Grant - others:AV ČR(CZ) AP1002 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985939 Keywords : biological invasions * pathways * management Subject RIV: EH - Ecology, Behaviour Impact factor: 4.294, year: 2015

One hundred million years of interhemispheric communication: the history of the corpus callosum

Directory of Open Access Journals (Sweden)

Aboitiz F.

2003-01-01

Full Text Available Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans. "...if the currently received statements are correct, the appearance of the corpus callosum in the placental mammals is the greatest and most sudden modification exhibited by the brain in the whole series of vertebrated animals..." T.H. Huxley (1.

Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

Directory of Open Access Journals (Sweden)

Q. Wang

Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

Overview of CO2 valorization pathways. Final document

International Nuclear Information System (INIS)

Tridant Bel, Jean-Philippe; Pairin, Cecile; Darcet, Cecile; Thybaud, Nathalie; Lebain, David; David, Marc; Morin, Dominique; Bigeon, Philippe; Mansilla, Christine; Amouroux, Jacques; De Witte, Marc; Ungerer, Philippe; Jarrin, Jacques; Blancheton, Jean-Paul; Rene, Francois; Farret, Regis; Gimenez, Michel; Sassi, William; Clin, Francois; Clodic, Denis; Desnost, Carole; Gresser, Robert; Yacono, Charles

2010-06-01

Reducing the emissions of the main anthropogenic greenhouse gases, such as carbon dioxide, is one of the major challenges of this century. The growth in energy demand does not allow, at the present time, the use of fossil fuels to be avoided. As a consequence, carbon capture and storage (CCS) is a solution with great potential and is the subject of many pilot projects. In this field, France is now well positioned, despite a strongly de-carbonated electricity. As a complement to these actions, it is also possible to reuse the CO 2 molecule, considering it as a raw material, as a source of carbon. CO 2 recovery in order to produce chemical compounds is then similar to recycling and would involve an environmental benefit and an economic opportunity at the same time. In this context, the French Agency for Energy and Environment (ADEME) and the French public authorities (MEEDDM, MSR, etc.) asked ALCIMED to better understand the different pathways of CO 2 recycling and to identify the main development opportunities of such technologies in France. The results of the study also relied on the knowledge and experience of a steering committee composed of key figures from the institutional and industrial sectors. A cross-sectional analysis of the literature and telephone interviews with experts (industrial and institutional) conducted to the identification of 12 pathways of carbon dioxide recycling, that have been divided into three segments: the use of CO 2 without processing, chemical processing and biological processing. The technological, economic and environmental factors have been evaluated for each pathway, and key stakeholders and related projects have been complemented. A first analysis has been then conducted in order to compare the different pathways to each other. In addition, ALCIMED and the members of the steering committee of this study have led a first discussion on the position of France in regard to carbon dioxide recycling, putting in light industrial and

Pathways to Resilience in Semi-Arid Economies | CRDI - Centre de ...

International Development Research Centre (IDRC) Digital Library (Canada)

Pathways to Resilience in Semi-Arid Economies. How can populations become resilient to climate change while pursuing economic growth? This question is at the heart of a research project designed to support climate-resilient economic development in semi-arid lands. It will do so by addressing the conditions for ...

Hanford Environmental Dose Reconstruction Project monthly report

International Nuclear Information System (INIS)

Finch, S.M.

1990-12-01

The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have been have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; and environmental pathways and dose estimates. 3 figs., 3 tabs

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

Directory of Open Access Journals (Sweden)

Saha Subhash

2003-10-01

Full Text Available Abstract Background Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. Results We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal

Development and Performance of Alternative Electricity Sector Pathways Subject to Multiple Climate and Water Projections

Science.gov (United States)

Newmark, R. L.; Vorosmarty, C. J.; Miara, A.; Cohen, S.; Macknick, J.; Sun, Y.; Corsi, F.; Fekete, B. M.; Tidwell, V. C.

2017-12-01

Climate change impacts on air temperatures and water availability have the potential to alter future electricity sector investment decisions as well as the reliability and performance of the power sector. Different electricity sector configurations are more or less vulnerable to climate-induced changes. For example, once-through cooled thermal facilities are the most cost-effective and efficient technologies under cooler and wetter conditions, but can be substantially affected by and vulnerable to warmer and drier conditions. Non-thermal renewable technologies, such as PV and wind, are essentially "drought-proof" but have other integration and reliability challenges. Prior efforts have explored the impacts of climate change on electric sector development for a limited set of climate and electricity scenarios. Here, we provide a comprehensive suite of scenarios that evaluate how different electricity sector pathways could be affected by a range of climate and water resource conditions. We use four representative concentration pathway (RCP) scenarios under five global circulation models (GCM) as climate drivers to a Water Balance Model (WBM), to provide twenty separate future climate-water conditions. These climate-water conditions influence electricity sector development from present day to 2050 as determined using the Regional Energy Deployment Systems (ReEDS) model. Four unique electricity sector pathways will be considered, including business-as-usual, carbon cap, high renewable energy technology costs, and coal reliance scenarios. The combination of climate-water and electricity sector pathway scenarios leads to 80 potential future cases resulting in different national and regional electricity infrastructure configurations. The vulnerability of these configurations in relation to climate change (including in-stream thermal pollution impacts and environmental regulations) is evaluated using the Thermoelectric Power and Thermal Pollution (TP2M) model, providing

Combustion kinetics and reaction pathways

Energy Technology Data Exchange (ETDEWEB)

Klemm, R.B.; Sutherland, J.W. [Brookhaven National Laboratory, Upton, NY (United States)

1993-12-01

This project is focused on the fundamental chemistry of combustion. The overall objectives are to determine rate constants for elementary reactions and to elucidate the pathways of multichannel reactions. A multitechnique approach that features three independent experiments provides unique capabilities in performing reliable kinetic measurements over an exceptionally wide range in temperature, 300 to 2500 K. Recent kinetic work has focused on experimental studies and theoretical calculations of the methane dissociation system (CH{sub 4} + Ar {yields} CH{sub 3} + H + Ar and H + CH{sub 4} {yields} CH{sub 3} + H{sub 2}). Additionally, a discharge flow-photoionization mass spectrometer (DF-PIMS) experiment is used to determine branching fractions for multichannel reactions and to measure ionization thresholds of free radicals. Thus, these photoionization experiments generate data that are relevant to both reaction pathways studies (reaction dynamics) and fundamental thermochemical research. Two distinct advantages of performing PIMS with high intensity, tunable vacuum ultraviolet light at the National Synchrotron Light Source are high detection sensitivity and exceptional selectivity in monitoring radical species.

Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

Science.gov (United States)

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

The Hanford Environmental Dose Reconstruction (HEDR) Project: Technical approach

International Nuclear Information System (INIS)

Napier, B.A.; Freshley, M.D.; Gilbert, R.O.; Haerer, H.A.; Morgan, L.G.; Rhoads, R.E.; Woodruff, R.K.

1990-01-01

Historical measurements and current assessment techniques are being combined to estimate potential radiation doses to people from radioactive releases to the air, the Columbia River, soils, and ground water at the Hanford Site since 1944. Environmental contamination from these releases has been monitored, at varying levels of detail, for 45 yr. Phase I of the Hanford Environmental Reconstruction Project will estimate the magnitude of potential doses, their areal extends, and their associated uncertainties. The Phase I study area comprises 10 counties in eastern Washington and northern Oregon, within a 100-mi radius of the site, including a stretch of the Columbia River that was most significantly affected. These counties contain a range of projected and measured contaminant levels, environmental exposure pathways, and population groups. Phase I dose estimates are being developed for the periods 1944 through 1947 for air pathways and 1964 through 1966 for river pathways. Important radionuclide/pathway combinations include fission products, such as 131 I, in milk for early atmospheric releases and activation products, such as 32 P and 65 Zn, in fish for releases to the river. Potential doses range over several orders of magnitude within the study area. We will expand the time periods and study are in three successive phases, as warranted by results of Phase I

Modelling climate change under no-policy and policy emissions pathways

International Nuclear Information System (INIS)

Wigley, T.M.L.

2003-01-01

Future emissions under the SRES scenarios are described as examples of no-climate-policy scenarios. The production of policy scenarios is guided by Article 2 of the UN Framework Convention on Climate Change, which requires stabilization of greenhouse-gas concentrations. It is suggested that the choice of stabilization targets should be governed by the need to avoid dangerous interference with the climate system, while the choice of the pathway towards a given target should be determined by some form of cost-benefit analysis. The WRE (Wigley, Richels and Edmonds) concentration profiles are given as examples of stabilization pathways, and an alternative 'overshoot' pathway is introduced. Probabilistic projections (as probability density functions - pdfs) for global-mean temperature under the SRES scenarios are given. The relative importance of different sources of uncertainty is determined by removing individual sources of uncertainty and examining the change in the output temperature pdf. Emissions and climate sensitivity uncertainties dominate, while carbon cycle, aerosol forcing and ocean mixing uncertainties are shown to be small. It is shown that large uncertainties remain even if the emissions are prescribed. Uncertainties in regional climate change are defined by comparing normalized changes (i.e., changes per 1C global-mean warming) across multiple models and using the inter-model standard deviation as an uncertainty metric. Global-mean temperature projections for the policy case are given using the WRE profiles. Different stabilization targets are considered, and the overshoot case for 550ppm stabilization is used to quantify the effects of pathway differences. It is shown that large emissions reductions (from the no-policy to the policy case) will lead to only relatively small reductions in warming over the next 100 years

Amygdaloid projections to the ventral striatum in mice: direct and indirect chemosensory inputs to the brain reward system.

Science.gov (United States)

Novejarque, Amparo; Gutiérrez-Castellanos, Nicolás; Lanuza, Enrique; Martínez-García, Fernando

2011-01-01

Rodents constitute good models for studying the neural basis of sociosexual behavior. Recent findings in mice have revealed the molecular identity of the some pheromonal molecules triggering intersexual attraction. However, the neural pathways mediating this basic sociosexual behavior remain elusive. Since previous work indicates that the dopaminergic tegmento-striatal pathway is not involved in pheromone reward, the present report explores alternative pathways linking the vomeronasal system with the tegmento-striatal system (the limbic basal ganglia) by means of tract-tracing experiments studying direct and indirect projections from the chemosensory amygdala to the ventral striato-pallidum. Amygdaloid projections to the nucleus accumbens, olfactory tubercle, and adjoining structures are studied by analyzing the retrograde transport in the amygdala from dextran amine and fluorogold injections in the ventral striatum, as well as the anterograde labeling found in the ventral striato-pallidum after dextran amine injections in the amygdala. This combination of anterograde and retrograde tracing experiments reveals direct projections from the vomeronasal cortex to the ventral striato-pallidum, as well as indirect projections through different nuclei of the basolateral amygdala. Direct projections innervate mainly the olfactory tubercle and the islands of Calleja, whereas indirect projections are more widespread and reach the same structures and the shell and core of nucleus accumbens. These pathways are likely to mediate innate responses to pheromones (direct projections) and conditioned responses to associated chemosensory and non-chemosensory stimuli (indirect projections). Comparative studies indicate that similar connections are present in all the studied amniote vertebrates and might constitute the basic circuitry for emotional responses to conspecifics in most vertebrates, including humans.

Columbia River Pathway Dosimetry Report, 1944-1992

International Nuclear Information System (INIS)

Farris, W.T.; Napier, B.A.; Simpson, J.C.; Snyder, S.F.; Shipler, D.B.

1994-04-01

The purpose of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation dose that individuals could have received as a result of radionuclide emissions since 1944 from the Hanford Site. One objective of the HEDR Project is to estimate doses to individuals who were exposed to the radionuclides released to the Columbia River (the river pathway). This report documents the last in a series of dose calculations conducted on the Columbia River pathway. The report summarizes the technical approach used to estimate radiation doses to three classes of representative individuals who may have used the Columbia River as a source of drinking water, food, or for recreational or occupational purposes. In addition, the report briefly explains the approaches used to estimate the radioactivity released to the river, the development of the parameters used to model the uptake and movement of radioactive materials in aquatic systems such as the Columbia River, and the method of calculating the Columbia River's transport of radioactive materials. Potential Columbia River doses have been determined for representative individuals since the initiation of site activities in 1944. For this report, dose calculations were performed using conceptual models and computer codes developed for the purpose of estimating doses. All doses were estimated for representative individuals who share similar characteristics with segments of the general population

Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms

Czech Academy of Sciences Publication Activity Database

Coesel, S.; Oborník, Miroslav; Varela, J.; Falciatore, A.; Bowler, C.

2008-01-01

Roč. 3, č. 8 (2008), s. 1-16 E-ISSN 1932-6203 R&D Projects: GA AV ČR IAA500220502 Institutional research plan: CEZ:AV0Z60220518 Keywords : marine diatoms * carotenoid pathway * evolution Subject RIV: EB - Genetics ; Molecular Biology

Novel "CHASER" pathway for the management of pericardial disease.

Science.gov (United States)

Argulian, Edgar; Halpern, Dan G; Aziz, Emad F; Uretsky, Seth; Chaudhry, Farooq; Herzog, Eyal

2011-06-01

The diagnosis and management of pericardial disease are very challenging for clinicians. The evidence base in this field is relatively scarce compared with other disease entities in cardiology. In this article, we outline a unified, stepwise pathway-based approach for the management of pericardial disease. We used the "CHASER" acronym to define the entry points into the pathway. These include chest pain, hypotension or arrest, shortness of breath, echocardiographic or other imaging finding of pericardial effusion, and right-predominant heart failure. We propose a score for the assessment of pericardial effusion that is composed of the following 3 parameters: the etiology of the effusion, the size of the effusion, and the echocardiographic assessment of hemodynamic parameters. The score is applied to clinically stable patients with pericardial effusion to quantify the necessity of pericardial effusion drainage. A stepwise, pathway-based approach to the management of pericardial disease is intended to provide guidance for clinicians in decision-making and a patient-tailored evidence-based approach to medical and surgical therapy for pericardial disease. The pathway for the management of pericardial disease is the ninth project to be incorporated into the "Advanced Cardiac Admission Program" at Saint Luke's Roosevelt Hospital Center of Columbia University in New York. Further studies should focus on the validation of the feasibility, efficacy, and reliability of this pathway.

The Pediatric Cancer Genome Project

Science.gov (United States)

Downing, James R; Wilson, Richard K; Zhang, Jinghui; Mardis, Elaine R; Pui, Ching-Hon; Ding, Li; Ley, Timothy J; Evans, William E

2013-01-01

The St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project (PCGP) is participating in the international effort to identify somatic mutations that drive cancer. These cancer genome sequencing efforts will not only yield an unparalleled view of the altered signaling pathways in cancer but should also identify new targets against which novel therapeutics can be developed. Although these projects are still deep in the phase of generating primary DNA sequence data, important results are emerging and valuable community resources are being generated that should catalyze future cancer research. We describe here the rationale for conducting the PCGP, present some of the early results of this project and discuss the major lessons learned and how these will affect the application of genomic sequencing in the clinic. PMID:22641210

A first approximation for modeling the liquid diffusion pathway at the greater confinement disposal facilities

International Nuclear Information System (INIS)

Olague, N.E.; Price, L.L.

1991-01-01

The greater confinement disposal (GCD) project is an ongoing project examining the disposal of orphan wastes in Area 5 of the Nevada Test Site. One of the major tasks for the project is performance assessment. With regard to performance assessment, a preliminary conceptual model for ground-water flow and radionuclide transport to the accessible environment at the GCD facilities has been developed. One of the transport pathways that has been postulated is diffusion of radionuclides in the liquid phase upward to the land surface. This pathway is not usually considered in a performance assessment, but is included in the GCD conceptual model because of relatively low recharge estimates at the GCD site and the proximity of the waste to the land surface. These low recharge estimates indicate that convective flow downward to the water table may be negligible; thus, diffusion upward to the land surface may then become important. As part of a preliminary performance assessment which considered a basecase scenario and a climate-change scenario, a first approximation for modeling the liquid-diffusion pathway was formulated. The model includes an analytical solution that incorporates both diffusion and radioactivity decay. Overall, these results indicate that, despite the configuration of the GCD facilities that establishes the need for considering the liquid-diffusion pathway, the GCD disposal concept appears to be a technically feasible method for disposing of orphan wastes. Future analyses will consist of investigating the underlying assumptions of the liquid-diffusion model, refining the model is necessary, and reducing uncertainty in the input parameters. 11 refs., 6 figs

Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

Science.gov (United States)

Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

2018-03-01

The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

Valuing of research project in energy field with real options

International Nuclear Information System (INIS)

De Blasio, N.; Marzo, G.; Turatto, R.

2008-01-01

This article presents an application of real options theory for valuing a research project in the field of stranded gas valorisation. After a presentation of the theory, the analysis addresses the use of real options evaluation for generating alternative pathways in order to add new value to the R D projects. It also shows how real option approach may be important for selecting among competitive projects, but also for providing a system for valorisation of decision-maker flexibility [it

Corpus callosum lesions after closed head injury in children: MRI, clinical features and outcome

International Nuclear Information System (INIS)

Mendelsohn, D.B.; Bruce, D.

1992-01-01

Thirty-four children who sustained moderate to severe closed head injury underwent magnetic resonance imaging (MRI). Eight (24%) had MRI evidence of corpus callosum injury, most commonly within the posterior body and splenium. In contradistinction to reports in adults, there was no definite relationship between callosal injury and lower initial Glasgow Coma Scale scores, nor was there a significantly higher incidence of primary brain-stem lesions, diffuse axonal shear injury or intraventricular hemorrhage. In none of these 8 children did the initial admission computed tomography show evidence of callosal injury. Callosal injuries on MRI are not necessarily a poor prognostic finding, the majority of the 8 children showing good functional recovery. (orig.)

Pathways to space: A mission to foster the next generation of scientists and engineers

Science.gov (United States)

Dougherty, Kerrie; Oliver, Carol; Fergusson, Jennifer

2014-06-01

The first education project funded under the Australian Government's Australian Space Research Program (ASRP), Pathways to Space was a unique project combining education, science communication research and research in astrobiology and robotics. It drew upon the challenges of space exploration to inspire students to consider study and careers in science and engineering. A multi-faceted program, Pathways to Space provided hands-on opportunities for high school and university students to participate in realistic simulations of a robotic Mars exploration mission for astrobiology. Its development was a collaboration between the Australian Centre for Astrobiology (University of New South Wales), the Australian Centre for Field Robotics (University of Sydney), the Powerhouse Museum and industry partner, Cisco. Focused on students in Years 9-10 (15-16 years of age), this program provided them with the opportunity to engage directly with space engineers and astrobiologists, while carrying out a simulated Mars mission using the digital learning facilities available at the Powerhouse Museum. As a part of their program, the students operated robotic mini-rovers in the Powerhouse Museum's “Mars Yard”, a highly accurate simulation of the Martian surface, where university students also carry out the development and testing of experimental Mars roving vehicles. This aspect of the program has brought real science and engineering research into the public space of the museum. As they undertook the education program, the students participated in a research study aimed at understanding the effectiveness of the project in achieving its key objective - encouraging students to consider space related courses and careers. This paper outlines the development and operation of the Pathways to Space project over its 3-year funding period, during which it met and exceeded all the requirements of its ASRP grant. It will look at the goals of the project, the rationale behind the education and

A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

Science.gov (United States)

Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

2015-01-01

Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

Determination of the contribution of livestock water ingestion to dose from the cow-milk pathway

International Nuclear Information System (INIS)

Ikenberry, T.A.

1992-12-01

As part of the Hanford Environmental Dose Reconstruction (HEDR) Project, a series of calculations has been undertaken to evaluate the absolute and relative contribution of different exposure pathways to thyroid doses that may have been received by individuals living in the vicinity of the Hanford Site. These evaluations include some pathways that were included in the Phase I air-pathway dose evaluations (HEDR staff 1991, page xx), as well as other potential exposure pathways being evaluated for possible inclusion in the future HEDR modeling efforts. This calculation (002) examined the possible doses that may have been received by individuals who drank milk from cows that drank from sources of water (stock tanks and farm ponds) exposed to iodine-131 in the atmosphere during 1945

A plasmodesmata-associated beta-1,3-glucanase in Arabidopsis.

Science.gov (United States)

Levy, Amit; Erlanger, Michael; Rosenthal, Michal; Epel, Bernard L

2007-02-01

Plasmodesmal conductivity is regulated in part by callose turnover, which is hypothesized to be determined by beta-1,3-glucan synthase versus glucanase activities. A proteomic analysis of an Arabidopsis thaliana plasmodesmata (Pd)-rich fraction identified a beta-1,3-glucanase as present in this fraction. The protein encoded by the putative plasmodesmal associated protein (ppap) gene, termed AtBG_ppap, had previously been found to be a post-translationally modified glycosylphosphatidylinositol (GPI) lipid-anchored protein. When fused to green fluorescent protein (GFP) and expressed in tobacco (Nicotiana tabacum) or Nicotiana benthamiana epidermal cells, this protein displays fluorescence patterns in the endoplasmic reticulum (ER) membrane system, along the cell periphery and in a punctate pattern that co-localizes with aniline blue-stained callose present around the Pd. Plasma membrane localization was verified by co-localization of AtBG_ppap:GFP together with a plasma membrane marker N-[3-triethylammoniumpropyl]-4-[p-diethylaminophenylhexatrienyl] pyridinium dibromide (FM4-64) in plasmolysed cells. In Arabidopsis T-DNA insertion mutants that do not transcribe AtBG_ppap, functional studies showed that GFP cell-to-cell movement between epidermal cells is reduced, and the conductivity coefficient of Pd is lower. Measurements of callose levels around Pd after wounding revealed that callose accumulation in the mutant plants was higher. Taken together, we suggest that AtBG_ppap is a Pd-associated membrane protein involved in plasmodesmal callose degradation, and functions in the gating of Pd.

Megasporogenesis and programmed cell death in Tillandsia (Bromeliaceae).

Science.gov (United States)

Papini, Alessio; Mosti, Stefano; Milocani, Eva; Tani, Gabriele; Di Falco, Pietro; Brighigna, Luigi

2011-10-01

The degeneration of three of four meiotic products is a very common process in the female gender of oogamous eukaryotes. In Tillandsia (and many other angiosperms), the surviving megaspore has a callose-free wall in chalazal position while the other three megaspores are completely embedded in callose. Therefore, nutrients and signals can reach more easily the functional megaspore from the nucellus through the chalazal pole with respect to the other megaspores. The abortion of three of four megaspores was already recognized as the result of a programmed cell death (PCD) process. We investigated the process to understand the modality of this specific type of PCD and its relationship to the asymmetric callose deposition around the tetrad. The decision on which of the four megaspores will be the supernumerary megaspores in angiosperms, and hence destined to undergo programmed cell death, appears to be linked to the callose layer deposition around the tetrad. During supernumerary megaspores degeneration, events leading to the deletion of the cells do not appear to belong to a single type of cell death. The first morphological signs are typical of autophagy, including the formation of autophagosomes. The TUNEL positivity and a change in morphology of mitochondria and chloroplasts indicate the passage to an apoptotic-like PCD phase, while the cellular remnants undergo a final process resembling at least partially (ER swelling) necrotic morphological syndromes, eventually leading to a mainly lipidic cell corpse still separated from the functional megaspore by a callose layer.

The tectopontine projection the the rat with comments on visual pathways to the basilar pons

International Nuclear Information System (INIS)

Burne, R.A.; Azizi, S.A.; Mihailoff, G.A.; Woodward, D.J.

1981-01-01

The projection from the superior and inferior colliculi to the basilar pons in the rat was studied with the technique of orthograde transport of labeled amino acids and autoradiography. Injections restricted to the medial or lateral regions of the superior colliculus gave rise to grain labeling representing terminal fields over the ipsilateral peduncular, dorsolateral, and ventrolateral regions of the caudal basilar pons and over the dorsomedial area of the contralateral nucleus reticularis tegmenti pontis (NRTP). The pontine projection from the superior colliculus to the lateral basilar pons is topographically organized; the medial superior colliculus projects primarily to the peduncular region, whereas the lateral superior colliculus terminates chiefly in ventrolateral pontine areas. A projection from the superior colliculus to the contralateral dorsomedial pontine and medial peduncular pontine regions, a previously undescribed finding, has also been shown. Descending fibers from the inferior colliculus do not appear to terminate extensively within the basilar pons but rather course adjacent to pontine cells of the dorsolateral region in the caudal pons. Pretectal nuclei project ipsilaterally to medial and lateral nuclei in the rostral and middle basilar pons, respectively. A rostrocaudal topography exists in the tectopontine projection; the pretectum projects to rostromiddle basilar pons, the superior colliculus to more caudal pontine regions, and the inferior colliculus (although sparsely) to further caudal areas. The pontine projection pattern from the colliculi and pretectum differs from the pontine afferents from the visual cortices

Virtual Institute of Microbial Stress and Survival: Deduction of Stress Response Pathways in Metal and Radionuclide Reducing Microorganisms

Energy Technology Data Exchange (ETDEWEB)

None

2004-04-17

The projects application goals are to: (1) To understand bacterial stress-response to the unique stressors in metal/radionuclide contamination sites; (2) To turn this understanding into a quantitative, data-driven model for exploring policies for natural and biostimulatory bioremediation; (3) To implement proposed policies in the field and compare results to model predictions; and (4) Close the experimental/computation cycle by using discrepancies between models and predictions to drive new measurements and construction of new models. The projects science goals are to: (1) Compare physiological and molecular response of three target microorganisms to environmental perturbation; (2) Deduce the underlying regulatory pathways that control these responses through analysis of phenotype, functional genomic, and molecular interaction data; (3) Use differences in the cellular responses among the target organisms to understand niche specific adaptations of the stress and metal reduction pathways; (4) From this analysis derive an understanding of the mechanisms of pathway evolution in the environment; and (5) Ultimately, derive dynamical models for the control of these pathways to predict how natural stimulation can optimize growth and metal reduction efficiency at field sites.

Development of a renal transplant clinical pathway: one hospital's journey.

Science.gov (United States)

Darrikhuma, I M

1999-05-01

Mounting pressures to resolve multiple challenges related to quality, cost, and access in a resource-driven, customer-focused health care environment have compelled clinicians to develop innovative strategies to provide cost-effective, state-of-the-art care. Targeted patient groups include those associated with high cost, high volume, or high resource use. Patients undergoing renal transplantation fall into one or more of these categories. Recently, the management of patients with end-stage renal disease (ESRD) has come under national focus, as evidenced by the fact that Health Care Financing Administration (HCFA) has commissioned an ESRD managed care demonstration project. The purpose of this article is to describe how one case management tool--the clinical pathway--can be used to decrease costs and improve outcomes associated with renal transplantation. This discussion will include a review of the origins and components of clinical pathways and a description of how one institution developed, implemented, evaluated, and refined a renal transplantation clinical pathway.

Pulvinar projections to the striatum and amygdala

Directory of Open Access Journals (Sweden)

Jonathan D Day-Brown

2010-11-01

Full Text Available Visually-guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as blindsight. Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri, a species considered to be a protypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd and central (Pc pulvinar both receive topographic (specific projections from SC, and Pd receives an additional nontopographic (diffuse projection from SC (Chomsung et al., 2008; JCN 510:24-46. Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP and parvalbumin (PV to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvinostriatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: 1 topographic visual information from SC to striatum to aid in guiding precise movements, and 2 nontopographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

Evaluation of skin and ingestion exposure pathways

Energy Technology Data Exchange (ETDEWEB)

Aaberg, Rosanne [Pacific Northwest Laboratory, Richland, WA (United States); Logsdon, Joe E [United States Environmental Protection Agency, Office of Radiation Programs, Washington, DC (United States)

1989-06-01

After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail.

Evaluation of skin and ingestion exposure pathways

International Nuclear Information System (INIS)

Aaberg, Rosanne; Logsdon, Joe E.

1989-06-01

After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail

EarthConnections: Integrating Community Science and Geoscience Education Pathways for More Resilient Communities.

Science.gov (United States)

Manduca, C. A.

2017-12-01

To develop a diverse geoscience workforce, the EarthConnections collective impact alliance is developing regionally focused, Earth education pathways. These pathways support and guide students from engagement in relevant, Earth-related science at an early age through the many steps and transitions to geoscience-related careers. Rooted in existing regional activities, pathways are developed using a process that engages regional stakeholders and community members with EarthConnections partners. Together they connect, sequence, and create multiple learning opportunities that link geoscience education and community service to address one or more local geoscience issues. Three initial pilots are demonstrating different starting points and strategies for creating pathways that serve community needs while supporting geoscience education. The San Bernardino pilot is leveraging existing academic relationships and programs; the Atlanta pilot is building into existing community activities; and the Oklahoma Tribal Nations pilot is co-constructing a pathway focus and approach. The project is using pathway mapping and a collective impact framework to support and monitor progress. The goal is to develop processes and activities that can help other communities develop similar community-based geoscience pathways. By intertwining Earth education with local community service we aspire to increase the resilience of communities in the face of environmental hazards and limited Earth resources.

A probabilistic atlas of human brainstem pathways based on connectome imaging data.

Science.gov (United States)

Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

2018-04-01

The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles

CAUDAL MEDULLARY PATHWAYS TO LUMBOSACRAL MOTONEURONAL CELL GROUPS IN THE CAT - EVIDENCE FOR DIRECT PROJECTIONS POSSIBLY REPRESENTING THE FINAL COMMON PATHWAY FOR LORDOSIS

NARCIS (Netherlands)

VANDERHORST, VGJM; HOLSTEGE, G

1995-01-01

The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

Caudal Medullary Pathways To Lumbosacral Motoneuronal Cell Groups In The Cat; Evidence For Direct Projections Possibly Representing The Final Common Pathway For Lordosis.

NARCIS (Netherlands)

VanderHorst, Veronique G.J.M.; Holstege, Gert

1995-01-01

The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

Hanford Environmental Dose Reconstruction Project monthly report, August 1992

International Nuclear Information System (INIS)

McMakin, A.H.; Cannon, S.D.; Finch, S.M.

1992-01-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography; food consumption; and agriculture; and environmental pathway and dose estimates

Freshwater exposure pathways in the Nordic countries

International Nuclear Information System (INIS)

Tveten, U.

1984-06-01

The report relates to a subproject under a Nordic project called ''Large reactor accidents - consequences and mitigating actions''. The report summarizes information available, primarily in the Nordic countries, on freshwater exposure pathways. Experimental and theoretical data concerning the deposition and run-off of the nuclides *sp90*Sr and*Sp137*Cs is presented. Internal exposure via drinking water and freshwater fish is dealt with, as well as external exposure due to swimming, boating, contact with fishing utensils and use of beach areas. In addition is exposure via irrigated agricultural products considered. (RF)

All projects related to | Page 34 | IDRC - International Development ...

International Development Research Centre (IDRC) Digital Library (Canada)

Mitochondrial contribution to innate immune pathways. Project. The ability of cells in the body to recognize bacteria and viruses is critical to survival. ... Diseases that result from an infection are most often resolved by cells that use an immune ...

DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis.

Science.gov (United States)

Juenger, Hendrik; Koerte, Inga K; Muehlmann, Marc; Mayinger, Michael; Mall, Volker; Krägeloh-Mann, Ingeborg; Shenton, Martha E; Berweck, Steffen; Staudt, Martin; Heinen, Florian

2014-11-01

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers. Copyright © 2014 European Paediatric Neurology Society

METABOLIC ENGINEERING TO DEVELOP A PATHWAY FOR THE SELECTIVE CLEAVAGE OF CARBON-NITROGEN BONDS

Energy Technology Data Exchange (ETDEWEB)

John J. Kilbane III

2003-12-01

The objective of the project is to develop biochemical pathways for the selective cleavage of C-N bonds in molecules found in petroleum. The initial phase of the project will focus on the isolation or development of an enzyme capable of cleaving the C-N bond in aromatic amides, specifically 2-aminobiphenyl. The objective of the second phase of the research will be to construct a biochemical pathway for the selective removal of nitrogen from carbazole by combining the carA genes from Sphingomonas sp. GTIN11 with the gene(s) encoding an appropriate amidase. The objective of the final phase of the project will be to develop derivative CN bond cleaving enzymes that have broader substrate ranges and to demonstrate the use of such strains to selectively remove nitrogen from petroleum. The project is on schedule and no major difficulties have been encountered. During the first year of the project (October, 2002-September, 2003) enrichment culture experiments have resulted in the isolation of promising cultures that may be capable of cleaving C-N bonds in aromatic amides, several amidase genes have been cloned and are currently undergoing directed evolution to obtain derivatives that can cleave C-N bonds in aromatic amides, and the carA genes from Sphingomonas sp. GTIN11, and Pseudomonas resinovorans CA10 were cloned in vectors capable of replicating in Escherichia coli. Future research will address expression of these genes in Rhodococcus erythropolis. Enrichment culture experiments and directed evolution experiments continue to be a main focus of research activity and further work is required to obtain an appropriate amidase that will selectively cleave C-N bonds in aromatic substrates. Once an appropriate amidase gene is obtained it must be combined with genes encoding an enzyme capable of converting carbazole to 2'aminobiphenyl-2,3-diol: specifically carA genes. The carA genes from two sources have been cloned and are ready for construction of C-N bond cleavage

Austin Children`s Museum ``Go Power`` project. Final report

Energy Technology Data Exchange (ETDEWEB)

1993-10-01

Go Power, was conceived as an interactive exhibit and related set of activities designed to promote in children and families an understanding and appreciation of energy concepts. Planned in 1990, the project culminated its first phase of activities with colorful, interactive exhibit about the pathways and transformations of energy, on display at the Austin Children`s Museum between February 5th and June 6th, 1993. The project was supported by the US Department of Energy, the National Science Foundation, the Lower Colorado River Authority and various local foundations and businesses. This report describes the process, product and outcomes of this project.

Prioritizing Acquisition Pathways in the State Level Concept

Energy Technology Data Exchange (ETDEWEB)

Murphy, Chantell L. [Los Alamos National Laboratory; Budlong-Sylvester, Kory [Los Alamos National Laboratory; Pilat, Joseph F. [Los Alamos National Laboratory

2012-06-27

The International Atomic Energy Agency's (IAEA) Department of Safeguards has launched a project to further develop the State-level concept for the planning, implementation, and evaluation of safeguards activities. In order to further evolve the safeguards system an emphasis is placed on integrating inspection-related activities and the State evaluation process to draw safeguards conclusions in the most efficient way. The credible implementation of acquisition pathway analysis is central to the success of the IAEA's State-level concept. NNSA's Office of Nuclear Safeguards and Security (NA-241) The Next Generation Safeguards Initiative (NGSI) is sponsoring Los Alamos National Laboratory (LANL) to produce a study that will examine the use of acquisition pathway analysis in: (1) Developing a State-specific, State-level approach (SLA) and Annual Implementation Plan (AIP); (2) Maximizing the utility of the physical model; and (3) Supporting resource allocation decisions through a pathway prioritization. To deal with the challenge of developing an effective and efficient SLA, this study looks at: (1) Prioritizing proliferation pathways based on an assessment of a State's capabilities and assumed proliferation strategies; and (2) Relevant State behavior (e.g., transparency, cooperation, etc.) while avoiding subjective judgments about States themselves. The study makes use of case studies and concrete examples in order to illustrate how new concepts and approaches will be implemented, and how they may differ from more traditional safeguards approaches.

Advanced energy projects FY 1994 research summaries

International Nuclear Information System (INIS)

1994-09-01

The Division of Advanced Energy Projects (AEP) provides support to explore the feasibility of novel, energy-related concepts that evolve from advances in basic research. These concepts are typically at an early stage of scientific definition and, therefore, are premature for consideration by applied research or technology development programs. The AEP also supports high-risk, exploratory concepts that do not readily fit into a program area but could have several applications that may span scientific disciplines or technical areas. Projects supported by the Division arise from unsolicited ideas and concepts submitted by researchers. The portfolio of projects is dynamic and reflects the broad role of the Department in supporting research and development for improving the Nation's energy outlook. FY 1994 projects include the following topical areas: novel materials for energy technology; renewable and biodegradable materials; exploring uses of new scientific discoveries; alternate pathways to energy efficiency; alternative energy sources; and innovative approaches to waste treatment and reduction. Summaries are given for 66 projects

Discovery of new enzymes and metabolic pathways using structure and genome context

Science.gov (United States)

Zhao, Suwen; Kumar, Ritesh; Sakai, Ayano; Vetting, Matthew W.; Wood, B. McKay; Brown, Shoshana; Bonanno, Jeffery B.; Hillerich, Brandan S.; Seidel, Ronald D.; Babbitt, Patricia C.; Almo, Steven C.; Sweedler, Jonathan V.; Gerlt, John A.; Cronan, John E.; Jacobson, Matthew P.

2014-01-01

Assigning valid functions to proteins identified in genome projects is challenging, with over-prediction and database annotation errors major concerns1. We, and others2, are developing computation-guided strategies for functional discovery using “metabolite docking” to experimentally derived3 or homology-based4 three-dimensional structures. Bacterial metabolic pathways often are encoded by “genome neighborhoods” (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by “predicting” the intermediates in the glycolytic pathway in E. coli5. Metabolite docking to multiple binding proteins/enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. We report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed i) the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and ii) the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guide functional predictions to enable the discovery of new metabolic pathways. PMID:24056934

Determination of key radionuclides and parameters related to dose from the Columbia River pathway

International Nuclear Information System (INIS)

Napier, B.A.

1993-03-01

A series of scoping calculations has been undertaken to evaluate the absolute and relative contributions of different radionuclides and exposure pathways to doses that may have been received by individuals living in the vicinity of the Hanford Site. These scoping calculations may include some radionuclides and pathways that were included in the Phase 1 Columbia River pathway dose evaluations, as well as other potential exposure pathways being evaluated for possible inclusion in future Hanford Environmental Dose Reconstruction Project (HEDR) modeling efforts. This scoping calculation (Calculation 009) examines the contributions of numerous radionuclides to dose via environmental exposures and accumulation in water, fish, and other aquatic biota. Addressed in these calculations are the contributions to effective dose from (1) external exposure to contaminated river water, ( 2) ingestion of contaminated drinking water, and (3) ingestion of contaminated resident Columbia River fish. Additional information on contamination of anadromous fish and waterfowl is provided

An Automated Pipeline for Engineering Many-Enzyme Pathways: Computational Sequence Design, Pathway Expression-Flux Mapping, and Scalable Pathway Optimization.

Science.gov (United States)

Halper, Sean M; Cetnar, Daniel P; Salis, Howard M

2018-01-01

Engineering many-enzyme metabolic pathways suffers from the design curse of dimensionality. There are an astronomical number of synonymous DNA sequence choices, though relatively few will express an evolutionary robust, maximally productive pathway without metabolic bottlenecks. To solve this challenge, we have developed an integrated, automated computational-experimental pipeline that identifies a pathway's optimal DNA sequence without high-throughput screening or many cycles of design-build-test. The first step applies our Operon Calculator algorithm to design a host-specific evolutionary robust bacterial operon sequence with maximally tunable enzyme expression levels. The second step applies our RBS Library Calculator algorithm to systematically vary enzyme expression levels with the smallest-sized library. After characterizing a small number of constructed pathway variants, measurements are supplied to our Pathway Map Calculator algorithm, which then parameterizes a kinetic metabolic model that ultimately predicts the pathway's optimal enzyme expression levels and DNA sequences. Altogether, our algorithms provide the ability to efficiently map the pathway's sequence-expression-activity space and predict DNA sequences with desired metabolic fluxes. Here, we provide a step-by-step guide to applying the Pathway Optimization Pipeline on a desired multi-enzyme pathway in a bacterial host.

Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

Directory of Open Access Journals (Sweden)

Wufeng Fan

2017-01-01

Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

Geoscience Academic Provenance: A Theoretical Framework for Understanding Geoscience Students' Pathways

Science.gov (United States)

Houlton, H.; Keane, C.

2012-04-01

The demand and employment opportunities for geoscientists in the United States are projected to increase 23% from 2008 to 2018 (Gonzales, 2011). Despite this trend, there is a disconnect between undergraduate geoscience students and their desire to pursue geoscience careers. A theoretical framework was developed to understand the reasons why students decide to major in the geosciences and map those decisions to their career aspirations (Houlton, 2010). A modified critical incident study was conducted to develop the pathway model from 17, one-hour long semi-structured interviews of undergraduate geoscience majors from two Midwest Research Institutions (Houlton, 2010). Geoscience Academic Provenance maps geoscience students' initial interests, entry points into the major, critical incidents and future career goals as a pathway, which elucidates the relationships between each of these components. Analyses identified three geoscience student population groups that followed distinct pathways: Natives, Immigrants and Refugees. A follow up study was conducted in 2011 to ascertain whether these students continued on their predicted pathways, and if not, reasons for attrition. Geoscientists can use this framework as a guide to inform future recruitment and retention initiatives and target these geoscience population groups for specific employment sectors.

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

Science.gov (United States)

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-04-16

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018. Published by Elsevier B.V.

Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

Science.gov (United States)

Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

2015-01-01

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

Pathway engineering to improve ethanol production by thermophilic bacteria

Energy Technology Data Exchange (ETDEWEB)

Lynd, L.R.

1998-12-31

Continuation of a research project jointly funded by the NSF and DOE is proposed. The primary project goal is to develop and characterize strains of C. thermocellum and C. thermosaccharolyticum having ethanol selectivity similar to more convenient ethanol-producing organisms. An additional goal is to document the maximum concentration of ethanol that can be produced by thermophiles. These goals build on results from the previous project, including development of most of the genetic tools required for pathway engineering in the target organisms. As well, we demonstrated that the tolerance of C. thermosaccharolyticum to added ethanol is sufficiently high to allow practical utilization should similar tolerance to produced ethanol be demonstrated, and that inhibition by neutralizing agents may explain the limited concentrations of ethanol produced in studies to date. Task 1 involves optimization of electrotransformation, using either modified conditions or alternative plasmids to improve upon the low but reproducible transformation, frequencies we have obtained thus far.

Selectively Reduced Posterior Corpus Callosum Size in a Population-Based Sample of Young Adults Born with Low Birth Weight

DEFF Research Database (Denmark)

Aukland, S M; Westerhausen, R; Plessen, K J

2011-01-01

BACKGROUND AND PURPOSE: Several studies suggest that VLBW is associated with a reduced CC size later in life. We aimed to clarify this in a prospective, controlled study of 19-year-olds, hypothesizing that those with LBWs had smaller subregions of CC than the age-matched controls, even after...... correcting for brain volume. MATERIALS AND METHODS: One hundred thirteen survivors of LBW (BW brain. The cross-sectional area of the CC (total callosal area, and the callosal subregions of the genu, truncus......, and posterior third) was measured. Callosal areas were adjusted for head size. RESULTS: The posterior third subregion of the CC was significantly smaller in individuals born with a LBW compared with controls, even after adjusting for size of the forebrain. Individuals who were born with a LBW had a smaller CC...

Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

Science.gov (United States)

Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

2017-08-01

The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with Ppathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in MATLAB.

Science.gov (United States)

Sinha, Shriprakash

2016-12-01

Simulation study in systems biology involving computational experiments dealing with Wnt signaling pathways abound in literature but often lack a pedagogical perspective that might ease the understanding of beginner students and researchers in transition, who intend to work on the modeling of the pathway. This paucity might happen due to restrictive business policies which enforce an unwanted embargo on the sharing of important scientific knowledge. A tutorial introduction to computational modeling of Wnt signaling pathway in a human colorectal cancer dataset using static Bayesian network models is provided. The walkthrough might aid biologists/informaticians in understanding the design of computational experiments that is interleaved with exposition of the Matlab code and causal models from Bayesian network toolbox. The manuscript elucidates the coding contents of the advance article by Sinha (Integr. Biol. 6:1034-1048, 2014) and takes the reader in a step-by-step process of how (a) the collection and the transformation of the available biological information from literature is done, (b) the integration of the heterogeneous data and prior biological knowledge in the network is achieved, (c) the simulation study is designed, (d) the hypothesis regarding a biological phenomena is transformed into computational framework, and (e) results and inferences drawn using d -connectivity/separability are reported. The manuscript finally ends with a programming assignment to help the readers get hands-on experience of a perturbation project. Description of Matlab files is made available under GNU GPL v3 license at the Google code project on https://code.google.com/p/static-bn-for-wnt-signaling-pathway and https: //sites.google.com/site/shriprakashsinha/shriprakashsinha/projects/static-bn-for-wnt-signaling-pathway. Latest updates can be found in the latter website.

Binocular depth processing in the ventral visual pathway.

Science.gov (United States)

Verhoef, Bram-Ernst; Vogels, Rufin; Janssen, Peter

2016-06-19

One of the most powerful forms of depth perception capitalizes on the small relative displacements, or binocular disparities, in the images projected onto each eye. The brain employs these disparities to facilitate various computations, including sensori-motor transformations (reaching, grasping), scene segmentation and object recognition. In accordance with these different functions, disparity activates a large number of regions in the brain of both humans and monkeys. Here, we review how disparity processing evolves along different regions of the ventral visual pathway of macaques, emphasizing research based on both correlational and causal techniques. We will discuss the progression in the ventral pathway from a basic absolute disparity representation to a more complex three-dimensional shape code. We will show that, in the course of this evolution, the underlying neuronal activity becomes progressively more bound to the global perceptual experience. We argue that these observations most probably extend beyond disparity processing per se, and pertain to object processing in the ventral pathway in general. We conclude by posing some important unresolved questions whose answers may significantly advance the field, and broaden its scope.This article is part of the themed issue 'Vision in our three-dimensional world'. © 2016 The Author(s).

Hanford Environmental Dose Reconstruction Project, Quarterly report, September--November 1993

International Nuclear Information System (INIS)

Cannon, S.D.; Finch, S.M.

1993-01-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates); Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates

Externalities of fuel cycles 'ExternE' project. Hydro fuel cycle. Estimation of physical impacts and monetary valuation for priority impact pathways

International Nuclear Information System (INIS)

Navrud, S.; Riise, J.; Strand, J.

1994-01-01

The aim of the External Costs of Fuel Cycles (ExternE) study is to develop methods to measure and monetize all the externalities associated with incremental investments in electric power production, taking account of the different stages of the fuel cycles. Since fuel cycle externalities are characterised by being very site-specific, the impact pathway damage function approach, developed in ExternE, has been implemented in different European countries for each of the selected fuel cycles. This is done to demonstrate that this methodological framework can be used at different locations, to motivate further development of the methods, and to look at the sensitivity of the estimates to different locations. Electricite de France (EdF) in France and ENCO Environmental Consultants a.s. in Norway have taken on a joint responsibility for adapting the methodological framework for hydroelectric fuel cycle analyses in Europe. We report the first implementation of the hydroelectric fuel cycle within ExternE. Choice of reference site and technology Two stages of the hydroelectric fuel cycle have been identified: 1. Electricity generation 2. Transmission There are three phases of each of these stages: construction, operation and dismantling. We have assumed a construction period of 5 years (starting in 1990) and an operation period of 40 years. Dismantling after 40 years is not a realistic option. Therefore, we have focused on the construction and operation phases, of both electricity generation and transmission. The Sauda Hydroelectric Development Project (SHDP) was selected, because it illustrates upgrading and extention of an existing hydro power project. Such projects are likely to be the dominating strategy for future hydroelectric development in Norway, many other European countries and in the U.S., due to the lack of new sites available for development. SHDP consists of an extention of a previously developed area (Basis project) and six new diversion projects. The

WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

Science.gov (United States)

Slenter, Denise N; Kutmon, Martina; Hanspers, Kristina; Riutta, Anders; Windsor, Jacob; Nunes, Nuno; Mélius, Jonathan; Cirillo, Elisa; Coort, Susan L; Digles, Daniela; Ehrhart, Friederike; Giesbertz, Pieter; Kalafati, Marianthi; Martens, Marvin; Miller, Ryan; Nishida, Kozo; Rieswijk, Linda; Waagmeester, Andra; Eijssen, Lars M T; Evelo, Chris T; Pico, Alexander R; Willighagen, Egon L

2018-01-04

WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Hydrogen fueling demonstration projects using compact PSA purification

International Nuclear Information System (INIS)

Ng, E.; Smith, T.

2004-01-01

'Full text:' Hydrogen fueling demonstration projects are critical to the success of hydrogen as an automotive fuel by building public awareness and demonstrating the technology required to produce, store, and dispense hydrogen. Over 75 of these demonstration projects have been undertaken or are in the planning stages world-wide, sponsored by both the public and private sectors. Each of these projects represents a unique combination of sponsors, participants, geographic location, and hydrogen production pathway. QuestAir Technologies Inc., as the industry leader in compact pressure swing adsorption equipment for purifying hydrogen, has participated in four hydrogen fueling demonstration projects with a variety of partners and in North America and Japan. QuestAir's experiences as a participant in the planning, construction, and commissioning of these demonstration projects will be presented in this paper. The unique challenges of each project and the critical success factors that must to be considered for successful deployment of high-profile, international, and multi-vendor collaborations will also be discussed. The paper will also provide insights on the requirements for hydrogen fueling demonstration projects in the future. (author)

Sequence Evidence for the Presence of Two Tetrapyrrole Pathways in Euglena gracilis

Czech Academy of Sciences Publication Activity Database

Kořený, Luděk; Oborník, Miroslav

2011-01-01

Roč. 3, - (2011), 359-364 ISSN 1759-6653 R&D Projects: GA ČR GA206/08/1423; GA ČR GD206/09/H026 Institutional research plan: CEZ:AV0Z60220518 Keywords : tetrapyrrole synthesis * heme pathway * Euglena gracilis * secondary endosymbiosis * evolution * plastid Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.618, year: 2011

Neurophysiology and itch pathways.

Science.gov (United States)

Schmelz, Martin

2015-01-01

As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

Introducing care pathway commissioning to primary dental care: measuring performance.

Science.gov (United States)

Harris, R; Bridgman, C; Ahmad, M; Bowes, L; Haley, R; Saleem, S; Singh, R; Taylor, S

2011-12-09

Care pathways have been used in a variety of ways: firstly to support quality improvement through standardising clinical processes, but also for secondary purposes, by purchasers of healthcare, to monitor activity and health outcomes and to commission services. This paper focuses on reporting a secondary use of care pathways: to commission and monitor performance of primary dental care services. Findings of a project involving three dental practices implementing a system based on rating patients according to their risk of disease and need for care are outlined. Data from surgery-based clinical databases and interviews from commissioners and providers are reported. The use of both process and outcome key performance indicators in this context is discussed, as well as issues which arise such as attributability of outcome measures and strategic approaches to improving quality of care.

Catchment Models and Management Tools for diffuse Contaminants (Sediment, Phosphorus and Pesticides): DIFFUSE Project

Science.gov (United States)

Mockler, Eva; Reaney, Simeon; Mellander, Per-Erik; Wade, Andrew; Collins, Adrian; Arheimer, Berit; Bruen, Michael

2017-04-01

The agricultural sector is the most common suspected source of nutrient pollution in Irish rivers. However, it is also often the most difficult source to characterise due to its predominantly diffuse nature. Particulate phosphorus in surface water and dissolved phosphorus in groundwater are of particular concern in Irish water bodies. Hence the further development of models and indices to assess diffuse sources of contaminants are required for use by the Irish Environmental Protection Agency (EPA) to provide support for river basin planning. Understanding connectivity in the landscape is a vital component of characterising the source-pathway-receptor relationships for water-borne contaminants, and hence is a priority in this research. The DIFFUSE Project will focus on connectivity modelling and incorporation of connectivity into sediment, nutrient and pesticide risk mapping. The Irish approach to understanding and managing natural water bodies has developed substantially in recent years assisted by outputs from multiple research projects, including modelling and analysis tools developed during the Pathways and CatchmentTools projects. These include the Pollution Impact Potential (PIP) maps, which are an example of research output that is used by the EPA to support catchment management. The PIP maps integrate an understanding of the pollution pressures and mobilisation pathways and, using the source-pathways-receptor model, provide a scientific basis for evaluation of mitigation measures. These maps indicate the potential risk posed by nitrate and phosphate from diffuse agricultural sources to surface and groundwater receptors and delineate critical source areas (CSAs) as a means of facilitating the targeting of mitigation measures. Building on this previous research, the DIFFUSE Project will develop revised and new catchment managements tools focused on connectivity, sediment, phosphorus and pesticides. The DIFFUSE project will strive to identify the state

Emissions Scenario Portal for Visualization of Low Carbon Pathways

Science.gov (United States)

Friedrich, J.; Hennig, R. J.; Mountford, H.; Altamirano, J. C.; Ge, M.; Fransen, T.

2016-12-01

This proposal for a presentation is centered around a new project which is developed collaboratively by the World Resources Institute (WRI), Google Inc., and Deep Decarbonization Pathways Project (DDPP). The project aims to develop an online, open portal, the Emissions Scenario Portal (ESP),to enable users to easily visualize a range of future greenhouse gas emission pathways linked to different scenarios of economic and energy developments, drawing from a variety of modeling tools. It is targeted to users who are not modelling experts, but instead policy analysts or advisors, investment analysts, and similar who draw on modelled scenarios to inform their work, and who can benefit from better access to, and transparency around, the wide range of emerging scenarios on ambitious climate action. The ESP will provide information from scenarios in a visually appealing and easy-to-understand manner that enable these users to recognize the opportunities to reduce GHG emissions, the implications of the different scenarios, and the underlying assumptions. To facilitate the application of the portal and tools in policy dialogues, a series of country-specific and potentially sector-specific workshops with key decision-makers and analysts, supported by relevant analysis, will be organized by the key partners and also in broader collaboration with others who might wish to convene relevant groups around the information. This project will provide opportunities for modelers to increase their outreach and visibility in the public space and to directly interact with key audiences of emissions scenarios, such as policy analysts and advisors. The information displayed on the portal will cover a wide range of indicators, sectors and important scenario characteristics such as macroeconomic information, emission factors and policy as well as technology assumptions in order to facilitate comparison. These indicators have been selected based on existing standards (such as the IIASA AR5

Pathways over Time: Functional Genomics Research in an Introductory Laboratory Course.

Science.gov (United States)

Reeves, Todd D; Warner, Douglas M; Ludlow, Larry H; O'Connor, Clare M

2018-01-01

National reports have called for the introduction of research experiences throughout the undergraduate curriculum, but practical implementation at many institutions faces challenges associated with sustainability, cost, and large student populations. We describe a novel course-based undergraduate research experience (CURE) that introduces introductory-level students to research in functional genomics in a 3-credit, multisection laboratory class. In the Pathways over Time class project, students study the functional conservation of the methionine biosynthetic pathway between divergent yeast species. Over the five semesters described in this study, students ( N = 793) showed statistically significant and sizable growth in content knowledge ( d = 1.85) and in self-reported research methods skills ( d = 0.65), experimental design, oral and written communication, database use, and collaboration. Statistical analyses indicated that content knowledge growth was larger for underrepresented minority students and that growth in content knowledge, but not research skills, varied by course section. Our findings add to the growing body of evidence that CUREs can support the scientific development of large numbers of students with diverse characteristics. The Pathways over Time project is designed to be sustainable and readily adapted to other institutional settings. © 2018 T. D. Reeves et al. CBE—Life Sciences Education © 2018 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways.

Science.gov (United States)

Gu, Xiang; Liu, Cong-Jian; Wei, Jian-Jie

2017-11-13

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

A search engine to identify pathway genes from expression data on multiple organisms

Directory of Open Access Journals (Sweden)

Zambon Alexander C

2007-05-01

Full Text Available Abstract Background The completion of several genome projects showed that most genes have not yet been characterized, especially in multicellular organisms. Although most genes have unknown functions, a large collection of data is available describing their transcriptional activities under many different experimental conditions. In many cases, the coregulatation of a set of genes across a set of conditions can be used to infer roles for genes of unknown function. Results We developed a search engine, the Multiple-Species Gene Recommender (MSGR, which scans gene expression datasets from multiple organisms to identify genes that participate in a genetic pathway. The MSGR takes a query consisting of a list of genes that function together in a genetic pathway from one of six organisms: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana, and Helicobacter pylori. Using a probabilistic method to merge searches, the MSGR identifies genes that are significantly coregulated with the query genes in one or more of those organisms. The MSGR achieves its highest accuracy for many human pathways when searches are combined across species. We describe specific examples in which new genes were identified to be involved in a neuromuscular signaling pathway and a cell-adhesion pathway. Conclusion The search engine can scan large collections of gene expression data for new genes that are significantly coregulated with a pathway of interest. By integrating searches across organisms, the MSGR can identify pathway members whose coregulation is either ancient or newly evolved.

Emission pathway modeling to analyze national ambition levels of decarbonization

International Nuclear Information System (INIS)

Kainuma, Mikiko; Waisman, Henri

2015-01-01

The Deep Decarbonization Pathways Project (DDPP) is a knowledge network comprising 15 Country Research Teams and several Partner Organizations which develop and share methods, assumptions, and findings related to deep decarbonization. It analyzes the technical decarbonization potential, exploring options for deep decarbonization, but also better taking into account existing infrastructure stocks. It shows the possibility to reduce total CO 2 -energy emissions by 45% by 2050, with bottom-up analyses by 15 Country Research Teams

Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

Science.gov (United States)

Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

2016-09-01

Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Dependency of climate change and carbon cycle on CO2 emission pathways

International Nuclear Information System (INIS)

Nohara, Daisuke; Yoshida, Yoshikatsu; Misumi, Kazuhiro; Ohba, Masamichi

2013-01-01

Previous research has indicated that the response of globally average temperature is approximately proportional to cumulative CO 2 emissions, yet evidence of the robustness of this relationship over a range of CO 2 emission pathways is lacking. To address this, we evaluate the dependency of climate and carbon cycle change on CO 2 emission pathways using a fully coupled climate–carbon cycle model. We design five idealized pathways (including an overshoot scenario for cumulative emissions), each of which levels off to final cumulative emissions of 2000 GtC. The cumulative emissions of the overshoot scenario reach 4000 GtC temporarily, subsequently reducing to 2000 GtC as a result of continuous negative emissions. Although we find that responses of climatic variables and the carbon cycle are largely independent of emission pathways, a much weakened Atlantic meridional overturning circulation (AMOC) is projected in the overshoot scenario despite cessation of emissions. This weakened AMOC is enhanced by rapid warming in the Arctic region due to considerable temporary elevation of atmospheric CO 2 concentration and induces the decline of surface air temperature and decrease of precipitation over the northern Atlantic and Europe region. Moreover, the weakened AMOC reduces CO 2 uptake by the Atlantic and Arctic oceans. However, the weakened AMOC contributes little to the global carbon cycle. In conclusion, although climate variations have been found to be dependent on emission pathways, the global carbon cycle is relatively independent of these emission pathways, at least superficially. (letter)

Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala.

Science.gov (United States)

Keistler, Colby R; Hammarlund, Emma; Barker, Jacqueline M; Bond, Colin W; DiLeone, Ralph J; Pittenger, Christopher; Taylor, Jane R

2017-04-26

The ability to inhibit drinking is a significant challenge for recovering alcoholics, especially in the presence of alcohol-associated cues. Previous studies have demonstrated that the regulation of cue-guided alcohol seeking is mediated by the basolateral amygdala (BLA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). However, given the high interconnectivity between these structures, it is unclear how mPFC projections to each subcortical structure, as well as projections between BLA and NAc, mediate alcohol-seeking behaviors. Here, we evaluate how cortico-striatal, cortico-amygdalar, and amygdalo-striatal projections control extinction and relapse in a rat model of alcohol seeking. Specifically, we used a combinatorial viral technique to express diphtheria toxin receptors in specific neuron populations based on their projection targets. We then used this strategy to create directionally selective ablations of three distinct pathways after acquisition of ethanol self-administration but before extinction and reinstatement. We demonstrate that ablation of mPFC neurons projecting to NAc, but not BLA, blocks cue-induced reinstatement of alcohol seeking and neither pathway is necessary for extinction of responding. Further, we show that ablating BLA neurons that project to NAc disrupts extinction of alcohol approach behaviors and attenuates reinstatement. Together, these data provide evidence that the mPFC→NAc pathway is necessary for cue-induced reinstatement of alcohol seeking, expand our understanding of how the BLA→NAc pathway regulates alcohol behavior, and introduce a new methodology for the manipulation of target-specific neural projections. SIGNIFICANCE STATEMENT The vast majority of recovering alcoholics will relapse at least once and understanding how the brain regulates relapse will be key to developing more effective behavior and pharmacological therapies for alcoholism. Given the high interconnectivity of cortical, striatal, and limbic

Hanford environmental dose reconstruction project - an overview

International Nuclear Information System (INIS)

Shipler, D.B.; Napier, B.A.; Farris, W.T.

1996-01-01

The Hanford Environmental Dose Reconstruction Project was initiated because of public interest in the historical releases of radioactive materials from the Hanford Site, located in southcentral Washington State. By 1986, over 38,000 pages of environmental monitoring documentation from the early years of Hanford operations had been released. Special committees reviewing the documents recommended initiation of the Hanford Environmental Dose Reconstruction Project, which began in October 1987, and is conducted by Battelle, Pacific Northwest Laboratories. The technical approach taken was to reconstruct releases of radioactive materials based on facility operating information; develop and/or adapt transport, pathway, and dose models and computer codes; reconstruct environmental, meterological, and hydrological monitoring information; reconstruct demographic, agricultural, and lifestyle characteristics; apply statistical methods to all forms of uncertainty in the information, parameters, and models; and perform scientific investigation that were technically defensible. The geographic area for the study includes ∼2 x 10 5 km 2 (75,000 mi 2 ) in eastern Washington, western Idaho, and northeastern Oregon (essentially the Mid-columbia Basin of the Pacific Northwest). Three exposure pathways were considered: the atmosphere, the Columbia River, and ground water

The logic of single-cell projections from visual cortex.

Science.gov (United States)

Han, Yunyun; Kebschull, Justus M; Campbell, Robert A A; Cowan, Devon; Imhof, Fabia; Zador, Anthony M; Mrsic-Flogel, Thomas D

2018-04-05

Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

Science.gov (United States)

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies.

Science.gov (United States)

Vitolo, Enrico; Tatu, Mona Karina; Pignolo, Claudia; Cauda, Franco; Costa, Tommaso; Ando', Agata; Zennaro, Alessandro

2017-12-30

Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions. Copyright © 2017 Elsevier B.V. All rights reserved.

Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding.

Science.gov (United States)

Ponce, Carlos R; Lomber, Stephen G; Livingstone, Margaret S

2017-05-10

In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells contribute to visual object recognition. They receive concurrent inputs from visual areas V4, V3, and V2. We asked how these different anatomical pathways shape PIT response properties by deactivating them while monitoring PIT activity in two male macaques. We found that cooling of V4 or V2|3 did not lead to consistent changes in population excitatory drive; however, population pattern analyses showed that V4-based pathways were more important than V2|3-based pathways. We did not find any image features that predicted decoding accuracy differences between both interventions. Using the HMAX hierarchical model of visual recognition, we found that different groups of simulated "PIT" units with different input histories (lacking "V2|3" or "V4" input) allowed for comparable levels of object-decoding performance and that removing a large fraction of "PIT" activity resulted in similar drops in performance as in the cooling experiments. We conclude that distinct input pathways to PIT relay similar types of shape information, with V1-dependent V4 cells providing more quantitatively useful information for overall encoding than cells in V2 projecting directly to PIT. SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of the visual system, but most emphasize input transformations across a serial hierarchy akin to the primary "ventral stream" (V1 → V2 → V4 → IT). However, the ventral stream also comprises parallel "bypass" pathways: V1 also connects to V4, and V2 to IT. To explore the advantages of mixing long and short pathways in the macaque brain, we used cortical cooling to silence inputs to posterior IT and compared the findings with an HMAX model with parallel pathways. Copyright © 2017 the authors 0270-6474/17/375019-16$15.00/0.

Pathways for implementing REDD+. Experiences from carbon markets and communities

Energy Technology Data Exchange (ETDEWEB)

Zhu, X; Ravnkilde Moeller, L; Lopez, T De; Romero, M Z

2011-07-01

This issue of Carbon Market Perspectives on 'Pathways for implementing REDD+: Experience from carbon markets and communities' discusses the role of carbon markets in scaling up investments for REDD+ in developing countries. Nine articles authored by experienced negotiators on REDD+, carbon market actors, project developers and other leading experts share experiences and make suggestions on the key elements of a future international REDD+ regime: Architecture and underlying principles, measuring, reporting and verification (MRV), private-sector involvement, the rights of indigenous people and local communities, biodiversity conservation and environmental integrity. The articles are grouped under three main topics: the lessons of existing REDD+ projects; the future REDD+ regime and the role of carbon markets; and experiences and ideas about the involvement of indigenous people and local communities. (LN)

DMPD: Parallel pathways of virus recognition. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16713969 Parallel pathways of virus recognition. Tenoever BR, Maniatis T. Immunity.... 2006 May;24(5):510-2. (.png) (.svg) (.html) (.csml) Show Parallel pathways of virus recognition. PubmedID 1...6713969 Title Parallel pathways of virus recognition. Authors Tenoever BR, Maniatis T. Publication Immunity.

Differentiation of endosperm transfer cells of barley: a comprehensive analysis at the micro-scale.

Science.gov (United States)

Thiel, Johannes; Riewe, David; Rutten, Twan; Melzer, Michael; Friedel, Swetlana; Bollenbeck, Felix; Weschke, Winfriede; Weber, Hans

2012-08-01

Barley endosperm cells differentiate into transfer cells (ETCs) opposite the nucellar projection. To comprehensively analyse ETC differentiation, laser microdissection-based transcript and metabolite profiles were obtained from laser microdissected tissues and cell morphology was analysed. Flange-like secondary-wall ingrowths appeared between 5 and 7 days after pollination within the three outermost cell layers. Gene expression analysis indicated that ethylene-signalling pathways initiate ETC morphology. This is accompanied by gene activity related to cell shape control and vesicle transport, with abundant mitochondria and endomembrane structures. Gene expression analyses indicate predominant formation of hemicelluloses, glucuronoxylans and arabinoxylans, and transient formation of callose, together with proline and 4-hydroxyproline biosynthesis. Activation of the methylation cycle is probably required for biosynthesis of phospholipids, pectins and ethylene. Membrane microdomains involving sterols/sphingolipids and remorins are potentially involved in ETC development. The transcriptional activity of assimilate and micronutrient transporters suggests ETCs as the main uptake organs of solutes into the endosperm. Accordingly, the endosperm grows maximally after ETCs are fully developed. Up-regulated gene expression related to amino acid catabolism, C:N balances, carbohydrate oxidation, mitochondrial activity and starch degradation meets high demands for respiratory energy and carbohydrates, required for cell proliferation and wall synthesis. At 10 days after pollination, ETCs undergo further differentiation, potentially initiated by abscisic acid, and metabolism is reprogrammed as shown by activated storage and stress-related processes. Overall, the data provide a comprehensive view of barley ETC differentiation and development, and identify candidate genes and associated pathways. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Metabolic Engineering to Develop a Pathway for the Selective Cleavage of Carbon-Nitrogen Bonds

Energy Technology Data Exchange (ETDEWEB)

John J. Kilbane II

2005-10-01

The objective of the project is to develop a biochemical pathway for the selective cleavage of C-N bonds in molecules found in petroleum. Specifically a novel biochemical pathway will be developed for the selective cleavage of C-N bonds in carbazole. The cleavage of the first C-N bond in carbazole is accomplished by the enzyme carbazole dioxygenase, that catalyzes the conversion of carbazole to 2-aminobiphenyl-2,3-diol. The genes encoding carbazole dioxygenase were cloned from Sphingomonas sp. GTIN11 and from Pseudomonas resinovorans CA10. The selective cleavage of the second C-N bond has been challenging, and efforts to overcome that challenge have been the focus of recent research in this project. Enrichment culture experiments succeeded in isolating bacterial cultures that can metabolize 2-aminobiphenyl, but no enzyme capable of selectively cleaving the C-N bond in 2-aminobiphenyl has been identified. Aniline is very similar to the structure of 2-aminobiphenyl and aniline dioxygenase catalyzes the conversion of aniline to catechol and ammonia. For the remainder of the project the emphasis of research will be to simultaneously express the genes for carbazole dioxygenase and for aniline dioxygenase in the same bacterial host and then to select for derivative cultures capable of using carbazole as the sole source of nitrogen.

MetaPathways v2.5: quantitative functional, taxonomic and usability improvements.

Science.gov (United States)

Konwar, Kishori M; Hanson, Niels W; Bhatia, Maya P; Kim, Dongjae; Wu, Shang-Ju; Hahn, Aria S; Morgan-Lang, Connor; Cheung, Hiu Kan; Hallam, Steven J

2015-10-15

Next-generation sequencing is producing vast amounts of sequence information from natural and engineered ecosystems. Although this data deluge has an enormous potential to transform our lives, knowledge creation and translation need software applications that scale with increasing data processing and analysis requirements. Here, we present improvements to MetaPathways, an annotation and analysis pipeline for environmental sequence information that expedites this transformation. We specifically address pathway prediction hazards through integration of a weighted taxonomic distance and enable quantitative comparison of assembled annotations through a normalized read-mapping measure. Additionally, we improve LAST homology searches through BLAST-equivalent E-values and output formats that are natively compatible with prevailing software applications. Finally, an updated graphical user interface allows for keyword annotation query and projection onto user-defined functional gene hierarchies, including the Carbohydrate-Active Enzyme database. MetaPathways v2.5 is available on GitHub: http://github.com/hallamlab/metapathways2. shallam@mail.ubc.ca Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

European history crossroads as pathways to intercultural and media education (EHISTO)

OpenAIRE

Popp, Susanne; Schumann, Jutta; Simmet, Oliver; Szczecińska, Joanna; Hadrysiak, Sylwia; Haydn, Terry; Lane, Kathleen; Belton, Teresa; Yarker, Patrick; García-Peñalvo, Francisco José; Zangrando, Valentina; Seoane Pardo, Antonio M.; Rodríguez-Conde, María José; García-Holgado, Alicia; Vinterek, Monika

2013-01-01

[EN] EHISTO (European history crossroads as pathways to intercultural and media education) is concerned with the mediation of history in popular (science) media and the question of social and political responsibility of journalists and other mediators of history, especially teachers, in the field of commercial presentation of history. The project responds to the increasing significance of a commercialised mediation of history within the public historical culture and reflects the fact...

DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathways activated by microorg...anisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

Pathway index models for construction of patient-specific risk profiles.

Science.gov (United States)

Eng, Kevin H; Wang, Sijian; Bradley, William H; Rader, Janet S; Kendziorski, Christina

2013-04-30

Statistical methods for variable selection, prediction, and classification have proven extremely useful in moving personalized genomics medicine forward, in particular, leading to a number of genomic-based assays now in clinical use for predicting cancer recurrence. Although invaluable in individual cases, the information provided by these assays is limited. Most often, a patient is classified into one of very few groups (e.g., recur or not), limiting the potential for truly personalized treatment. Furthermore, although these assays provide information on which individuals are at most risk (e.g., those for which recurrence is predicted), they provide no information on the aberrant biological pathways that give rise to the increased risk. We have developed an approach to address these limitations. The approach models a time-to-event outcome as a function of known biological pathways, identifies important genomic aberrations, and provides pathway-based patient-specific assessments of risk. As we demonstrate in a study of ovarian cancer from The Cancer Genome Atlas project, the patient-specific risk profiles are powerful and efficient characterizations useful in addressing a number of questions related to identifying informative patient subtypes and predicting survival. Copyright © 2012 John Wiley & Sons, Ltd.

Mapping and changing informal nurse leadership communication pathways in a health system.

Science.gov (United States)

Benton, David C

2015-03-01

Social network analysis (SNA) is increasingly being used to provide a visual and quantitative analysis of relationships among groups of staff and other subjects of interest. This paper examines the role SNA can play in identifying existing networks, and measures the impact of participation in brief task-focused project groups on the underlying communication pathways. An SNA of a closed group of nurse leaders was conducted in a health system in Scotland, UK. Data were collected on two occasions 6 months apart. Analysis of both whole network and individual node-based (nurse leader) measures were undertaken. Analysis revealed that the initial network structure was related to functional departments. By establishing task and finish groups, network density and other key measures could be improved. SNA is a useful tool in mapping existing networks and evaluating how these can be strengthened through the use of task orientated project work. This easy-to-use technique can provide useful insights and a means of targeting management action to improve communication pathways in a moderately large and complex nurse leadership group. Further clinical and academic potential uses of the technique are suggested. Copyright © 2015. Published by Elsevier B.V.

PAPA: a flexible tool for identifying pleiotropic pathways using genome-wide association study summaries.

Science.gov (United States)

Wen, Yan; Wang, Wenyu; Guo, Xiong; Zhang, Feng

2016-03-15

: Pleiotropy is common in the genetic architectures of complex diseases. To the best of our knowledge, no analysis tool has been developed for identifying pleiotropic pathways using multiple genome-wide association study (GWAS) summaries by now. Here, we present PAPA, a flexible tool for pleiotropic pathway analysis utilizing GWAS summary results. The performance of PAPA was validated using publicly available GWAS summaries of body mass index and waist-hip ratio of the GIANT datasets. PAPA identified a set of pleiotropic pathways, which have been demonstrated to be involved in the development of obesity. PAPA program, document and illustrative example are available at http://sourceforge.net/projects/papav1/files/ : fzhxjtu@mail.xjtu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Clinical pathway for patients with Chronic Myeloid Leukaemia: The Euriclea Project.

Science.gov (United States)

Botti, Stefano; Gargiulo, Gianpaolo; Bombaci, Felice; Artioli, Giovanna; Cosentino, Chiara; Pignatelli, Adriana Concetta; Torino, Daniela; Lionetti, Maria Marcella; Samarani, Emanuela; Cappucciati, Lorella; Bordiga, Paola; Diodati, Antonella; Caffarri, Cristiana; Rosini, Irene; Pane, Fabrizio

2017-07-18

The use of Tirosine Kinase Ihnibitors (TKIs) for the treatment of Chronic Myeloid Leukemia (CML) has definitely represented a turning point in the treatment of the onco-hematological diseases. Over the years, the interest of physicians, nurses, patients and caregivers has increasingly focused on the aspects of the humanization of care, the management of side effects and on the full and constant therapeutic adherence. The aim of the project was to define patient-oriented care processes, based on a proactive approach that can fully respond to the new health needs of CML patients. A nursing expert Working Group (WG) was established. WG reviewed literature about CML patients assistance and then it was conducted a survey on organizational models for the treatment of CML patients, adopted by Italian haematologic and transplant centers.  Finally, the main issues regarding CML patients care were identified and discussed on a multiprofessional basis. Euriclea Project for care of CML patients with the description of a new and expanded nurse role was defined. The Nurse Case Manager or Nursing Clinical Experts were identified as key people for the management of the side effects of treatment, the promotion of the therapeutic adherence and the evaluation of efficacy and effectiveness of the process through the identification of specific indicators for structure, process and outcome. The focal areas of the care process were identified so as to define a different approach to the CML patient, through a holistic view of care and the multidisciplinary interventions.

Pathways Intern Report

Science.gov (United States)

Bell, Evan A.

2015-01-01

During my time at NASA, I worked with the Granular Mechanics and Regolith Organization (GMRO), better known as Swamp Works. The goal of the lab is to find ways to utilize resources found after the astronaut or robot has landed on another planet or asteroid. This concept is known as in-situ resource utilization and it is critical to long term missions such as those to Mars. During my time here I worked on the Asteroid and Lava Tube Free Flyer project (ALTFF). A lava tube, such as the one shown in figure 1, is a long tear drop shaped cavern that is produced when molten lava tunnels through the surrounding rock creating large unground pathways. Before mining for resources on Mars or on asteroids, a sampling mission must be done to scout out useful resource deposits. ALTFF's goal is to provide a low cost, autonomous scout robot that can sample the surface and return to the mother ship or lander for further processing of the samples. The vehicle will be looking for water ice in the regolith that can be processed into either potable water, hydrogen and oxygen fuel, or a binder material for 3D printing. By using a low cost craft to sample, there is much less risk to the more expensive mother ship or lander. While my main task was the construction of a simulation environment to test control code in and the construction of the asteroid free flyer prototype, there were other tasks that I performed relating to the ALTFF project.

Pathways Intern Report

Science.gov (United States)

Huggett, Daniel James

2017-01-01

The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

Changes in water availability in the Upper Blue Nile basin under the representative concentration pathways scenario

NARCIS (Netherlands)

Haile, Alemseged Tamiru; Akawka, Ashenafi Lekasa; Berhanu, Beza; Rientjes, T.H.M.

2017-01-01

Climatic and hydrological changes will likely be intensified in the Upper Blue Nile (UBN) basin by the effects of global warming. The extent of such effects for representative concentration pathways (RCP) climate scenarios is unknown. We evaluated projected changes in rainfall and evapotranspiration

Getting to Gender Equality in Energy Infrastructure : Lessons from Electricity Generation, Transmission, and Distribution Projects

OpenAIRE

Orlando, Maria Beatriz; Janik, Vanessa Lopes; Vaidya, Pranav; Angelou, Nicolina; Zumbyte, Ieva; Adams, Norma

2018-01-01

Getting to Gender Equality in Electricity Infrastructure: Lessons from Electricity Generation, Transmission, and Distribution Projects examines the social and gender footprint of large-scale electricity generation, transmission, and distribution projects to establish a foundation on which further research and replication of good practices can be built. The main impact pathways analyzed are...

Interleukins and their signaling pathways in the Reactome biological pathway database.

Science.gov (United States)

Jupe, Steve; Ray, Keith; Roca, Corina Duenas; Varusai, Thawfeek; Shamovsky, Veronica; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

2018-04-01

There is a wealth of biological pathway information available in the scientific literature, but it is spread across many thousands of publications. Alongside publications that contain definitive experimental discoveries are many others that have been dismissed as spurious, found to be irreproducible, or are contradicted by later results and consequently now considered controversial. Many descriptions and images of pathways are incomplete stylized representations that assume the reader is an expert and familiar with the established details of the process, which are consequently not fully explained. Pathway representations in publications frequently do not represent a complete, detailed, and unambiguous description of the molecules involved; their precise posttranslational state; or a full account of the molecular events they undergo while participating in a process. Although this might be sufficient to be interpreted by an expert reader, the lack of detail makes such pathways less useful and difficult to understand for anyone unfamiliar with the area and of limited use as the basis for computational models. Reactome was established as a freely accessible knowledge base of human biological pathways. It is manually populated with interconnected molecular events that fully detail the molecular participants linked to published experimental data and background material by using a formal and open data structure that facilitates computational reuse. These data are accessible on a Web site in the form of pathway diagrams that have descriptive summaries and annotations and as downloadable data sets in several formats that can be reused with other computational tools. The entire database and all supporting software can be downloaded and reused under a Creative Commons license. Pathways are authored by expert biologists who work with Reactome curators and editorial staff to represent the consensus in the field. Pathways are represented as interactive diagrams that include as

High-throughput screening identifies novel agents eliciting hypersensitivity in Fanconi pathway-deficient cancer cells

Czech Academy of Sciences Publication Activity Database

Gallmeier, E.; Hucl, T.; Brody, J.R.; Dezentje, D.A.; Tahir, K.; Kašpárková, Jana; Brabec, Viktor; Bachman, K.E.; Kern, S.E.

2007-01-01

Roč. 67, č. 5 (2007), s. 2169-2177 ISSN 0008-5472 R&D Projects: GA ČR(CZ) GA305/05/2030; GA MZd(CZ) NR8562 Institutional research plan: CEZ:AV0Z50040702 Keywords : cancer * Fanconi anemia pathway * p53 Subject RIV: BO - Biophysics Impact factor: 7.672, year: 2007

Diffusion Tensor Imaging of Human Cerebellar Pathways and their Interplay with Cerebral Macrostructure

Directory of Open Access Journals (Sweden)

Zafer eKeser

2015-04-01

Full Text Available Cerebellar white matter connections to the central nervous system are classified functionally into the spinocerebellar, vestibulocerebellar, and cerebrocerebellar subdivisions. The Spinocerebellar (SC pathways project from spinal cord to cerebellum, whereas the vestibulocerebellar (VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI. Ten right-handed healthy subjects (7 males and 3 females, age range 20-51 years were studied. DT-MRI data were acquired with a voxel size = 2mm x 2mm x 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC, parieto-ponto-cerebellar (PPC, temporo-ponto-cerebellar (TPC and occipito-ponto-cerebellar (OPC. The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM, cerebral white matter (WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~ 3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~ 25.8 ± 7.3 mL, or a percentage of 1.52 ± 0.43 of the total intracranial volume.

Mapping and Changing Informal Nurse Leadership Communication Pathways in a Health System

Directory of Open Access Journals (Sweden)

David C. Benton, PhD, RN, FRCN

2015-03-01

Conclusions: SNA is a useful tool in mapping existing networks and evaluating how these can be strengthened through the use of task orientated project work. This easy-to-use technique can provide useful insights and a means of targeting management action to improve communication pathways in a moderately large and complex nurse leadership group. Further clinical and academic potential uses of the technique are suggested.

Parasubthalamic and calbindin nuclei in the posterior lateral hypothalamus are the major hypothalamic targets for projections from the central and anterior basomedial nuclei of the amygdala.

Science.gov (United States)

Barbier, Marie; Chometton, Sandrine; Peterschmitt, Yvan; Fellmann, Dominique; Risold, Pierre-Yves

2017-09-01

The parasubthalamic nucleus (PSTN) and the ventrally adjacent calbindin nucleus (CbN) form a nuclear complex in the posterior lateral hypothalamic area (LHA), recently characterized as connected with the central nucleus of the amygdala (CEA). The aim of the present work is to analyze in detail the projections from the amygdala into the PSTN/CbN, also focusing on pathways into the LHA. After fluorogold injections into the PSTN/CbN, the medial part of the CEA (CEAm) appears to be the main supplier of projections from the CEA. Other amygdalar nuclei contribute to the innervation of the PSTN/CbN complex, including the anterior part of the basomedial nucleus (BMAa). Injections of the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHAL), into the CEAm and BMAa revealed that projections from the CEAm follow two pathways into the LHA: a dorsal pathway formed by axons that also innervate the paraventricular hypothalamic nucleus, the anterior perifornical LHA and the PSTN, and a ventral pathway that runs laterally adjacent to the ventrolateral hypothalamic tract (vlt) and ends in the CbN. By contrast, the BMAa and other telencephalic structures, such as the fundus striatum project to the CbN via the ventral pathway. Confirming the microscopic observation, a semi-quantitative analysis of the density of these projections showed that the PSTN and the CbN are the major hypothalamic targets for the projections from the CEAm and the BMAa, respectively. PSTN and CbN receive these projections through distinct dorsal and ventral routes in the LHA. The ventral pathway forms a differentiated tract, named here the ventrolateral amygdalo-hypothalamic tract (vlah), that is distinct from, but runs adjacent to, the vlt. Both the vlt and the vlah had been previously described as forming an olfactory path into the LHA. These results help to better characterize the CbN within the PSTN/CbN complex and are discussed in terms of the functional organization of the network involving the

Signaling pathways in a Citrus EST database

Directory of Open Access Journals (Sweden)

Angela Mehta

2007-01-01

Full Text Available Citrus spp. are economically important crops, which in Brazil are grown mainly in the State of São Paulo. Citrus cultures are attacked by several pathogens, causing severe yield losses. In order to better understand this culture, the Millenium Project (IAC Cordeirópolis was launched in order to sequence Citrus ESTs (expressed sequence tags from different tissues, including leaf, bark, fruit, root and flower. Plants were submitted to biotic and abiotic stresses and investigated under different development stages (adult vs. juvenile. Several cDNA libraries were constructed and the sequences obtained formed the Citrus ESTs database with almost 200,000 sequences. Searches were performed in the Citrus database to investigate the presence of different signaling pathway components. Several of the genes involved in the signaling of sugar, calcium, cytokinin, plant hormones, inositol phosphate, MAPKinase and COP9 were found in the citrus genome and are discussed in this paper. The results obtained may indicate that similar mechanisms described in other plants, such as Arabidopsis, occur in citrus. Further experimental studies must be conducted in order to understand the different signaling pathways present.

Local differentiation of cell wall matrix polysaccharides in sinuous pavement cells: its possible involvement in the flexibility of cell shape.

Science.gov (United States)

Sotiriou, P; Giannoutsou, E; Panteris, E; Galatis, B; Apostolakos, P

2018-03-01

The distribution of homogalacturonans (HGAs) displaying different degrees of esterification as well as of callose was examined in cell walls of mature pavement cells in two angiosperm and two fern species. We investigated whether local cell wall matrix differentiation may enable pavement cells to respond to mechanical tension forces by transiently altering their shape. HGA epitopes, identified with 2F4, JIM5 and JIM7 antibodies, and callose were immunolocalised in hand-made or semithin leaf sections. Callose was also stained with aniline blue. The structure of pavement cells was studied with light and transmission electron microscopy (TEM). In all species examined, pavement cells displayed wavy anticlinal cell walls, but the waviness pattern differed between angiosperms and ferns. The angiosperm pavement cells were tightly interconnected throughout their whole depth, while in ferns they were interconnected only close to the external periclinal cell wall and intercellular spaces were developed between them close to the mesophyll. Although the HGA epitopes examined were located along the whole cell wall surface, the 2F4- and JIM5- epitopes were especially localised at cell lobe tips. In fern pavement cells, the contact sites were impregnated with callose and JIM5-HGA epitopes. When tension forces were applied on leaf regions, the pavement cells elongated along the stretching axis, due to a decrease in waviness of anticlinal cell walls. After removal of tension forces, the original cell shape was resumed. The presented data support that HGA epitopes make the anticlinal pavement cell walls flexible, in order to reversibly alter their shape. Furthermore, callose seems to offer stability to cell contacts between pavement cells, as already suggested in photosynthetic mesophyll cells. © 2017 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

Assessing patterns in introduction pathways of alien species by linking major invasion data bases

Czech Academy of Sciences Publication Activity Database

Saul, W.-C.; Roy, H. E.; Booy, O.; Carnevali, L.; Chen, H.-J.; Genovesi, P.; Harrower, C.; Hulme, P. E.; Pagad, S.; Pergl, Jan; Jeschke, J.M.

2017-01-01

Roč. 54, č. 2 (2017), s. 657-669 ISSN 0021-8901 R&D Projects: GA ČR(CZ) GAP504/11/1028 Grant - others:COST(XE) TD1209 Program:FA Institutional support: RVO:67985939 Keywords : invasions * pathways * databases Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biodiversity conservation Impact factor: 5.301, year: 2016

Pathways for implementing REDD+. Experiences from carbon markets and communities

Energy Technology Data Exchange (ETDEWEB)

Zhu, X.; Ravnkilde Moeller, L.; Lopez, T. De; Romero, M.Z.

2011-07-01

This issue of Carbon Market Perspectives on 'Pathways for implementing REDD+: Experience from carbon markets and communities' discusses the role of carbon markets in scaling up investments for REDD+ in developing countries. Nine articles authored by experienced negotiators on REDD+, carbon market actors, project developers and other leading experts share experiences and make suggestions on the key elements of a future international REDD+ regime: Architecture and underlying principles, measuring, reporting and verification (MRV), private-sector involvement, the rights of indigenous people and local communities, biodiversity conservation and environmental integrity. The articles are grouped under three main topics: the lessons of existing REDD+ projects; the future REDD+ regime and the role of carbon markets; and experiences and ideas about the involvement of indigenous people and local communities. (LN)

DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

Proliferation Resistance: Acquisition/Diversion Pathway Analysis for the DUPIC Fuel Cycle

International Nuclear Information System (INIS)

Ko, Won Il; Chang, Hong Lae; Song, Dae Yong; Lee, Ho Hee; Kwon, Eun Ha; Jeong, Chang Joon; Kim, Ho Dong

2009-07-01

Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation - innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures. Since this requires an acquisition/diversion pathway analysis, this report describes a systematic approach developed for the identification and analysis of pathways for the acquisition of weapons-usable nuclear material using the DUPIC fuel cycle system. At the first step, the objectives of the proliferation were identified, including the quality and quantity of the material, the time required to acquire the material for the proliferation, thr capability of the potential proliferant country, etc. At the second step, the possible strategies, which the potential proliferant country could adopt, were identified: undeclared removal of nuclear material from the fuel cycle facilities; and further treatment of the diverted nuclear materials needed to acquire weapons-usable materials. At the final step, a systematic approach to select the plausible pathways for the acquisition/diversion of nuclear material during the whole fuel cycle has been developed. The coarse material diversion pathways for the DUPIC fuel cycle and the approach developed was reviewed and discussed at the experts meeting at the IAEA for its appropriateness and comprehensiveness

Quadrupolar transfer pathways

Science.gov (United States)

Antonijevic, Sasa; Bodenhausen, Geoffrey

2006-06-01

A set of graphical conventions called quadrupolar transfer pathways is proposed to describe a wide range of experiments designed for the study of quadrupolar nuclei with spin quantum numbers I = 1, 3/2, 2, 5/2, etc. These pathways, which inter alea allow one to appreciate the distinction between quadrupolar and Zeeman echoes, represent a generalization of the well-known coherence transfer pathways. Quadrupolar transfer pathways not merely distinguish coherences with different orders -2 I ⩽ p ⩽ +2 I, but allow one to follow the fate of coherences associated with single transitions that have the same coherence orderp=mIr-mIs but can be distinguished by a satellite orderq=(mIr)2-(mIs)2.

Design of Adaptive Policy Pathways under Deep Uncertainties

Science.gov (United States)

Babovic, Vladan

2013-04-01

The design of large-scale engineering and infrastructural systems today is growing in complexity. Designers need to consider sociotechnical uncertainties, intricacies, and processes in the long- term strategic deployment and operations of these systems. In this context, water and spatial management is increasingly challenged not only by climate-associated changes such as sea level rise and increased spatio-temporal variability of precipitation, but also by pressures due to population growth and particularly accelerating rate of urbanisation. Furthermore, high investment costs and long term-nature of water-related infrastructure projects requires long-term planning perspective, sometimes extending over many decades. Adaptation to such changes is not only determined by what is known or anticipated at present, but also by what will be experienced and learned as the future unfolds, as well as by policy responses to social and water events. As a result, a pathway emerges. Instead of responding to 'surprises' and making decisions on ad hoc basis, exploring adaptation pathways into the future provide indispensable support in water management decision-making. In this contribution, a structured approach for designing a dynamic adaptive policy based on the concepts of adaptive policy making and adaptation pathways is introduced. Such an approach provides flexibility which allows change over time in response to how the future unfolds, what is learned about the system, and changes in societal preferences. The introduced flexibility provides means for dealing with complexities of adaptation under deep uncertainties. It enables engineering systems to change in the face of uncertainty to reduce impacts from downside scenarios while capitalizing on upside opportunities. This contribution presents comprehensive framework for development and deployment of adaptive policy pathway framework, and demonstrates its performance under deep uncertainties on a case study related to urban

Troubling travellers: are ecologically harmful alien species associated with particular introduction pathways?

Czech Academy of Sciences Publication Activity Database

Pergl, Jan; Pyšek, Petr; Bacher, S.; Essl, F.; Genovesi, P.; Harrower, C.; Hulme, P. E.; Jeschke, J.M.; Kenis, M.; Kühn, I.; Perglová, Irena; Rabitsch, W.; Roques, A.; Roy, D. B.; Roy, H. E.; Vila, M.; Winter, M.; Nentwig, W.

2017-01-01

Roč. 32, č. 1 (2017), s. 1-20 ISSN 1619-0033 R&D Projects: GA ČR GB14-36079G; GA ČR(CZ) GAP504/11/1028 Grant - others:AV ČR(CZ) AP1002; COST(XE) TD1209 Program:Akademická prémie - Praemium Academiae; FA Institutional support: RVO:67985939 Keywords : invasions * pathways * impact Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biodiversity conservation

Final Report: Hydrogen Production Pathways Cost Analysis (2013 – 2016)

Energy Technology Data Exchange (ETDEWEB)

James, Brian David [Strategic Analysis Inc., Arlington, VA (United States); DeSantis, Daniel Allan [Strategic Analysis Inc., Arlington, VA (United States); Saur, Genevieve [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-09-30

This report summarizes work conducted under a three year Department of Energy (DOE) funded project to Strategic Analysis, Inc. (SA) to analyze multiple hydrogen (H₂) production technologies and project their corresponding levelized production cost of H₂. The analysis was conducted using the H2A Hydrogen Analysis Tool developed by the DOE and National Renewable Energy Laboratory (NREL). The project was led by SA but conducted in close collaboration with the NREL and Argonne National Laboratory (ANL). In-depth techno-economic analysis (TEA) of five different H₂ production methods was conducted. These TEAs developed projections for capital costs, fuel/feedstock usage, energy usage, indirect capital costs, land usage, labor requirements, and other parameters, for each H₂ production pathway, and use the resulting cost and system parameters as inputs into the H2A discounted cash flow model to project the production cost of H₂ ($/kgH₂). Five technologies were analyzed as part of the project and are summarized in this report: Proton Exchange Membrane technology (PEM), High temperature solid oxide electrolysis cell technology (SOEC), Dark fermentation of biomass for H₂ production, H₂ production via Monolithic Piston-Type Reactors with rapid swing reforming and regeneration reactions, and Reformer-Electrolyzer-Purifier (REP) technology developed by Fuel Cell Energy, Inc. (FCE).

Nucleus retroambiguous projections to lumbosacral motoneuronal cell groups in the male cat

NARCIS (Netherlands)

Vanderhorst, VGJM; Holstege, G

1997-01-01

Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat, Lumbosacral injections of wheat

Spatial distribution of intermingling pools of projection neurons with distinct targets: A 3D analysis of the commissural ganglia in Cancer borealis.

Science.gov (United States)

Follmann, Rosangela; Goldsmith, Christopher John; Stein, Wolfgang

2017-06-01

Projection neurons play a key role in carrying long-distance information between spatially distant areas of the nervous system and in controlling motor circuits. Little is known about how projection neurons with distinct anatomical targets are organized, and few studies have addressed their spatial organization at the level of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric nervous system of the crab Cancer borealis, projection neurons convey sensory, motor, and modulatory information to several distinct anatomical regions. While the functions of descending projection neurons (dPNs) which control downstream motor circuits in the stomatogastric ganglion are well characterized, their anatomical distribution as well as that of neurons projecting to the labrum, brain, and thoracic ganglion have received less attention. Using cell membrane staining, we investigated the spatial distribution of CoG projection neurons in relation to all CoG neurons. Retrograde tracing revealed that somata associated with different axonal projection pathways were not completely spatially segregated, but had distinct preferences within the ganglion. Identified dPNs had diameters larger than 70% of CoG somata and were restricted to the most medial and anterior 25% of the ganglion. They were contained within a cluster of motor neurons projecting through the same nerve to innervate the labrum, indicating that soma position was independent of function and target area. Rather, our findings suggest that CoG neurons projecting to a variety of locations follow a generalized rule: for all nerve pathway origins, the soma cluster centroids in closest proximity are those whose axons project down that pathway. © 2017 Wiley Periodicals, Inc.

Emissions pathways, climate change, and impacts on California

Science.gov (United States)

Hayhoe, Katharine; Cayan, Daniel; Field, Christopher B.; Frumhoff, Peter C.; Maurer, Edwin P.; Miller, Norman L.; Moser, Susanne C.; Schneider, Stephen H.; Cahill, Kimberly Nicholas; Cleland, Elsa E.; Dale, Larry; Drapek, Ray; Hanemann, R. Michael; Kalkstein, Laurence S.; Lenihan, James; Lunch, Claire K.; Neilson, Ronald P.; Sheridan, Scott C.; Verville, Julia H.

2004-01-01

The magnitude of future climate change depends substantially on the greenhouse gas emission pathways we choose. Here we explore the implications of the highest and lowest Intergovernmental Panel on Climate Change emissions pathways for climate change and associated impacts in California. Based on climate projections from two state-of-the-art climate models with low and medium sensitivity (Parallel Climate Model and Hadley Centre Climate Model, version 3, respectively), we find that annual temperature increases nearly double from the lower B1 to the higher A1fi emissions scenario before 2100. Three of four simulations also show greater increases in summer temperatures as compared with winter. Extreme heat and the associated impacts on a range of temperature-sensitive sectors are substantially greater under the higher emissions scenario, with some interscenario differences apparent before midcentury. By the end of the century under the B1 scenario, heatwaves and extreme heat in Los Angeles quadruple in frequency while heat-related mortality increases two to three times; alpine/subalpine forests are reduced by 50–75%; and Sierra snowpack is reduced 30–70%. Under A1fi, heatwaves in Los Angeles are six to eight times more frequent, with heat-related excess mortality increasing five to seven times; alpine/subalpine forests are reduced by 75–90%; and snowpack declines 73–90%, with cascading impacts on runoff and streamflow that, combined with projected modest declines in winter precipitation, could fundamentally disrupt California's water rights system. Although interscenario differences in climate impacts and costs of adaptation emerge mainly in the second half of the century, they are strongly dependent on emissions from preceding decades. PMID:15314227

Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

Science.gov (United States)

Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

2017-11-20

Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A designated centre for people with disabilities, operated by St John of God Community Services Ltd., Kerry

LENUS (Irish Health Repository)

Gobius, Ilan

2016-01-01

The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

LENUS (Irish Health Repository)

Gobius, Ilan

2016-01-01

The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

Determination of positions and curved transition pathways of screw dislocations in BCC crystals from atomic displacements

Czech Academy of Sciences Publication Activity Database

Gröger, Roman; Vítek, V.

2015-01-01

Roč. 643, SEP (2015), s. 203-210 ISSN 0921-5093 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : Screw dislocation * BCC metal * Dislocation pathway Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.647, year: 2015

Pathway Processor 2.0: a web resource for pathway-based analysis of high-throughput data.

Science.gov (United States)

Beltrame, Luca; Bianco, Luca; Fontana, Paolo; Cavalieri, Duccio

2013-07-15

Pathway Processor 2.0 is a web application designed to analyze high-throughput datasets, including but not limited to microarray and next-generation sequencing, using a pathway centric logic. In addition to well-established methods such as the Fisher's test and impact analysis, Pathway Processor 2.0 offers innovative methods that convert gene expression into pathway expression, leading to the identification of differentially regulated pathways in a dataset of choice. Pathway Processor 2.0 is available as a web service at http://compbiotoolbox.fmach.it/pathwayProcessor/. Sample datasets to test the functionality can be used directly from the application. duccio.cavalieri@fmach.it Supplementary data are available at Bioinformatics online.

Probabilistic pathway construction.

Science.gov (United States)

Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

2011-07-01

Expression of novel synthesis pathways in host organisms amenable to genetic manipulations has emerged as an attractive metabolic engineering strategy to overproduce natural products, biofuels, biopolymers and other commercially useful metabolites. We present a pathway construction algorithm for identifying viable synthesis pathways compatible with balanced cell growth. Rather than exhaustive exploration, we investigate probabilistic selection of reactions to construct the pathways. Three different selection schemes are investigated for the selection of reactions: high metabolite connectivity, low connectivity and uniformly random. For all case studies, which involved a diverse set of target metabolites, the uniformly random selection scheme resulted in the highest average maximum yield. When compared to an exhaustive search enumerating all possible reaction routes, our probabilistic algorithm returned nearly identical distributions of yields, while requiring far less computing time (minutes vs. years). The pathways identified by our algorithm have previously been confirmed in the literature as viable, high-yield synthesis routes. Prospectively, our algorithm could facilitate the design of novel, non-native synthesis routes by efficiently exploring the diversity of biochemical transformations in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

Representative Agricultural Pathways: A Trans-Disciplinary Approach to Agricultural Model Inter-comparison, Improvement, Climate Impact Assessment and Stakeholder Engagement

Science.gov (United States)

Antle, J. M.; Valdivia, R. O.; Claessens, L.; Nelson, G. C.; Rosenzweig, C.; Ruane, A. C.; Vervoort, J.

2013-12-01

The global change research community has recognized that new pathway and scenario concepts are needed to implement impact and vulnerability assessment that is logically consistent across local, regional and global scales. For impact and vulnerability assessment, new socio-economic pathway and scenario concepts are being developed. Representative Agricultural Pathways (RAPs) are designed to extend global pathways to provide the detail needed for global and regional assessment of agricultural systems. In addition, research by the Agricultural Model Inter-comparison and Improvement Project (AgMIP) shows that RAPs provide a powerful way to engage stakeholders in climate-related research throughout the research process and in communication of research results. RAPs are based on the integrated assessment framework developed by AgMIP. This framework shows that both bio-physical and socio-economic drivers are essential components of agricultural pathways and logically precede the definition of adaptation and mitigation scenarios that embody associated capabilities and challenges. This approach is based on a trans-disciplinary process for designing pathways and then translating them into parameter sets for bio-physical and economic models that are components of agricultural integrated assessments of climate impact, adaptation and mitigation. RAPs must be designed to be part of a logically consistent set of drivers and outcomes from global to regional and local. Global RAPs are designed to be consistent with higher-level global socio-economic pathways, but add key agricultural drivers such as agricultural growth trends that are not specified in more general pathways, as illustrated in a recent inter-comparison of global agricultural models. To create pathways at regional or local scales, further detail is needed. At this level, teams of scientists and other experts with knowledge of the agricultural systems and regions work together through a step-wise process. Experiences

Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis.

Science.gov (United States)

Kammen, Alexandra; Law, Meng; Tjan, Bosco S; Toga, Arthur W; Shi, Yonggang

2016-01-15

Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone-air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer's Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome.

Science.gov (United States)

Campbell, Malcolm G; Kohane, Isaac S; Kong, Sek Won

2013-09-24

Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Two previously published blood gene expression data sets--the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members)--were analyzed. All individuals of each dataset were projected to biological pathways, and each sample's Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression

Integrated task plans for the Hanford Environmental Dose Reconstruction Project, June 1992 through May 1994

International Nuclear Information System (INIS)

Shipler, D.B.

1993-09-01

The purpose of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate radiation doses from Hanford Site operations since 1944 to representative individuals. The primary objective of work to be performed through May 1994 is to determine the project's appropriate scope: space, time, radionuclides, pathways and representative individuals; determine the project's appropriate level of accuracy/level of uncertainty in dose estimates; complete model and data development; and estimate doses for the Hanford Thyroid Disease Study and representative individuals. A major objective of the HEDR Project is to estimate doses to the thyroid of individuals who were exposed to iodine-131. A principal pathway for many of these individuals was milk from cows that ate vegetation contaminated by iodine-131 released into the air from Hanford facilities. The plan for June 1992 through May 1994 has been prepared based on activities and budgets approved by the Technical Steering Panel (TSP) at its meetings on January 7--9, 1993 and February 25--26, 1993. The activities can be divided into three broad categories: (1) computer code and data development activities, (2) calculation of doses, and (3) technical and communication support to the TSP and the TSP Native American Working Group (NAWG). The following activities will be conducted to accomplish project objectives through May 1994

METABOLIC ENGINEERING TO DEVELOP A PATHWAY FOR THE SELECTIVE CLEAVAGE OF CARBON-NITROGEN BONDS

Energy Technology Data Exchange (ETDEWEB)

John J. Kilbane II

2004-10-01

The objective of the project is to develop biochemical pathways for the selective cleavage of C-N bonds in molecules found in petroleum. The initial phase of the project was focused on the isolation or development of an enzyme capable of cleaving the C-N bond in aromatic amides, specifically 2-aminobiphenyl. The objective of the second phase of the research will be to construct a biochemical pathway for the selective removal of nitrogen from carbazole by combining the carA genes from Sphingomonas sp. GTIN11 with the gene(s) encoding an appropriate deaminase. The objective of the final phase of the project will be to develop derivative C-N bond cleaving enzymes that have broader substrate ranges and to demonstrate the use of such strains to selectively remove nitrogen from petroleum. During the first year of the project (October, 2002-September, 2003) enrichment culture experiments resulted in the isolation of microbial cultures that utilize aromatic amides as sole nitrogen sources, several amidase genes were cloned and were included in directed evolution experiments to obtain derivatives that can cleave C-N bonds in aromatic amides, and the carA genes from Sphingomonas sp. GTIN11, and Pseudomonas resinovorans CA10 were cloned in vectors capable of replicating in Escherichia coli. During the second year of the project (October, 2003-September, 2004) enrichment culture experiments succeeded in isolating a mixed bacterial culture that can utilize 2-aminobiphenyl as a sole nitrogen source, directed evolution experiments were focused on the aniline dioxygenase enzyme that is capable of deaminating aniline, and expression vectors were constructed to enable the expression of genes encoding C-N bond cleaving enzymes in Rhodococcus hosts. The construction of a new metabolic pathway to selectively remove nitrogen from carbazole and other molecules typically found in petroleum should lead to the development of a process to improve oil refinery efficiency by reducing the

Direct and indirect pathways to lamina I in the medulla oblongata and spinal cord of the cat

Science.gov (United States)

Holstege, Gert

1988-01-01

The pathways to lamina I in the medulla oblongata and spinal cord of the cat were traced using horse-radish-peroxidase (HRP) and autoradiographic techniques. The HRP results indicated that several neuronal cell groups in the brain stem and hypothalamus project to the spinal cord throughout its total length. The autoradiographic tracing results demonstrated that the strongest projections to lamina I are derived from the following four areas: the caudal nucleus raphe magnus (NRM), the ventral part of the caudal pontine and NRM, the contralaterally projecting lateral pontine or paralemniscal tegmentum, and the paraventricular nucleus of the hypothalamus. In addition, a limited, especially at lumbosacral levels, distinct projection to lamina I was found to originate in the most caudal part of the medullary tegmentum.

Novel metabolic pathways in Archaea.

Science.gov (United States)

Sato, Takaaki; Atomi, Haruyuki

2011-06-01

The Archaea harbor many metabolic pathways that differ to previously recognized classical pathways. Glycolysis is carried out by modified versions of the Embden-Meyerhof and Entner-Doudoroff pathways. Thermophilic archaea have recently been found to harbor a bi-functional fructose-1,6-bisphosphate aldolase/phosphatase for gluconeogenesis. A number of novel pentose-degrading pathways have also been recently identified. In terms of anabolic metabolism, a pathway for acetate assimilation, the methylaspartate cycle, and two CO2-fixing pathways, the 3-hydroxypropionate/4-hydroxybutyrate cycle and the dicarboxylate/4-hydroxybutyrate cycle, have been elucidated. As for biosynthetic pathways, recent studies have clarified the enzymes responsible for several steps involved in the biosynthesis of inositol phospholipids, polyamine, coenzyme A, flavin adeninedinucleotide and heme. By examining the presence/absence of homologs of these enzymes on genome sequences, we have found that the majority of these enzymes and pathways are specific to the Archaea. Copyright © 2011 Elsevier Ltd. All rights reserved.

Phase 1 of the Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

1991-08-01

The work described in this report was prompted by the public's concern about potential effect from the radioactive materials released from the Hanford Site. The Hanford Environmental Dose Reconstruction (HEDR) Project was established to estimate radiation dose the public might have received from the Hanford Site since 1944, when facilities began operating. Phase 1 of the HEDR Project is a ''pilot'' or ''demonstration'' phase. The objectives of this initial phase were to determine whether enough historical information could be found or reconstructed to be used for dose estimation and develop and test conceptual and computational models for calculating credible dose estimates. Preliminary estimates of radiation doses were produced in Phase 1 because they are needed to achieve these objectives. The reader is cautioned that the dose estimates provided in this and other Phase 1 HEDR reports are preliminary. As the HEDR Project continues, the dose estimates will change for at least three reasons: more complete input information for models will be developed; the models themselves will be refined; and the size and shape of the geographic study area will change. This is one of three draft reports that summarize the first phase of the four-phased HEDR Project. This, the Summary Report, is directed to readers who want a general understanding of the Phase 1 work and preliminary dose estimates. The two other reports -- the Air Pathway Report and the Columbia River Pathway Report -- are for readers who understand the radiation dose assessment process and want to see more technical detail. Detailed descriptions of the dose reconstruction process are available in more than 20 supporting reports listed in Appendix A. 32 refs., 46 figs

The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila

Czech Academy of Sciences Publication Activity Database

Horváth, Matěj; Mihajlović, Zorana; Slaninová, Věra; Perez-Gomez, Raquel; Moshkin, Y.; Krejčí, Alena

2016-01-01

Roč. 473, č. 22 (2016), s. 4129-4143 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GA14-08583S Institutional support: RVO:60077344 Keywords : Drosophila * silent information regulator 1 * Notch pathway Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.797, year: 2016

Sea level rise under the Shared Socioeconomic Pathways (SSPs)

Science.gov (United States)

Schleussner, C. F.; Nauels, A.; Rogelj, J.; Mengel, M.; Meinshausen, M.

2017-12-01

In order to assess future sea level rise and its impacts, we need to study climate change pathways combined with different scenarios of socioeconomic development. Here, we present Sea Level Rise (SLR) projections for the Shared Socioeconomic Pathway (SSP) storylines and different year-2100 radiative Forcing Targets (FTs). Future SLR is estimated with a comprehensive SLR emulator that accounts for latest research on additional Antarctic rapid discharge dynamics from hydrofracturing and ice cliff instability. Across all baseline scenario realizations (no dedicated climate mitigation), we find 2100 median SLR relative to 1986-2005 of 102 cm (likely range: 77 to 135 cm) for SSP1, 118 cm (90 to 151 cm) for SSP2, 118 cm (91 to 149 cm) for SSP3, 107 cm (81 to 137 cm) for SSP4, and 144 cm (112 to 184 cm) for SSP5. The 2100 sea level responses for combined SSP-FT scenarios is dominated by the mitigation targets and yield median estimates of 68 cm (56 to 87 cm) for FT 2.6 Wm-2, 76 cm (61 to 107 cm) for FT 3.4 Wm-2, 90 cm (68 to 120 cm) for FT 4.5 Wm-2, and 105 cm (79 to 136 cm) for FT 6.0 Wm-2. Average 2081-2100 annual rates of SLR are 6 mm/yr and 19 mm/yr for the FT 2.6 Wm-2 and the baseline scenarios, respectively. Our model setup allows linking scenario-specific emission and socioeconomic indicators to projected SLR. For limiting median 2100 SSP SLR projections to below 80 cm, we find that 2050 cumulative CO2 emissions since pre-industrial should not exceed around 860 GtC, with the global coal phase-out nearly completed. For SSP mitigation scenarios, the median 2050 carbon price of 90 US$2005 tCO2-1 would correspond to a median 2100 SLR of around 80 cm. Our results confirm that rapid and early emission reductions are essential for limiting 2100 SLR.

Integrated Risk Management Within NASA Programs/Projects

Science.gov (United States)

Connley, Warren; Rad, Adrian; Botzum, Stephen

2004-01-01

As NASA Project Risk Management activities continue to evolve, the need to successfully integrate risk management processes across the life cycle, between functional disciplines, stakeholders, various management policies, and within cost, schedule and performance requirements/constraints become more evident and important. Today's programs and projects are complex undertakings that include a myriad of processes, tools, techniques, management arrangements and other variables all of which must function together in order to achieve mission success. The perception and impact of risk may vary significantly among stakeholders and may influence decisions that may have unintended consequences on the project during a future phase of the life cycle. In these cases, risks may be unintentionally and/or arbitrarily transferred to others without the benefit of a comprehensive systemic risk assessment. Integrating risk across people, processes, and project requirements/constraints serves to enhance decisions, strengthen communication pathways, and reinforce the ability of the project team to identify and manage risks across the broad spectrum of project management responsibilities. The ability to identify risks in all areas of project management increases the likelihood a project will identify significant issues before they become problems and allows projects to make effective and efficient use of shrinking resources. By getting a total team integrated risk effort, applying a disciplined and rigorous process, along with understanding project requirements/constraints provides the opportunity for more effective risk management. Applying an integrated approach to risk management makes it possible to do a better job at balancing safety, cost, schedule, operational performance and other elements of risk. This paper will examine how people, processes, and project requirements/constraints can be integrated across the project lifecycle for better risk management and ultimately improve the

Two visual pathways to the telencephalon in the nurse shark (Ginglymostoma cirratum). I. Retinal projections.

Science.gov (United States)

Luiten, P G

1981-03-10

The central projections of the retina in the nurse shark were studied by anterograde transport of horseradish peroxidase and tritiated proline. With regard to efferent retinal fibers, both techniques gave completely identical results. Projections were found to pretectal area, dorsal thalamus, basal optic nucleus, and optic tectum, all at the contralateral side. The retinal target cells in the dorsal thalamus are restricted to the ventrolateral optic nucleus and the posterior optic nucleus. No evidence was found for an earlier-reported projection to the lateral geniculate nucleus. The present findings show that the ventrolateral optic nucleus exhibits homological features of the dorsal lateral geniculate nucleus in other vertebrate groups, whereas the lateral geniculate nucleus of the nurse shark is much more comparable to the nucleus rotundus of teleosts and birds and would be more appropriately so named. The application of the HRP technique also allowed us to study afferents to the retina by retrograde transport of tracer. Retrogradely labeled cells were observed in the contralateral optic tectum and are apparently similar to those reported for teleosts and birds.

Non-Smad signaling pathways.

Science.gov (United States)

Mu, Yabing; Gudey, Shyam Kumar; Landström, Maréne

2012-01-01

Transforming growth factor-beta (TGFβ) is a key regulator of cell fate during embryogenesis and has also emerged as a potent driver of the epithelial-mesenchymal transition during tumor progression. TGFβ signals are transduced by transmembrane type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively). The activated TβR complex phosphorylates Smad2 and Smad3, converting them into transcriptional regulators that complex with Smad4. TGFβ also uses non-Smad signaling pathways such as the p38 and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways to convey its signals. Ubiquitin ligase tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6) and TGFβ-associated kinase 1 (TAK1) have recently been shown to be crucial for the activation of the p38 and JNK MAPK pathways. Other TGFβ-induced non-Smad signaling pathways include the phosphoinositide 3-kinase-Akt-mTOR pathway, the small GTPases Rho, Rac, and Cdc42, and the Ras-Erk-MAPK pathway. Signals induced by TGFβ are tightly regulated and specified by post-translational modifications of the signaling components, since they dictate the subcellular localization, activity, and duration of the signal. In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways.

Engineered Photorespiratory Bypass Pathways Improve Photosynthetic Efficiency and Growth as Temperature Increases

Science.gov (United States)

Cavanagh, A. P.; South, P. F.; Ort, D. R.; Bernacchi, C.

2017-12-01

In C3 plants grown under ambient [CO2] at 25°C, 23% of the fixed carbon dioxide is lost to photorespiration, the energy expensive metabolic pathway that recycles toxic compounds produced by Rubisco oxygenation reactions. Furthermore, rates of photorespiration increase with rising temperature, as higher temperatures favor increased Rubisco oxygenation. Modelling suggests that the absence of photorespiration could improve gross photosynthesis by 12-55% under projected climate conditions; however, this is difficult to measure empirically, as photorespiration interacts with several metabolic pathways and is an essential process for all C3 plants grown at ambient [O2]. Introduced biochemical bypasses to the native photorespiration pathway hold promise as a strategy to mitigate the impact of temperature on photorespiratory losses. We grew tobacco containing engineered pathways to bypass photorespiration under ambient and elevated temperatures (+5°C) in the field to determine if bypassing photorespiration could mitigate high temperature induced losses in growth and physiology. Our preliminary results show that engineered plants have a higher quantum efficiency under heated conditions than do non-engineered plants, resulting in up to 20% lower yield losses under heated conditions compared to non-engineered plants. These results support the theoretical modelling of temperature impacts on photorespiratory losses, and suggest the bypassing photorespiration could be an important strategy to increase crop yields.

FASSET - An European project for environmental protection

International Nuclear Information System (INIS)

Bruchertseifer, F.

2003-01-01

The European research project ''FASSET'' (Framework ASSessment of Enviromental ImpacT) will provide a framework of the environmental impact of the effects of ionising radiation and will identify protection aims for the environmental protection. This project represent a collaboration of different organisations from the European community: Sweden, Norway, Finland, Great Britain, Spain, France and Germany. The German participants are the GSF-research centre for environment and health and the German radiation protection office. The project is founded by the 5 th EC research programme. The existing national and international radiation protection regulations are focused to the humans. Other species, like plants and animals, are protected indirectly, if their habitat are close to urban areas or they represent a part of the food chain. The ICRP position ''if the man is protected, nature is protected as well'' is now under reconsideration by a ICRP-Taskgroup. The identification of perilled real reference organism by the FASSET-project is an working tool for the definition of the protection aims. For that purpose the project is divided into three working packages: dosimetry, exposure pathways and effects. Another working package is responsible for the developing of the concept using the results provided by the other working packages. (orig.)

KeyPathwayMinerWeb

DEFF Research Database (Denmark)

List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin

2016-01-01

, for instance), KeyPathwayMiner extracts connected sub-networks containing a high number of active or differentially regulated genes (proteins, metabolites) in the molecular profiles. The web interface at (http://keypathwayminer.compbio.sdu.dk) implements all core functionalities of the KeyPathwayMiner tool set......We present KeyPathwayMinerWeb, the first online platform for de novo pathway enrichment analysis directly in the browser. Given a biological interaction network (e.g. protein-protein interactions) and a series of molecular profiles derived from one or multiple OMICS studies (gene expression...... such as data integration, input of background knowledge, batch runs for parameter optimization and visualization of extracted pathways. In addition to an intuitive web interface, we also implemented a RESTful API that now enables other online developers to integrate network enrichment as a web service...

What Climate Sensitivity Index Is Most Useful for Projections?

Science.gov (United States)

Grose, Michael R.; Gregory, Jonathan; Colman, Robert; Andrews, Timothy

2018-02-01

Transient climate response (TCR), transient response at 140 years (T140), and equilibrium climate sensitivity (ECS) indices are intended as benchmarks for comparing the magnitude of climate response projected by climate models. It is generally assumed that TCR or T140 would explain more variability between models than ECS for temperature change over the 21st century, since this timescale is the realm of transient climate change. Here we find that TCR explains more variability across Coupled Model Intercomparison Project phase 5 than ECS for global temperature change since preindustrial, for 50 or 100 year global trends up to the present, and for projected change under representative concentration pathways in regions of delayed warming such as the Southern Ocean. However, unexpectedly, we find that ECS correlates higher than TCR for projected change from the present in the global mean and in most regions. This higher correlation does not relate to aerosol forcing, and the physical cause requires further investigation.

Identifying pathways affected by cancer mutations.

Science.gov (United States)

Iengar, Prathima

2017-12-16

Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnocellular pathway for rotation invariant Neocognitron.

Science.gov (United States)

Ting, C H

1993-03-01

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

Deep Uncertainty Surrounding Coastal Flood Risk Projections: A Case Study for New Orleans

Science.gov (United States)

Wong, Tony E.; Keller, Klaus

2017-10-01

Future sea-level rise drives severe risks for many coastal communities. Strategies to manage these risks hinge on a sound characterization of the uncertainties. For example, recent studies suggest that large fractions of the Antarctic ice sheet (AIS) may rapidly disintegrate in response to rising global temperatures, leading to potentially several meters of sea-level rise during the next few centuries. It is deeply uncertain, for example, whether such an AIS disintegration will be triggered, how much this would increase sea-level rise, whether extreme storm surges intensify in a warming climate, or which emissions pathway future societies will choose. Here, we assess the impacts of these deep uncertainties on projected flooding probabilities for a levee ring in New Orleans, LA. We use 18 scenarios, presenting probabilistic projections within each one, to sample key deeply uncertain future projections of sea-level rise, radiative forcing pathways, storm surge characterization, and contributions from rapid AIS mass loss. The implications of these deep uncertainties for projected flood risk are thus characterized by a set of 18 probability distribution functions. We use a global sensitivity analysis to assess which mechanisms contribute to uncertainty in projected flood risk over the course of a 50-year design life. In line with previous work, we find that the uncertain storm surge drives the most substantial risk, followed by general AIS dynamics, in our simple model for future flood risk for New Orleans.

FY 1992 revised task plans for the Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Shipler, D.B.

1992-04-01

The purpose of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate radiation doses from Hanford Site operations since 1944 to populations and individuals. The primary objectives of work to be performed in FY 1992 is to determine the appropriate scope (space, time, and radionuclides, pathways and individuals/population groups) and accuracy (level of uncertainty in dose estimates) for the project. Another objective is to use a refined computer model to estimate Native American tribal doses and individual doses for the Hanford Thyroid Disease Study (HTDS). Project scope and accuracy requirements defined in FY 1992 can translated into model and data requirements that must be satisfied during FY 1993

Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

Science.gov (United States)

Lee, Hyeonjeong; Shin, Miyoung

2017-01-01

The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into

New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives

DEFF Research Database (Denmark)

Minssen, Timo

2014-01-01

) and the COMBACTE and TRANSLOCATION projects under NewDrugs4BadBugs program, involving the EU Commission and the pharma industry. But also national initiatives, such as the successful Danish ban and regulations on antibiotic use in animal production, as well as educational efforts (the European Antibiotic Awareness......New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives Posted on March 19, 2014 by Timo Minssen Please find attached a ppt presentation on “New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives” given...... on March 7, 2014 at the Broad Institute of MIT and Harvard. The presentation was followed by a discussion moderated by US patent attorney Melissa Hunter-Ensor, Partner at Saul Ewing, Boston I started out by emphasizing increasing problems of antimicrobial resistance (AMR) on a global level, providing new...

Computational Modeling of Fluctuations in Energy and Metabolic Pathways of Methanogenic Archaea

Energy Technology Data Exchange (ETDEWEB)

Luthey-Schulten, Zaida [Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry; Carl R. Woese Inst. for Genomic Biology

2017-01-04

The methanogenic archaea, anaerobic microbes that convert CO2 and H2 and/or other small organic fermentation products into methane, play an unusually large role in the global carbon cycle. As they perform the final step in the anaerobic breakdown of biomass, methanogens are a biogenic source of an estimated one billion tons methane each year. Depending on the location, produced methane can be considered as either a greenhouse gas (agricultural byproduct), sequestered carbon storage (methane hydrate deposits), or a potential energy source (organic wastewater treatment). These microbes therefore represent an important target for biotechnology applications. Computational models of methanogens with predictive power are useful aids in the adaptation of methanogenic systems, but need to connect processes of wide-ranging time and length scales. In this project, we developed several computational methodologies for modeling the dynamic behavior of entire cells that connects stochastic reaction-diffusion dynamics of individual biochemical pathways with genome-scale modeling of metabolic networks. While each of these techniques were in the realm of well-defined computational methods, here we integrated them to develop several entirely new approaches to systems biology. The first scientific aim of the project was to model how noise in a biochemical pathway propagates into cellular phenotypes. Genetic circuits have been optimized by evolution to regulate molecular processes despite stochastic noise, but the effect of such noise on a cellular biochemical networks is currently unknown. An integrated stochastic/systems model of Escherichia coli species was created to analyze how noise in protein expression gives—and therefore noise in metabolic fluxes—gives rise to multiple cellular phenotype in isogenic population. After the initial work developing and validating methods that allow characterization of the heterogeneity in the model organism E. coli, the project shifted toward

Automatically visualise and analyse data on pathways using PathVisioRPC from any programming environment.

Science.gov (United States)

Bohler, Anwesha; Eijssen, Lars M T; van Iersel, Martijn P; Leemans, Christ; Willighagen, Egon L; Kutmon, Martina; Jaillard, Magali; Evelo, Chris T

2015-08-23

used by data analysis pipelines for functional analysis of processed genomics data. PathVisioRPC enables data visualisation and pathway analysis directly from within various analytical environments used for preliminary analyses. It supports the use of existing pathways from WikiPathways or pathways created using the RPC itself. It also enables automation of tasks performed using PathVisio, making it useful to PathVisio users performing repeated visualisation and analysis tasks. PathVisioRPC is freely available for academic and commercial use at http://projects.bigcat.unimaas.nl/pathvisiorpc.

Determine metrics and set targets for soil quality on agriculture residue and energy crop pathways

Energy Technology Data Exchange (ETDEWEB)

Ian Bonner; David Muth

2013-09-01

There are three objectives for this project: 1) support OBP in meeting MYPP stated performance goals for the Sustainability Platform, 2) develop integrated feedstock production system designs that increase total productivity of the land, decrease delivered feedstock cost to the conversion facilities, and increase environmental performance of the production system, and 3) deliver to the bioenergy community robust datasets and flexible analysis tools for establishing sustainable and viable use of agricultural residues and dedicated energy crops. The key project outcome to date has been the development and deployment of a sustainable agricultural residue removal decision support framework. The modeling framework has been used to produce a revised national assessment of sustainable residue removal potential. The national assessment datasets are being used to update national resource assessment supply curves using POLYSIS. The residue removal modeling framework has also been enhanced to support high fidelity sub-field scale sustainable removal analyses. The framework has been deployed through a web application and a mobile application. The mobile application is being used extensively in the field with industry, research, and USDA NRCS partners to support and validate sustainable residue removal decisions. The results detailed in this report have set targets for increasing soil sustainability by focusing on primary soil quality indicators (total organic carbon and erosion) in two agricultural residue management pathways and a dedicated energy crop pathway. The two residue pathway targets were set to, 1) increase residue removal by 50% while maintaining soil quality, and 2) increase soil quality by 5% as measured by Soil Management Assessment Framework indicators. The energy crop pathway was set to increase soil quality by 10% using these same indicators. To demonstrate the feasibility and impact of each of these targets, seven case studies spanning the US are presented

NEURAL PAIN PATHWAY TRACING OF RABBIT ISCHEMIC HEART BY DOUBLE-RETROGRADE NEUROTRACING

OpenAIRE

Theodorus Dapamede; Obed Trinurcahyo Kinantyo Paundralingga; Masruroh Rahayu; Bambang Soemantri

2015-01-01

Background. Myocardial ischaemia occurs due to inadequate supply of oxygen to fulfill the myocardial tissue oxygen demand. This leads to angina pectoris or referred pain, whichhappens because of the inability of the brain to distinguish the visceral afferent inputs from the somatic afferent inputs since they run along a common pathway via the dorsal root ganglia. Aims. This study aims to distinguish specific areas of the rabbit heart that are projected to specific dorsal root ganglia, whic...

Visual-Cerebellar Pathways and Their Roles in the Control of Avian Flight

Directory of Open Access Journals (Sweden)

Douglas R. Wylie

2018-04-01

Full Text Available In this paper, we review the connections and physiology of visual pathways to the cerebellum in birds and consider their role in flight. We emphasize that there are two visual pathways to the cerebellum. One is to the vestibulocerebellum (folia IXcd and X that originates from two retinal-recipient nuclei that process optic flow: the nucleus of the basal optic root (nBOR and the pretectal nucleus lentiformis mesencephali (LM. The second is to the oculomotor cerebellum (folia VI-VIII, which receives optic flow information, mainly from LM, but also local visual motion information from the optic tectum, and other visual information from the ventral lateral geniculate nucleus (Glv. The tectum, LM and Glv are all intimately connected with the pontine nuclei, which also project to the oculomotor cerebellum. We believe this rich integration of visual information in the cerebellum is important for analyzing motion parallax that occurs during flight. Finally, we extend upon a suggestion by Ibbotson (2017 that the hypertrophy that is observed in LM in hummingbirds might be due to an increase in the processing demands associated with the pathway to the oculomotor cerebellum as they fly through a cluttered environment while feeding.

Robust de novo pathway enrichment with KeyPathwayMiner 5

DEFF Research Database (Denmark)

Alcaraz, Nicolas; List, Markus; Dissing-Hansen, Martin

2016-01-01

Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks tha...

NASA Space Radiation Risk Project: Overview and Recent Results

Science.gov (United States)

Blattnig, Steve R.; Chappell, Lori J.; George, Kerry A.; Hada, Megumi; Hu, Shaowen; Kidane, Yared H.; Kim, Myung-Hee Y.; Kovyrshina, Tatiana; Norman, Ryan B.; Nounu, Hatem N.;

Cultural pathways through universal development.

Science.gov (United States)

Greenfield, Patricia M; Keller, Heidi; Fuligni, Andrew; Maynard, Ashley

2003-01-01

We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks.

Crystallization Pathways in Biomineralization

Science.gov (United States)

Weiner, Steve; Addadi, Lia

2011-08-01

A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

Comparison of pathways associated with hepatitis B- and C-infected hepatocellular carcinoma using pathway-based class discrimination method.

Science.gov (United States)

Lee, Sun Young; Song, Kwang Hoon; Koo, Imhoi; Lee, Kee-Ho; Suh, Kyung-Suk; Kim, Bu-Yeo

2012-06-01

Molecular signatures causing hepatocellular carcinoma (HCC) from chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) are not clearly known. Using microarray datasets composed of HCV-positive HCC or HBV-positive HCC, pathways that could discriminate tumor tissue from adjacent non-tumor liver tissue were selected by implementing nearest shrunken centroid algorithm. Cancer-related signaling pathways and lipid metabolism-related pathways were predominantly enriched in HCV-positive HCC, whereas functionally diverse pathways including immune-related pathways, cell cycle pathways, and RNA metabolism pathways were mainly enriched in HBV-positive HCC. In addition to differentially involved pathways, signaling pathways such as TGF-β, MAPK, and p53 pathways were commonly significant in both HCCs, suggesting the presence of common hepatocarcinogenesis process. The pathway clustering also verified segregation of pathways into the functional subgroups in both HCCs. This study indicates the functional distinction and similarity on the pathways implicated in the development of HCV- and/or HBV-positive HCC. Copyright © 2012 Elsevier Inc. All rights reserved.

ALL-PATHWAYS DOSE ANALYSIS FOR THE PORTSMOUTH ON-SITE WASTE DISPOSAL FACILITY

Energy Technology Data Exchange (ETDEWEB)

Smith, F.; Phifer, M.

2014-04-10

A Portsmouth On-Site Waste Disposal Facility (OSWDF) All-Pathways analysis has been conducted that considers the radiological impacts to a resident farmer. It is assumed that the resident farmer utilizes a farm pond contaminated by the OSWDF to irrigate a garden and pasture and water livestock from which food for the resident farmer is obtained, and that the farmer utilizes groundwater from the Berea sandstone aquifer for domestic purposes (i.e. drinking water and showering). As described by FBP 2014b the Hydrologic Evaluation of Landfill Performance (HELP) model (Schroeder et al. 1994) and the Surface Transport Over Multiple Phases (STOMP) model (White and Oostrom 2000, 2006) were used to model the flow and transport from the OSWDF to the Points of Assessment (POAs) associated with the 680-ft elevation sandstone layer (680 SSL) and the Berea sandstone aquifer. From this modeling the activity concentrations radionuclides were projected over time at the POAs. The activity concentrations were utilized as input to a GoldSimTM (GTG 2010) dose model, described herein, in order to project the dose to a resident farmer over time. A base case and five sensitivity cases were analyzed. The sensitivity cases included an evaluation of the impacts of using a conservative inventory, an uncased well to the Berea sandstone aquifer, a low waste zone uranium distribution coefficient (Kd), different transfer factors, and reference person exposure parameters (i.e. at 95 percentile). The maximum base case dose within the 1,000 year assessment period was projected to be 1.5E-14 mrem/yr, and the maximum base case dose at any time less than 10,000 years was projected to be 0.002 mrem/yr. The maximum projected dose of any sensitivity case was approximately 2.6 mrem/yr associated with the use of an uncased well to the Berea sandstone aquifer. This sensitivity case is considered very unlikely because it assumes leakage from the location of greatest concentration in the 680 SSL in to the

Risk methodology for geologic disposal of radioactive waste: model description and user manual for Pathways model

International Nuclear Information System (INIS)

Helton, J.C.; Kaestner, P.C.

1981-03-01

A model for the environmental movement and human uptake of radionuclides is presented. This model is designated the Pathways-to-Man Model and was developed as part of a project funded by the Nuclear Regulatory Commission to design a methodology to assess the risk associated with the geologic disposal of high-level radioactive waste. The Pathways-to-Man Model is divided into two submodels. One of these, the Environmental Transport Model, represents the long-term distribution and accumulation of radionuclides in the environment. This model is based on a mixed-cell approach and describes radionuclide movement with a system of linear differential equations. The other, the Transport-to-Man Model, represents the movement of radionuclides from the environment to man. This model is based on concentration ratios. General descriptions of these models are provided in this report. Further, documentation is provided for the computer program which implements the Pathways Model

Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

Directory of Open Access Journals (Sweden)

Karina E. J. Tripodi

2011-01-01

Full Text Available Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi, leishmaniasis (Leishmania spp., and African trypanosomiasis (Trypanosoma brucei. Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.

Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

Science.gov (United States)

London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

2018-04-04

The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

Migration pathways in soils

International Nuclear Information System (INIS)

Gronow, J.R.

1986-01-01

This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

Birth of projection neurons in adult avian brain may be related to perceptual or motor learning

International Nuclear Information System (INIS)

Alvarez-Buylla, A.; Kirn, J.R.; Nottebohm, F.

1990-01-01

Projection neurons that form part of the motor pathway for song control continue to be produced and to replace older projection neurons in adult canaries and zebra finches. This is shown by combining [3H]thymidine, a cell birth marker, and fluorogold, a retrogradely transported tracer of neuronal connectivity. Species and seasonal comparisons suggest that this process is related to the acquisition of perceptual or motor memories. The ability of an adult brain to produce and replace projection neurons should influence our thinking on brain repair

Coniferous tree plantations in forest conditions-economic analysis of dedicated and semi-dedicated pathways to increase wood production

International Nuclear Information System (INIS)

Rakotoarison, Hanitra; Richter, Claudine; Cailly, Priscilla; Deleuze, Christine; Berthelot, Alain

2015-01-01

To meet growing demand for wood, particularly softwoods, the authors study a number of new silvicultural pathways for planting 3 species: Douglas fir, spruce and maritime pine. The goal of these pathways is to achieve specialised production of either industrial and workable timber, or a mixture of industrial and workable timber with medium-diameter workable timber. Pathways of this type have already been standardised for hardwoods, generally on fertile farmland. In a less fertile forest context, softwoods have a significant potential for woody production but specialized pathways and their profitability have yet to be studied. This article describes the innovative work being done to construct and simulate profitable production, new potential pathways, where plantation density, rotation time, the level of fertility are made to vary using the data from the FCBA test network in conjunction with the FCBA growth models (Oasis for spruce and Douglas fir, Sylveco for maritime pine). Economic data is derived from auction sales statistics and the ONF management and forestry work costs for the period 2012-2015. The Economics module developed by FCBA and ONF on the Capsis platform in the framework of the ICI project (Futurol) was used for the economic simulations. The analyses show that compared to conventional pathways, these pathways generally increase productivity but are nonetheless less profitable than current economic assumptions, although results vary according to species, fertility and the particular pathway. The sensitivity study shows that variations in the price of wood could alter the performance ratings as between conventional and specialised pathways. (authors)

Projected climate change futures for Southern Africa

CSIR Research Space (South Africa)

Tadross, M

2017-10-01

Full Text Available of the Council for Scientific and Industrial Research (CSIR) in South Africa. In these experiments, a variable-resolution atmospheric global circulation model, CCAM, was applied as a regional climate model (RCM) to simulate both present-day and future climate... climate projection Observed climate RCM Climate forcing Climate simulation Statistical downscaling Dynamical downscaling 22 | Second Edition There are four pathways – RCP2.6, RCP4.5, RCP6.0 and RCP8.5. RCP 2.6 describes a scenario of very low...

Global Analysis of Climate Change Projection Effects on Atmospheric Rivers

Science.gov (United States)

Espinoza, Vicky; Waliser, Duane E.; Guan, Bin; Lavers, David A.; Ralph, F. Martin

2018-05-01

A uniform, global approach is used to quantify how atmospheric rivers (ARs) change between Coupled Model Intercomparison Project Phase 5 historical simulations and future projections under the Representative Concentration Pathway (RCP) 4.5 and RCP8.5 warming scenarios. The projections indicate that while there will be 10% fewer ARs in the future, the ARs will be 25% longer, 25% wider, and exhibit stronger integrated water vapor transports (IVTs) under RCP8.5. These changes result in pronounced increases in the frequency (IVT strength) of AR conditions under RCP8.5: 50% (25%) globally, 50% (20%) in the northern midlatitudes, and 60% (20%) in the southern midlatitudes. The models exhibit systematic low biases across the midlatitudes in replicating historical AR frequency ( 10%), zonal IVT ( 15%), and meridional IVT ( 25%), with sizable intermodel differences. A more detailed examination of six regions strongly impacted by ARs suggests that the western United States, northwestern Europe, and southwestern South America exhibit considerable intermodel differences in projected changes in ARs.

The life of phi: the development of phi thickenings in roots of the orchids of the genus Miltoniopsis.

Science.gov (United States)

Idris, Nurul A; Collings, David A

2015-02-01

Phi thickenings, bands of secondary wall thickenings that reinforce the primary wall of root cortical cells in a wide range of species, are described for the first time in the epiphytic orchid Miltoniopsis. As with phi thickenings found in other plants, the phi thickenings in Miltoniopsis contain highly aligned cellulose running along the lengths of the thickenings, and are lignified but not suberized. Using a combination of histological and immunocytochemical techniques, thickening development can be categorized into three different stages. Microtubules align lengthwise along the thickening during early and intermediate stages of development, and callose is deposited within the thickening in a pattern similar to the microtubules. These developing thickenings also label with the fluorescently tagged lectin wheat germ agglutinin (WGA). These associations with microtubules and callose, and the WGA labeling, all disappear when the phi thickenings are mature. This pattern of callose and WGA deposition show changes in the thickened cell wall composition and may shed light on the function of phi thickenings in plant roots, a role for which has yet to be established.

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

DEFF Research Database (Denmark)

Huang, Sijia; Chong, Nicole; Lewis, Nathan

2016-01-01

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

The role of the dopaminergic projections in MFB self-stimulation.

Science.gov (United States)

Gallistel, C R

1986-11-01

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

Science.gov (United States)

Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

2010-06-30

Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

Directory of Open Access Journals (Sweden)

Paweletz Cloud

2010-06-01

Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

Direct and Indirect Pathways From Social Support to Health?

Science.gov (United States)

Kim, Seoyoun; Thomas, Patricia A

2017-07-04

We aimed to investigate potential direct and indirect pathways linking social support and health, while considering mental health and chronic inflammation as inter-related outcomes. The study also contributes to the literature through testing potential bidirectional relationships between social support, mental health, and chronic inflammation. This study uses Structural Equation Modeling and two waves of the National Social Life, Health, and Aging Project (NSHAP), including 1,124 community-living older adults aged 57-85 years at Wave 1 (2005). Analyses show that social support influenced mental health indirectly through better self-esteem. Moreover, social support was associated with lower levels of chronic inflammation but chronic inflammation did not influence social support. The growing number of older adults with an aging population urgently calls for a greater understanding of factors influencing their physical and mental health. The results of this study demonstrate the importance of social support in older adults' health, while specifically focusing on understudied indirect pathways from social support to health. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathways Post-Participation Outcomes: Preliminary Findings. Carnegie Math Pathways Research Brief

Science.gov (United States)

Norman, Jon

2017-01-01

The Carnegie Foundation for the Advancement of Teaching's Math Pathways seek to improve outcomes for community college students who take remedial math courses. The Pathways include two comprehensive instructional systems--Statway® and Quantaway® and are described in this report. They are designed to support students to achieve the necessary math…

Ubiquitylation and the Fanconi Anemia Pathway

Science.gov (United States)

Garner, Elizabeth; Smogorzewska, Agata

2012-01-01

The Fanconi anemia (FA) pathway maintains genome stability through co-ordination of DNA repair of interstrand crosslinks (ICLs). Disruption of the FA pathway yields hypersensitivity to interstrand crosslinking agents, bone marrow failure and cancer predisposition. Early steps in DNA damage dependent activation of the pathway are governed by monoubiquitylation of FANCD2 and FANCI by the intrinsic FA E3 ubiquitin ligase, FANCL. Downstream FA pathway components and associated factors such as FAN1 and SLX4 exhibit ubiquitin-binding motifs that are important for their DNA repair function, underscoring the importance of ubiquitylation in FA pathway mediated repair. Importantly, ubiquitylation provides the foundations for cross-talk between repair pathways, which in concert with the FA pathway, resolve interstrand crosslink damage and maintain genomic stability. PMID:21605559

Pathways from Poverty.

Science.gov (United States)

Baldwin, Barbara, Ed.

1995-01-01

Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

A Conceptual Framework: The Musical Self as a Unique Pathway to Outcomes in the Acute Pediatric Health Setting.

Science.gov (United States)

Shoemark, Helen; Rimmer, Jo; Bower, Janeen; Tucquet, Belinda; Miller, Lauren; Fisher, Michelle; Ogburn, Nicholas; Dun, Beth

2018-03-09

This article reports on a project at the Royal Children's Hospital Melbourne in which the music therapy team synthesized their practice and related theories to propose a new conceptual framework for music therapy in their acute pediatric setting. The impetus for the project was the realization that in the process of producing key statements about the non-musical benefits of music therapy, the cost was often the suppression of information about the patient's unique musical potential as the major (mediating) pathway from referral reason, to music therapy, and to effective outcomes. The purpose of the project was to articulate how this team of clinicians conceive of the patient's musical self as the major theoretical pathway for music therapy in an evidence-based acute medical setting. The clinicians' shared reflexive process across six months involved robust directed discussion, annotation of shared reading, and documentation of all engagement in words and diagrams. The outcome was a consensus framework including three constructs: the place of music in the life of the infant, child, and young people, Culture and Context, and Musical Manifestations. The constructs were tested in a clinical audit, and found to be robustly inclusive. In addition to the conceptual framework, this project serves to demonstrate a process by which clinical teams may reflect on their individual practice and theory together to create a consensus stance for the overall service they provide in the one setting.

Protein design for pathway engineering.

Science.gov (United States)

Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

2014-02-01

Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

DEFF Research Database (Denmark)

Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E

2016-01-01

Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin...... acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist...... into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings...

PHOTOBIOMODULATION-MEDIATED PATHWAY DIAGNOSTICS

Directory of Open Access Journals (Sweden)

TIMON CHENG-YI LIU

2013-01-01

Full Text Available Cellular pathways are ordinarily diagnosed with pathway inhibitors, related gene regulation, or fluorescent protein markers. They are also suggested to be diagnosed with pathway activation modulation of photobiomodulation (PBM in this paper. A PBM on a biosystem function depends on whether the biosystem is in its function-specific homeostasis (FSH. An FSH, a negative feedback response for the function to be performed perfectly, is maintained by its FSH-essential subfunctions and its FSH-non-essential subfunctions (FNSs. A function in its FSH or far from its FSH is called a normal or dysfunctional function. A direct PBM may self-adaptatively modulate a dysfunctional function until it is normal so that it can be used to discover the optimum pathways for an FSH to be established. An indirect PBM may self-adaptatively modulate a dysfunctional FNS of a normal function until the FNS is normal, and the normal function is then upgraded so that it can be used to discover the redundant pathways for a normal function to be upgraded.

Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway

Energy Technology Data Exchange (ETDEWEB)

Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

1992-09-01

This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides.

Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway

International Nuclear Information System (INIS)

Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

1992-09-01

This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides

Identification of mutated driver pathways in cancer using a multi-objective optimization model.

Science.gov (United States)

Zheng, Chun-Hou; Yang, Wu; Chong, Yan-Wen; Xia, Jun-Feng

2016-05-01

New-generation high-throughput technologies, including next-generation sequencing technology, have been extensively applied to solve biological problems. As a result, large cancer genomics projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium are producing large amount of rich and diverse data in multiple cancer types. The identification of mutated driver genes and driver pathways from these data is a significant challenge. Genome aberrations in cancer cells can be divided into two types: random 'passenger mutation' and functional 'driver mutation'. In this paper, we introduced a Multi-objective Optimization model based on a Genetic Algorithm (MOGA) to solve the maximum weight submatrix problem, which can be employed to identify driver genes and driver pathways promoting cancer proliferation. The maximum weight submatrix problem defined to find mutated driver pathways is based on two specific properties, i.e., high coverage and high exclusivity. The multi-objective optimization model can adjust the trade-off between high coverage and high exclusivity. We proposed an integrative model by combining gene expression data and mutation data to improve the performance of the MOGA algorithm in a biological context. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupational Dermatoses Among Kitchen Workers In A Chain Of Vegetarian Hotel

Directory of Open Access Journals (Sweden)

Rai Reena

2003-01-01

Full Text Available This study was undertaken to identify occupation related skin problems among hotel workers. One thousand three hindered and ninety employees of a chain of vegetarian hotels were examined. Of the 273 people working in the kitchen, 206 (75.4% had dermatosis related to work. The Kitchen workers were classified according to the type of work they routinely performed. Forty eight out of the 63 (76.1% cooks who were involved in stirring had callosity at sites of contact with ladle and 28 of the40 (70% cooks who were involved in frying had pigmentation and scars due to contact with hot oil and water. All the onion peelers had staining and fissuring of the palmer aspect of the fingers. Thirty two of the 46(69.5% vegetable cutters had callosity on the palm at areas of contact with knife. Poori markers had pigmentation and callosity of knuckles due to pressing the dough with their knuckles. Nine of the 12 (66% rice cleaners had chapping of nails. Seven of the 12 (58.3% paratha markers had erythema of palm due to contact with hot tava. Tandoori experts had singing of hair over right forearm. Two workers (0.73% had pigmentation of the face probably due to prolonged exposure to heat. Two of the16 (12.5% grinders had paronychia and onychomycosis due to constant contact with water and dough. Nine of the 15 (60% coconut graters had callosities of the palms. We conclude the minor occupational dermatosis is prevalent among kitchen workers employed in hotels

Quantitative analysis of structural variations in corpus callosum in adults with multiple system atrophy (MSA)

Science.gov (United States)

Bhattacharya, Debanjali; Sinha, Neelam; Saini, Jitender

2017-03-01

Multiple system atrophy (MSA) is a rare, non-curable, progressive neurodegenerative disorder that affects nervous system and movement, poses a considerable diagnostic challenge to medical researchers. Corpus callosum (CC) being the largest white matter structure in brain, enabling inter-hemispheric communication, quantification of callosal atrophy may provide vital information at the earliest possible stages. The main objective is to identify the differences in CC structure for this disease, based on quantitative analysis on the pattern of callosal atrophy. We report results of quantification of structural changes in regional anatomical thickness, area and length of CC between patient-groups with MSA with respect to healthy controls. The method utilizes isolating and parcellating the mid-sagittal CC into 100 segments along the length - measuring the width of each segment. It also measures areas within geometrically defined five callosal compartments of the well-known Witelson, and Hofer-Frahma schemes. For quantification, statistical tests are performed on these different callosal measurements. From the statistical analysis, it is concluded that compared to healthy controls, width is reduced drastically throughout CC for MSA group and as well as changes in area and length are also significant for MSA. The study is further extended to check if any significant difference in thickness is found between the two variations of MSA, Parkinsonian MSA and Cerebellar MSA group, using the same methodology. However area and length of this two sub-MSA group, no substantial difference is obtained. The study is performed on twenty subjects for each control and MSA group, who had T1-weighted MRI.

Updating the Wnt pathways

Science.gov (United States)

Yu, Jia; Virshup, David M.

2014-01-01

In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

My care pathways - creating open innovation in healthcare.

Science.gov (United States)

Lundberg, Nina; Koch, Sabine; Hägglund, Maria; Bolin, Peter; Davoody, Nadia; Eltes, Johan; Jarlman, Olof; Perlich, Anja; Vimarlund, Vivian; Winsnes, Casper

2013-01-01

In this paper we describe initial results from the Swedish innovation project "My Care Pathways" which envisions enabling citizens to track their own health by providing them with online access to their historical, current and prospective future events. We describe an information infrastructure and its base services as well as the use of this solution as an open source platform for open innovation in healthcare. This will facilitate the development of end-user e-services for citizens. We have technically enabled the information infrastructure in close collaboration with decision makers in three Swedish health care regions, and system vendors as well as with National eHealth projects. Close collaboration between heterogeneous actors made implementation in real practice possible. However, a number of challenges, mainly related to legal and business issues, persist when implementing our results. Future work should therefore target the development of business models for sustainable provision of end-user e-services in a public health care system such as the Swedish one. Also, a legal analysis of the development of third party provider (nonhealthcare based) personal health data e-services should be done.

Survival pathways under stress

Indian Academy of Sciences (India)

First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

Genetic variants in two pathways influence serum urate levels and gout risk: a systematic pathway analysis.

Science.gov (United States)

Dong, Zheng; Zhou, Jingru; Xu, Xia; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Zhang, Juan; Yuan, Ziyu; Yang, Yajun; Wang, Xiaofeng; Pang, Yafei; Jin, Li; Zou, Hejian; Wang, Jiucun

2018-03-01

The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with P FDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (P FDR  = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (P FDR  = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, P FDR  = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

Expression of the Grape VaSTS19 Gene in Arabidopsis Improves Resistance to Powdery Mildew and Botrytis cinerea but Increases Susceptibility to Pseudomonas syringe pv Tomato DC3000.

Science.gov (United States)

Wang, Yaqiong; Wang, Dejun; Wang, Fan; Huang, Li; Tian, Xiaomin; van Nocker, Steve; Gao, Hua; Wang, Xiping

2017-09-17

Stilbene synthase (STS) is a key enzyme that catalyzes the biosynthesis of resveratrol compounds and plays an important role in disease resistance. The molecular pathways linking STS with pathogen responses and their regulation are not known. We isolated an STS gene, VaSTS19 , from a Chinese wild grape, Vitis amurensis Rupr. cv. "Tonghua-3", and transferred this gene to Arabidopsis . We then generated VaSTS19 -expressing Arabidopsis lines and evaluated the functions of VaSTS19 in various pathogen stresses, including powdery mildew, B. cinerea and Pseudomonas syringae pv. tomato DC3000 ( Pst DC3000). VaSTS19 enhanced resistance to powdery mildew and B. cinerea , but increased susceptibility to Pst DC3000. Aniline blue staining revealed that VaSTS19 transgenic lines accumulated more callose compared to nontransgenic control plants, and showed smaller stomatal apertures when exposed to pathogen-associated molecular patterns (flagellin fragment (flg22) or lipopolysaccharides (LPS)). Analysis of the expression of several disease-related genes suggested that VaSTS19 expression enhanced defense responses though salicylic acid (SA) and/or jasmonic acid (JA) signaling pathways. These findings provide a deeper insight into the function of STS genes in defense against pathogens, and a better understanding of the regulatory cross talk between SA and JA pathways.

Alien plants introduced by different pathways differ in invasion success: unintentional introductions as a threat to natural areas

Czech Academy of Sciences Publication Activity Database

Pyšek, Petr; Jarošík, Vojtěch; Pergl, Jan

2011-01-01

Roč. 6, č. 9 (2011), e24890 E-ISSN 1932-6203 R&D Projects: GA MŠk LC06073; GA ČR(CZ) GAP504/11/1028 Institutional research plan: CEZ:AV0Z60050516 Keywords : plant invasions * pathways * naturalization and invasion Subject RIV: EF - Botanics Impact factor: 4.092, year: 2011

Origin and neurochemical properties of bulbospinal neurons projecting to the rat lumbar spinal cord via the medal longitudinal fasciculus and caudal ventrolateral medulla

Directory of Open Access Journals (Sweden)

Zilli eHuma

2014-04-01

Full Text Available Bulbospinal systems (BS originate from various regions of the brainstem and influence spinal neurons by classical synaptic and modulatory mechanisms. Our aim was to determine the brainstem locations of cells of origin of BS pathways passing through the medial longitudinal fasciculus (MLF and the caudal ventrolateral medulla (CVLM. We also examined the transmitter content of spinal terminations of the CVLM pathway. Six adult rats received Fluorogold (FG injections to the right intermediate grey matter of the lumbar cord (L1-L2 and the b-subunit of cholera toxin (CTb was injected either into the MLF or the right CVLM (3 animals each. Double-labelled cells were identified within brainstem structures with confocal microscopy and mapped onto brainstem diagrams. An additional 3 rats were injected with CTb in the CVLM to label axon terminals in the lumbar spinal cord. Double-labelled cells projecting via the MLF or CVLM were found principally in reticular regions of the medulla and pons but small numbers of cells were also located within the midbrain. CVLM projections to the lumbar cord were almost exclusively ipsilateral and concentrated within the intermediate grey matter. Most (62% of terminals were immunoreactive for the vesicular glutamate transporter 2 while 23% contained the vesicular GABA transporter. The inhibitory subpopulation was glycinergic, GABAergic or contained both transmitters. The proportions of excitatory and inhibitory axons projecting via the CVLM to the lumbar cord are similar to those projecting via the MLF. Unlike the MLF pathway, CVLM projections are predominantly ipsilateral and concentrated within intermediate grey but do not extend into motor nuclei or laminia VIII. Terminations of the CVLM pathway are located in a region of the grey matter that is rich in premotor interneurons; thus its primary function may be to coordinate activity of premotor networks.

Pathways of topological rank analysis (PoTRA): a novel method to detect pathways involved in hepatocellular carcinoma.

Science.gov (United States)

Li, Chaoxing; Liu, Li; Dinu, Valentin

2018-01-01

Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher's exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov-Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC) and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several significant pathways in subtypes

Continuous national gross domestic product (GDP) time series for 195 countries: past observations (1850-2005) harmonized with future projections according to the Shared Socio-economic Pathways (2006-2100)

Science.gov (United States)

Geiger, Tobias

2018-04-01

Gross domestic product (GDP) represents a widely used metric to compare economic development across time and space. GDP estimates have been routinely assembled only since the beginning of the second half of the 20th century, making comparisons with prior periods cumbersome or even impossible. In recent years various efforts have been put forward to re-estimate national GDP for specific years in the past centuries and even millennia, providing new insights into past economic development on a snapshot basis. In order to make this wealth of data utilizable across research disciplines, we here present a first continuous and consistent data set of GDP time series for 195 countries from 1850 to 2009, based mainly on data from the Maddison Project and other population and GDP sources. The GDP data are consistent with Penn World Tables v8.1 and future GDP projections from the Shared Socio-economic Pathways (SSPs), and are freely available at http://doi.org/10.5880/pik.2018.010 (Geiger and Frieler, 2018). To ease usability, we additionally provide GDP per capita data and further supplementary and data description files in the online archive. We utilize various methods to handle missing data and discuss the advantages and limitations of our methodology. Despite known shortcomings this data set provides valuable input, e.g., for climate impact research, in order to consistently analyze economic impacts from pre-industrial times to the future.

Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

Energy Technology Data Exchange (ETDEWEB)

Beildeck, Marcy E. [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States); Gelmann, Edward P. [Columbia University, Department of Medicine, New York, NY (United States); Byers, Stephen W., E-mail: byerss@georgetown.edu [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States)

2010-07-01

Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

International Nuclear Information System (INIS)

Beildeck, Marcy E.; Gelmann, Edward P.; Byers, Stephen W.

2010-01-01

Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

Comparing projections of industrial energy demand and greenhouse gas emissions in long-term energy models

NARCIS (Netherlands)

Edelenbosch, O. Y.|info:eu-repo/dai/nl/412493373; Kermeli, K.|info:eu-repo/dai/nl/411260553; Crijns-Graus, W.|info:eu-repo/dai/nl/308005015; Worrell, E.|info:eu-repo/dai/nl/106856715; Bibas, R.; Fais, B.; Fujimori, S.; Kyle, P.; Sano, F.; van Vuuren, Detlef|info:eu-repo/dai/nl/11522016X

2017-01-01

The industry sector is a major energy consumer and GHG emitter. Effective climate change mitigation strategies will require a significant reduction of industrial emissions. To better understand the variations in the projected industrial pathways for both baseline and mitigation scenarios, we compare

Mechanism of Notch Pathway Activation and Its Role in the Regulation of Olfactory Plasticity in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Simon Kidd

Full Text Available The neural plasticity of sensory systems is being increasingly recognized as playing a role in learning and memory. We have previously shown that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila melanogaster olfactory receptor neurons (ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. In this paper we address how long-term exposure to odor activates Notch and how Notch in conjunction with chronic odor mediates olfactory plasticity. We show that upon chronic odor exposure a non-canonical Notch pathway mediates an increase in the volume of glomeruli by a mechanism that is autonomous to ORNs. In addition to activating a pathway that is autonomous to ORNs, chronic odor exposure also activates the Notch ligand Delta in second order projection neurons (PNs, but this does not appear to require acetylcholine receptor activation in PNs. Delta on PNs then feeds back to activate canonical Notch signaling in ORNs, which restricts the extent of the odor induced increase in glomerular volume. Surprisingly, even though the pathway that mediates the increase in glomerular volume is autonomous to ORNs, nonproductive transsynaptic Delta/Notch interactions that do not activate the canonical pathway can block the increase in volume. In conjunction with chronic odor, the canonical Notch pathway also enhances cholinergic activation of PNs. We present evidence suggesting that this is due to increased acetylcholine release from ORNs. In regulating physiological plasticity, Notch functions solely by the canonical pathway, suggesting that there is no direct connection between morphological and physiological plasticity.

DECHEM: A remedial planning tool for metallic contaminants in soil at UMTRA Project sites

International Nuclear Information System (INIS)

1989-03-01

The DECHEM (DEcontamination of CHEMicals) method was developed for the Uranium Mill Tailings Remedial Action (UMTRA) Project to guide characterization and remedial planning for metals contamination in soils. This is necessary because non-radiological hazardous constituents may be more mobile than radium-226 (Ra-226), and hence may migrate more deeply into subpile soils (beneath tailings that are to be relocated) or into adjacent contaminated soils at UMTRA Project sites. The result is that remedial action to the Ra-226 excavation limit, as specified in the US Environmental Protection Agency (EPA) standards, may not adequately remove hazardous non-radiological contamination. Unmitigated, these contaminants in soil may cause health risks because of their presence in resuspended particles, their uptake by crops or fodder their seepage into aquifers used for drinking water or other possible exposure pathways. The DECHEM method was developed in response to the need for advanced planning for the remediation of chemical contaminants at UMTRA Project sites, and includes the following elements: Establishment of acceptable exposure rates for humans to chemicals, based on EPA guidelines or other toxicological literature. Modeling of chemical migration through environmental pathways from a remediated UMTRA Project site to humans. Determination of allowable residual concentrations (i.e., cleanup guidelines) for chemicals in soils that results in doses to humans that are below established acceptable exposure rates. The initial development and application of the DECHEM method has focused upon hazardous metallic contaminants such as arsenic, lead, molybdenum, and selenium, which are known to occur in elevated concentrations at some UMTRA Project sites

PATHway: Decision Support in Exercise Programmes for Cardiac Rehabilitation.

Science.gov (United States)

Filos, Dimitris; Triantafyllidis, Andreas; Chouvarda, Ioanna; Buys, Roselien; Cornelissen, Véronique; Budts, Werner; Walsh, Deirdre; Woods, Catherine; Moran, Kieran; Maglaveras, Nicos

2016-01-01

Rehabilitation is important for patients with cardiovascular diseases (CVD) to improve health outcomes and quality of life. However, adherence to current exercise programmes in cardiac rehabilitation is limited. We present the design and development of a Decision Support System (DSS) for telerehabilitation, aiming to enhance exercise programmes for CVD patients through ensuring their safety, personalising the programme according to their needs and performance, and motivating them toward meeting their physical activity goals. The DSS processes data originated from a Microsoft Kinect camera, a blood pressure monitor, a heart rate sensor and questionnaires, in order to generate a highly individualised exercise programme and improve patient adherence. Initial results within the EU-funded PATHway project show the potential of our approach.

Non-Smad pathways in TGF-β signaling

OpenAIRE

Zhang, Ying E

2009-01-01

Transforming growth factor-β utilizes a multitude of intracellular signaling pathways in addition to Smads to regulate a wide array of cellular functions. These non-canonical, non-Smad pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. These non-Smad pathways include various branches of MAP kinase pathways, Rho-like GTPase signaling pathways, and phosphatidylinositol-3-kinase/AKT pathways. This review focu...

PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

Science.gov (United States)

Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

2018-04-24

Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

Science.gov (United States)

Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

2017-01-01

Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602

Pathways-driven sparse regression identifies pathways and genes associated with high-density lipoprotein cholesterol in two Asian cohorts.

Directory of Open Access Journals (Sweden)

Matt Silver

2013-11-01

Full Text Available Standard approaches to data analysis in genome-wide association studies (GWAS ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK

Pathways-Driven Sparse Regression Identifies Pathways and Genes Associated with High-Density Lipoprotein Cholesterol in Two Asian Cohorts

Science.gov (United States)

Silver, Matt; Chen, Peng; Li, Ruoying; Cheng, Ching-Yu; Wong, Tien-Yin; Tai, E-Shyong; Teo, Yik-Ying; Montana, Giovanni

2013-01-01

Standard approaches to data analysis in genome-wide association studies (GWAS) ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs) or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK signalling and immune

FY 1991 Task plans for the Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

1991-04-01

The purpose of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate radiation doses from Hanford Site operations since 1944 to populations and individuals. The objectives of work in Fiscal Year (FY) 1991 are to analyze data and models used in Phase 1 and restructure the models to increase accuracy and reduce uncertainty in dose estimation capability. Databases will be expanded and efforts will begin to determine the appropriate scope (space, time, radionuclides, pathways and individuals/population groups) and accuracy (level of uncertainty in dose estimates) for the project. Project scope and accuracy requirements, once defined, can be translated into additional model and data requirements later in the project. Task plans for FY 1991 have been prepared based on activities approved by the Technical Steering Panel (TSP) in October 1990 and mid-year revisions discussed at the TSP planning/budget workshop in February 1991. The activities can be divided into two broad categories: (1) model and data development and evaluation, (2) project, technical and communication support. 3 figs., 1 tab

DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 16920490 Title Signal inte...gration between IFNgamma and TLR signalling pathways in

The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases

Science.gov (United States)

Caspi, Ron; Altman, Tomer; Dale, Joseph M.; Dreher, Kate; Fulcher, Carol A.; Gilham, Fred; Kaipa, Pallavi; Karthikeyan, Athikkattuvalasu S.; Kothari, Anamika; Krummenacker, Markus; Latendresse, Mario; Mueller, Lukas A.; Paley, Suzanne; Popescu, Liviu; Pujar, Anuradha; Shearer, Alexander G.; Zhang, Peifen; Karp, Peter D.

2010-01-01

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. With more than 1400 pathways, MetaCyc is the largest collection of metabolic pathways currently available. Pathways reactions are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than 500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs also contain additional features, such as predicted operons, transport systems, and pathway hole-fillers. The BioCyc Web site offers several tools for the analysis of the PGDBs, including Omics Viewers that enable visualization of omics datasets on two different genome-scale diagrams and tools for comparative analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party interested in curation of metabolic, regulatory, and genome-related information about an organism. PMID:19850718

Linked Analysis of East Asia Emission Reduction Pathways

Science.gov (United States)

Kim, Y.; Woo, J. H.; Bu, C.; Lee, Y.; Kim, J.; Jang, Y.; Park, M.

2017-12-01

Air pollution and its impacts over the Northeast Asia are very severe because of the massive pollutant emissions and high population. Korea has been trying to improve air quality with the enhanced environmental legislation. The air quality over Korea, however, does not entirely dependent on its local emissions. Transboundary air pollution from China highly affects Korean atmosphere. The purpose of this research is to understand role of local and transbounday efforts to improve air quality changes over Korea. In this research, we have tried to set up the multiple emission scenario pathways for Korea and China using IIASA's GAINS (Greenhouse gas - Air pollution Interactions aNd Synergies) modeling framework. More up-to-date growth factors and control policy packets were made using regional socio-economic data and control policy information from local governments and international statistics. Four major scenario pathways, 1) Base (Baseline: current legislation), 2) OTB/OTB(On the book/On the way : existing control measure/planed control measure), 3) BOTW_GHG(Beyond on the way : OTW with GHG reduction plan), 4) BOTW_NH3 (OTW with additional NH3 reduction measure) were developed to represent air quality improvement pathways in consideration of both Korean and Chinese efforts. Strict ambient PM2.5 standards from Seoul metropolitan Air quality Improvement Plan(SAIP) seems too enthusiastic without linking air quality control efforts of China. Step-by-step emission controls and following air quality, control cost, health impact from each scenario will be presented at the conference. This subject is supported by Korea Ministry of Environment as "Climate Change Correspondence Program". And This work was supported under the framework of national strategy project on fine particulate matters by Ministry of Science, ICT and Future Planning.

DMPD: All is not Toll: new pathways in DNA recognition. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16446382 All is not Toll: new pathways in DNA recognition. Wagner H, Bauer S. J Exp... Med. 2006 Feb 20;203(2):265-8. Epub 2006 Jan 30. (.png) (.svg) (.html) (.csml) Show All is not Toll: new pathways in DNA recognition.... PubmedID 16446382 Title All is not Toll: new pathways in DNA recognition. Authors

Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

Science.gov (United States)

Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

2014-01-01

Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

Technological Education for the Rural Community (TERC) Project: Technical Mathematics for the Advanced Manufacturing Technician

Science.gov (United States)

McCormack, Sherry L.; Zieman, Stuart

2017-01-01

Hopkinsville Community College's Technological Education for the Rural Community (TERC) project is funded through the National Science Foundation Advanced Technological Education (NSF ATE) division. It is advancing innovative educational pathways for technological education promoted at the community college level serving rural communities to fill…

Transport fuel demand responses to fuel price and income projections : Comparison of integrated assessment models

NARCIS (Netherlands)

Edelenbosch, O. Y.; van Vuuren, Detlef; Bertram, C.; Carrara, S.; Emmerling, J.; Daly, H.; Kitous, A.; McCollum, D. L.; Saadi Failali, N.

Income and fuel price pathways are key determinants in projections of the energy system in integrated assessment models. In recent years, more details have been added to the transport sector representation in these models. To better understand the model dynamics, this manuscript analyses transport

DMPD: The negative regulation of Toll-like receptor and associated pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17621314 The negative regulation of Toll-like receptor and associated pathways. Lan...) Show The negative regulation of Toll-like receptor and associated pathways. PubmedID 17621314 Title The ne...gative regulation of Toll-like receptor and associated pathways. Authors Lang T,

Management of environmental and radiation data - the Olympic Dam project

International Nuclear Information System (INIS)

Jenkins, B.

1987-01-01

In terms of data management the Olympic Dam Project is in a process of transition from investigative studies to operational monitoring. The data management requirements for investigative studies are quite different requirements and indicates the progress taken in this transition, as well as the directions being taken to complete this transition. The environmental and radiation management programs for the Olympic Dam Project have already stored 70 megabytes of data on computer. With the comprehensive monitoring requirements which have been, or are in the process of being established for production operations, the volume of data is increasing. There are six main areas involving environmental and radiation data management: project area environmental monitoring; monitoring of the impact pathway from groundwater extraction for water supply to possible effects on mound springs; radiation levels in the environment; radiation exposures to designated employees; other occupational exposures in the mine; medical records relevant to occupational health

Degenerative Pathways of Lumbar Motion Segments

DEFF Research Database (Denmark)

Jensen, Rikke K.; Kjaer, Per; Jensen, Tue S.

2016-01-01

pathways of degeneration based on scientific knowledge of disco-vertebral degeneration, and (iii) compare these clusters and degenerative pathways between samples. METHODS: We performed a secondary cross-sectional analysis on two dissimilar MRI samples collected in a hospital department: (1) data from...... pathways of degeneration. RESULTS: Six clusters of MRI findings were identified in each of the two samples. The content of the clusters in the two samples displayed some differences but had the same overall pattern of MRI findings. Although the hypothetical degenerative pathways identified in the two...... samples were not identical, the overall pattern of increasing degeneration within the pathways was the same. CONCLUSIONS: It was expected that different clusters could emerge from different samples, however, when organised into hypothetical pathways of degeneration, the overall pattern of increasing...

Stochasticity in the yeast mating pathway

International Nuclear Information System (INIS)

Hong-Li, Wang; Zheng-Ping, Fu; Xin-Hang, Xu; Qi, Ouyang

2009-01-01

We report stochastic simulations of the yeast mating signal transduction pathway. The effects of intrinsic and external noise, the influence of cell-to-cell difference in the pathway capacity, and noise propagation in the pathway have been examined. The stochastic temporal behaviour of the pathway is found to be robust to the influence of inherent fluctuations, and intrinsic noise propagates in the pathway in a uniform pattern when the yeasts are treated with pheromones of different stimulus strengths and of varied fluctuations. In agreement with recent experimental findings, extrinsic noise is found to play a more prominent role than intrinsic noise in the variability of proteins. The occurrence frequency for the reactions in the pathway are also examined and a more compact network is obtained by dropping most of the reactions of least occurrence

Molecular Pathways

Science.gov (United States)

Lok, Benjamin H.; Powell, Simon N.

2012-01-01

The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

Downscaled projections of Sea Surface Temperatures and Degree Heating Weeks in the wider Caribbean and Gulf of Mexico

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Projections of the onset of annual coral bleaching conditions in the Caribbean under Representative Concentration Pathway (RCP) 8.5 are produced using an ensemble of...

Global zero-carbon energy pathways using viable mixes of nuclear and renewables

International Nuclear Information System (INIS)

Hong, Sanghyun; Bradshaw, Corey J.A.; Brook, Barry W.

2015-01-01

Highlights: • A proper mix of nuclear power and renewables achieves sustainable energy future. • A high nuclear share provides cost and land effectiveness compared to nuclear-free. • Only-renewable mix will increase negative economic and environmental impacts. • A deployment of advanced reactor technologies is essential to overcome limitations. - Abstract: What are the most viable global pathways for a major expansion of zero-carbon emissions electricity sources given the diversity of regional technical, socio-political and economic constraints? We modelled a range of zero-emissions energy scenarios across nations that were designed to meet projected final energy demand in 2060, and optimised to derive the best globally aggregated results in terms of minimising costs and land use (a surrogate for environmental impacts). We found that a delayed energy transition to a zero-emissions pathway will decrease investment costs (−$3,431 billion), but increase cumulative CO 2 emissions (additional 696 Gt). A renewable-only scenario would convert >7.4% of the global land area to energy production, whereas a maximum nuclear scenario would affect <0.4% of land area, including mining, spent-fuel storage, and buffer zones. Moreover, a nuclear-free pathway would involve up to a 50% greater cumulative capital investment compared to a high nuclear penetration scenario ($73.7 trillion). However, for some nations with a high current share of renewables and a low projected future energy demand (e.g., Norway), pursuit of a higher nuclear share is suboptimal. In terms of the time frame for replacement of fossil fuels, achieving a global nuclear share of about 50% by 2060 would be a technically and economically plausible target if progressing at a pace of the average historical growth of nuclear power penetration in France from 1970 to 1986 (0.28 MWh person −1 year -1 ). For effective climate-change mitigation, a high penetration of nuclear in association with a nationally

Examination of corticothalamic fiber projections in United States service members with mild traumatic brain injury

Science.gov (United States)

Rashid, Faisal M.; Dennis, Emily L.; Villalon-Reina, Julio E.; Jin, Yan; Lewis, Jeffrey D.; York, Gerald E.; Thompson, Paul M.; Tate, David F.

2017-11-01

Mild traumatic brain injury (mTBI) is characterized clinically by a closed head injury involving differential or rotational movement of the brain inside the skull. Over 3 million mTBIs occur annually in the United States alone. Many of the individuals who sustain an mTBI go on to recover fully, but around 20% experience persistent symptoms. These symptoms often last for many weeks to several months. The thalamus, a structure known to serve as a global networking or relay system for the rest of the brain, may play a critical role in neurorehabiliation and its integrity and connectivity after injury may also affect cognitive outcomes. To examine the thalamus, conventional tractography methods to map corticothalamic pathways with diffusion-weighted MRI (DWI) lead to sparse reconstructions that may contain false positive fibers that are anatomically inaccurate. Using a specialized method to zero in on corticothalamic pathways with greater robustness, we noninvasively examined corticothalamic fiber projections using DWI, in 68 service members. We found significantly lower fractional anisotropy (FA), a measure of white matter microstructural integrity, in pathways projecting to the left pre- and postcentral gyri - consistent with sensorimotor deficits often found post-mTBI. Mapping of neural circuitry in mTBI may help to further our understanding of mechanisms underlying recovery post-TBI.

RNA-Seq analysis for indigo biosynthesis pathway genes in Indigofera tinctoria and Polygonum tinctorium

Directory of Open Access Journals (Sweden)

Bijaya K. Sarangi

2015-12-01

Full Text Available Natural indigo is the most important blue dye for textile dyeing and valuable secondary metabolite biosynthesized in Indigofera tinctoria and Polygonum tinctorium plants. Present investigation is made to generation of gene resource for pathway enrichment and to understand possible gene expression involved in indigo biosynthesis. The data about raw reads and the transcriptome assembly project has been deposited at GenBank under the accessions SRA180766 and SRX692542 for I. tinctoria and P. tinctorium, respectively.

Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel.

Science.gov (United States)

Baugh, Christopher W; Clark, Carol L; Wilson, Jason W; Stiell, Ian G; Kocheril, Abraham G; Luck, Krista K; Myers, Troy D; Pollack, Charles V; Roumpf, Steven K; Tomassoni, Gery F; Williams, James M; Patel, Brian B; Wu, Fred; Pines, Jesse M

2018-03-10

Atrial fibrillation and flutter (AF) is a common condition among emergency department (ED) patients in the United States. Traditionally, ED care for primary complaints related to AF focus on rate control, and patients are often admitted to an inpatient setting for further care. Inpatient care may include further telemetry monitoring and diagnostic testing, rhythm control, a search for identification of AF etiology, and stroke prophylaxis. However, many patients are eligible for safe and effective outpatient management pathways. They are widely used in Canada and other countries but less widely adopted in the United States. In this project, we convened an expert panel to create a practical framework for the process of creating, implementing, and maintaining an outpatient AF pathway for emergency physicians to assess and treat AF patients, safely reduce hospitalization rates, ensure appropriate stroke prophylaxis, and effectively transition patients to longitudinal outpatient treatment settings from the ED and/or observation unit. To support local pathway creation, the panel also reached agreement on a protocol development plan, a sample pathway, consensus recommendations for pathway components, sample pathway metrics, and a structured literature review framework using a modified Delphi technique by a technical expert panel of emergency medicine, cardiology, and other stakeholder groups. © 2018 by the Society for Academic Emergency Medicine.

Primary Metabolic Pathways and Metabolic Flux Analysis

DEFF Research Database (Denmark)

Villadsen, John

2015-01-01

his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

Metabolic signature of sun exposed skin suggests catabolic pathway overweighs anabolic pathway.

Directory of Open Access Journals (Sweden)

Manpreet Randhawa

Full Text Available Skin chronically exposed to sun results in phenotypic changes referred as photoaging. This aspect of aging has been studied extensively through genomic and proteomic tools. Metabolites, the end product are generated as a result of biochemical reactions are often studied as a culmination of complex interplay of gene and protein expression. In this study, we focused exclusively on the metabolome to study effects from sun-exposed and sun-protected skin sites from 25 human subjects. We generated a highly accurate metabolomic signature for the skin that is exposed to sun. Biochemical pathway analysis from this data set showed that sun-exposed skin resides under high oxidative stress and the chains of reactions to produce these metabolites are inclined toward catabolism rather than anabolism. These catabolic activities persuade the skin cells to generate metabolites through the salvage pathway instead of de novo synthesis pathways. Metabolomic profile suggests catabolic pathways and reactive oxygen species operate in a feed forward fashion to alter the biology of sun exposed skin.

Neurochemical properties of BDNF-containing neurons projecting to rostral ventromedial medulla in the ventrolateral periaqueductal gray

Directory of Open Access Journals (Sweden)

Jun-Bin eYin

2014-11-01

Full Text Available The periaqueductal gray (PAG modulates nociception via a descending pathway that relays in the rostral ventromedial medulla (RVM and terminates in the spinal cord. Previous behavioral pharmacology and electrophysiological evidence suggests that brain-derived neurotrophic factor (BDNF plays an important role in descending pain modulation, likely through the PAG-RVM pathway. However, there still lacks detailed information on the distribution of BDNF, activation of BDNF-containing neurons projecting to RVM in the condition of pain, and neurochemical properties of these neurons within the PAG. Through fluorescent in situ hybridization (FISH and immunofluorescent staining, the homogenous distributions of BDNF mRNA and protein were observed in the four subregions of PAG. Both neurons and astrocytes expressed BDNF, but not microglias. By combining retrograde tracing methods and formalin pain model, there were more BDNF-containing neurons projecting to RVM being activated in the ventrolateral PAG (vlPAG than other subregions of PAG. The neurochemical properties of BDNF-containing projection neurons in the vlPAG were investigated. BDNF-containing projection neurons expressed auto receptor Tropomyosin-related kinase B (TrkB in addition to serotonin (5-HT, neurotensin (NT, substance P (SP, calcitonin gene related peptide (CGRP, nitric oxide synthase (NOS, and parvalbumin (PV but not tyrosine decarboxylase (TH. It is speculated that BDNF released from projection neurons in the vlPAG might participate in the descending pain modulation through enhancing the presynaptic release of other neuroactive substances (NSs in the RVM.

SR 97 - Alternative models project. Discrete fracture network modelling for performance assessment of Aberg

International Nuclear Information System (INIS)

Dershowitz, B.; Eiben, T.; Follin, S.; Andersson, Johan

1999-08-01

As part of studies into the siting of a deep repository for nuclear waste, Swedish Nuclear Fuel and Waste Management Company (SKB) has commissioned the Alternative Models Project (AMP). The AMP is a comparison of three alternative modeling approaches for geosphere performance assessment for a single hypothetical site. The hypothetical site, arbitrarily named Aberg is based on parameters from the Aespoe Hard Rock Laboratory in southern Sweden. The Aberg model domain, boundary conditions and canister locations are defined as a common reference case to facilitate comparisons between approaches. This report presents the results of a discrete fracture pathways analysis of the Aberg site, within the context of the SR 97 performance assessment exercise. The Aberg discrete fracture network (DFN) site model is based on consensus Aberg parameters related to the Aespoe HRL site. Discrete fracture pathways are identified from canister locations in a prototype repository design to the surface of the island or to the sea bottom. The discrete fracture pathways analysis presented in this report is used to provide the following parameters for SKB's performance assessment transport codes FARF31 and COMP23: * F-factor: Flow wetted surface normalized with regards to flow rate (yields an appreciation of the contact area available for diffusion and sorption processes) [TL -1 ]. * Travel Time: Advective transport time from a canister location to the environmental discharge [T]. * Canister Flux: Darcy flux (flow rate per unit area) past a representative canister location [LT -1 ]. In addition to the above, the discrete fracture pathways analysis in this report also provides information about: additional pathway parameters such as pathway length, pathway width, transport aperture, reactive surface area and transmissivity, percentage of canister locations with pathways to the surface discharge, spatial pattern of pathways and pathway discharges, visualization of pathways, and statistical

SR 97 - Alternative models project. Discrete fracture network modelling for performance assessment of Aberg

Energy Technology Data Exchange (ETDEWEB)

Dershowitz, B.; Eiben, T. [Golder Associates Inc., Seattle (United States); Follin, S.; Andersson, Johan [Golder Grundteknik KB, Stockholm (Sweden)

1999-08-01

As part of studies into the siting of a deep repository for nuclear waste, Swedish Nuclear Fuel and Waste Management Company (SKB) has commissioned the Alternative Models Project (AMP). The AMP is a comparison of three alternative modeling approaches for geosphere performance assessment for a single hypothetical site. The hypothetical site, arbitrarily named Aberg is based on parameters from the Aespoe Hard Rock Laboratory in southern Sweden. The Aberg model domain, boundary conditions and canister locations are defined as a common reference case to facilitate comparisons between approaches. This report presents the results of a discrete fracture pathways analysis of the Aberg site, within the context of the SR 97 performance assessment exercise. The Aberg discrete fracture network (DFN) site model is based on consensus Aberg parameters related to the Aespoe HRL site. Discrete fracture pathways are identified from canister locations in a prototype repository design to the surface of the island or to the sea bottom. The discrete fracture pathways analysis presented in this report is used to provide the following parameters for SKB's performance assessment transport codes FARF31 and COMP23: * F-factor: Flow wetted surface normalized with regards to flow rate (yields an appreciation of the contact area available for diffusion and sorption processes) [TL{sup -1}]. * Travel Time: Advective transport time from a canister location to the environmental discharge [T]. * Canister Flux: Darcy flux (flow rate per unit area) past a representative canister location [LT{sup -1}]. In addition to the above, the discrete fracture pathways analysis in this report also provides information about: additional pathway parameters such as pathway length, pathway width, transport aperture, reactive surface area and transmissivity, percentage of canister locations with pathways to the surface discharge, spatial pattern of pathways and pathway discharges, visualization of pathways, and

Microglial Janus kinase/signal transduction and activator of transcription 3 pathway activity directly impacts astrocyte and spinal neuron characteristics

Czech Academy of Sciences Publication Activity Database

Molet, J.; Mauborgne, A.; Diallo, Michael; Armand, V.; Geny, D.; Villanueva, L.; Boucher, Y.; Pohl, M.

2016-01-01

Roč. 136, č. 1 (2016), s. 133-147 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : astrocytes * cell plasticity * JAK/STAT3 pathway * microglia conditioned media * spinal cord neurons Subject RIV: FH - Neurology Impact factor: 4.083, year: 2016

Developing milk industry estimates for dose reconstruction projects

International Nuclear Information System (INIS)

Beck, D.M.; Darwin, R.F.

1991-01-01

One of the most important contributors to radiation doses from hanford during the 1944-1947 period was radioactive iodine. Consumption of milk from cows that ate vegetation contaminated with iodine is likely the dominant pathway of human exposure. To estimate the doses people could have received from this pathway, it is necessary to reconstruct the amount of milk consumed by people living near Hanford, the source of the milk, and the type of feed that the milk cows ate. This task is challenging because the dairy industry has undergone radical changes since the end of World War 2, and records that document the impact of these changes on the study area are scarce. Similar problems are faced by researchers on most dose reconstruction efforts. The purpose of this work is to document and evaluate the methods used on the Hanford Environmental Dose Reconstruction (HEDR) Project to reconstruct the milk industry and to present preliminary results

Pathways of topological rank analysis (PoTRA: a novel method to detect pathways involved in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Chaoxing Li

2018-04-01

Full Text Available Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway’s topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher’s exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov–Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several

Foot and ankle problems in Thai monks.

Science.gov (United States)

Vaseenon, Tanawat; Wattanarojanaporn, Thongaek; Intharasompan, Piyapong; Theeraamphon, Nipon; Auephanviriyakul, Sansanee; Phisitkul, Phinit

2015-01-01

Foot and ankle problems in Thai monks have not been explored. This is an unshod population, and its members have a unique lifestyle living among others in our modern era. Beginning at their ordainment, they follow strict rules about barefoot walking, the amount of daily walking, and their sitting position, practices that theoretically can increase their risk of developing foot and ankle problems. To evaluate the prevalence ofcommon foot and ankle problems in Thai monks. A cross-sectional survey was conducted in combination with foot and ankle examinations of monks living in northern Thailand Foot morphology was examined using a Harris mat footprint. Results of the interviews and the foot and ankle examinations were evaluated. Two hundred and nine monks from 28 temples were included in this study. Common foot and ankle problems found included callosity (70.8%), toe deformities (18.2%), plantar fasciitis (13.4%), metatarsalgia (3.8%), and numbness (2.9%). Callosity and toe deformities were associated with prolonged barefoot walking over extended periods since ordainment (p < 0.05). The callosity was found on the forefoot (47.3%), lateral malleolus (40.7%), and heel (12%). Arch types were considered normal in 66.4% of cases, high in 21.6%, and low in 12%. No association was found between arch type and foot and ankle problems. Callosity and toe deformity were the most common foot and ankle problems found in Thai monks, especially those with prolonged period of barefoot walking and long-term duration ofordainment. The unique pattern of walking and sitting of Thai monks may have contributed to the development of those feet and ankle problems.

Rising utilization of inpatient pediatric asthma pathways.

Science.gov (United States)

Kaiser, Sunitha V; Rodean, Jonathan; Bekmezian, Arpi; Hall, Matt; Shah, Samir S; Mahant, Sanjay; Parikh, Kavita; Morse, Rustin; Puls, Henry; Cabana, Michael D

2018-02-01

Clinical pathways are detailed care plans that operationalize evidence-based guidelines into an accessible format for health providers. Their goal is to link evidence to practice to optimize patient outcomes and delivery efficiency. It is unknown to what extent inpatient pediatric asthma pathways are being utilized nationally. (1) Describe inpatient pediatric asthma pathway design and implementation across a large hospital network. (2) Compare characteristics of hospitals with and without pathways. We conducted a descriptive, cross-sectional, survey study of hospitals in the Pediatric Research in Inpatient Settings Network (75% children's hospitals, 25% community hospitals). Our survey determined if each hospital used a pathway and pathway characteristics (e.g. pathway elements, implementation methods). Hospitals with and without pathways were compared using Chi-square tests (categorical variables) and Student's t-tests (continuous variables). Surveys were distributed to 3-5 potential participants from each hospital and 302 (74%) participants responded, representing 86% (106/123) of surveyed hospitals. From 2005-2015, the proportion of hospitals utilizing inpatient asthma pathways increased from 27% to 86%. We found variation in pathway elements, implementation strategies, electronic medical record integration, and compliance monitoring across hospitals. Hospitals with pathways had larger inpatient pediatric programs [mean 12.1 versus 6.1 full-time equivalents, p = 0.04] and were more commonly free-standing children's hospitals (52% versus 23%, p = 0.05). From 2005-2015, there was a dramatic rise in implementation of inpatient pediatric asthma pathways. We found variation in many aspects of pathway design and implementation. Future studies should determine optimal implementation strategies to better support hospital-level efforts in improving pediatric asthma care and outcomes.

Applying behavioral science to behavior change communication: the pathways to change tools.

Science.gov (United States)

Petraglia, Joseph; Galavotti, Christine; Harford, Nicola; Pappas-DeLuca, Katina A; Mooki, Maungo

2007-10-01

Entertainment-education (EE) is a popular vehicle for behavior change communication (BCC) in many areas of public health, especially in the developing world where soap operas and other serial drama formats play a central role in encouraging people to avoid risky behavior. Yet BCC/EE developers have been largely unable to integrate behavioral theory and research systematically into storylines and scripts, depending instead on external, technical oversight of what should be an essentially local, creative process. This article describes how the Modeling and Reinforcement to Combat HIV/AIDS project at the Centers for Disease Control and Prevention has developed a set of tools through which creative writers can exercise greater control over the behavioral content of their stories. The Pathways to Change tools both guide scriptwriters as they write BCC/EE storylines and help project managers monitor BCC/EE products for theoretical fidelity and sensitivity to research.

Working with Climate Projections to Estimate Disease Burden: Perspectives from Public Health

Directory of Open Access Journals (Sweden)

Kathryn C. Conlon

2016-08-01

Full Text Available There is interest among agencies and public health practitioners in the United States (USA to estimate the future burden of climate-related health outcomes. Calculating disease burden projections can be especially daunting, given the complexities of climate modeling and the multiple pathways by which climate influences public health. Interdisciplinary coordination between public health practitioners and climate scientists is necessary for scientifically derived estimates. We describe a unique partnership of state and regional climate scientists and public health practitioners assembled by the Florida Building Resilience Against Climate Effects (BRACE program. We provide a background on climate modeling and projections that has been developed specifically for public health practitioners, describe methodologies for combining climate and health data to project disease burden, and demonstrate three examples of this process used in Florida.

Pathway Design, Engineering, and Optimization.

Science.gov (United States)

Garcia-Ruiz, Eva; HamediRad, Mohammad; Zhao, Huimin

The microbial metabolic versatility found in nature has inspired scientists to create microorganisms capable of producing value-added compounds. Many endeavors have been made to transfer and/or combine pathways, existing or even engineered enzymes with new function to tractable microorganisms to generate new metabolic routes for drug, biofuel, and specialty chemical production. However, the success of these pathways can be impeded by different complications from an inherent failure of the pathway to cell perturbations. Pursuing ways to overcome these shortcomings, a wide variety of strategies have been developed. This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.

Plasmodesmata-mediated intercellular signaling during plant growth and development

Directory of Open Access Journals (Sweden)

Shri Ram eYadav

2014-02-01

Full Text Available Plasmodesmata (PD are cytoplasmic channels that connect neighboring cells for cell-to-cell communication. PD structure and function vary temporally and spatially to allow formation of symplastic domains during different stages of plant development. Reversible deposition of callose at PD plays an important role in controlling molecular trafficking through PD by regulating their size exclusion limit (SEL. Previously, we reported several semi-dominant mutants for CALLOSE SYNTHASE 3 (CALS3 gene, which overproduce callose at PD in Arabidopsis. By combining two of these mutations in a LexA-VP16-ER (XVE-based estradiol inducible vector system, a tool known as the icals3m system was developed to temporally obstruct the symplastic connections in a specified spatial domain. The system has been successfully tested and used, in combination with other methods, to investigate the route for mobile signals such as the SHR protein, microRNA165/6, and cytokinins in Arabidopsis roots, and also to understand the role of symplastic domain formation during lateral root development. We envision that this tool may also be useful for identifying tissue-specific symplastic regulatory networks and to analyze symplastic movement of metabolites.

Plasmodesmata-mediated intercellular signaling during plant growth and development.

Science.gov (United States)

Yadav, Shri R; Yan, Dawei; Sevilem, Iris; Helariutta, Ykä

2014-01-01

Plasmodesmata (PD) are cytoplasmic channels that connect neighboring cells for cell-to-cell communication. PD structure and function vary temporally and spatially to allow formation of symplastic domains during different stages of plant development. Reversible deposition of callose at PD plays an important role in controlling molecular trafficking through PD by regulating their size exclusion limit. Previously, we reported several semi-dominant mutants for CALLOSE SYNTHASE 3 (CALS3) gene, which overproduce callose at PD in Arabidopsis. By combining two of these mutations in a LexA-VP16-ER (XVE)-based estradiol inducible vector system, a tool known as the "icals3m system" was developed to temporally obstruct the symplastic connections in a specified spatial domain. The system has been successfully tested and used, in combination with other methods, to investigate the route for mobile signals such as the SHR protein, microRNA165/6, and cytokinins in Arabidopsis roots, and also to understand the role of symplastic domain formation during lateral root development. We envision that this tool may also be useful for identifying tissue-specific symplastic regulatory networks and to analyze symplastic movement of metabolites.

Sieve Tube Geometry in Relation to Phloem Flow

Science.gov (United States)

Mullendore, Daniel L.; Windt, Carel W.; Van As, Henk; Knoblauch, Michael

2010-01-01

Sieve elements are one of the least understood cell types in plants. Translocation velocities and volume flow to supply sinks with photoassimilates greatly depend on the geometry of the microfluidic sieve tube system and especially on the anatomy of sieve plates and sieve plate pores. Several models for phloem translocation have been developed, but appropriate data on the geometry of pores, plates, sieve elements, and flow parameters are lacking. We developed a method to clear cells from cytoplasmic constituents to image cell walls by scanning electron microscopy. This method allows high-resolution measurements of sieve element and sieve plate geometries. Sieve tube–specific conductivity and its reduction by callose deposition after injury was calculated for green bean (Phaseolus vulgaris), bamboo (Phyllostachys nuda), squash (Cucurbita maxima), castor bean (Ricinus communis), and tomato (Solanum lycopersicum). Phloem sap velocity measurements by magnetic resonance imaging velocimetry indicate that higher conductivity is not accompanied by a higher velocity. Studies on the temporal development of callose show that small sieve plate pores might be occluded by callose within minutes, but plants containing sieve tubes with large pores need additional mechanisms. PMID:20354199

The development of a methodology to assess population doses from multiple sources and exposure pathways of radioactivity

International Nuclear Information System (INIS)

Hancox, J.; Stansby, S.; Thorne, M.

2002-01-01

The Environment Agency (EA) has new duties in accordance with the Basic Safety Standards Directive under which it is required to ensure that doses to individuals received from exposure to anthropogenic sources of radioactivity are within defined limits. In order to assess compliance with these requirements, the EA needs to assess the doses to members of the most highly exposed population groups ('critical' groups) from all relevant potential sources of anthropogenic radioactivity and all relevant potential exposure pathways to such radioactivity. The EA has identified a need to develop a methodology for the retrospective assessment of effective doses from multiple sources of radioactive materials and exposure pathways associated with those sources. Under contract to the EA, AEA Technology has undertaken the development of a suitable methodology as part of EA R and D Project P3-070. The methodology developed under this research project has been designed to support the EA in meeting its obligations under the Euratom Basic Safety Standards Directive and is consistent with UK and international approaches to radiation dosimetry and radiological protection. The development and trial application of the methodology is described in this report

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

Science.gov (United States)

Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

2017-10-01

To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Junction detection and pathway selection

Science.gov (United States)

Peck, Alex N.; Lim, Willie Y.; Breul, Harry T.

1992-02-01

The ability to detect junctions and make choices among the possible pathways is important for autonomous navigation. In our script-based navigation approach where a journey is specified as a script of high-level instructions, actions are frequently referenced to junctions, e.g., `turn left at the intersection.' In order for the robot to carry out these kind of instructions, it must be able (1) to detect an intersection (i.e., an intersection of pathways), (2) know that there are several possible pathways it can take, and (3) pick the pathway consistent with the high level instruction. In this paper we describe our implementation of the ability to detect junctions in an indoor environment, such as corners, T-junctions and intersections, using sonar. Our approach uses a combination of partial scan of the local environment and recognition of sonar signatures of certain features of the junctions. In the case where the environment is known, we use additional sensor information (such as compass bearings) to help recognize the specific junction. In general, once a junction is detected and its type known, the number of possible pathways can be deduced and the correct pathway selected. Then the appropriate behavior for negotiating the junction is activated.

CD137 pathway: immunology and diseases

National Research Council Canada - National Science Library

Chen, Lieping

2006-01-01

... may work in either interconnected or linear fashion. Therefore, the combined understanding of each pathway, their interactions with other pathways, and the functional consequence, is a cornerstone for our interpretation of pathological basis of diseases and future treatments. It is important to stay abreast on the pace of progress, which I refer to as periodic summary of incremental and breakthrough discoveries in each pathway by the experts and the leader in the field. The CD137 Pathway: Immu...

Heat-Related Mortality in a Warming Climate: Projections for 12 U.S. Cities

Directory of Open Access Journals (Sweden)

Elisaveta P. Petkova

2014-10-01

Full Text Available Heat is among the deadliest weather-related phenomena in the United States, and the number of heat-related deaths may increase under a changing climate, particularly in urban areas. Regional adaptation planning is unfortunately often limited by the lack of quantitative information on potential future health responses. This study presents an assessment of the future impacts of climate change on heat-related mortality in 12 cities using 16 global climate models, driven by two scenarios of greenhouse gas emissions. Although the magnitude of the projected heat effects was found to differ across time, cities, climate models and greenhouse pollution emissions scenarios, climate change was projected to result in increases in heat-related fatalities over time throughout the 21st century in all of the 12 cities included in this study. The increase was more substantial under the high emission pathway, highlighting the potential benefits to public health of reducing greenhouse gas emissions. Nearly 200,000 heat-related deaths are projected to occur in the 12 cities by the end of the century due to climate warming, over 22,000 of which could be avoided if we follow a low GHG emission pathway. The presented estimates can be of value to local decision makers and stakeholders interested in developing strategies to reduce these impacts and building climate change resilience.

Heat-Related Mortality in a Warming Climate: Projections for 12 U.S. Cities

Science.gov (United States)

Petkova, Elisaveta P.; Bader, Daniel A.; Anderson, G. Brooke; Horton, Radley M.; Knowlton, Kim; Kinney, Patrick L.

2014-01-01

Heat is among the deadliest weather-related phenomena in the United States, and the number of heat-related deaths may increase under a changing climate, particularly in urban areas. Regional adaptation planning is unfortunately often limited by the lack of quantitative information on potential future health responses. This study presents an assessment of the future impacts of climate change on heat-related mortality in 12 cities using 16 global climate models, driven by two scenarios of greenhouse gas emissions. Although the magnitude of the projected heat effects was found to differ across time, cities, climate models and greenhouse pollution emissions scenarios, climate change was projected to result in increases in heat-related fatalities over time throughout the 21st century in all of the 12 cities included in this study. The increase was more substantial under the high emission pathway, highlighting the potential benefits to public health of reducing greenhouse gas emissions. Nearly 200,000 heat-related deaths are projected to occur in the 12 cities by the end of the century due to climate warming, over 22,000 of which could be avoided if we follow a low GHG emission pathway. The presented estimates can be of value to local decision makers and stakeholders interested in developing strategies to reduce these impacts and building climate change resilience.

The Cardiopulmonary Effects of Ambient Air Pollution and Mechanistic Pathways: A Comparative Hierarchical Pathway Analysis

Science.gov (United States)

Thomas, Duncan C.; Zhang, Junfeng; Kipen, Howard M.; Rich, David Q.; Zhu, Tong; Huang, Wei; Hu, Min; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott R.; Eckel, Sandrah P.

2014-01-01

Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2–3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system. PMID:25502951

The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

Directory of Open Access Journals (Sweden)

Ananya Roy

Full Text Available Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001 and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005. These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

The urban and community health pathway: preparing socially responsive physicians through community-engaged learning.

Science.gov (United States)

Meurer, Linda N; Young, Staci A; Meurer, John R; Johnson, Sheri L; Gilbert, Ileen A; Diehr, Sabina

2011-10-01

One of five options for the new required Medical College of Wisconsin Pathways program, the Urban and Community Health Pathway (UCHP), links training with community needs and assets to prepare students with the knowledge, skills, and attitudes to provide effective care in urban, underserved settings; promote community health; and reduce health disparities. Students spend at least 10 hours per month on pathway activities: 4 hours of core material delivered through readings, didactics, case discussions, and site visits; and at least 6 hours of experiential noncore activities applying core competencies, guided by an Individualized Learning Plan and faculty advisor. Noncore activities include community-engaged research, service-learning activities or other relevant experiences, and submission of a synthesis paper addressing pathway competencies. The first cohort of students began their pathways in January 2010. Of 560 participating students, 95 (of which 48 were first-year, 21 second-year, and 26 third-year students) selected UCHP. Core sessions focused on public health, social determinants, cultural humility, poverty, the local healthcare system, and safety net. During noncore time, students engaged in projects addressing homelessness, obesity, advocacy, Hmong and Latino health, HIV, asthma, and violence prevention. Students enjoyed working with peers across classes and favored interactive, community-based sessions over didactics in the classroom. Students' papers reflected a range of service and scholarly activities and a deepened appreciation of social and economic influences on health. The UCHP enriches the traditional curriculum with individualized, community-based experiences to build knowledge about health determinants and skills in partnering with communities to improve health. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

Integrated analysis of transportation demand pathway options for hydrogen production, storage, and distribution

Energy Technology Data Exchange (ETDEWEB)

Thomas, C.E.S. [Directed Technologies Inc., Arlington, VA (United States)

1996-10-01

Directed Technologies, Inc. has begun the development of a computer model with the goal of providing guidance to the Hydrogen Program Office regarding the most cost effective use of limited resources to meet national energy security and environmental goals through the use of hydrogen as a major energy carrier. The underlying assumption of this programmatic pathway model is that government and industry must work together to bring clean hydrogen energy devices into the marketplace. Industry cannot provide the long term resources necessary to overcome technological, regulatory, institutional, and perceptual barriers to the use of hydrogen as an energy carrier, and government cannot provide the substantial investments required to develop hydrogen energy products and increased hydrogen production capacity. The computer model recognizes this necessary government/industry partnership by determining the early investments required by government to bring hydrogen energy end uses within the time horizon and profitability criteria of industry, and by estimating the subsequent investments required by industry. The model then predicts the cost/benefit ratio for government, based on contributions of each hydrogen project to meeting societal goals, and it predicts the return on investment for industry. Sensitivity analyses with respect to various government investments such as hydrogen research and development and demonstration projects will then provide guidance as to the most cost effective mix of government actions. The initial model considers the hydrogen transportation market, but this programmatic pathway methodology will be extended to other market segments in the future.

miR2Pathway: A Novel Analytical Method to Discover MicroRNA-mediated Dysregulated Pathways Involved in Hepatocellular Carcinoma.

Science.gov (United States)

Li, Chaoxing; Dinu, Valentin

2018-03-22

MicroRNAs (miRNAs) are small, non-coding RNAs involved in the regulation of gene expression at a post-transcriptional level. Recent studies have shown miRNAs as key regulators of a variety of biological processes, such as proliferation, differentiation, apoptosis, metabolism, etc. Aberrantly expressed miRNAs influence individual gene expression level, but rewired miRNA-mRNA connections can influence the activity of biological pathways. Here, we define rewired miRNA-mRNA connections as the differential (rewiring) effects on the activity of biological pathways between hepatocellular carcinoma (HCC) and normal phenotypes. Our work presented here uses a PageRank-based approach to measure the degree of miRNA-mediated dysregulation of biological pathways between HCC and normal samples based on rewired miRNA-mRNA connections. In our study, we regard the degree of miRNA-mediated dysregulation of biological pathways as disease risk of biological pathways. Therefore, we propose a new method, miR2Pathway, to measure and rank the degree of miRNA-mediated dysregulation of biological pathways by measuring the total differential influence of miRNAs on the activity of pathways between HCC and normal states. miR2Pathway proposed here systematically shows the first evidence for a mechanism of biological pathways being dysregulated by rewired miRNA-mRNA connections, and provides new insight into exploring mechanisms behind HCC. Thus, miR2Pathway is a novel method to identify and rank miRNA-dysregulated pathways in HCC. Copyright © 2018. Published by Elsevier Inc.

Nuclear and radiological preparedness: the achievements of the European research project prepare

International Nuclear Information System (INIS)

Schneider, Thierry; Gering, Florian; Charron, Sylvie; Zhelezniak, Mark; Andronopoulos, Spyros; Heriard-Dubreuil, Gilles; Camps, Johan; Raskob, Wolfgang

2017-01-01

The PREPARE project aimed closing gaps identified in nuclear and radiological preparedness in Europe following the first evaluation of the Fukushima disaster. With 46 partners from Europe and Japan, it collected the key players in the area of emergency management and rehabilitation preparedness. Starting from February 2013, the project ended in January 2016. Among others, the project reviewed existing operational procedures for long-lasting releases, cross-border problems in radiation monitoring and food safety and further developed missing functionalities in decision support systems ranging from improved source term estimation and dispersion modelling to the inclusion of hydrological pathways for European water bodies. In addition, a so-called Analytical Platform has been developed to explore the scientific and operational means to improve information collection, information exchange and the evaluation of such types of disasters. The tools developed within the project will be partly integrated into the decision support systems ARGOS and JRODOS. (authors)

Adaptation pathways in planning for uncertain climate change: Applications in Portugal, the Czech Republic and the Netherlands

Czech Academy of Sciences Publication Activity Database

Zandvoort, M.; Campos, I. S.; Vizinho, A.; Penha-Lopes, G.; Lorencová, Eliška; Van der Brugge, R.; van der Vlist, M. J.; van der Brink, A.; Jeuken, A. B. M.

2017-01-01

Roč. 78, dec (2017), s. 18-26 ISSN 1462-9011 R&D Projects: GA MŠk(CZ) LO1415; GA TA ČR(CZ) TD03000106 Institutional support: RVO:67179843 Keywords : Planning tools * Policy-making * Design choices * Climate adaptation * Uncertainty * Adaptation pathways Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 3.751, year: 2016

ICLUS v2.1.1 land use projections for SSP5 and RCP8.5 pathways

Data.gov (United States)

U.S. Environmental Protection Agency — The methodology used to produce these projections differs from ICLUS v2.0 (https://cfpub.epa.gov/ncea/iclus/recordisplay.cfm?deid=322479). The demographic components...

ICLUS v2.1.1 land use projections for SSP2 and RCP4.5 pathways

Data.gov (United States)

U.S. Environmental Protection Agency — The methodology used to produce these projections differs from ICLUS v2.0 (https://cfpub.epa.gov/ncea/iclus/recordisplay.cfm?deid=322479). The demographic components...

The 2016-2018 National Plan of Management of Radioactive Materials and Wastes - Project

International Nuclear Information System (INIS)

Gazzo, Alexis; Robert, Jean-Gabriel; Abraham, Christophe; Benaze, Manon de

2015-01-01

A first document contains the project of the National Plan of Management of Radioactive Materials and Wastes (PNGMDR) for the period 2016-2018: principles and objectives (presentation of radioactive materials and wastes, principles to be taken into account to define pathways of management of radioactive wastes, legal and institutional framework, information transparency), the management of radioactive materials (context and challenges, management pathways, works on fast breeder reactors of fourth generation), assessment and perspectives of existing pathways of management of radioactive wastes (management of historical situations, management of residues of mining and sterile processing, management of waste with a high natural radioactivity, management of very short life waste, of very low activity wastes, and low and medium activity wastes), needs and perspectives regarding management processes to be implemented for the different types of radioactive wastes. Appendices to this document contain a recall of the content of previous PNGMDR since 2007, a synthesis of realisations and researches performed abroad, research orientations for the concerned period, and international agreement on spent fuel and radioactive waste management. A second document, released by the ASN, proposes an environmental and strategic assessment of the plan. A third one and a fourth one contain the opinion of the Environmental Authority, respectively on the plan preliminary focus, and on the plan itself. An answer to this last one is then proposed, followed by a synthesis of the plan project and the text of the corresponding decree

Pathways to youth homelessness.

Science.gov (United States)

Martijn, Claudine; Sharpe, Louise

2006-01-01

Research documents high levels of psychopathology among homeless youth. Most research, however, has not distinguished between disorders that are present prior to homelessness and those that develop following homelessness. Hence whether psychological disorders are the cause or consequence of homelessness has not been established. The aim of this study is to investigate causal pathways to homelessness amongst currently homeless youth in Australia. The study uses a quasi-qualitative methodology to generate hypotheses for larger-scale research. High rates of psychological disorders were confirmed in the sample 35 homeless youth aged 14-25. The rates of psychological disorders at the point of homelessness were greater than in normative samples, but the rates of clinical disorder increased further once homeless. Further in-depth analyses were conducted to identify the temporal sequence for each individual with a view to establishing a set of causal pathways to homelessness and trajectories following homelessness that characterised the people in the sample. Five pathways to homelessness and five trajectories following homelessness were identified that accounted for the entire sample. Each pathway constituted a series of interactions between different factors similar to that described by Craig and Hodson (1998. Psychological Medicine, 28, 1379-1388) as "complex subsidiary pathways". The major findings were that (1) trauma is a common experience amongst homeless youth prior to homelessness and figured in the causal pathways to homelessness for over half of the sample; (2) once homeless, for the majority of youth there is an increase in the number of psychological diagnoses including drug and alcohol diagnoses; and (3) crime did not precede homelessness for all but one youth; however, following homelessness, involvement in criminal activity was common and became a distinguishing factor amongst youth. The implications of these findings for future research and service

Pathway-based analyses.

Science.gov (United States)

Kent, Jack W

2016-02-03

New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

Dexter energy transfer pathways.

Science.gov (United States)

Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

2016-07-19

Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

Turbidite pathways in Cascadia Basin and Tufts abyssal plain, Part A, Astoria Channel, Blanco Valley, and Gorda Basin

Science.gov (United States)

Wolf, Stephen C.; Hamer, Michael R.

1999-01-01

This open-file report was prepared in support of the USGS Earthquake Hazards of Cascadia Project. The primary objective of this phase of the project is to determine recurrence intervals of turbidites in Cascadia basin-floor channel systems and evaluate implications of this event record for the paleoseismic history of the Cascadia subduction zone. The purpose of this study is to determine whether the canyon/channel systems themselves are blocked or deformed in such a way that the downstream turbidite stratigraphy might be biased. To accomplish this investigation approximately 7500 kilometers of pre-existing 3.5 KHz seismic data were evaluated to determine the direction and extent of the Astoria Channel/pathway system, which originates at the base of the Astoria Fan. Additionally, distribution and thickness of turbidite sediment sequences were determined along each identified pathway. Bathymetery and distance were used to determine gradients along the main pathway axis and for each of the secondary pathways that feed into it. Channel pathways were identified on the basis of channel phyisiography, where visible at the seafloor, subbottom channel configuration, and acoustic packets of sediments that might represent turbidite deposits. A principal result of this study is that the Astoria Channel/pathway extends continuously from the base of the Astoria Fan southward along the base of the continental slope through the Blanco Valley, then heads southwestward through the Gorda Basin and into the region of the Escanaba Trough. Additionally it was determined that the Astoria Channel is filled and basically buried for it's full length south of 44 degrees latitude. The 44 North Slump, as defined by Goldfinger (1999, see Map 3 ref.), may have been instrumental in blocking the pathway and thus contributed to the filling of the channel/pathway. Sheets 1 and 2 show the Astoria and secondary turbidite pathways highlighted in blue. Ship survey tracklines are shown for the area

Guiding Principles for Data Architecture to Support the Pathways Community HUB Model.

Science.gov (United States)

Zeigler, Bernard P; Redding, Sarah; Leath, Brenda A; Carter, Ernest L; Russell, Cynthia

2016-01-01

The Pathways Community HUB Model provides a unique strategy to effectively supplement health care services with social services needed to overcome barriers for those most at risk of poor health outcomes. Pathways are standardized measurement tools used to define and track health and social issues from identification through to a measurable completion point. The HUB use Pathways to coordinate agencies and service providers in the community to eliminate the inefficiencies and duplication that exist among them. Experience with the Model has brought out the need for better information technology solutions to support implementation of the Pathways themselves through decision-support tools for care coordinators and other users to track activities and outcomes, and to facilitate reporting. Here we provide a basis for discussing recommendations for such a data infrastructure by developing a conceptual model that formalizes the Pathway concept underlying current implementations. The main contribution is a set of core recommendations as a framework for developing and implementing a data architecture to support implementation of the Pathways Community HUB Model. The objective is to present a tool for communities interested in adopting the Model to learn from and to adapt in their own development and implementation efforts. Experience with the Community Health Access Project (CHAP) data base system (the core implementation of the Model) has identified several issues and remedies that have been developed to address these issues. Based on analysis of issues and remedies, we present several key features for a data architecture meeting the just mentioned recommendations. Presentation of features is followed by a practical guide to their implementation allowing an organization to consider either tailoring off-the-shelf generic systems to meet the requirements or offerings that are specialized for community-based care coordination. Looking to future extensions, we discuss the

Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

Directory of Open Access Journals (Sweden)

Ramón A Piñol

Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

Understanding Contaminant Transport Pathways at Rocky Flats - A Basis for the Remediation Strategy

International Nuclear Information System (INIS)

Paton, Ian

2008-01-01

The Rocky Flats Environmental Technology Site (RFETS) is a Department of Energy facility located approximately 16 miles northwest of Denver, Colorado. Processing and fabrication of nuclear weapons components occurred at Rocky Flats from 1952 through 1989. Operations at the Site included the use of several radionuclides, including plutonium-239/240 (Pu), americium-241 (Am), and various uranium (U) isotopes, as well as several types of chlorinated solvents. The historic operations resulted in legacy contamination, including contaminated facilities, process waste lines, buried wastes and surface soil contamination. Decontamination and removal of buildings at the site was completed in late 2005, culminating more than ten years of active environmental remediation work. The Corrective Action Decision/Record of Decision was subsequently approved in 2006, signifying regulatory approval and closure of the site. The use of RFETS as a National Wildlife Refuge is scheduled to be in full operation by 2012. To develop a plan for remediating different types of radionuclide contaminants present in the RFETS environment required understanding the different environmental transport pathways for the various actinides. Developing this understanding was the primary objective of the Actinide Migration Evaluation (AME) project. Findings from the AME studies were used in the development of RFETS remediation strategies. The AME project focused on issues of actinide behavior and mobility in surface water, groundwater, air, soil and biota at RFETS. For the purposes of the AME studies, actinide elements addressed included Pu, Am, and U. The AME program, funded by DOE, brought together personnel with a broad range of relevant expertise in technical investigations. The AME advisory panel identified research investigations and approaches that could be used to solve issues related to actinide migration at the Site. An initial step of the AME was to develop a conceptual model to provide a

Metabolic pathways for the whole community.

Science.gov (United States)

Hanson, Niels W; Konwar, Kishori M; Hawley, Alyse K; Altman, Tomer; Karp, Peter D; Hallam, Steven J

2014-07-22

A convergence of high-throughput sequencing and computational power is transforming biology into information science. Despite these technological advances, converting bits and bytes of sequence information into meaningful insights remains a challenging enterprise. Biological systems operate on multiple hierarchical levels from genomes to biomes. Holistic understanding of biological systems requires agile software tools that permit comparative analyses across multiple information levels (DNA, RNA, protein, and metabolites) to identify emergent properties, diagnose system states, or predict responses to environmental change. Here we adopt the MetaPathways annotation and analysis pipeline and Pathway Tools to construct environmental pathway/genome databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a highly curated database of metabolic pathways and components covering all domains of life. We evaluate Pathway Tools' performance on three datasets with different complexity and coding potential, including simulated metagenomes, a symbiotic system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity relationships between read length, coverage and pathway recovery and evaluate the impact of taxonomic pruning on ePGDB construction and interpretation. Resulting ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways associated with biosynthesis and energy production and differentiate between genomic potential and phenotypic expression across defined environmental gradients. This multi-tiered analysis provides the user community with specific operating guidelines, performance metrics and prediction hazards for more reliable ePGDB construction and interpretation. Moreover, it demonstrates the power of Pathway Tools in predicting metabolic interactions in natural and engineered ecosystems.

Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary Gland

Science.gov (United States)

2014-11-01

breast cancer stem cells with oncolytic herpes simplex virus. Cancer Gene Therapy 2012;19(10):707-14. June 21, 2012 – Poster Presentation – Presented...AD_________________ Award Number: W81XWH-11-1-0152 TITLE: Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary... Identification of Target Genes in the 5b. GRANT NUMBER W81XWH-11-1-0152 Mouse Mammary Gland 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

Tetrapyrrole Synthesis of Photosynthetic Chromerids Is Likely Homologous to the Unusual Pathway of Apicomplexan Parasites

Czech Academy of Sciences Publication Activity Database

Kořený, Luděk; Sobotka, Roman; Janouškovec, J.; Keeling, P. J.; Oborník, Miroslav

2011-01-01

Roč. 23, č. 9 (2011), s. 3454-3462 ISSN 1040-4651 R&D Projects: GA ČR GA206/08/1423; GA AV ČR IAA601410907 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z50200510 Keywords : YEAST SACCHAROMYCES-CEREVISIAE * HEME-BIOSYNTHESIS PATHWAY * PLASMODIUM-FALCIPARUM * MALARIA PARASITE * 5-AMINOLEVULINATE SYNTHASE * SECONDARY PLASTIDS * TOXOPLASMA-GONDII * PROTEIN-TRANSPORT * EUGLENA-GRACILIS * METABOLIC MAPS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.987, year: 2011

Hierarchically organized layout for visualization of biochemical pathways.

Science.gov (United States)

Tsay, Jyh-Jong; Wu, Bo-Liang; Jeng, Yu-Sen

2010-01-01

Many complex pathways are described as hierarchical structures in which a pathway is recursively partitioned into several sub-pathways, and organized hierarchically as a tree. The hierarchical structure provides a natural way to visualize the global structure of a complex pathway. However, none of the previous research on pathway visualization explores the hierarchical structures provided by many complex pathways. In this paper, we aim to develop algorithms that can take advantages of hierarchical structures, and give layouts that explore the global structures as well as local structures of pathways. We present a new hierarchically organized layout algorithm to produce layouts for hierarchically organized pathways. Our algorithm first decomposes a complex pathway into sub-pathway groups along the hierarchical organization, and then partition each sub-pathway group into basic components. It then applies conventional layout algorithms, such as hierarchical layout and force-directed layout, to compute the layout of each basic component. Finally, component layouts are joined to form a final layout of the pathway. Our main contribution is the development of algorithms for decomposing pathways and joining layouts. Experiment shows that our algorithm is able to give comprehensible visualization for pathways with hierarchies, cycles as well as complex structures. It clearly renders the global component structures as well as the local structure in each component. In addition, it runs very fast, and gives better visualization for many examples from previous related research. 2009 Elsevier B.V. All rights reserved.

HDR-Pathways

Data.gov (United States)

Department of Veterans Affairs — Pathways is a SOAP/REST web service interface accessed via HTTPS that provides administrative data (Appointments, Exam Requests and Exams information) from VistA in...

The health sciences librarian in medical education: a vital pathways project task force.

Science.gov (United States)

Schwartz, Diane G; Blobaum, Paul M; Shipman, Jean P; Markwell, Linda Garr; Marshall, Joanne Gard

2009-10-01

The Medical Education Task Force of the Task Force on Vital Pathways for Hospital Librarians reviewed current and future roles of health sciences librarians in medical education at the graduate and undergraduate levels and worked with national organizations to integrate library services, education, and staff into the requirements for training medical students and residents. Standards for medical education accreditation programs were studied, and a literature search was conducted on the topic of the role of the health sciences librarian in medical education. Expectations for library and information services in current standards were documented, and a draft standard prepared. A comprehensive bibliography on the role of the health sciences librarian in medical education was completed, and an analysis of the services provided by health sciences librarians was created. An essential role and responsibility of the health sciences librarian will be to provide the health care professional with the skills needed to access, manage, and use library and information resources effectively. Validation and recognition of the health sciences librarian's contributions to medical education by accrediting agencies will be critical. The opportunity lies in health sciences librarians embracing the diverse roles that can be served in this vital activity, regardless of accrediting agency mandates.

An optimization model for metabolic pathways.

Science.gov (United States)

Planes, F J; Beasley, J E

2009-10-15

Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

Method for determining heterologous biosynthesis pathways

KAUST Repository

Gao, Xin

2017-08-10

The present invention relates to a method and system for dynamically analyzing, determining, predicting and displaying ranked suitable heterologous biosynthesis pathways for a specified host. The present invention addresses the problem of finding suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived and developed to systematically and dynamically search for, determine, analyze, and display promising heterologous pathways while considering competing endogenous reactions in a given host organism.

Modularized TGFbeta-Smad Signaling Pathway

Science.gov (United States)

Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

2011-01-01

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

A long slanted transseptal accessory pathway

Directory of Open Access Journals (Sweden)

Hui-Min Wang

2011-05-01

Full Text Available A 63-year-old male with Wolff-Parkinson-White syndrome was admitted for ablation of accessory pathway. Intracardiac electrogram revealed a left-side accessory pathway during tachycardia, which was successfully ablated from the right posterior tricuspid annulus because of a long slanted transseptal accessory pathway (2.2 cm.

Certification Criteria for Linked Learning Pathways

Science.gov (United States)

ConnectEd: The California Center for College and Career, 2010

2010-01-01

Pathways offer a promising strategy for transforming high schools and improving student outcomes. However, to achieve these desired results, pathways must be of high quality. To guide sites in planning and implementing such pathways, a design team of experts developed the criteria outlined in this document. Sites can choose to go through a…

Pathways to URM Retention: IBP's Professional Development and Mentoring Activities

Science.gov (United States)

Johnson, A.; Williamson Whitney, V.; Ricciardi, L.; Detrick, L.; Siegfried, D.; Fauver, A.; Ithier-Guzman, W.; Thomas, S. H.; Valaitis, S.

2013-05-01

As a not for profit organization, the Institute for Broadening Participation (IBP) hosts a variety of initiatives designed to increase the retention of underrepresented minority (URM) students pursuing pathways in STEM. IBP also assists with formative program evaluation design and implementation to help strengthen URM recruitment and retention elements. Successful initiatives include virtual and face-to-face components that bring together URM students with established URM and other scientists in academia, government and industry. These connections provide URMs with mentoring, networking opportunities, and professional skill development contributing to an improved retention rate of URM students. IBP's initiatives include the NASA One Stop Shopping Initiative (NASA OSSI), Pathways to Ocean Science and Engineering, and the Minorities Striving and Pursuing Higher Degrees of Success (MS PHD'S) in Earth System Science (ESS) Professional Development Program. The NASA OSSI recruits and facilitates student engagement in NASA education and employment opportunities. Pathways to Ocean Science connects and supports URM students with Ocean Science REU programs and serves as a resource for REU program directors. Pathways to Engineering has synthesized mentoring resources into an online mentoring manual for URM students that has been extensively vetted by mentoring experts throughout the country. The mentoring manual, which is organized by roles, provides undergraduates, graduates, postdocs, faculty and project directors with valuable resources. MS PHD'S, one of IBP's longest running and most successful initiatives, focuses on increasing the retention rate of URM students receiving advanced degrees in ESS. The program addresses barriers to retention in ESS including isolation, lack of preparation and professional development, and lack of mentoring. Program activities center on peer-to-peer community building, professional development exercises, networking experiences, one

The Biocatalytic Desulfurization Project

Energy Technology Data Exchange (ETDEWEB)

David Nunn; James Boltz; Philip M. DiGrazia; Larry Nace

2006-03-03

The material in this report summarizes the Diversa technical effort in development of a biocatalyst for the biodesulfurization of Petro Star diesel as well as an economic report of standalone and combined desulfurization options, prepared by Pelorus and Anvil, to support and inform the development of a commercially viable process. We will discuss goals of the projected as originally stated and their modification as guided by parallel efforts to evaluate commercialization economics and process parameters. We describe efforts to identify novel genes and hosts for the generation of an optimal biocatalyst, analysis of diesel fuels (untreated, chemically oxidized and hydrotreated) for organosulfur compound composition and directed evolution of enzymes central to the biodesulfurization pathway to optimize properties important for their use in a biocatalyst. Finally we will summarize the challenges and issues that are central to successful development of a viable biodesulfurization process.

Antiviral Roles of Abscisic Acid in Plants

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Mazen Alazem

2017-10-01

Full Text Available Abscisic acid (ABA is a key hormone involved in tuning responses to several abiotic stresses and also has remarkable impacts on plant defense against various pathogens. The roles of ABA in plant defense against bacteria and fungi are multifaceted, inducing or reducing defense responses depending on its time of action. However, ABA induces different resistance mechanisms to viruses regardless of the induction time. Recent studies have linked ABA to the antiviral silencing pathway, which interferes with virus accumulation, and the micro RNA (miRNA pathway through which ABA affects the maturation and stability of miRNAs. ABA also induces callose deposition at plasmodesmata, a mechanism that limits viral cell-to-cell movement. Bamboo mosaic virus (BaMV is a member of the potexvirus group and is one of the most studied viruses in terms of the effects of ABA on its accumulation and resistance. In this review, we summarize how ABA interferes with the accumulation and movement of BaMV and other viruses. We also highlight aspects of ABA that may have an effect on other types of resistance and that require further investigation.

Robust de novo pathway enrichment with KeyPathwayMiner 5 [version 1; referees: 2 approved

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Nicolas Alcaraz

2016-06-01

Full Text Available Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks that are enriched for differentially active entities from a series of molecular profiles encoded as binary indicator matrices. Since interaction networks constantly evolve, an important question is how robust the extracted results are when the network is modified. We enable users to study this effect through several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network.

The mevalonate pathway in C. Elegans

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Rauthan Manish

2011-12-01

Full Text Available Abstract The mevalonate pathway in human is responsible for the synthesis of cholesterol and other important biomolecules such as coenzyme Q, dolichols and isoprenoids. These molecules are required in the cell for functions ranging from signaling to membrane integrity, protein prenylation and glycosylation, and energy homeostasis. The pathway consists of a main trunk followed by sub-branches that synthesize the different biomolecules. The majority of our knowledge about the mevalonate pathway is currently focused on the cholesterol synthesis branch, which is the target of the cholesterol-lowering statins; less is known about the function and regulation of the non-cholesterol-related branches. To study them, we need a biological system where it is possible to specifically modulate these metabolic branches individually or in groups. The nematode Caenorhabditis elegans (C. elegans is a promising model to study these non-cholesterol branches since its mevalonate pathway seems very well conserved with that in human except that it has no cholesterol synthesis branch. The simple genetic makeup and tractability of C. elegans makes it relatively easy to identify and manipulate key genetic components of the mevalonate pathway, and to evaluate the consequences of tampering with their activity. This general experimental approach should lead to new insights into the physiological roles of the non-cholesterol part of the mevalonate pathway. This review will focus on the current knowledge related to the mevalonate pathway in C. elegans and its possible applications as a model organism to study the non-cholesterol functions of this pathway.

Allowable residual contamination levels of radionuclides in soil from pathway analysis

International Nuclear Information System (INIS)

Nyquist, J.E.; Baes, C.F. III

1987-01-01

The Remedial Action Program (RAP) at Oak Ridge National Laboratory will include well drilling, facility upgrades, and other waste management operations likely to involve soils contaminated with radionuclides. A preliminary protocol and generalized criteria for handling contaminated soils is needed to coordinate and plan RAP activities, but there exists only limited information on contaminate nature and distribution at ORNL RAP sites. Furthermore, projections of long-term decommissioning and closure options for these sites are preliminary. They have adapted a pathway analysis model, DECOM, to quantify risks to human health from radionuclides in soil and used it to outline preliminary criteria for determining the fate of contaminated soil produced during RAP activities. They assumed that the site could be available for unrestricted use immediately upon decontamination. The pathways considered are consumption of food grown on the contaminated soil, including direct ingestion of soil from poorly washed vegetables, direct radiation from the ground surface, inhalation of resuspended radioactive soil, and drinking water from a well drilled through or near the contaminated soil. We will discuss the assumptions and simplifications implicit in DECOM, the site-specific data required, and the results of initial calculations for the Oak Ridge Reservation

NEURAL PAIN PATHWAY TRACING OF RABBIT ISCHEMIC HEART BY DOUBLE-RETROGRADE NEUROTRACING

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Theodorus Dapamede

2015-01-01

Full Text Available Background. Myocardial ischaemia occurs due to inadequate supply of oxygen to fulfill the myocardial tissue oxygen demand. This leads to angina pectoris or referred pain, whichhappens because of the inability of the brain to distinguish the visceral afferent inputs from the somatic afferent inputs since they run along a common pathway via the dorsal root ganglia. Aims. This study aims to distinguish specific areas of the rabbit heart that are projected to specific dorsal root ganglia, which then associates to its specific dermatomes. Methods. A double-retrograde neurotracing method was used, with True Blue and Nuclear Yellow as the neurotracers. Rabbits were divided into 3 groups, which the first and second groups were ligated at the left anterior descending artery and at the left circumflex artery, respectively.The third group acted as the control group, without ligation.True blue was injected at ischaemic sites following ligation. Nuclear yellowwas injected at the skin, dermatomes T1-T4. Dorsal root ganglia levels T1-T4 were then examined for both neurotracers at 3 days post injection. Results. There is significant association between the site of ligation to the projection of the neurotracers at specific dorsal root ganglia (p<0.05. The first group showed high tendency to be projected to T2 and the second group showed a high tendency to project to T1. Conclusion. This study shows that the rabbit heart can be specifically projected neuronally to specific dorsal root ganglia, following coronary artery ligation.

Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway.

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Oosterholt, Robin I; Simonse, Lianne Wl; Boess, Stella U; Vehmeijer, Stephan Bw

2017-03-09

Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. The design addressed existing problems and is an optimisation of the case hospital's pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

Different Pathways for Achieving Cleaner Urban Areas

DEFF Research Database (Denmark)

Schippl, J.; Gudmundsson, Henrik; Sørensen, Claus Hedegaard

2016-01-01

The 2011 White Paper on Transport of the European Commission spells out a series of targets for 2030 and 2050. One of the 10 targets is explicitly related to urban transport and stipulates: ''Halve the use of 'conventionally fuelled' cars in urban transport by 2030; phase them out in cities by 2050....... Achieve essentially CO2-free city logistics in major urban centres by 2030.'' With this paper we present and discuss a roadmap that deals with the question who needs to do what by when in order to reach the White Paper goal for urban transport. The ''stakeholder-driven'' roadmap was developed in the FP7...... project TRANSFORuM. The paper will present the key findings and the suggested action steps identified in the roadmap. The paper will also exemplify three possible urban transformation pathways towards the urban target. This approach emerged from stakeholder consultations which highlighted the need to take...

Modularized Smad-regulated TGFβ signaling pathway.

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Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

2012-12-01

The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

Tools and strategies for discovering novel enzymes and metabolic pathways

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John A. Gerlt

2016-12-01

Full Text Available The number of entries in the sequence databases continues to increase exponentially – the UniProt database is increasing with a doubling time of ∼4 years (2% increase/month. Approximately 50% of the entries have uncertain, unknown, or incorrect function annotations because these are made by automated methods based on sequence homology. If the potential in complete genome sequences is to be realized, strategies and tools must be developed to facilitate experimental assignment of functions to uncharacterized proteins discovered in genome projects. The Enzyme Function Initiative (EFI; previously supported by U54GM093342 from the National Institutes of Health, now supported by P01GM118303 developed web tools for visualizing and analyzing (1 sequence and function space in protein families (EFI-EST and (2 genome neighbourhoods in microbial and fungal genomes (EFI-GNT to assist the design of experimental strategies for discovering the in vitro activities and in vivo metabolic functions of uncharacterized enzymes. The EFI developed an experimental platform for large-scale production of the solute binding proteins (SBPs for ABC, TRAP, and TCT transport systems and their screening with a physical ligand library to identify the identities of the ligands for these transport systems. Because the genes that encode transport systems are often co-located with the genes that encode the catabolic pathways for the transported solutes, the identity of the SBP ligand together with the EFI-EST and EFI-GNT web tools can be used to discover new enzyme functions and new metabolic pathways. This approach is demonstrated with the characterization of a novel pathway for ethanolamine catabolism.

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

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Dahl, D; Sarvey, J M

1989-01-01

The study presented here indicates that norepinephrine (NE) selectively induces long-lasting modifications of synaptically mediated responses in the dentate gyrus of the rat hippocampal slice. A low concentration of NE (1.0 microM; in the presence of 50 microM phentolamine, an alpha-adrenergic antagonist) or a 1.0 microM concentration of the specific beta-adrenergic agonist isoproterenol induced long-lasting pathway-specific alterations of granule cell electrophysiological responses. Excitatory postsynaptic potentials and population spikes evoked by stimulation of the medial perforant pathway (PP) were potentiated for more than 45 min. In contrast, responses to lateral PP stimulation were depressed for the same period. Both potentiation and depression were blocked by the beta-adrenergic antagonist propranolol (1.0 microM). These results indicate that NE can act differentially on projections to the dentate gyrus arising in the entorhinal cortex. Such selective persistent modifications of cortical circuits may be involved in processes in the mammalian brain underlying attention, learning, and memory. PMID:2734319

Machine learning methods for metabolic pathway prediction

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Karp Peter D

2010-01-01

Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

Machine learning methods for metabolic pathway prediction

Science.gov (United States)

2010-01-01

Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations. PMID:20064214

Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

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Gregory P. Way

2018-04-01

Full Text Available Summary: Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these “hidden responders” may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. : Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines. Keywords: Gene expression, machine learning, Ras, NF1, KRAS, NRAS, HRAS, pan-cancer, TCGA, drug sensitivity

A theory of blindsight--the anatomy of the unconscious: a proposal for the koniocellular projections and intralaminar thalamus.

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Vakalopoulos, Costa

2005-01-01

This paper extends the concepts introduced by the theory of premotor relations to unconscious cognitive mechanisms. According to the theory conscious mechanisms are associated with behavioural diversity, whereas unconscious output is proposed to have an obligatory association with stereotypical behaviour. The respective processes are by definition a function of the type of reafferent motor input. Concepts of simple and complex premotor networks are introduced as a means of describing unconscious and conscious processes, respectively. Evidence shows that unconscious cognitive performance differs qualitatively from conscious mechanisms suggesting parallel processes. Although the postulated anatomical substrates for conscious and unconscious processes will function in this model as parallel segregated networks, it is proposed they are distributed throughout the same cortical areas of the brain. Motor reafference is postulated to be mediated via pallidal projections to the thalamic reticular nucleus, which is known to modulate thalamocortical pathways. The role of the koniocellular pathway of the lateral geniculate nucleus remains an enigma and has some properties in common with the well-described magnocellular and parvocellular projections. There is also much speculation about the intralaminar and midline nuclei, the so-called non-specific thalamus. The paper will examine the distinctive features of thalamocortical networks and the role of the koniocellular pathway and intralaminar nuclei (ILN) of the thalamus and suggest that they form a neuroanatomical substrate for the categorizing of unconscious cognitive processes. The ILN has unique projections back to the basal ganglia, which could serve in constraining associated neocortical networks with stereotypical behaviour and thus putative unconscious processing. Only after establishing such a theoretical framework can one hope to successfully analyze the empirical literature on the syndrome of blindsight, of which a

Ocean acidification over the next three centuries using a simple global climate carbon-cycle model: projections and sensitivities

Energy Technology Data Exchange (ETDEWEB)

Hartin, Corinne A.; Bond-Lamberty, Benjamin; Patel, Pralit; Mundra, Anupriya

2016-08-01

Continued oceanic uptake of anthropogenic CO₂ is projected to significantly alter the chemistry of the upper oceans over the next three centuries, with potentially serious consequences for marine ecosystems. Relatively few models have the capability to make projections of ocean acidification, limiting our ability to assess the impacts and probabilities of ocean changes. In this study we examine the ability of Hector v1.1, a reduced-form global model, to project changes in the upper ocean carbonate system over the next three centuries, and quantify the model's sensitivity to parametric inputs. Hector is run under prescribed emission pathways from the Representative Concentration Pathways (RCPs) and compared to both observations and a suite of Coupled Model Intercomparison (CMIP5) model outputs. Current observations confirm that ocean acidification is already taking place, and CMIP5 models project significant changes occurring to 2300. Hector is consistent with the observational record within both the high- (> 55°) and low-latitude oceans (< 55°). The model projects low-latitude surface ocean pH to decrease from preindustrial levels of 8.17 to 7.77 in 2100, and to 7.50 in 2300; aragonite saturation levels (Ω_Ar) decrease from 4.1 units to 2.2 in 2100 and 1.4 in 2300 under RCP 8.5. These magnitudes and trends of ocean acidification within Hector are largely consistent with the CMIP5 model outputs, although we identify some small biases within Hector's carbonate system. Of the parameters tested, changes in [H⁺] are most sensitive to parameters that directly affect atmospheric CO₂ concentrations – Q₁₀ (terrestrial respiration temperature response) as well as changes in ocean circulation, while changes in Ω_Ar saturation levels are sensitive to changes in ocean salinity and Q₁₀. We conclude that Hector is a robust tool well suited for rapid ocean acidification